greenmedinfo--2020-12-27--Bioactive components of pomegranate oil and their influence on mycotoxin secretion.

Pomegranate , similar to other fruits , has juice-extraction by-products .
Pomegranate seed oil ( PGO ) is a non-traditional oil with health benefits , rich in bioactive components .
This study was aimed to assess PGO phytochemicals and their influence as bioactive components to reduce mycotoxin secretion .
The encapsulation was applied in micro and nanoforms to protect the quality and enhance the efficacy of the oil .
The PGO was extracted using ultrasound-assisted methods .
Carotenoids , tocochromanols , sterols , phenolic , flavonoid , antioxidant , and antimicrobial activity were determined .
The fatty acid profile was @ @ @ @ @ @ @ was determined utilizing the HPLC apparatus .
The toxicity and protective action of oil were examined using the hepatocytes ' cell line .
The resultant oil acts as oleoresin that is rich in bioactive molecules .
Phenolics and antioxidant potency recorded higher values compared to traditional vegetable oils , whereas polyunsaturated fatty acids were 87.51 % .
The major fatty acid was conjugated punicic acid ( 81.29 % ) , which has high biological effects .
Application of the PGO on fungal media reduced aflatoxins secretion up to 63 % , and zearalenone @ @ @ @ @ @ @ confirm the bio-functionality of oil to regulate the fungal secondary metabolites process .
The PGO is a unique prospective non-traditional oil and has several functionalities in food , which achieve nutritional , antioxidant , and anti-mycotoxigenic activities .

Pomegranate, similar to other fruits, has juice-extraction by-products. Pomegranate seed oil (PGO) is a non-traditional oil with health benefits, rich in bioactive components. This study was aimed to assess PGO phytochemicals and their influence as bioactive components to reduce mycotoxin secretion. The encapsulation was applied in micro and nanoforms to protect the quality and enhance the efficacy of the oil. The PGO was extracted using ultrasound-assisted methods. Carotenoids, tocochromanols, sterols, phenolic, flavonoid, antioxidant, and antimicrobial activity were determined. The fatty acid profile was analyzed by the GC-MS, while mycotoxin was determined utilizing the HPLC apparatus. The toxicity and protective action of oil were examined using the hepatocytes' cell line. The resultant oil acts as oleoresin that is rich in bioactive molecules. Phenolics and antioxidant potency recorded higher values compared to traditional vegetable oils, whereas polyunsaturated fatty acids were 87.51%. The major fatty acid was conjugated punicic acid (81.29%), which has high biological effects. Application of the PGO on fungal media reduced aflatoxins secretion up to 63%, and zearalenone up to 78.5%. These results confirm the bio-functionality of oil to regulate the fungal secondary metabolites process. The PGO is a unique prospective non-traditional oil and has several functionalities in food, which achieve nutritional, antioxidant, and anti-mycotoxigenic activities.


greenmedinfo--2020-12-27--P. granatum fruits peel extract revealed promising antioxidant, anti-diabetic, anti-obesity, and ant

P. granatum fruits peel extract revealed promising antioxidant, anti-diabetic, anti-obesity, and anti-hypertensive properties.

This context was investigated to assess theantioxidant , anti-diabetic , anti-obesity , and angiotensin-converting enzyme ( ACE ) inhibition traits offruits peel extract .
Initially , among various extracts tested , aqueous and ethanolic peel extracts depicted the presence of diverse phytoconstituents.antioxidative properties of peel extracts were determined using standard methodologies .
Results showed that aqueous and ethanolic extracts had ICvalues of 471.7 and 509.16 μg/mL , respectively in terms of 1,1 , diphenyl 2,2 , picrylhydrazyl scavenging .
Likewise , ICvalues of aqueous and ethanol extract were obtained as 488.76 and 478.47 μg/mL towards the degradation of hydrogen peroxide @ @ @ @ @ @ @ inhibition of αglucosidase by showing activity of 53.34 ± 2.0 to 15.18 ± 1.4 U/L in a dose dependent manner ( 100-1000 µg/mL ) .
Ethanolic extract was reported as the most active inhibitor of lipase with an ICvalue of 603.50 µg/mL .
Ethanolic extract showed increased inhibition of ACE in a concentration dependent manner ( 100-1000 µg/mL ) with ICvalue of 519.45 µg/mL .
Fourier transform-infrared spectrum revealed the availability of various functional groups in the ethanolic extract of peel .
Gas chromatography-mass spectrometry chromatogram of peel extract illustrated 23 diversified chemical @ @ @ @ @ @ @ and Pentadecanoic acid as predominant compounds .
In summary , fruits peel extract revealed promising antioxidant , anti-diabetic , anti-obesity , and anti-hypertensive properties .

This context was investigated to assess theantioxidant, anti-diabetic, anti-obesity, and angiotensin-converting enzyme (ACE) inhibition traits offruits peel extract. Initially, among various extracts tested, aqueous and ethanolic peel extracts depicted the presence of diverse phytoconstituents.antioxidative properties of peel extracts were determined using standard methodologies. Results showed that aqueous and ethanolic extracts had ICvalues of 471.7 and 509.16 μg/mL, respectively in terms of 1,1,diphenyl 2,2,picrylhydrazyl scavenging. Likewise, ICvalues of aqueous and ethanol extract were obtained as 488.76 and 478.47 μg/mL towards the degradation of hydrogen peroxide. The ethanolic extract exhibited the highest inhibition of αglucosidase by showing activity of 53.34 ± 2.0 to 15.18 ± 1.4 U/L in a dose dependent manner (100-1000 µg/mL). Ethanolic extract was reported as the most active inhibitor of lipase with an ICvalue of 603.50 µg/mL. Ethanolic extract showed increased inhibition of ACE in a concentration dependent manner (100-1000 µg/mL) with ICvalue of 519.45 µg/mL. Fourier transform-infrared spectrum revealed the availability of various functional groups in the ethanolic extract of peel. Gas chromatography-mass spectrometry chromatogram of peel extract illustrated 23 diversified chemical constituents including 1,2,3,4-butanetetrol, Dimethyl sulfone,9-octadecenamide, and Pentadecanoic acid as predominant compounds. In summary,fruits peel extract revealed promising antioxidant, anti-diabetic, anti-obesity, and anti-hypertensive properties.


greenmedinfo--2020-12-27--Tangeretin ameliorates glucose-Induced podocyte injury.

Podocyte injury inevitably results in leakage of proteins from the glomerular filter and is vital in the pathogenesis of diabetic nephropathy ( DN ) .
The underlying mechanisms of podocyte injury facilitate finding of new therapeutic targets for DN treatment and prevention .
Tangeretin is an O-polymethoxylated flavone present in citrus peels with anti-inflammatory and antioxidant properties .
This study investigated the renoprotective effects of tangeretin on epithelial-to-mesenchymal transition-mediated podocyte injury and fibrosis through oxidative stress and hypoxia caused by hyperglycemia .
Mouse podocytes were incubated in media containing 33 mM glucose in the absence and presence of 1-20μM tangeretin @ @ @ @ @ @ @ in vivo animal model employed db/db mice orally administrated with 10 mg/kg tangeretin for 8 weeks .
Non-toxic tangeretin inhibited glucose-induced expression of the mesenchymal markers of N-cadherin and α-smooth muscle actin in podocytes .
However , the reduced induction of the epithelial markers of E-cadherin and P-cadherin was restored by tangeretin in diabetic podocytes .
Further , tangeretin enhanced the expression of the podocyte slit diaphragm proteins of nephrin and podocin down-regulated by glucose stimulation .
The transmission electron microscopic images revealed that foot process effacement and loss of podocytes occurred in @ @ @ @ @ @ @ administration of 10 mg/kg tangeretin reduced urine albumin excretion and improved foot process effacement of diabetic podocytes through inhibiting loss of slit junction and adherenesjunction proteins .
Glucose enhanced ROS production and HIF-1α induction in podocytes , leading to induction of oxidative stress and hypoxia .
Similarly , in diabetic glomeruli reactive oxygen species ( ROS ) production and HIF-1α induction were observed .
Furthermore , hypoxia-evoking cobalt chloride induced epithelial-to-mesenchymal transition ( EMT ) process and loss of slit diaphragm proteins and junction proteins in podocytes , which was inhibited by treating @ @ @ @ @ @ @ demonstrate that tangeretin inhibited podocyte injury and fibrosis through blocking podocyte EMT caused by glucose-induced oxidative stress and hypoxia .

Podocyte injury inevitably results in leakage of proteins from the glomerular filter and is vital in the pathogenesis of diabetic nephropathy (DN). The underlying mechanisms of podocyte injury facilitate finding of new therapeutic targets for DN treatment and prevention. Tangeretin is an O-polymethoxylated flavone present in citrus peels with anti-inflammatory and antioxidant properties. This study investigated the renoprotective effects of tangeretin on epithelial-to-mesenchymal transition-mediated podocyte injury and fibrosis through oxidative stress and hypoxia caused by hyperglycemia. Mouse podocytes were incubated in media containing 33 mM glucose in the absence and presence of 1-20μM tangeretin for up to 6 days. The in vivo animal model employed db/db mice orally administrated with 10 mg/kg tangeretin for 8 weeks. Non-toxic tangeretin inhibited glucose-induced expression of the mesenchymal markers of N-cadherin and α-smooth muscle actin in podocytes. However, the reduced induction of the epithelial markers of E-cadherin and P-cadherin was restored by tangeretin in diabetic podocytes. Further, tangeretin enhanced the expression of the podocyte slit diaphragm proteins of nephrin and podocin down-regulated by glucose stimulation. The transmission electron microscopic images revealed that foot process effacement and loss of podocytes occurred in diabetic mouse glomeruli. However, oral administration of 10 mg/kg tangeretin reduced urine albumin excretion and improved foot process effacement of diabetic podocytes through inhibiting loss of slit junction and adherenesjunction proteins. Glucose enhanced ROS production and HIF-1α induction in podocytes, leading to induction of oxidative stress and hypoxia. Similarly, in diabetic glomeruli reactive oxygen species (ROS) production and HIF-1α induction were observed. Furthermore, hypoxia-evoking cobalt chloride induced epithelial-to-mesenchymal transition (EMT) process and loss of slit diaphragm proteins and junction proteins in podocytes, which was inhibited by treating submicromolar tangeretin. Collectively, these results demonstrate that tangeretin inhibited podocyte injury and fibrosis through blocking podocyte EMT caused by glucose-induced oxidative stress and hypoxia.


greenmedinfo--2020-12-27--Tangeretin is a novel cardioprotective therapeutic target for sepsis induced myocardial dysfunction.

Sepsis aggregates undesirable immune response causing depression of ventricular myocardium and diastolic dysfunction .
This present study examined the effect of a plant-derived flavone tangeretin ( TG ) on autophagy and reduction in myocardial dysfunction .
The sepsis was induced by cecum ligation and puncture ( CLP ) in male Sprague-Dawley rats .
Abnormal changes were seen in the heart after the sepsis induction .
These abnormalities were analyzed based on the cardiac markers , namely Cardiac myosin light chain-1 ( cMLC1 ) and Cardiac troponin I ( cTnl ) , echocardiography , and plasma parameters , like Lactate dehydrogenase @ @ @ @ @ @ @ CK ) .
Microanatomy of the heart was studied using hematoxylin and eosin stained histopathological samples of cardiac tissue .
Western blot technique was used to detect the nature and extent of protein with the amount of a specific RNA ( gene expression ) in the cardiac homogenate .
Oxidative damage was analyzed using redox marker , reduced glutathione .
This study successfully showed that TG attenuated sepsis-induced myocardial dysfunction by inhibiting myocardial autophagy via silencing the Phosphatase and tensin homolog ( PTEN ) expression and acting on the AKT/mTOR pathway .
The @ @ @ @ @ @ @ novel cardioprotective therapeutic target for sepsis induced myocardial dysfunction .

Sepsis aggregates undesirable immune response causing depression of ventricular myocardium and diastolic dysfunction. This present study examined the effect of a plant-derived flavone tangeretin (TG) on autophagy and reduction in myocardial dysfunction. The sepsis was induced by cecum ligation and puncture (CLP) in male Sprague-Dawley rats. Abnormal changes were seen in the heart after the sepsis induction. These abnormalities were analyzed based on the cardiac markers, namely Cardiac myosin light chain-1 (cMLC1) and Cardiac troponin I (cTnl), echocardiography, and plasma parameters, like Lactate dehydrogenase (LDH) and Creatinine kinase (CK). Microanatomy of the heart was studied using hematoxylin and eosin stained histopathological samples of cardiac tissue. Western blot technique was used to detect the nature and extent of protein with the amount of a specific RNA (gene expression) in the cardiac homogenate. Oxidative damage was analyzed using redox marker, reduced glutathione. This study successfully showed that TG attenuated sepsis-induced myocardial dysfunction by inhibiting myocardial autophagy via silencing the Phosphatase and tensin homolog (PTEN) expression and acting on the AKT/mTOR pathway. The present findings supported that TG is a novel cardioprotective therapeutic target for sepsis induced myocardial dysfunction.


greenmedinfo--2020-12-27--The combined effect of pomegranate extract and tangeretin on the DMBA-induced breast cancer model.

The aim of this study was to investigate the protective effects of pomegranate extract and tangeretin alone or in combination in DMBA-induced rat breast cancer model .
A total of 68 female rats were randomly divided into 8 groups .
The first 4 groups were designed as controls for cancer and treatment groups , and the control groups were composed of only control ( C ) , Pomegranate ( P ) , Tangeretin ( T ) and Pomegranate+Tangeretin ( P+T ) groups .
The other 4 groups were designed as cancer and treatment groups and were composed of DMBA ( @ @ @ @ @ @ @ , DMBA+Tangeretin ( D+T ) , DMBA+Pomegranate+Tangeretin ( D+P+T ) groups .
Tumor markers and angiogenesis parameters were studied from plasma samples obtained from rats .
Histopathological , immunohistochemical and TUNEL analyses and expressions of proteins affecting apoptosis and cell cycle were determined in breast tissue samples .
In the DMBA group , plasma CA15-3 , CEA , VEGF , MMP-9 and NF-κB levels were significantly increased compared to the controls , but significant decreases were observed in these parameters except MMP-9 in the treatment groups .
It was observed that p53 and @ @ @ @ @ @ @ and D+P+T groups compared to the DMBA group , and thesefindings were supported by Tunel and immunohistochemical findings .
Cyclin D1 expressions were found to be significantly decreased only in the D+T group and supported by TUNEL and immunohistochemical findings .
Immunohistochemical ER-α and Ki-67 immune reactivities were significantly decreased in alltreatment groups compared to the DMBA group .
Our results showed that combined application of pomegranate extract and tangeretin may be more beneficial in preventing breast cancer development .

The aim of this study was to investigate the protective effects of pomegranate extract and tangeretin alone or in combination in DMBA-induced rat breast cancer model. A total of 68 female rats were randomly divided into 8 groups. The first 4 groups were designed as controls for cancer and treatment groups, and the control groups were composed of only control (C), Pomegranate (P), Tangeretin (T) and Pomegranate+Tangeretin (P+T) groups. The other 4 groups were designed as cancer and treatment groups and were composed of DMBA (D) and DMBA+Pomegranate (D+P), DMBA+Tangeretin (D+T), DMBA+Pomegranate+Tangeretin (D+P+T) groups. Tumor markers and angiogenesis parameters were studied from plasma samples obtained from rats. Histopathological, immunohistochemical and TUNEL analyses and expressions of proteins affecting apoptosis and cell cycle were determined in breast tissue samples. In the DMBA group, plasma CA15-3, CEA, VEGF, MMP-9 and NF-κB levels were significantly increased compared to the controls, but significant decreases were observed in these parameters except MMP-9 in the treatment groups. It was observed that p53 and Bax expressions significantly increased in both D+P and D+P+T groups compared to the DMBA group, and thesefindings were supported by Tunel and immunohistochemical findings. Cyclin D1 expressions were found to be significantly decreased only in the D+T group and supported by TUNEL and immunohistochemical findings. Immunohistochemical ER-α and Ki-67 immune reactivities were significantly decreased in alltreatment groups compared to the DMBA group. Our results showed that combined application of pomegranate extract and tangeretin may be more beneficial in preventing breast cancer development.


greenmedinfo--2020-12-27--Natural product heme oxygenase inducers as treatment for nonalcoholic fatty liver disease.

Heme oxygenase ( HO ) is a critical component of the defense mechanism to a wide variety of cellular stressors .
HO induction affords cellular protection through the breakdown of toxic heme into metabolites , helping preserve cellular integrity .
Nonalcoholic fatty liver disease ( NAFLD ) is a pathological condition by which the liver accumulates fat .
The incidence of NAFLD has reached all-time high levels driven primarily by the obesity epidemic .
NALFD can progress to nonalcoholic steatohepatitis ( NASH ) , advancing further to liver cirrhosis or cancer .
NAFLD is also a contributing factor to cardiovascular @ @ @ @ @ @ @ no drugs to specifically treat NAFLD , with most treatments focused on lifestyle modifications .
One emerging area for NAFLD treatment is the use of dietary supplements such as curcumin , pomegranate seed oil , milk thistle oil , cold-pressedoil , and resveratrol , among others .
Recent studies have demonstrated that several of these natural dietary supplements attenuate hepatic lipid accumulation and fibrosis in NAFLD animal models .
The beneficial actions of several of these compounds are associated with the induction of heme oxygenase-1 ( HO-1 ) .
Thus , targeting HO-1 @ @ @ @ @ @ @ for NAFLD either alone or with lifestyle modifications .

Heme oxygenase (HO) is a critical component of the defense mechanism to a wide variety of cellular stressors. HO induction affords cellular protection through the breakdown of toxic heme into metabolites, helping preserve cellular integrity. Nonalcoholic fatty liver disease (NAFLD) is a pathological condition by which the liver accumulates fat. The incidence of NAFLD has reached all-time high levels driven primarily by the obesity epidemic. NALFD can progress to nonalcoholic steatohepatitis (NASH), advancing further to liver cirrhosis or cancer. NAFLD is also a contributing factor to cardiovascular and metabolic diseases. There are currently no drugs to specifically treat NAFLD, with most treatments focused on lifestyle modifications. One emerging area for NAFLD treatment is the use of dietary supplements such as curcumin, pomegranate seed oil, milk thistle oil, cold-pressedoil, and resveratrol, among others. Recent studies have demonstrated that several of these natural dietary supplements attenuate hepatic lipid accumulation and fibrosis in NAFLD animal models. The beneficial actions of several of these compounds are associated with the induction of heme oxygenase-1 (HO-1). Thus, targeting HO-1 through dietary-supplements may be a useful therapeutic for NAFLD either alone or with lifestyle modifications.


greenmedinfo--2020-12-27--Assessment of the biological activity and phenolic composition of ethanol extracts of pomegranate.

Pomegranate ( L. ) is a rich source of constituents with confirmed strong biological activities .
However , pomegranate peel , which encompasses approximately 30-40 % of its weight , is treated as a biological waste .
The aim of this paper was to evaluate the potential of pomegranate peel extracts and to propose its functional properties that can be used for development of functional products .
Eight ethanol extracts of pomegranate peels ( PPEs ) were characterized by use of direct infusion quadrupole-time of flight ( Q-TOF ) , and afterwards tested on their antioxidant , antibacterial and antiproliferative @ @ @ @ @ @ @ the most prevalent compounds in pomegranate peels were punicalagin , granatin and their derivatives .
Analysed extracts had high total phenolic contents that ranged from 5766.44 to 10599.43 mg GAE/100 g , and strong antioxidant activity ( 7551.31-7875.42 and 100.25-176.60μmol TE/100 g for DPPH and FRAP assays , respectively ) .
The results of biological activity assays showed that all PPEs possessed antibacterial activity , and thatwas the most sensitive specie with minimum inhibitory concentration and minimum bactericidal concentrations ranging from 0.8 to 6.4 mg/mL .
Additionally , the analysis of antiproliferative activity @ @ @ @ @ @ @ the IC50 values ranged from 0.132 mg/mL to 0.396 mg/mL .
Multivariate analysis pointed out the most discriminative metabolites for antioxidant or antiproliferative activity .
Overall , the pomegranate peel confirmed to be a highly valuable source of bioactive compounds that could be used to improve the food functional characteristics .

Pomegranate (L.) is a rich source of constituents with confirmed strong biological activities. However, pomegranate peel, which encompasses approximately 30-40% of its weight, is treated as a biological waste. The aim of this paper was to evaluate the potential of pomegranate peel extracts and to propose its functional properties that can be used for development of functional products. Eight ethanol extracts of pomegranate peels (PPEs) were characterized by use of direct infusion quadrupole-time of flight (Q-TOF), and afterwards tested on their antioxidant, antibacterial and antiproliferative activities. Mass spectrometry analysis revealed that the most prevalent compounds in pomegranate peels were punicalagin, granatin and their derivatives. Analysed extracts had high total phenolic contents that ranged from 5766.44 to 10599.43 mg GAE/100 g, and strong antioxidant activity (7551.31-7875.42 and 100.25-176.60μmol TE/100 g for DPPH and FRAP assays, respectively). The results of biological activity assays showed that all PPEs possessed antibacterial activity, and thatwas the most sensitive specie with minimum inhibitory concentration and minimum bactericidal concentrations ranging from 0.8 to 6.4 mg/mL. Additionally, the analysis of antiproliferative activity revealed high potency of PPEs, as the IC50 values ranged from 0.132 mg/mL to 0.396 mg/mL. Multivariate analysis pointed out the most discriminative metabolites for antioxidant or antiproliferative activity. Overall, the pomegranate peel confirmed to be a highly valuable source of bioactive compounds that could be used to improve the food functional characteristics.


greenmedinfo--2020-12-27--Antibacterial effects of the lectin from pomegranate sarcotesta (PgTeL) against Listeria monocytogen

Antibacterial effects of the lectin from pomegranate sarcotesta (PgTeL) against Listeria monocytogenes.

AIMS : To investigate the effects of the lectin from Punica granatum sarcotesta ( PgTeL ) on growth , viability @ @ @ @ @ formation and chitinase activity of Listeria monocytogenes .
In addition , the effect of PgTeL @ @ @ @ @ of human cells ( HeLa ) was determined .
METHODS AND RESULTS : PgTeL showed @ @ @ @ @ the strains Listeria monocytogenes N53-1 and EGD-e , causing morphometric alterations , cell aggregation , @ @ @ @ @ disruption .
PgTeL inhibited biofilm formation by EGD-e and N53-1 and also interfered with the @ @ @ @ @ EGD-e and N53-1 in HeLa cells .
Finally , the chitinase activity of L. monocytogenes @ @ @ @ @ presence of PgTeL , which can be involved in the inhibition of adhesion process .
@ @ @ @ @ antibacterial agent against L. monocytogenes , inhibiting growth and promoting cell death , as well @ @ @ @ @ bacterial adhesion and invasion into human cells .
SIGNIFICANCE AND IMPACT OF THE STUDY : @ @ @ @ @ on the potential of PgTeL for protection of contamination in food products .

AIMS: To investigate the effects of the lectin from Punica granatum sarcotesta (PgTeL) on growth, viability, cell structure, biofilm formation and chitinase activity of Listeria monocytogenes. In addition, the effect of PgTeL on the adhesion and invasion of human cells (HeLa) was determined.
METHODS AND RESULTS: PgTeL showed bacteriostatic and bactericidal effects on the strains Listeria monocytogenes N53-1 and EGD-e, causing morphometric alterations, cell aggregation, strong deformation, and cell disruption. PgTeL inhibited biofilm formation by EGD-e and N53-1 and also interfered with the adhesion and invasion processes of EGD-e and N53-1 in HeLa cells. Finally, the chitinase activity of L. monocytogenes EGD-e was reduced in the presence of PgTeL, which can be involved in the inhibition of adhesion process.
CONCLUSION: PgTeL is an antibacterial agent against L. monocytogenes, inhibiting growth and promoting cell death, as well as impairing biofilm formation and bacterial adhesion and invasion into human cells.
SIGNIFICANCE AND IMPACT OF THE STUDY: The results stimulate future investigations on the potential of PgTeL for protection of contamination in food products.


greenmedinfo--2020-12-27--Punica granatum L.-derived omega-5 nanoemulsion improves hepatic steatosis in a high fat diet.

Pomegranate seed oil ( PSO ) is mainly composed of punicic acid ( PA ) , a polyunsaturated fatty acid @ @ @ @ @ ω-5 ) , a potent antioxidant associated with a variety of metabolic and cellular beneficial @ @ @ @ @ potential benefits of a nanoemulsified version of ω-5 ( PSOn ) have not been evaluated @ @ @ @ @ .
Here , we examined whether PSOn had beneficial effects on C57BL/6Nmice fed a high-fat @ @ @ @ @ specifically on hepatic steatosis .
We observed that PSOn supplementation decreased body weight and body @ @ @ @ @ , whereas glucose intolerance , insulin resistance , energy expenditure , and hepatic steatosis were @ @ @ @ @ and in micefed a HFD .
Interestingly , PSOn increased fatty acid oxidation in primary @ @ @ @ @ .
Altogether , our data indicate that PSOn effectively reduces some of the HFD-derived metabolic @ @ @ @ @ an increase in fatty acid oxidation within hepatocytes .

Pomegranate seed oil (PSO) is mainly composed of punicic acid (PA), a polyunsaturated fatty acid also known as omega-5 (ω-5), a potent antioxidant associated with a variety of metabolic and cellular beneficial effects. However, the potential benefits of a nanoemulsified version of ω-5 (PSOn) have not been evaluated in a pathological liver condition. Here, we examined whether PSOn had beneficial effects on C57BL/6Nmice fed a high-fat diet (HFD), specifically on hepatic steatosis. We observed that PSOn supplementation decreased body weight and body fat mass in control mice, whereas glucose intolerance, insulin resistance, energy expenditure, and hepatic steatosis were improved in both control mice and in micefed a HFD. Interestingly, PSOn increased fatty acid oxidation in primary hepatocytes and antioxidant gene expression. Altogether, our data indicate that PSOn effectively reduces some of the HFD-derived metabolic syndrome indicators by means of an increase in fatty acid oxidation within hepatocytes.


greenmedinfo--2020-12-27--Orthosiphon stamineus Benth leaves promote antihypertensive effects by reducing vasoconstriction.

Orthosiphon stamineus Benth has been traditionally used to treat hypertension .
The study aimed to investigate the vascular reactivity of water extract ( WOS ) and water : methanolic ( 1 : 1 ) extract ( WMOS ) of Orthosiphon stamineus Benth and AT1 receptors blocker in the mechanisms of antihypertensive mediated by α 1-adrenergic receptor and EDNO and PGI2 releases in the SHR aortic rings .
SHR ( 230-280 g ) were divided into four groups : control , WOS , WMOS , and losartan .
After being fed orally for 14 days , the aorta was harvested and @ @ @ @ @ @ @ ) to 10 ( -5 ) M ) and ACh ( 10 ( -9 ) to 10 ( -5 ) M ) with and without L-NAME ( 100 µM ) and indomethacin ( 10 µM ) , respectively .
WOS , WMOS , and losartan significantly reduced the contractile responses toPE intact suggesting the importance of endothelium in vasorelaxation .
Losartan significantly enhanced the ACh-induced vasorelaxation .
L-NAME significantly inhibited the ACh-induced relaxation in all groups .
Indomethacin enhanced ACh-induced vasorelaxation in WMOS .
Collectively , Orthosiphon stamineusleaves extract reduced vasoconstriction responses by @ @ @ @ @ @ @ receptors activities .
The involvement of EDNO releases was clearly observed in this plant .
In WOS , PGI2 releases might not participate in the ACh-induced vasorelaxation .
However , in WMOS , enhancement of vasorelaxation possibly due to continuous release of PGI2 .

Orthosiphon stamineus Benth has been traditionally used to treat hypertension. The study aimed to investigate the vascular reactivity of water extract (WOS) and water : methanolic (1 : 1) extract (WMOS) of Orthosiphon stamineus Benth and AT1 receptors blocker in the mechanisms of antihypertensive mediated by α 1-adrenergic receptor and EDNO and PGI2 releases in the SHR aortic rings. SHR (230-280 g) were divided into four groups: control, WOS, WMOS, and losartan. After being fed orally for 14 days, the aorta was harvested and subjected to PE (10(-9) to 10(-5) M) and ACh (10(-9) to 10(-5) M) with and without L-NAME (100 µM) and indomethacin (10 µM), respectively. WOS, WMOS, and losartan significantly reduced the contractile responses toPE intact suggesting the importance of endothelium in vasorelaxation. Losartan significantly enhanced the ACh-induced vasorelaxation. L-NAME significantly inhibited the ACh-induced relaxation in all groups. Indomethacin enhanced ACh-induced vasorelaxation in WMOS. Collectively, Orthosiphon stamineusleaves extract reduced vasoconstriction responses by the alteration of α 1-adrenergic and AT1 receptors activities. The involvement of EDNO releases was clearly observed in this plant. In WOS, PGI2 releases might not participate in the ACh-induced vasorelaxation. However, in WMOS, enhancement of vasorelaxation possibly due to continuous release of PGI2.


greenmedinfo--2020-12-27--Prophylactic effects of Orthosiphon stamineus extracts on experimental induction of calcium oxalate

Prophylactic effects of Orthosiphon stamineus extracts on experimental induction of calcium oxalate nephrolithiasis.

ETHNOPHARMACOLOGICAL RELEVANCE : Orthosiphon stamineus ( OS ) popularly known as '' diuretic agent '' are traditionally used in folk medicine in the treatment of hyperuricemia , rheumatism , gout , nephritis , nephrolithiasis , urethritis and cystitis .
AIM OF THE STUDY : To evaluate prophylactic potentials of total flavonoids , total phenolics and polysaccharides from OS on experimental induction of calcium oxalate ( CaOx ) nephrolithiasis in rats .
MATERIALS AND METHODS : Nephrolithic rats were induced by treating with 1.0 % ethylene glycol and 1.0 % ammonium chloride for 7 days .
Rats in the treated groups @ @ @ @ @ @ @ doses of 80 mg/kg and 160 mg/kg .
Urine samples ( 4h ) and serum samples were collected at 7th day for biochemical analysis .
Kidney tissues were stained with H.E .
and analyzed by light microscopy .
Expressions of OPN protein were detected by immunohistochemistry .
Rates of nucleation and aggregation of calcium oxalate crystals were derived from 20-min time-course measurements of optic density at 620 nm after mixing solutions containing calcium chloride , sodium oxalate and OS extracts at 37°C , pH 5.7 .
RESULTS : Polysaccharides exhibited the most significant @ @ @ @ @ @ @ ( cr ) levels , ameliorating histopathological changes , increasing urine C ( 2 ) O ( 4 ) ( 2- ) and Ca ( 2+ ) excretion and down-regulating OPN protein expression of kidney in the model rats in comparison with those effects of total flavonoids and total phenolics .
Polysaccharides could also significantly inhibit both nucleation and aggregation of CaOx crystals .
CONCLUSIONS : Polysaccharides were the main therapeutic materials in OS .
It had impressive prophylactic effects on CaOx stones in nephrolithic rats , playing a role as a regulator @ @ @ @ @ @ @ C ( 2 ) O ( 4 ) ( 2- ) and Ca ( 2+ ) excretion and also as an inhibitor of CaOx crystallization .

ETHNOPHARMACOLOGICAL RELEVANCE: Orthosiphon stamineus (OS) popularly known as"diuretic agent"are traditionally used in folk medicine in the treatment of hyperuricemia, rheumatism, gout, nephritis, nephrolithiasis, urethritis and cystitis.
AIM OF THE STUDY: To evaluate prophylactic potentials of total flavonoids, total phenolics and polysaccharides from OS on experimental induction of calcium oxalate (CaOx) nephrolithiasis in rats.
MATERIALS AND METHODS: Nephrolithic rats were induced by treating with 1.0% ethylene glycol and 1.0% ammonium chloride for 7 days. Rats in the treated groups were also given OS extracts at the doses of 80 mg/kg and 160 mg/kg. Urine samples (4h) and serum samples were collected at 7th day for biochemical analysis. Kidney tissues were stained with H.E. and analyzed by light microscopy. Expressions of OPN protein were detected by immunohistochemistry. Rates of nucleation and aggregation of calcium oxalate crystals were derived from 20-min time-course measurements of optic density at 620 nm after mixing solutions containing calcium chloride, sodium oxalate and OS extracts at 37°C, pH 5.7.
RESULTS: Polysaccharides exhibited the most significant prophylactic effects by reversing BUN and S(cr) levels, ameliorating histopathological changes, increasing urine C(2)O(4)(2-) and Ca(2+) excretion and down-regulating OPN protein expression of kidney in the model rats in comparison with those effects of total flavonoids and total phenolics. Polysaccharides could also significantly inhibit both nucleation and aggregation of CaOx crystals.
CONCLUSIONS: Polysaccharides were the main therapeutic materials in OS. It had impressive prophylactic effects on CaOx stones in nephrolithic rats, playing a role as a regulator of OPN protein expression to increase urine C(2)O(4)(2-) and Ca(2+) excretion and also as an inhibitor of CaOx crystallization.


greenmedinfo--2020-12-27--Orthosipon stamineus extract exerts inhibition of bacterial adhesion and chaperon-usher system of ur

Orthosipon stamineus extract exerts inhibition of bacterial adhesion and chaperon-usher system of uropathogenic Escherichia coli.

Specific recognition and bacterial adhesion to host cells by uropathogenic Escherichia coli ( UPEC ) are the first steps towards infection of epithelial tissue of the human urogenital system .
Therefore , targeting of UPEC virulence factors , relevant for adhesion , is a promising approach for prevention of recurrent urinary tract infections ( UTI ) .
A fully characterized plant-derived aqueous extract from the leaves of Orthosiphon stamineus ( OWE ) , a plant traditionally used in clinical practice in Europe and Asia for UTI , has been shown to exert strong antiadhesive effects under in vitro and in @ @ @ @ @ @ @ the underlying mechanisms , transcriptome analysis of OWE-treated UPEC strain UTI89 by Illumina sequencing and cross-validation of these data by qPCR indicated significant downregulation of bacterial adhesins ( curli , type 1- , F1C- , and P fimbriae ) and of the chaperone-mediated protein folding/unfolding and pilus assembly process ; in contrast , flagellar and motility-related genes were upregulated .
We conclude that OWE transforms the sessile lifestyle of bacteria into a motile one and therefore disables bacterial attachment to the host cell .
Additionally , the extract inhibited gene expression of multiple @ @ @ @ @ @ @ feo , fhu , chu , sit , ybt ) .
The present study explains the antiadhesive and anti-infective effect of the plant extract by pinpointing specific biochemical and molecular targets .

Specific recognition and bacterial adhesion to host cells by uropathogenic Escherichia coli (UPEC) are the first steps towards infection of epithelial tissue of the human urogenital system. Therefore, targeting of UPEC virulence factors, relevant for adhesion, is a promising approach for prevention of recurrent urinary tract infections (UTI). A fully characterized plant-derived aqueous extract from the leaves of Orthosiphon stamineus (OWE), a plant traditionally used in clinical practice in Europe and Asia for UTI, has been shown to exert strong antiadhesive effects under in vitro and in vivo conditions. For improved understanding of the underlying mechanisms, transcriptome analysis of OWE-treated UPEC strain UTI89 by Illumina sequencing and cross-validation of these data by qPCR indicated significant downregulation of bacterial adhesins (curli, type 1-, F1C-, and P fimbriae) and of the chaperone-mediated protein folding/unfolding and pilus assembly process; in contrast, flagellar and motility-related genes were upregulated. We conclude that OWE transforms the sessile lifestyle of bacteria into a motile one and therefore disables bacterial attachment to the host cell. Additionally, the extract inhibited gene expression of multiple iron-acquisition systems (ent, fep, feo, fhu, chu, sit, ybt). The present study explains the antiadhesive and anti-infective effect of the plant extract by pinpointing specific biochemical and molecular targets.


greenmedinfo--2020-12-27--Antiproliferative and antiangiogenic effects of flavone eupatorin, an active constituent of chlorofo

Antiproliferative and antiangiogenic effects of flavone eupatorin, an active constituent of chloroform extract of Orthosiphon stamineus leaves.

Flavone eupatorin is one of the constituents of Orthosiphon stamineus , a medicinal herb used in folk medicine in South East Asia for treatment of various disorders .
In our study , we investigated the antiproliferative properties of a chloroform extract of the leaves of O. stamineus and of pure eupatorin .
The compound was able to reduce the number of viable cancer cells to the same extent as the extract , with IC ( 50 ) values in micromolar range .
Moreover , both the eupatorin standard and the extract caused cells to arrest in the G2/M phase of @ @ @ @ @ @ @ that eupatorin contributes significantly to the overall extract activity .
Induction of mitotic catastrophe , accompanied by key molecular events defining apoptosis , is the mechanism of eupatorin-induced cell death .
Importantly , eupatorin ( at the doses cytotoxic to cancer cells ) did not kill normal cells ; it only limited migration of HUVEC endothelial cells and their ability to create tubes .
The ability of eupatorin to nonspecifically inhibit many protein kinases was proven and is the probable cause of its cellular effects .
In summary , eupatorin emerges as a @ @ @ @ @ @

Flavone eupatorin is one of the constituents of Orthosiphon stamineus, a medicinal herb used in folk medicine in South East Asia for treatment of various disorders. In our study, we investigated the antiproliferative properties of a chloroform extract of the leaves of O. stamineus and of pure eupatorin. The compound was able to reduce the number of viable cancer cells to the same extent as the extract, with IC(50) values in micromolar range. Moreover, both the eupatorin standard and the extract caused cells to arrest in the G2/M phase of the cell cycle. This clearly demonstrates that eupatorin contributes significantly to the overall extract activity. Induction of mitotic catastrophe, accompanied by key molecular events defining apoptosis, is the mechanism of eupatorin-induced cell death. Importantly, eupatorin (at the doses cytotoxic to cancer cells) did not kill normal cells; it only limited migration of HUVEC endothelial cells and their ability to create tubes. The ability of eupatorin to nonspecifically inhibit many protein kinases was proven and is the probable cause of its cellular effects. In summary, eupatorin emerges as a promising agent in anticancer research.


greenmedinfo--2020-12-27--Antioxidant and anti-inflammatory effects of Orthosiphon aristatus and its bioactive compounds.

Orthosiphon aristatus ( Blume ) Miq.
, which can be used as a food ingredient , is grown throughout Southeast Asia and Australia .
O. aristatus is frequently used for the treatment of renal inflammation , kidney stones and dysuria .
The focus of the current work was to study the antioxidant and anti-inflammatory effects of methanol , ethanol and water extracts from O. aristatus ( abbreviated as MEOA , EEOA and WEOA , respectively ) .
The evaluation of antioxidant activity was determined by total phenolics , Trolox equivalent antioxidant capacity ( TEAC ) , oxygen-radical absorbance capacity ( @ @ @ @ @ @ @ CAA ) assays .
These assays demonstrated a relatively high antioxidant activity for MEOA and EEOA .
These results revealed that EEOA had the most prominent inhibitory effect on lipopolysaccharide ( LPS ) -stimulated nitric oxide ( NO ) , prostaglandin E ( 2 ) ( PGE ( 2 ) ) and intracellular reactive oxygen species ( ROS ) production in RAW 264.7 cells .
A high performance liquid chromatography profile indicated that MEOA and EEOA contained both ursolic acid and oleanolic acid .
Moreover , ursolic acid significantly reduced NO production in @ @ @ @ @ @ @ and ursolic acid inhibited LPS-stimulated protein and mRNA expression of both inducible nitric oxide synthase ( iNOS ) and cyclooxygenase-2 ( COX-2 ) in these cells .
These results demonstrate that EEOA and its bioactive compound , ursolic acid , suppress LPS-induced NO and PGE ( 2 ) production by inhibiting ROS generation , along with reducing expression of iNOS and COX-2 in RAW 264.7 cells .

Orthosiphon aristatus (Blume) Miq., which can be used as a food ingredient, is grown throughout Southeast Asia and Australia. O. aristatus is frequently used for the treatment of renal inflammation, kidney stones and dysuria. The focus of the current work was to study the antioxidant and anti-inflammatory effects of methanol, ethanol and water extracts from O. aristatus (abbreviated as MEOA, EEOA and WEOA, respectively). The evaluation of antioxidant activity was determined by total phenolics, Trolox equivalent antioxidant capacity (TEAC), oxygen-radical absorbance capacity (ORAC) and cellular antioxidant activity (CAA) assays. These assays demonstrated a relatively high antioxidant activity for MEOA and EEOA. These results revealed that EEOA had the most prominent inhibitory effect on lipopolysaccharide (LPS)-stimulated nitric oxide (NO), prostaglandin E(2) (PGE(2)) and intracellular reactive oxygen species (ROS) production in RAW 264.7 cells. A high performance liquid chromatography profile indicated that MEOA and EEOA contained both ursolic acid and oleanolic acid. Moreover, ursolic acid significantly reduced NO production in LPS-stimulated RAW 264.7 cells. Both EEOA and ursolic acid inhibited LPS-stimulated protein and mRNA expression of both inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in these cells. These results demonstrate that EEOA and its bioactive compound, ursolic acid, suppress LPS-induced NO and PGE(2) production by inhibiting ROS generation, along with reducing expression of iNOS and COX-2 in RAW 264.7 cells.


greenmedinfo--2020-12-27--The leaf extract of O. aristatus and W. floribunda exhibited a significant anti-candidal effect.

CONTEXT : In many regions of Indonesia , there are numerous traditional herbal preparations for treatment of infectious diseases .
However , their antimicrobial potential has been poorly studied by modern laboratory methods .
OBJECTIVE : This study investigates in vitro antimicrobial activity of 49 ethanol extracts from 37 plant species used in Indonesian traditional medicine for treatment against Candida albicans , Enterococcus faecalis , Escherichia coli , Pseudomonas aeruginosa and Staphylococcus aureus .
MATERIALS AND METHODS : The plants were collected from the Biopharmaca collection garden , Bogor , Indonesia .
The plant material was dried , finely grounded @ @ @ @ @ @ @ and the dried residue was dissolved in 100 % DMSO .
Antimicrobial activity was determined in terms of a minimum inhibitory concentration ( MIC ) using a broth microdilution method in 96-well microplates .
RESULTS : The extract of Orthosiphon aristatus ( Blume ) Miq .
( Lamiaceae ) leaf produced the strongest antimicrobial effect , inhibiting the growth of C. albicans ( MIC 128 μg/mL ) , S. aureus ( MIC 256 μg/mL ) , E. faecalis ( MIC 256 μg/mL ) and P. aeruginosa ( MIC 256 μg/mL ) .
The @ @ @ @ @ @ @ ( Lythraceae ) also exhibited significant effect against C. albicans ( MIC 128 μg/mL ) , S. aureus ( MIC 256 μg/mL ) and E. faecalis ( MIC 256 μg/mL ) .
Rotheca serrata ( L. ) Steane & Mabb .
( Lamiaceae ) leaf extract inhibited the growth of S. aureus ( MIC 256 µg/mL ) and C. albicans ( MIC 256 µg/mL ) .
DISCUSSION AND CONCLUSIONS : The leaf extract of O. aristatus and W. floribunda exhibited a significant anti-candidal effect .
Therefore , both of these plants can serve @ @ @ @ @ @ @ of new anti-candidal agents .

CONTEXT: In many regions of Indonesia, there are numerous traditional herbal preparations for treatment of infectious diseases. However, their antimicrobial potential has been poorly studied by modern laboratory methods.
OBJECTIVE: This study investigates in vitro antimicrobial activity of 49 ethanol extracts from 37 plant species used in Indonesian traditional medicine for treatment against Candida albicans, Enterococcus faecalis, Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus.
MATERIALS AND METHODS: The plants were collected from the Biopharmaca collection garden, Bogor, Indonesia. The plant material was dried, finely grounded, extracted using ethanol, concentrated, and the dried residue was dissolved in 100% DMSO. Antimicrobial activity was determined in terms of a minimum inhibitory concentration (MIC) using a broth microdilution method in 96-well microplates.
RESULTS: The extract of Orthosiphon aristatus (Blume) Miq. (Lamiaceae) leaf produced the strongest antimicrobial effect, inhibiting the growth of C. albicans (MIC 128 μg/mL), S. aureus (MIC 256 μg/mL), E. faecalis (MIC 256 μg/mL) and P. aeruginosa (MIC 256 μg/mL). The leaf extract of Woodfordia floribunda Salisb. (Lythraceae) also exhibited significant effect against C. albicans (MIC 128 μg/mL), S. aureus (MIC 256 μg/mL) and E. faecalis (MIC 256 μg/mL). Rotheca serrata (L.) Steane&Mabb. (Lamiaceae) leaf extract inhibited the growth of S. aureus (MIC 256 µg/mL) and C. albicans (MIC 256 µg/mL).
DISCUSSION AND CONCLUSIONS: The leaf extract of O. aristatus and W. floribunda exhibited a significant anti-candidal effect. Therefore, both of these plants can serve as prospective source materials for the development of new anti-candidal agents.


greenmedinfo--2020-12-29--In silico studies reveal antiviral effects of traditional Indian spices on COVID-19.

BACKGROUND : The global health emergency due to SARS-CoV-2 causing the COVID-19 pandemic emphasized the scientific community to intensify their research work for its therapeutic solution .
In this study , Indian traditional spices owing to various medicinal properties were tested in silico for their inhibitory activity against SARS-CoV-2 proteins .
SARS-CoV-2 spike proteins ( SP ) and main proteases ( Mpro ) play a significant role in infection development were considered as potential drug targets .
METHODS : A total of 75 phytochemicals present in traditional Indian spices retrieved from the published literature and Dr. Duke 's Phytochemical and @ @ @ @ @ @ @ ( PDB IDs : 6YNQ ) , and the SP ( PDB IDs : 6LXT and 6YOR ) .
RESULTS : Through the screening process , 75 retrieved phytochemicals were docked with spike protein ( PDB IDs : 6LXT and 6YOR ) and main protease ( PDB ID : 6YNQ ) of SARS-CoV-2 .
Among them , myricetin , a flavonoid ( rank score : 6LXT : -11.72383 ; 6YOR : -9.87943 ; 6YNQ : -11.68164 ) from Allium sativumL and Isovitexin , an example of flavone ( rank score:6LXT : -12.14922 ; @ @ @ @ @ @ @ 12.60603 ) from Pimpinella anisumL were the most potent ligands against SP and Mproof SARS-CoV-2 .
Whereas , Astragalin from Crocus sativusL .
; Rutin from Illicium verum , Oxyguttiferone from Garcinia cambogia ; Scopolin from Apium graveolens L , Luteolin from Salvia officinalis , Emodin , Aloe-emodin from Cinnamomum zeylanicium and Apigenin from Allium sativumL showed better inhibition against Mpro than SP of SARS-CoV-2 .
The amino acid residues like SER , LYS , ASP and TYR were found playing important role in protein-ligand interactions via hydrogen bonding and Vander Waals forces @ @ @ @ @ @ @ spices in our daily meals may help fight against COVID-19 .
This study also paves the path for herbal drug formulation against SARS-CoV-2 after wet lab validation .

BACKGROUND: The global health emergency due to SARS-CoV-2 causing the COVID-19 pandemic emphasized the scientific community to intensify their research work for its therapeutic solution. In this study, Indian traditional spices owing to various medicinal properties were tested in silico for their inhibitory activity against SARS-CoV-2 proteins. SARS-CoV-2 spike proteins (SP) and main proteases (Mpro) play a significant role in infection development were considered as potential drug targets.
METHODS: A total of 75 phytochemicals present in traditional Indian spices retrieved from the published literature and Dr. Duke's Phytochemical and Ethnobotanical Database, were docked with Mpro (PDB IDs: 6YNQ), and the SP (PDB IDs: 6LXT and 6YOR).
RESULTS: Through the screening process, 75 retrieved phytochemicals were docked with spike protein (PDB IDs: 6LXT and 6YOR) and main protease (PDB ID: 6YNQ) of SARS-CoV-2. Among them, myricetin, a flavonoid (rank score: 6LXT: -11.72383; 6YOR: -9.87943; 6YNQ: -11.68164) from Allium sativumL and Isovitexin, an example of flavone (rank score:6LXT: -12.14922; 6YOR: -10.19443; 6YNQ: - 12.60603) from Pimpinella anisumL were the most potent ligands against SP and Mproof SARS-CoV-2. Whereas, Astragalin from Crocus sativusL.; Rutin from Illicium verum, Oxyguttiferone from Garcinia cambogia; Scopolin from Apium graveolens L, Luteolin from Salvia officinalis, Emodin, Aloe-emodin from Cinnamomum zeylanicium and Apigenin from Allium sativumL showed better inhibition against Mpro than SP of SARS-CoV-2. The amino acid residues like SER, LYS, ASP and TYR were found playing important role in protein-ligand interactions via hydrogen bonding and Vander Waals forces.
CONCLUSION: Optimal use of traditional spices in our daily meals may help fight against COVID-19. This study also paves the path for herbal drug formulation against SARS-CoV-2 after wet lab validation.


greenmedinfo--2020-12-28--[VIDEO] WHAT IS A PUBLIC ACCOMMODATION? DIRECT THREAT? Peggy Hall

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greenmedinfo--2020-12-28--Attacking Ourselves: Top Doctors Reveal Vaccines Turn Our Immune System Against Us

The research is hard to ignore , vaccines can trigger autoimmunity with a laundry list of diseases to follow .
With harmful and toxic metals as some vaccine ingredients , who is susceptible and which individuals are more at risk ?
No one would accuse Yehuda Shoenfeld of being a quack .
The Israeli clinician has spent more than three decades studying the human immune system and is at the pinnacle of his profession .
You might say he is more foundation than fringe in his specialty ; he wrote the textbooks .
The Mosaic of Autoimmunity , Autoantibodies , @ @ @ @ @ @ @ and Autoimmunity , Cancer and Autoimmunity – the list is 25 titles long and some of them are cornerstones of clinical practice .
Hardly surprising that Shoenfeld has been called the `` Godfather of Autoimmunology '' – the study of the immune system turned on itself in a wide array of diseases from type 1 diabetes to ulcerative colitis and multiple sclerosis .
But something strange is happening in the world of immunology lately and a small evidence of it is that the Godfather of Autoimmunology is pointing to vaccines – specifically , @ @ @ @ @ @ @ metal aluminum – as a significant contributor to the growing global epidemic of autoimmune diseases .
The bigger evidence is a huge body of research that 's poured in in the past 15 years , and particularly in the past five years .
Take for example , a recent article published in the journal Pharmacological Research in which Shoenfeld and colleagues issue unprecedented guidelines naming four categories of people who are most at risk for vaccine-induced autoimmunity .
`` On one hand , '' vaccines prevent infections which can trigger autoimmunity , say @ @ @ @ @ @ @ , of the Department of Clinical Medicine and Rheumatology at the Campus Bio-Medico University in Rome , Gideon Nesher , of the Hebrew University Medical School in Jerusalem and Shoenfeld , founder and head of the Zabludowicz Center of Autoimmune Diseases in the Sheba Medical Center at Tel Hashomer .
He is also editor of three medical journals and author of more than 1,500 research papers across the spectrum of medical journalism and founder of the International Congress on Autoimmunology .
`` On the other hand , many reports that describe post-vaccination autoimmunity @ @ @ @ @ @ @ autoimmunity .
Defined autoimmune diseases that may occur following vaccinations include arthritis , lupus ( systemic lupus erythematosus , SLE ) diabetes mellitus , thrombocytopenia , vasculitis , dermatomyosiositis , Guillain-Barre syndrome and demyelinating disorders .
Almost all types of vaccines have been reported to be associated with the onset of ASIA . ''
ASIA – or Autoimmune/inflammatory Syndrome Induced by Adjuvants ( also known as Shoenfeld 's syndrome ) -- first appeared in the Journal of Autoimmunology four years ago .
It is an umbrella term for a collection of similar symptoms @ @ @ @ @ @ @ result after exposure to an adjuvant – an environmental agent including common vaccine ingredients that stimulate the immune system .
Since then an enormous body of research , using ASIA as a paradigm , has begun to unravel the mystery of how environmental toxins , particularly the metal aluminum used in vaccines , can trigger an immune system chain reaction in susceptible individuals and may lead to overt autoimmune disease .
Autoimmune disease results when the body 's system meant to attack foreign invaders turns instead to attack part of the body it @ @ @ @ @ @ @ self ) .
If the immune system is like a national defence system , antibodies are like drones programmed to recognize a certain type of invader ( a bacteria say ) and to destroy them or mark them for destruction by other special forces .
Autoantibodies are like drones that are misidentifying a component of the human body and have launched a sustained attack on it .
If they mistakenly target a component of the conductive sheath around neurons , for example , nerve impulses stop conducting properly , muscles go into spasm @ @ @ @ @ @ @ .
If autoantibodies erroneously focus on joint tissue ; rheumatoid arthritis results .
If they target the islets of Langerhans in the pancreas , Type 1 diabetes , and so on '' Throughout our lifetime the normal immune system walks a fine line between preserving normal immune reactions and developing autoimmune diseases , '' says the paper .
`` The healthy immune system is tolerant to self-antigens .
When self-tolerance is disturbed , dysregulation of the immune system follows , resulting in emergence of an autoimmune disease .
Vaccination is one of the @ @ @ @ @ @ @ susceptible individuals , resulting in autoimmune phenomena and ASIA . ''
Who is `` susceptible '' is the subject of the paper entitled , `` Predicting post-vaccination autoimmunity : Who might be at risk ? ''
It lists four categories of people : 1 ) those who have had a previous autoimmune reaction to a vaccine , 2 ) anyone with a medical history of autoimmunity , 3 ) patients with a history of allergic reactions , 4 ) anyone at high risk of developing autoimmune disease including anyone with a family history @ @ @ @ @ @ @ are detectable by blood tests and other factors including low vitamin D and smoking .
Regarding those who have had a previous adverse reaction to vaccines , the paper cites five relevant studies including the case of a death of a teenage girl six months following her third Gardasil injection against HPV virus .
She had experienced a range of symptoms shortly after her first dose , including dizziness , numbness and tingling in her hands , and memory lapses .
After her second injection , she developed `` intermittent arm weakness , @ @ @ @ @ @ @ worse tingling , night sweats , chest pain and palpitations .
A full autopsy was unrevealing but blood and spleen tissue analysis revealed HPV-16 L1 gene DNA fragments – matching the DNA found in vials of the Gardasil vaccine against cervical cancer – `` thus implicating the vaccine as a causal factor . ''
The DNA fragments had also been found to be `` complexed with the aluminum adjuvant '' which , according to the report , have been shown to persist for up to 8 to 10 years causing chronic immune system @ @ @ @ @ @ @ , '' Shoenfeld and his colleagues concluded , `` it seems preferable that individuals with prior autoimmune or autoimmune-like reactions to vaccinations , should not be immunized , at least not with the same type of vaccine . ''
The second group which the paper cites for vaccine exemption is patients with `` established autoimmune conditions . ''
Vaccines do n't work so well in them , say Shoenfeld and his colleagues , and they are at `` risk for flares following vaccination . ''
Inoculations that contain live viruses including chickenpox , @ @ @ @ @ @ @ and rubella triple vaccine ( MMR ) are `` generally contraindicated '' for people with autoimmune conditions because of the risk of `` uncontrolled viral replication . ''
But inactivated vaccines are not such a good idea either because they usually contain the added ingredient aluminum , linked to autoimmunity .
The immunologists describe recent studies in which patients with autoimmune rheumatic disease given the influenza vaccine ( without aluminum ) suffered more joint pain and fever than controls and whose levels of autoantibodies ( the drones that attack self ) increased after @ @ @ @ @ @ @ more , they developed new types of autoantibodies that were n't present before the vaccines , and those persisted .
As the presence of autoantibodies can be predictive of developing autoimmune disease in patients without symptoms , even years ahead of disease onset , this is troubling to those who understand immunology .
A number of studies claim vaccines are safe for the `` overwhelming majority of patients with established autoimmune diseases , '' the study allows , but they only looked at rheumatoid arthritis and lupus and not at severe and active @ @ @ @ @ @ @ vaccination should be weighed against its potential risk , '' they cautioned .
Vaccine trials have usually excluded `` vulnerable '' individuals -- only extremely healthy individuals with no allergies are recruited .
It 's a `` selection bias , '' say Soriano and Shoenfeld , and has likely resulted in serious adverse events being `` considerably underestimated '' in `` real life where vaccines are mandated to all individuals regardless of their susceptibility . ''
The true incidence of allergic reactions to vaccines , normally estimated at between one in 50,000 to @ @ @ @ @ @ @ probably much higher and particularly where gelatin or egg proteins are on the ingredients list , they say .
There 's a long list of vaccine ingredients that are potential allergens : besides the infectious agents themselves , there are those from hen 's egg , horse serum , baker 's yeast , numerous antibiotics , formaldehyde and lactose , as well `` inadvertent '' ingredients such as latex .
People 's allergic histories have to be taken before vaccination say the researchers .
But some signs of reaction do n't show up @ @ @ @ @ @ @ health nurse or GP might tell patients that a long-lasting swelling around the injection site after a vaccine is a normal reaction , for example .
But that is not what the immunologists say .
`` [ A ] luminum sensitization manifests as nodules [ hard lumps ] at the injection site that often regress after weeks or months , but may persist for years . ''
In such cases , they say , a patch test can be done to confirm sensitivity and to avoid vaccination .
According to a growing body @ @ @ @ @ @ @ be only the beginning of many dangerous aluminum-induced phenomena .
Aluminum has been added to vaccines since about 1926 when Alexander Glenny and colleagues noticed it would produce better antibody responses in vaccines than the antigen alone .
Glenny figured the alum was inducing what he called a `` depot effect '' – slowing the release of the antigen and heightening the immune response .
For 60 years his theory was accepted dogma .
And over the same time , the vaccine schedule grew decade on decade , but few ever questioned the @ @ @ @ @ @ @ , which is strange considering its known toxicity .
A PubMed search on aluminum and `` toxicity '' turns up 4,258 entries .
Its neurotoxicity is well documented .
It affects memory , cognition , psychomotor control ; it damages the blood brain barrier , activates brain inflammation , depresses mitochondrial function and plenty of research suggests it is a key player in the formation of the amyloid `` plaques '' and tangles in the brains of Alzheimer 's patients .
It 's been implicated in Amyotrophic Lateral Sclerosis and autism and demonstrated @ @ @ @ @ @ @ patients were accidentally infused with aluminum , the `` dialysis-induced encephalopathy '' ( DAE ) they developed neurological symptoms : speech abnormalities , tremors , memory loss , impaired concentration and behavioural changes .
Many of the patients eventually went into comas and died .
The lucky ones survived : when the source of toxicity , aluminum , was removed from their dialysis they recovered rapidly .
With these new observations , researchers began investigating the adjuvant effects of aluminum and in the past decade there has been a flurry of research .
@ @ @ @ @ @ @ the antigen for a while and then gets excreted , it turns out that aluminum salts trigger a storm of defence action .
Within hours of injection of the same aluminum oxyhydroxide in vaccines into mice , for example , armies of specialized immune cells are on the move , calling in grid coordinates for more specialist assault forces .
Within a day , a whole host of immune system commandos are in play -- neutrophils , eosinophils , inflammatory monocytes , myeloid and dendritic cells , activating lymphocytes and secreting proteins called @ @ @ @ @ @ @ damage but they send out signals , directing cell-to-cell communication and recruiting other cells into action .
If the next phase of the attack is launched : fibroblast growth factor , interferons , interleukins , platelet derived growth factor , transforming growth factor and tumour necrosis factor might all be engaged .
There 's evidence that poorly understood and pesky inflammasomes , ( currently a topic of cutting- edge cancer causation research ) such as the Nod-like receptor 3 ( NLRP ) are activated too , but it 's all still too early @ @ @ @ @ @ @ .
New research emerging from University of British Columbia has found that aluminum adjuvant injected into mice can alter the expression of genes associated with autoimmunity .
And in their recent study published in the Proceedings of the National Academy of Sciences , immunologists at the University of Colorado found that even host DNA is recruited into the aluminum assault , that it rapidly coats injected alum , triggering effects that scientists have barely scratched the surface of understanding .
This mobility or `` translocation '' of aluminum in the body is perhaps @ @ @ @ @ @ @ in current aluminum research .
In 1998 , French researcher Romain Gherardi and his colleagues observed an emerging condition of unknown origin which presented in patients post-vaccination with Chronic Fatigue like symptoms including swollen lymph nodes , joint and muscle pain and exhaustion .
Tissue biopsies of the patients ' deltoid revealed lesions up to 1 cm in diameter and unique from similar lesions of other diseases .
They went to the lab for analysis and to Gherardi 's astonishment , they mainly consisted of macrophages – large white blood cells in the @ @ @ @ @ @ @ up foreign invaders in the body .
Enclosed in the cellular fluid of these phagocytes were agglomerates of nanocrystals of aluminum .
Gherardi and his colleagues began injecting mice with aluminum to see what happened .
Their research published in 2013 revealed that the metal particles were engulfed by macrophages and formed MMF-like granulomas that dispersed -- to distant lymph nodes , spleen , liver and eventually brain .
`` This strongly suggests that long-term adjuvant biopersistence within phagocytic cells is a prerequisite of slow brain translocation and delayed neurotoxicity , '' writes @ @ @ @ @ @ @ the relevant research in Frontiers in Neurology .
A more frightening animal study of aluminum is that of Spanish veterinary researcher Lluis Lujan 's study of ovine ASIA .
After huge numbers of sheep in Spain died in 2008 in the wake of a compulsory multiple vaccine campaign against bluetongue in Spain in 2008 , Lujan set out to find out what killed them – and he began by inoculating them with aluminum .
His 2013 study found that only 0.5 % of sheep inoculated with aluminum vaccines showed immediate reactions of lethargy @ @ @ @ @ @ @ and seizures – `` characterized by a severe meningoencephalitis , similar to postvaccine reactions seen in humans . ''
Most of them recovered , temporarily , but postmortem exams of the ones who did n't revealed acute brain inflammation .
The delayed onset `` chronic '' phase of the disease affected far more of the sheep -- 50-70 % of flocks and sometimes virtually 100 % of animals within a given flock , usually including all of those who had previously recovered .
The reaction was frequently triggered by exposure to cold and @ @ @ @ @ @ @ then progressed to acute redness of the skin , generalized weakness , extreme weight loss and muscle tremors , and finally , entered the terminal phase where the animals went down on their front quarters , became comatose and died .
Post-mortem examinations revealed `` severe neuron necrosis '' and aluminum in the nerve tissue .
The immune system 's reaction to aluminum `` represents a major health challenge , '' Gerhardi declares in his recent review , and he adds that `` attempts to seriously examine safety concerns raised by the bio-persistent @ @ @ @ @ @ @ have not been made ... A lot must be done to understand how , in certain individuals , alum-containing vaccines may become insidiously unsafe . ''
Back to the problem of which `` certain individuals '' should avoid vaccination to avoid autoimmune disease .
Soriano and Shoenfeld 's identify a final category : anyone at risk of developing autoimmune disease .
Since a number of them have been shown to have genetic factors that would include anyone with a family history of autoimmune disease .
It also includes anyone who has tested positive @ @ @ @ @ @ @ before symptoms show up .
Vaccinations , the doctors say , `` may trigger or worsen the disease . ''
Smokers too , have an exceptionally high risk of developing an autoimmune disease , says the report .
The American Cancer Society estimates that about 18 % of Americans smoke .
That means about 42 million Americans have an elevated risk of developing an autoimmune disease and they 're stacking the odds with every vaccine .
And finally , factors that Shoenfeld and Soriano associate with high risk of developing autoimmunity are high @ @ @ @ @ @ @ means anyone taking birth control or hormone replacement therapy and , according to one 2009 study of vitamin D status , about three quarters of American teens and adults should be wary of vaccines .
Shoenfeld does n't seem to mean to exclude all of these people from immunization , however .
The paper concludes that `` for the overwhelming majority of individuals , vaccines carry no risk of systemic autoimmune disease and should be administered according to current recommendations . ''
Which is in stark contrast to the body of the paper @ @ @ @ @ @ @ weighing the `` potential benefit of vaccination ... against its potential risk . ''
It 's exemplary of a strange sort of schizophrenia in a wide range of recent immunology papers .
The doctors seem to be trying to reconcile a century of `` safe and effective '' vaccine dogma with the last decade 's worth of terrifying research findings .
There 's a lot of `` on the one hand '' and `` on the other hand '' in them .
The new research seems about to gain the upper hand , @ @ @ @ @ @ @ by six immunologists including Shoenfeld , for example , is a catalogue of vaccine side effects from Gardasil deaths , narcolepsy epidemics , infertility , chronic fatigue , dead sheep and aluminum-addled brains .
It is rife with statements that would have been virtually unheard of inside mainstream medicine a decade ago .
Like this shocker : '' Perhaps , in twenty years , physicians will be dueling with better characterized particles of autoimmunity , and the vaccines may become fully safe as well as effective .
Nonetheless the recognition of ASIA has @ @ @ @ @ @ @ in identifying the good , the bad and the ugly of vaccines and in particular of adjuvants as triggers of autoimmunity . ''
Bad and ugly of vaccines ?
What 's wrong with the adjuvants ?
That 's not in the CDC hand-out .
Or how about this one : '' Despite the huge amount of money invested in studying vaccines , there are few observational studies and virtually no randomized clinical trials documenting the effect on mortality of any of the existing vaccines .
One recent paper found an increased hospitalization rate @ @ @ @ @ @ @ vaccine doses and a mortality rate ratio for 5-8 vaccine doses to 1-4 doses of 1.5 , indicating a statistically significant increase of deaths associated with higher vaccine doses .
Since vaccines are given to millions of infants annually , it is imperative that health authorities have scientific data from synergistic toxicity studies on all combinations of vaccines ... '' That could be any anti-vaxxer jabbering on ... but it 's not .
But here is the topper : '' The US Supreme Court ruled that vaccines makers are immune from lawsuits charging @ @ @ @ @ @ @ defective .
Thus there is need for innovative clinical trial design and the vaccines themselves should be redesigned . ''
Immunologists including the world 's leading authority on autoimmunity are saying it is time to take vaccines back to the drawing board .
Autoimmune disease is the third leading cause of morbidity and mortality worldwide and now among the top 10 killers of young American women .
The American Autoimmune Related Diseases Association estimates that 50 million Americans suffer from one of 88 autoimmune diseases -- from type 1 diabetes to systemic lupus @ @ @ @ @ @ @ figure at one in five globally .
At least 40 more diseases are suspected to be immune-mediated .
Most of them are devastating -- frequently crippling , expensive to treat and incurable .
And they are increasing at an astonishing pace .
At this stage , it looks like the more the research pours in , the harder it is going to get for pro-vaccine immunologists to keep multiple personality disorder – or complete nervous breakdown -- at bay .
Ten years of cutting edge research into aluminum 's effects on the immune @ @ @ @ @ @ @ were .
And how little they know .
If , after 90 years , doctors finally have begun to seriously examine the mechanism and question the merits of injecting metal toxins into newborn babies , what have they yet to discover ?
ASIA sounds awful .
( Too bad for all the people whose kids suffered through chronic fatigue when it was just a Freudian yearning to sleep with their mother . )
But what if , like Lujan 's sheep , the `` negligible '' minority that has been paying the price @ @ @ @ @ @ @ only the tip of the iceberg ?
What if some people with no apparent adverse immune reactions still have nanocrystals of aluminum silently depositing in their brains ?
What if ASIA really includes Alzheimer 's ?
ALS , autism ?
ADD ?
And that 's just the A 's .
Even if immunologists keep wearing their rose coloured glasses , and vaccine ingredients are only responsible for a tiny fraction of the exploding autoimmunity , the `` ugly '' in vaccines will still get harder and harder to ignore .
When everyone on @ @ @ @ @ @ @ years is a long time for disabled people to stack up while scientists `` duel with the characterized particles of autoimmunity . ''
In the fury over the Disneyland measles outbreak that is gripping the world 's vaccine promoters , time is running out for doctors and researchers who see the `` bad and ugly '' side of vaccines and their adjuvants to do something about it .
There 's slim chance of a vaccine redesign in the absence of a profit incentive and a strong chance of universal vaccine mandates for one @ @ @ @ @ @ @ or not .

Visit our Re-post guidelines This article is copyrighted by GreenMedInfo LLC, 2020
The research is hard to ignore, vaccines can trigger autoimmunity with a laundry list of diseases to follow. With harmful and toxic metals as some vaccine ingredients, who is susceptible and which individuals are more at risk?
No one would accuse Yehuda Shoenfeld of being a quack. The Israeli clinician has spent more than three decades studying the human immune system and is at the pinnacle of his profession. You might say he is more foundation than fringe in his specialty; he wrote the textbooks. The Mosaic of Autoimmunity, Autoantibodies, Diagnostic Criteria in Autoimmune Diseases, Infection and Autoimmunity, Cancer and Autoimmunity – the list is 25 titles long and some of them are cornerstones of clinical practice. Hardly surprising that Shoenfeld has been called the "Godfather of Autoimmunology" – the study of the immune system turned on itself in a wide array of diseases from type 1 diabetes to ulcerative colitis and multiple sclerosis.
But something strange is happening in the world of immunology lately and a small evidence of it is that the Godfather of Autoimmunology is pointing to vaccines – specifically, some of their ingredients including the toxic metal aluminum – as a significant contributor to the growing global epidemic of autoimmune diseases. The bigger evidence is a huge body of research that's poured in in the past 15 years, and particularly in the past five years. Take for example, a recent article published in the journal Pharmacological Research in which Shoenfeld and colleagues issue unprecedented guidelines naming four categories of people who are most at risk for vaccine-induced autoimmunity.
"On one hand," vaccines prevent infections which can trigger autoimmunity, say the paper's authors, Alessandra Soriano, of the Department of Clinical Medicine and Rheumatology at the Campus Bio-Medico University in Rome, Gideon Nesher, of the Hebrew University Medical School in Jerusalem and Shoenfeld, founder and head of the Zabludowicz Center of Autoimmune Diseases in the Sheba Medical Center at Tel Hashomer. He is also editor of three medical journals and author of more than 1,500 research papers across the spectrum of medical journalism and founder of the International Congress on Autoimmunology. "On the other hand, many reports that describe post-vaccination autoimmunity strongly suggest that vaccines can indeed trigger autoimmunity. Defined autoimmune diseases that may occur following vaccinations include arthritis, lupus (systemic lupus erythematosus, SLE) diabetes mellitus, thrombocytopenia, vasculitis, dermatomyosiositis, Guillain-Barre syndrome and demyelinating disorders. Almost all types of vaccines have been reported to be associated with the onset of ASIA."
ASIA – or Autoimmune/inflammatory Syndrome Induced by Adjuvants (also known as Shoenfeld's syndrome) -- first appeared in the Journal of Autoimmunology four years ago. It is an umbrella term for a collection of similar symptoms, including Chronic Fatigue Syndrome, that result after exposure to an adjuvant – an environmental agent including common vaccine ingredients that stimulate the immune system. Since then an enormous body of research, using ASIA as a paradigm, has begun to unravel the mystery of how environmental toxins, particularly the metal aluminum used in vaccines, can trigger an immune system chain reaction in susceptible individuals and may lead to overt autoimmune disease.
Autoimmune disease results when the body's system meant to attack foreign invaders turns instead to attack part of the body it belongs to (auto is Greek for self). If the immune system is like a national defence system, antibodies are like drones programmed to recognize a certain type of invader (a bacteria say) and to destroy them or mark them for destruction by other special forces. Autoantibodies are like drones that are misidentifying a component of the human body and have launched a sustained attack on it. If they mistakenly target a component of the conductive sheath around neurons, for example, nerve impulses stop conducting properly, muscles go into spasm and coordination fails; multiple sclerosis results. If autoantibodies erroneously focus on joint tissue; rheumatoid arthritis results. If they target the islets of Langerhans in the pancreas, Type 1 diabetes, and so on
"Throughout our lifetime the normal immune system walks a fine line between preserving normal immune reactions and developing autoimmune diseases," says the paper. "The healthy immune system is tolerant to self-antigens. When self-tolerance is disturbed, dysregulation of the immune system follows, resulting in emergence of an autoimmune disease. Vaccination is one of the conditions that may disturb this homeostasis in susceptible individuals, resulting in autoimmune phenomena and ASIA."
Who is "susceptible" is the subject of the paper entitled, "Predicting post-vaccination autoimmunity: Who might be at risk?" It lists four categories of people: 1) those who have had a previous autoimmune reaction to a vaccine, 2) anyone with a medical history of autoimmunity, 3) patients with a history of allergic reactions, 4) anyone at high risk of developing autoimmune disease including anyone with a family history of autoimmunity, presence of autoantibodies which are detectable by blood tests and other factors including low vitamin D and smoking.
PREVIOUS REACTION
Regarding those who have had a previous adverse reaction to vaccines, the paper cites five relevant studies including the case of a death of a teenage girl six months following her third Gardasil injection against HPV virus. She had experienced a range of symptoms shortly after her first dose, including dizziness, numbness and tingling in her hands, and memory lapses. After her second injection, she developed "intermittent arm weakness, frequent tiredness requiring daytime naps," worse tingling, night sweats, chest pain and palpitations. A full autopsy was unrevealing but blood and spleen tissue analysis revealed HPV-16 L1 gene DNA fragments – matching the DNA found in vials of the Gardasil vaccine against cervical cancer – "thus implicating the vaccine as a causal factor." The DNA fragments had also been found to be "complexed with the aluminum adjuvant" which, according to the report, have been shown to persist for up to 8 to 10 years causing chronic immune system stimulation.
"Although data is limited," Shoenfeld and his colleagues concluded, "it seems preferable that individuals with prior autoimmune or autoimmune-like reactions to vaccinations, should not be immunized, at least not with the same type of vaccine."
ESTABLISHED AUTOIMMUNE CONDITION
The second group which the paper cites for vaccine exemption is patients with "established autoimmune conditions." Vaccines don't work so well in them, say Shoenfeld and his colleagues, and they are at "risk for flares following vaccination." Inoculations that contain live viruses including chickenpox, yellow fever and the measles, mumps and rubella triple vaccine (MMR) are "generally contraindicated" for people with autoimmune conditions because of the risk of "uncontrolled viral replication." But inactivated vaccines are not such a good idea either because they usually contain the added ingredient aluminum, linked to autoimmunity.
The immunologists describe recent studies in which patients with autoimmune rheumatic disease given the influenza vaccine (without aluminum) suffered more joint pain and fever than controls and whose levels of autoantibodies (the drones that attack self) increased after receiving the flu vaccine. What's more, they developed new types of autoantibodies that weren't present before the vaccines, and those persisted. As the presence of autoantibodies can be predictive of developing autoimmune disease in patients without symptoms, even years ahead of disease onset, this is troubling to those who understand immunology.
A number of studies claim vaccines are safe for the "overwhelming majority of patients with established autoimmune diseases," the study allows, but they only looked at rheumatoid arthritis and lupus and not at severe and active cases so "the potential benefit of vaccination should be weighed against its potential risk," they cautioned.
PATIENTS WITH A HISTORY OF ALLERGY
Vaccine trials have usually excluded "vulnerable" individuals -- only extremely healthy individuals with no allergies are recruited. It's a "selection bias," say Soriano and Shoenfeld, and has likely resulted in serious adverse events being "considerably underestimated" in "real life where vaccines are mandated to all individuals regardless of their susceptibility." The true incidence of allergic reactions to vaccines, normally estimated at between one in 50,000 to one in a million doses, is probably much higher and particularly where gelatin or egg proteins are on the ingredients list, they say.
There's a long list of vaccine ingredients that are potential allergens: besides the infectious agents themselves, there are those from hen's egg, horse serum, baker's yeast, numerous antibiotics, formaldehyde and lactose, as well "inadvertent" ingredients such as latex. People's allergic histories have to be taken before vaccination say the researchers. But some signs of reaction don't show up until after the shot.
The public health nurse or GP might tell patients that a long-lasting swelling around the injection site after a vaccine is a normal reaction, for example. But that is not what the immunologists say. "[A]luminum sensitization manifests as nodules [hard lumps] at the injection site that often regress after weeks or months, but may persist for years." In such cases, they say, a patch test can be done to confirm sensitivity and to avoid vaccination.
According to a growing body of research, though, allergy may be only the beginning of many dangerous aluminum-induced phenomena.
THE TROUBLE WITH ALUMINUM
Aluminum has been added to vaccines since about 1926 when Alexander Glenny and colleagues noticed it would produce better antibody responses in vaccines than the antigen alone. Glenny figured the alum was inducing what he called a "depot effect" – slowing the release of the antigen and heightening the immune response. For 60 years his theory was accepted dogma. And over the same time, the vaccine schedule grew decade on decade, but few ever questioned the effects of injecting aluminum into the body, which is strange considering its known toxicity.
A PubMed search on aluminum and "toxicity" turns up 4,258 entries. Its neurotoxicity is well documented. It affects memory, cognition, psychomotor control; it damages the blood brain barrier, activates brain inflammation, depresses mitochondrial function and plenty of research suggests it is a key player in the formation of the amyloid "plaques" and tangles in the brains of Alzheimer's patients. It's been implicated in Amyotrophic Lateral Sclerosis and autism and demonstrated to induce allergy.
When kidney dialysis patients were accidentally infused with aluminum, the "dialysis-induced encephalopathy" (DAE) they developed neurological symptoms: speech abnormalities, tremors, memory loss, impaired concentration and behavioural changes. Many of the patients eventually went into comas and died. The lucky ones survived: when the source of toxicity, aluminum, was removed from their dialysis they recovered rapidly.
With these new observations, researchers began investigating the adjuvant effects of aluminum and in the past decade there has been a flurry of research. Far from being a sandbag that holds the antigen for a while and then gets excreted, it turns out that aluminum salts trigger a storm of defence action. Within hours of injection of the same aluminum oxyhydroxide in vaccines into mice, for example, armies of specialized immune cells are on the move, calling in grid coordinates for more specialist assault forces. Within a day, a whole host of immune system commandos are in play -- neutrophils, eosinophils, inflammatory monocytes, myeloid and dendritic cells, activating lymphocytes and secreting proteins called cytokines. The cytokines themselves cause collateral damage but they send out signals, directing cell-to-cell communication and recruiting other cells into action. If the next phase of the attack is launched: fibroblast growth factor, interferons, interleukins, platelet derived growth factor, transforming growth factor and tumour necrosis factor might all be engaged. There's evidence that poorly understood and pesky inflammasomes, (currently a topic of cutting- edge cancer causation research) such as the Nod-like receptor 3( NLRP) are activated too, but it's all still too early to say exactly what they're doing.
New research emerging from University of British Columbia has found that aluminum adjuvant injected into mice can alter the expression of genes associated with autoimmunity. And in their recent study published in the Proceedings of the National Academy of Sciences, immunologists at the University of Colorado found that even host DNA is recruited into the aluminum assault, that it rapidly coats injected alum, triggering effects that scientists have barely scratched the surface of understanding.
THE SIGNIFICANCE OF MACROPHAGIC MYOFASCIITIS
This mobility or "translocation" of aluminum in the body is perhaps the most disturbing of the mounting evidence in current aluminum research. In 1998, French researcher Romain Gherardi and his colleagues observed an emerging condition of unknown origin which presented in patients post-vaccination with Chronic Fatigue like symptoms including swollen lymph nodes, joint and muscle pain and exhaustion. Tissue biopsies of the patients' deltoid revealed lesions up to 1 cm in diameter and unique from similar lesions of other diseases. They went to the lab for analysis and to Gherardi's astonishment, they mainly consisted of macrophages – large white blood cells in the immune system whose job is to swallow up foreign invaders in the body. Enclosed in the cellular fluid of these phagocytes were agglomerates of nanocrystals of aluminum.
Gherardi and his colleagues began injecting mice with aluminum to see what happened. Their research published in 2013 revealed that the metal particles were engulfed by macrophages and formed MMF-like granulomas that dispersed -- to distant lymph nodes, spleen, liver and eventually brain.
"This strongly suggests that long-term adjuvant biopersistence within phagocytic cells is a prerequisite of slow brain translocation and delayed neurotoxicity," writes Gherardi in his February 2015 review of the relevant research in Frontiers in Neurology.
A more frightening animal study of aluminum is that of Spanish veterinary researcher Lluis Lujan's study of ovine ASIA. After huge numbers of sheep in Spain died in 2008 in the wake of a compulsory multiple vaccine campaign against bluetongue in Spain in 2008, Lujan set out to find out what killed them – and he began by inoculating them with aluminum.
His 2013 study found that only 0.5% of sheep inoculated with aluminum vaccines showed immediate reactions of lethargy, transient blindness, stupor, prostration and seizures – "characterized by a severe meningoencephalitis, similar to postvaccine reactions seen in humans." Most of them recovered, temporarily, but postmortem exams of the ones who didn't revealed acute brain inflammation.
The delayed onset "chronic" phase of the disease affected far more of the sheep -- 50-70% of flocks and sometimes virtually 100% of animals within a given flock, usually including all of those who had previously recovered. The reaction was frequently triggered by exposure to cold and began with restlessness and compulsive wool-biting, then progressed to acute redness of the skin, generalized weakness, extreme weight loss and muscle tremors, and finally, entered the terminal phase where the animals went down on their front quarters, became comatose and died. Post-mortem examinations revealed "severe neuron necrosis" and aluminum in the nerve tissue.
The immune system's reaction to aluminum "represents a major health challenge," Gerhardi declares in his recent review, and he adds that "attempts to seriously examine safety concerns raised by the bio-persistent character and brain accumulation of alum particles have not been made... A lot must be done to understand how, in certain individuals, alum-containing vaccines may become insidiously unsafe."
Back to the problem of which "certain individuals" should avoid vaccination to avoid autoimmune disease.
PEOPLE PRONE TO DEVELOP AUTOIMMUNITY
Soriano and Shoenfeld's identify a final category: anyone at risk of developing autoimmune disease. Since a number of them have been shown to have genetic factors that would include anyone with a family history of autoimmune disease. It also includes anyone who has tested positive for autoantibodies which can indicate disease years before symptoms show up. Vaccinations, the doctors say, "may trigger or worsen the disease."
Smokers too, have an exceptionally high risk of developing an autoimmune disease, says the report. The American Cancer Society estimates that about 18% of Americans smoke. That means about 42 million Americans have an elevated risk of developing an autoimmune disease and they're stacking the odds with every vaccine.
And finally, factors that Shoenfeld and Soriano associate with high risk of developing autoimmunity are high estrogen and low vitamin D -- which means anyone taking birth control or hormone replacement therapy and, according to one 2009 study of vitamin D status, about three quarters of American teens and adults should be wary of vaccines.
Shoenfeld doesn't seem to mean to exclude all of these people from immunization, however. The paper concludes that "for the overwhelming majority of individuals, vaccines carry no risk of systemic autoimmune disease and should be administered according to current recommendations." Which is in stark contrast to the body of the paper. The final word is cautionary about weighing the "potential benefit of vaccination...against its potential risk."
It's exemplary of a strange sort of schizophrenia in a wide range of recent immunology papers. The doctors seem to be trying to reconcile a century of "safe and effective" vaccine dogma with the last decade's worth of terrifying research findings. There's a lot of "on the one hand" and "on the other hand" in them.
The new research seems about to gain the upper hand, however. A 2013 overview of ASIA by six immunologists including Shoenfeld, for example, is a catalogue of vaccine side effects from Gardasil deaths, narcolepsy epidemics, infertility, chronic fatigue, dead sheep and aluminum-addled brains. It is rife with statements that would have been virtually unheard of inside mainstream medicine a decade ago. Like this shocker:
"Perhaps, in twenty years, physicians will be dueling with better characterized particles of autoimmunity, and the vaccines may become fully safe as well as effective. Nonetheless the recognition of ASIA has initiated the change to put more efforts in identifying the good, the bad and the ugly of vaccines and in particular of adjuvants as triggers of autoimmunity." Bad and ugly of vaccines? What's wrong with the adjuvants? That's not in the CDC hand-out.
Or how about this one:
"Despite the huge amount of money invested in studying vaccines, there are few observational studies and virtually no randomized clinical trials documenting the effect on mortality of any of the existing vaccines. One recent paper found an increased hospitalization rate with the increase of the number of vaccine doses and a mortality rate ratio for 5-8 vaccine doses to 1-4 doses of 1.5, indicating a statistically significant increase of deaths associated with higher vaccine doses. Since vaccines are given to millions of infants annually, it is imperative that health authorities have scientific data from synergistic toxicity studies on all combinations of vaccines..." That could be any anti-vaxxer jabbering on...but it's not.
But here is the topper:
"The US Supreme Court ruled that vaccines makers are immune from lawsuits charging that the design of the vaccine is defective. Thus there is need for innovative clinical trial design and the vaccines themselves should be redesigned." Immunologists including the world's leading authority on autoimmunity are saying it is time to take vaccines back to the drawing board.
Autoimmune disease is the third leading cause of morbidity and mortality worldwide and now among the top 10 killers of young American women. The American Autoimmune Related Diseases Association estimates that 50 million Americans suffer from one of 88 autoimmune diseases -- from type 1 diabetes to systemic lupus erythematosus -- and some research puts the figure at one in five globally. At least 40 more diseases are suspected to be immune-mediated. Most of them are devastating -- frequently crippling, expensive to treat and incurable. And they are increasing at an astonishing pace.
At this stage, it looks like the more the research pours in, the harder it is going to get for pro-vaccine immunologists to keep multiple personality disorder – or complete nervous breakdown -- at bay. Ten years of cutting edge research into aluminum's effects on the immune system has revealed primarily how wrong they were. And how little they know. If, after 90 years, doctors finally have begun to seriously examine the mechanism and question the merits of injecting metal toxins into newborn babies, what have they yet to discover? ASIA sounds awful. (Too bad for all the people whose kids suffered through chronic fatigue when it was just a Freudian yearning to sleep with their mother.) But what if, like Lujan's sheep, the "negligible" minority that has been paying the price for the good of humanity is actually only the tip of the iceberg? What if some people with no apparent adverse immune reactions still have nanocrystals of aluminum silently depositing in their brains? What if ASIA really includes Alzheimer's? ALS, autism? ADD? And that's just the A's.
Even if immunologists keep wearing their rose coloured glasses, and vaccine ingredients are only responsible for a tiny fraction of the exploding autoimmunity, the "ugly" in vaccines will still get harder and harder to ignore. When everyone on the planet is getting injected, 20 years is a long time for disabled people to stack up while scientists "duel with the characterized particles of autoimmunity." In the fury over the Disneyland measles outbreak that is gripping the world's vaccine promoters, time is running out for doctors and researchers who see the "bad and ugly" side of vaccines and their adjuvants to do something about it. There's slim chance of a vaccine redesign in the absence of a profit incentive and a strong chance of universal vaccine mandates for one and all -- previous anaphylactic shock reaction or not.