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ukrfeminism · 10 months ago

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The number of women dying from alcohol-related diseases has soared in recent years, new figures show, with experts blaming the rise on brands deliberately targeting marketing at women.

The latest data reveals the number of women who lost their lives this way in the UK increased by 37 per cent in five years – surging from 2,399 to 3,293 between 2016 and 2021 and marking the highest levels since records began.

While more men than women still die from alcohol-related diseases, the Office for National Statistics figures show deaths are rising substantially quicker for women than for men, with the latter seeing a 28 per cent in the same period – from 4,928 to 6,348.

Professor Debbie Shawcross, a professor of hepatology and chronic liver failure at King’s College London’s Institute of Liver Studies, said liver disease was a particular problem in female patients.

“Women tend to present with more severe liver disease, particularly alcohol-related hepatitis, and do so after a shorter period of excessive drinking and at a lower daily alcohol intake than men,” she said. “This can be accounted for by differences in body size and composition – less muscle mass.”

Richard Piper, chief executive of the charity Alcohol Change, claimed the main factor causing the surge is the “incessant marketing of drinks towards women” as he called for stricter regulation of alcohol advertising.

Abigail Wilson, from WithYou, a drug, alcohol and mental health charity, described the rise in women dying from alcohol-related liver disease as “very concerning” as she argued alcohol was as damaging as heroin and crack cocaine. “Women generally are less likely to die of alcohol-related causes than men. There is always a gap there but the gap is closing, and that is really concerning.”

The Independent can also report that:

The number of deaths among women attributed to alcohol-related liver disease in England increased from 1,533 to 2,190 deaths between 2015 and 2021 – a 42 per cent rise

The total number of male deaths linked to alcohol-related liver disease climbed by 34 per cent to 3,870 deaths in the same timeframe

Recent research from 33 countries found that British women are the biggest female binge drinkers

Exclusive polling from WithYou shows almost two-thirds of those who seek support online are women, with more than half seeking support for their alcohol use

Roxanne Knighton, who lives in Staffordshire, told The Independent of the pain of losing her mother Melanie to alcohol-related liver disease in March 2022. She was diagnosed with the illness in her late forties.

“All the earliest memories were mum drinking,” the 34-year-old recalled. “She was alcohol dependent – it made her function.”

Ms Knighton said her mother never went to the doctor and was in denial about her drinking. So Ms Knighton made the call instead.

“It was me who called the doctors as she couldn’t get up off the sofa – she was full of fluid,” she added. “It had gone into her belly, she had to be drained, they got 12 litres from her.

“I was looking after her each day. It was four years until she died. It still hurts. I didn’t just lose her, I lost her to the alcohol first. You lose them twice.”

Raising concerns about the “feminisation” of alcohol marketing, Dr Piper highlighted annual reports of major alcohol brands which reveal they are deliberately targeting women.

“This is leading to deaths,” he said. “The second reason would be pricing – alcohol is more affordable now than it has been at any point in the last 20 years so people are drinking more.”

He called for ministers to introduce tighter rules on alcohol marketing and roll out minimum unit pricing for alcohol to make drinks with higher alcohol content more expensive.

Other campaigners warned it is harder for women to get support for alcohol misuse due to services often being tailored towards men. Women routinely do the lion’s share of childcare, meaning they cannot physically find the time, they say.

Helena Conibear, chief executive of the Alcohol Education Trust, attributed the rise in women dying from alcohol-related liver disease to a significant increase in binge drinking in the late Nineties and early 2000s.

Meanwhile, Prof Shawcross argued women who struggle with alcoholism endure greater “cultural stigma” than their male counterparts, which may deter women from pursuing help.

Alcohol-related liver disease often has no symptoms for many years, she added, while women also have lower levels of the enzyme which breaks down alcohol.

Vanessa Hebditch, of the British Liver Trust, said: “With alcohol becoming increasingly accessible and affordable, as well as more ingrained in our culture, more women are drinking to levels that put their health at risk.”

Siobhan Herbert, a project manager, told The Independent she started drinking a bottle of wine a night – and sometimes two bottles on weekend evenings – around 20 years ago.

“When I went out, I drank less,” the 52-year-old added. “I was a bit of a closet drinker. At home, there would be nobody around to witness me getting trollied. My mother was an alcoholic, she was exactly the same. You would have thought growing up, seeing all that through my teenage years, it would stop you, but it is very addictive.”

Ms Herbert said she eventually stopped drinking in June 2022 due to growing fed up with the impact alcohol was having on her physical and mental health.

She added: “I wasn’t putting Baileys on my cornflakes but every day I felt awful. I felt tired and anxious.

“I am a whole new woman now. I feel alive. I have more energy. I am sharper. I do not have anxiety. My depression is gone and all of the problems I was blaming on the menopause have massively improved.”

Sandra Parker, a self-professed “classic binge drinker”, said she would struggle to know how much alcohol she had consumed due to blacking out and would sometimes be in bed for two days afterwards.

The 54-year-old, who stopped drinking in 2018, now coaches women to help them stop or cut down on their alcohol consumption, describing her clients as successful professional middle-class women who are secretly drinking harmful amounts of wine at home.

“They may have a single drink when they are out with people from work, or they may not even drink, but they come home and they have a bottle of wine,” she added. “They have learnt that when they have a drink, they feel less stressed, and it becomes a dependency where they really crave that feeling each night.”

A Department of Health spokesperson said. “Alcohol misuse can ruin lives and destroy families, which is why we are acting to support those most at risk.

“We’ve published a 10-year plan for tackling drug and alcohol-related harms and are investing an extra £532m between 2022 and 2025 to create places for 50,000 people in drug and alcohol treatment services. We are also funding specialist alcohol care teams at one in four hospitals in England, based on those with the greatest need.

“Our 10-year women’s health strategy sets out our plan for improving care and support for women.”

#articles #health

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helen0086 · 10 days ago

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Progress in the Study of the Protective Effect and Mechanism of C-phycocyanin on Liver Injury

Abstract: C-phycocyanin (C-phycocyanin) is a pigment-containing protein from marine algae that has shown promising results in the treatment of many inflammatory diseases and tumors. C-alpha-cyanobilin is a pigment-containing protein from marine algae that has been shown to be effective in the treatment of various inflammatory diseases and tumors. C-alpha-cyanobilin has a protective effect on various liver diseases, such as drug-induced or toxic substance-induced liver damage, non-alcoholic fatty liver disease, hepatic fibrosis, and hepatic ischemia-reperfusion injury. The protective effect of C-alginin on liver injury is mainly realized through the regulation of signaling pathways such as nuclear factor (NF)-κB, phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) and AMP-dependent protein kinase (AMPK), and the inhibition of oxidative stress, etc., and is not toxic to normal cells. Therefore, C-alginin has a broad application prospect as a potential natural hepatoprotective marine active substance. In recent years, the research progress of the protective effect of C-alginin on liver injury and its mechanism is summarized.

C-phycocyanin (C-phycocyanin) is a complex protein of cyanobacteria and a natural food protein pigment with pharmacological effects such as antioxidant, anti-inflammatory and anti-tumor effects, as well as fast-acting and low-toxicity, it can be used as a functional food [1-2]. C-Alginin can also enhance immunity and is safe, without causing acute and subacute toxic reactions [3]. Selenium-enriched PC has been shown to have stronger pharmacological effects [4]. Therefore, C-alginate has important research value both as a drug and a functional food, and has become a hot spot in the field of pharmaceutical research [5]. In this paper, we summarize the progress of research on the application and mechanism of C-alginin in liver diseases.

1 Ameliorative effect of C-phycocyanin on liver injury caused by drugs and toxic substances

The liver is the metabolic center of drugs and exogenous toxic substances, and metabolites are prone to liver injury. C-PC can inhibit the synthesis and release of inflammatory factors such as tumor necrosis factor (TNF)-α and interferon-γ, and increase the activities of catalase and superoxide dismutase (SOD), which can inhibit hepatic inflammation and alleviate hepatic injury [3]. It has been found that C-PC can significantly prevent thioacetamide-induced liver injury, significantly reduce the levels of alanine aminotransferase (ALT) and aliquot aminotransferase (AST), shorten the prothrombin time and reduce the hepatic histopathological damage, and improve the survival rate of rats with fulminant hepatic failure [6]. C-alginin also has a good effect on thioacetamide-induced hepatic encephalopathy, which can be seen in the reduction of tryptophan and lipid peroxidation indexes in different regions of the brain, and the enhancement of catalase and glutathione peroxidase activities in rats with fulminant hepatic failure [6].

Another study found that C-alginin not only attenuates the oxidative stress induced by 2-acetylaminofluorene and reduces the generation of reactive oxygen species (ROS) radicals, but also inhibits the phosphorylation of protein kinase B (Akt) and the nuclear translocation of nuclear factor (NF)-κB induced by 2-acetylaminofluorene, thus inhibiting the expression of multidrug resistance genes [7]. Osman et al. [8] also showed that C-alginin could normalize the levels of ALT, AST, catalase, urea, creatinine, SOD and glutathione-s-transferase in the livers of rats poisoned with carbon tetrachloride (CCl4). This result was also verified in human liver cell line (L02) [9]. C-phycocyanin can effectively scavenge ROS and inhibit CCl4-induced lipid peroxidation in rat liver [10], and C-PC can improve the antioxidant defense system and restore the structure of hepatocytes and hepatic enzymes in the liver of gibberellic acid-poisoned albino rats [11]. As a PC chromophore, phycocyanin can also significantly inhibit ROS generation and improve liver injury induced by a variety of drugs and toxic substances [10]. Liu et al. [12] found that phycocyanin showed strong anti-inflammatory effects in a CCl4-induced hepatic injury model in mice, which could significantly reduce the levels of ALT, AST, the expression of TNF-α and cytochrome C, increase the levels of albumin and SOD, and proliferate cytosolic nuclei. It can significantly reduce ALT and AST levels and the expression of TNF-α and cytochrome C, increase albumin levels and the expression of SOD and proliferating cell nuclear antigen, promote hepatocyte regeneration and improve the survival rate of mice with acute liver failure.

Gammoudi et al [13] used response surface method to optimize the extraction process of C-phycocyanin, and obtained high extraction recovery. C-phycocyanin extracted by the optimized method has the ability of scavenging hydroxyl, superoxide anion and nitric oxide radicals as well as the ability of metal chelating, and it has stronger antioxidant effect; C-PC significantly increased the activity of SOD and inhibited the increase of ALT, AST, and bilirubin in cadmium-poisoned rats. C-PC significantly increased the activity of SOD and inhibited the increase of ALT, AST and bilirubin in rats with cadmium poisoning. The above studies show that C-phycocyanin can effectively protect liver injury caused by drugs and toxic substances, and has the efficacy as the basis for drug development.

2 Preventive effect of C-alginin on hepatic fibrosis

Liver fibrosis is an inevitable process in the development of various chronic liver diseases and may be reversed with early and timely treatment. The key to liver fibrosis is the activation of hepatic stellate cells. Previous studies have found that low-dose C-alginin combined with soy isoflavones can inhibit hepatic stellate cell activation by inhibiting the activity of reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase［14］, but it is not clear whether C-alginin alone can inhibit the activity of NADPH oxidase. Therefore, the combination of C-algin and soy isoflavones at appropriate doses may have a preventive effect on liver fibrosis in high-risk groups. C-alginin may inhibit the progression of NADPH by suppressing oxidative damage, thereby inhibiting the development of hepatic fibrosis [15].

Epithelial mesenchymal transition (EMT) is one of the key mechanisms contributing to the development of fibrotic diseases. C-alginin inhibits transforming growth factor β1 (TGF-β1)-induced human EMT [16]. Although the effect of C-alginin on EMT in hepatic fibrosis has not been reported, it has been found that C-alginin can reduce pulmonary fibrosis by inhibiting epithelial mesenchymal transition [17]. Another study found that C-alginin could reduce the expression of α-smooth muscle actin (α-SMA) and connective tissue growth factor (CTGF) mRNA in human dermal fibroblasts and alleviate fibrous contracture [18]. The results of these studies also have significance for the inhibition of hepatic fibrosis, and provide a theoretical basis for the further study of C-PC as a potential antifibrotic drug.

3 Protective effect of C-alginin on hepatic ischemia-reperfusion injury

Liver ischemia/reperfusion injury is an important clinicopathophysiological phenomenon. It was found that the addition of two different doses (0.1 g/L and 0.2 g/L) of C-alginin to the Krebs Henseleit preservation solution significantly decreased hepatic ALT, AST and alkaline phosphatase activities, and reduced the rate of lipid peroxidation and malondialdehyde content in an isolated perfused rat liver model, and increased the activities of hepatic glutathione-s-transferase and glutathione peroxidase, as well as sulfhydryl groups in hepatic tissue. On the other hand, it can increase the activities of hepatic glutathione-s-transferase and glutathione peroxidase and the content of sulfhydryl groups in liver tissues, therefore, C-alginin can significantly reduce hepatic ischemia/reperfusion injury as an antioxidant [19]. In isolated perfused mouse livers, it was found that C-alginin significantly reduced the phagocytosis and respiratory burst activity of hepatic macrophages (Kupffer cells), attenuated cytotoxicity and inflammation induced by highly active Kupffer cells, and dose-dependently inhibited carbon phagocytosis and carbon-induced oxygen uptake by perfused livers, and then inhibited the increase of hepatic nitric oxide synthase activity induced by gonadotropins [20]. and thus inhibit the thyroid hormone-induced elevation of hepatic nitric oxide synthase activity [20].

However, C-alginin has a very short half-life in vivo, which limits its application in vivo. It was found that the use of polyethylene glycol-b-(polyglutamic acid-g-polyethyleneimine), a macromolecular material with good drug-carrying capacity and slow-release properties, as a nanocarrier of C-alginin could solve this problem, and the release of C-alginin could be delayed by subcutaneous injection into the abdominal region of rats, which could attenuate islet damage caused by hepatic ischemia/reperfusion and enhance the function of the islets [21]. This study broadens the scope of application of C-alginin in vivo and improves the therapeutic effect of C-alginin.

4 Inhibitory effect of C-alginin on hepatocellular carcinoma

It was found that C-alginin significantly reduced the expression of matrix metalloproteinase (MMP)-2 and MMP-9 and the expression of tissue inhibitor of metalloproteinase 2 (TIMP2) mRNA in human hepatocellular carcinoma cells (HepG2 cells) [22]. C-alginin is a natural photosensitizer, and photodynamic therapy (PDT) mediated by alginin microcystin induced a large accumulation of ROS in HepG2 cells, which promoted mitochondrial damage and cytochrome C release, and led to apoptosis of hepatocellular carcinoma cells [23].

Liu et al. [24] used nanoscale C-alginate particles prepared by lactobionic acid grafting and adriamycin loading to enhance the growth inhibition of HepG2 cells when combined with chemo-PDT, and the C-alginate particles could effectively accumulate and diffuse in tumor multicellular spheres. In vitro and in vivo studies on the effects of selenium-enriched PCs on PDT in hepatocellular carcinoma showed that selenium-enriched PCs could migrate from lysosomes to mitochondria in a time-dependent manner, and that selenium-enriched PCs could induce the death of tumor cells through the generation of free radicals in vivo, increase the activities of antioxidant enzymes in vivo, induce mitochondria-mediated apoptosis, and inhibit autophagy, thus offering a relatively safe pathway to tumor treatment and showing new development perspectives [4]. It can provide a relatively safe way to treat tumors and shows a new development prospect [4].

Lin et al. [25] combined C-phycocyanin with single-walled carbon nanohorns and prepared phycocyanin-functionalized single-walled carbon nanohorn hybrids, which enhanced the photostability of C-phycocyanin and protected the single-walled carbon nanohorns from adsorption of plasma proteins, and synergistically used with PDT and photothermal therapy (PTT) to treat tumors. C-phycocyanin covalently coupled with biosilica and PDT or non-covalently coupled with indocyanine green and PTT on tumor-associated macrophages can also increase the apoptosis rate of tumor cells [26-27]. The development of PDT and PTT synergistic methods for the treatment of cancer has broadened the application of C-PC and enhanced its value in the treatment of hepatocellular carcinoma.

In addition, C-phycocyanin can inhibit the expression of multidrug-resistant genes in HepG2 cells through NF-κB and activated protein-1 (AP-1)-mediated pathways, and C-phycocyanin increases the accumulation of adriamycin in HepG2 cells in a dose-dependent manner, which results in a 5-fold increase in the susceptibility of cells to adriamycin [28]. Even in adriamycin-resistant HepG2 cells, C-PC induced the activation of apoptotic pathways such as cytochrome C and caspase-3 [29], and the results of Prabakaran et al. [30] also confirmed the inhibitory effect of C-PC on the proliferation of HepG2 cells, mediated by the inactivation of BCR-ABL signaling and the downstream PI3K/Akt pathway. mediated by BCR-ABL signaling and inactivation of downstream PI3K/Akt pathway. In addition, C-phycocyanin modifies the mitochondrial membrane potential and promotes apoptosis in cancer cells [30]. Currently, C-phycocyanin is a synergistic molecule with other drugs that have been widely used in the treatment of cancer [31]. The above studies demonstrate that C-phycocyanin has good therapeutic potential in the field of hepatocellular carcinoma.

5 Amelioration of metabolic syndrome and non-alcoholic fatty liver disease by C-phycocyanin

It has been found that C-alginin can reduce ALT and AST levels, decrease ROS production and NF-κB activation, and attenuate hepatic fibrosis in rats induced by high-fat choline-deficient diets, and thus C-alginin has a protective effect on NAFLD rats through anti-inflammatory and antioxidant mechanisms [15].

Another study on the effects of aqueous extract of Spirulina (mainly C-alginin) on NAFLD induced by a high-calorie/high-fat Western diet in C57Bl/6J mice showed that aqueous extract of Spirulina significantly improved glucose tolerance, lowered plasma cholesterol, and increased ursodeoxycholic acid in bile in mice [32]. Kaspi-Chadli et al. Kasbi-Chadli et al. [33] showed that aqueous extract of Spirulina could reduce cholesterol and sphingolipid levels in the liver and aortic cholesterol levels in hamsters fed a high-fat diet by significantly decreasing the expression of hydroxy-3-methylglutaryl-coenzyme A reductase (HMG CoA) gene, a limiting enzyme for cholesterol synthesis, and TGF-β1 gene, and that ursodeoxycholic acid levels in the feces of hamsters fed high-fat diets were increased in the high Spirulina aqueous extract treatment group.

A daily dose of C-alginin-enriched Spirulina can reduce the harmful effects of oxidative stress induced by a diet rich in lipid peroxides [34]. Ma et al. [35] found that C-alginin promoted the phosphorylation of hepatocyte AMP-dependent protein kinase (AMPK) in vivo and ex vivo, and increased the phosphorylation of acetyl coenzyme A carboxylase. In the treatment of NAFLD in mice, C-alginin can improve liver inflammation by up-regulating the expression of phosphorylated AMPK and AMPK-regulated transcription factor peroxisome proliferator-activated receptor α (PPAR-α) and its target gene, CPT1, and by down-regulating the expression of pro-inflammatory factors such as TNF-α and CD36 [35]. This suggests that C-phycocyanin can also improve lipid deposition in the liver through the AMPK pathway.

Endothelial dysfunction is associated with hypertension, atherosclerosis and metabolic syndrome. Studies in animal models of spontaneous hypertension have shown that long-term administration of C-alginin may improve systemic blood pressure in rats by increasing aortic endothelial nitric oxide synthase levels, with a dose-dependent decrease in blood pressure, and thus C-alginin may be useful in preventing endothelial dysfunction-related diseases in the metabolic syndrome [36]. In the offspring of ApoE-deficient mice fed C-alginate during gestation and lactation, male littermates had an elevated hepatic reduced/oxidized glutathione ratio and significantly lower hepatic SOD and glutathione peroxidase gene expression.

C-PC is effective in preventing atherosclerosis in adult hereditary hypercholesterolemic mice [37]. In vitro, C-phycocyanin also improved glucose production and expression of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G-6-Pase) in high-glucose-induced insulin-resistant HepG2 cells [38]. C-alginin also increases glucose uptake in high glucose-induced insulin-resistant HepG2 cells through the insulin receptor substrate (IRS)/PI3K/Akt and Sirtuin-1 (SIRT1)/liver kinase B1 (LKB1)/AMPK signaling pathways, activates glycogen synthase, and increases the amount of glycogen [38]. C-phycocyanin can improve blood glucose and fasting serum insulin levels in tetracycline-induced diabetic mice [39]. Therefore, C-phycocyanin can maintain cellular glucose homeostasis by improving insulin resistance in hepatocytes.

6 Hepatoprotective role of C-phycocyanin in other liver diseases

Studies have shown that C-alginin can inhibit total serum cholesterol, triacylglycerol, LDL, ALT, AST, and malondialdehyde levels in mice modeled with alcoholic liver injury, significantly increase SOD levels in the liver, and promote the activation and proliferation of CD4+ T cells, which can have an ameliorative effect on alcoholic liver injury [40]. In addition, C-phycocyanin may enhance the intestinal barrier function, regulate the intestinal flora, reduce the translocation of bacteria and metabolites to the liver, and inhibit the activity of the Toll-like receptor 4 (TLR4)/NF-κB pathway, which may reduce the inflammation of the liver and prevent the occurrence of hepatic fibrosis in mice [41]. In mice with X-ray radiation-induced liver injury, C-phycocyanin can reduce radiation-induced DNA damage and oxidative stress injury by up-regulating the expression of nuclear factor (NF)-E2-related factor 2 (Nrf2) and downstream genes, such as HO-1, and play a hepatoprotective role by enhancing the activities of SOD and glutathione peroxidase [42].

7 Outlook

Liver fibrosis is the common final process of chronic liver diseases, and there is no effective therapeutic drug at present. Although some research progress has been made in the field of traditional Chinese medicine (TCM) on the reversal of liver fibrosis [43], its toxicological effects have not yet been clarified. Although the incidence of viral hepatitis has gradually decreased with the development and popularization of vaccines and antiviral drugs, the incidence of drug-induced liver injury (DILI) and liver diseases such as NAFLD has been increasing year by year with the improvement of people's living conditions [44]. Therefore, there is an urgent need to find drugs or nutrients that can help maintain normal hepatocyte function and effectively inhibit liver inflammation and fibrosis. C-alginin, with its anti-inflammatory, antioxidant, and antitumor effects, as well as good food coloring, has a wide range of applications in both the pharmaceutical and food industries.

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［28］NISHANTH R P, RAMAKRISHNA B S, JYOTSNA R G, et al. C- phycocyanin inhibits MDR1 through reactive oxygen species and cyclooxygenase-2 mediated pathways in human hepatocellular carcinoma cell line[J]. Eur J Pharmacol, 2010, 649(1/3):74-83. doi: 10. 1016/j.ejphar.2010.09.011.

[29] ROY K R, ARUNASREE K M, REDDY N P, et al. Alteration of mitochondrial membrane potential by spirulina platensis C- phycocyanin induces apoptosis in the doxorubicinresistant human hepatocellular-carcinoma cell line HepG2[J]. Biotechnol Appl Biochem, 2007, 47 (Pt 3): 159-167. doi: 10. 1042/BA20060206.

[30] PRABAKARAN G, SAMPATHKUMAR P, KAVISRI M, et al. Extraction and characterization of phycocyanin from spirulina platensis and evaluation of its anticancer , antidiabetic and antiinflammatory effect[J]. Int J Biol Macromol, 2020, 153: 256- 263. doi: 10. 1016/j.ijbiomac.2020.03.009.

[31] SILVA M R O B D, M DA SILVA G, SILVA A L F D, et al. Bioactive compounds of Arthrospira spp. (spirulina) with potential anticancer activities: a systematic review[J]. ACS Chem Biol, 2021, 16 (11): 2057-2067. doi: 10. 1021/acschembio.1c00568.

[32] COUÉ M, TESSE A, FALEWÉE J, et al. Spirulina liquid extract protects against fibrosis related to non-alcoholic steatohepatitis and increases ursodeoxycholic acid [J]. Nutrients, 2019, 11 (1): 194. doi:10.3390/nu11010194.

[33] KASBI-CHADLI F, COUÉ M, AGUESSE A, et al. Spirulina liquid extract prevents metabolic disturbances and improves liver sphingolipids profile in hamster fed a high-fat diet[J]. Eur J Nutr, 2021, 60(8):4483-4494. doi: 10. 1007/s00394-021-02589-x.

[34] OULD AMARA-LEFFAD L, RAMDANE H, NEKHOUL K, et al. Spirulina effect on modulation of toxins provided by food, impact on hepatic and renal functions [J] . . Arch Physiol Biochem, 2019, 125 (2): 184-194. doi: 10. 1080/13813455.2018.1444059.

[35] MA P, HUANG R, JIANG J, et al. Potential use of C-phycocyanin in non-alcoholic fatty liver disease [J]. Biochem Biophys Res Commun, 2020, 526(4):906-912. doi: 10. 1016/j.bbrc.2020.04.001.

［36］ICHIMURA M, KATO S, TSUNEYAMA K, et al. Phycocyanin prevents hypertension and low serum adiponectin level in a rat model of metabolic syndrome［J］. Nutr Res, 2013, 33(5): 397-405. doi: 10. 1016/j.nutres.2013.03.006.

[37] COUÉ M, CROYAL M, HABIB M, et al. Perinatal administration of C-phycocyanin protects against atherosclerosis in apoE-deficient mice by modulating cholesterol and trimethylamine-N-oxide metabolisms[J]. Arterioscler Thromb Vasc Biol, 2021, 41(12): e512-e523. doi: 10. 1161/ATVBAHA.121.316848.

［38］REN Z, XIE Z, CAO D, et al. C-phycocyanin inhibits hepatic gluconeogenesis and increases glycogen synthesis via activating Akt and AMPK in insulin resistant hepatocytes [J]. Food Funct, 2018, 9(5): 2829-2839. doi: 10. 1039/c8fo00257f.

［39］OU Y, REN Z, WANG J, et al. Phycocyanin ameliorates alloxan- induced diabetes mellitus in mice ：involved in insulin signaling pathway and GK expression [J]. Chem Biol Interact, 2016, 247: 49- 54. doi: 10. 1016/j.cbi.2016.01.018.

[40] XIA D, LIU B, XIN W, et al. Protective effects of C-phycocyanin on alcohol-induced subacute liver injury in mice [J]. Journal of Applied Phycology, 2015, 28(2):765-772. doi: 10. 1007/s10811- 015-0677-3.

[41] XIE Y, LI W, ZHU L, et al. Effects of phycocyanin in modulating the intestinal microbiota of mice [J]. Microbiologyopen, 2019, 8 (9): e00825. doi: 10. 1002/mbo3.825.

［42］LIU Q, LI W, QIN S. Therapeutic effect of phycocyanin on acute liver oxidative damage caused by X-ray［J］. Biomed Pharmacother, 2020, 130: 110553. doi: 10. 1016/j.biopha.2020.110553.

［43］SONG Y N, CHEN J, CAI F F, et al. A metabolic mechanism analysis of fuzheng-huayu formula for improving liver cirrhosis with traditional chinese medicine syndromes [J]. Acta Pharmacol Sin, 2018, 39(6): 942-951. doi: 10. 1038/aps.2017.101.

［44］XIAO J, WANG F, WONG N K, et al. Global liver disease burdens and research trends : analysis from a chinese perspective［J］. J Hepatol, 2019, 71(1):212-221. doi: 10. 1016/j.jhep.2019.03.004.

#phycocyanin #cphycocyanin #phycocyaninspirulina

#healthy eating #health products #nutrition #veganfood

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read-watch-sleep · 4 months ago

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I am being so silly in your inbox (+ Discord) I have managed to convert you to the ScarVi verse and Im cackling like an evil villian about it

Well, my dear Kai, you're not the only one with the capacity for evil. (It is a delight to hear from you always). I'm using your ask as an opportunity to spread propaganda featuring my Pokémon conspiracy theory about a game I've never played (I only play pkmn Emerald on an emulator and Diamond on my jalbroken 3DS). You already know about this, of course. But I digress,

^ This Guy Is a Reference to the Toxic Oil Syndrome Outbreak of 1981

(gifs by @/ianime0 and rant under the cut)

His name in the Japanese game is Colza, and in the English translation is Brassius, both names for the plant known as Rapeseed, and the plant that makes Canola Oil. We also know that he looks sickly, and at one point, he was deathly ill with something unknown, which is part of what inspired his work Surrendering Sunflora.

In the 80s, canola/colza oil was illegal to sell for cooking in Spain (mostly for economic reasons) and had to be denatured for industrial use to be imported in as lubricant or biodiesel.

Now, in 1981, some 20,000+ people developed a strange musculoskeletal disease, that resulted in pulmonary edema (fluid in the lungs), muscle pain and failure, fever, and eosinophilia (too many eosinophil white blood cells), scleroderma (autoimmune rash) ect. The progression was brutal. Patients would go from a cough and a fever to strange rashes and rapidly losing weight, to having their muscles seize permanently and lifelong hepatitis. Thousands of people were permanently disabled, and more than 400 people died.

The cause?

Colza/Rapeseed oil, having been denatured with the chemical aniline, then filtered and mixed with olive oil to sell as edible cooking oil (which wasn't at all safe to eat).

It's just a bit of a coincidence that one of the few canonically ill characters in the Pokémon universe just happens to be named after a plant that caused an epidemic in the place where he's meant to be from, especially when he always battles with Pokémon from the Arboliva line.

So yeah, my theory is that he's got Toxic Oil Syndrome.

#Brassius #pokemon scarlet and violet #asks #pokemon brassius #smoliv #wild if true honestly #he's just a reference to that time in the 80s that hundreds of people died

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funkyness · 2 months ago

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yay!! really glad about ur cat :)

yayyyy she still has hepatic lipidosis which is causing liver failure, but fortunately that's treatable and they didn't find any tumours

#shes an old lady so any problem is really worrisome u know #we aren't sure what her age is but she's 15 at the youngest #probably 17 ish #answers

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thepastisalreadywritten · 2 years ago

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Ludwig van Beethoven died in Vienna about 200 years ago after a lifetime of composing some of the most influential works in classical music — and biographers have long struggled to explain his death.

The German composer died at the age of 56 after lengthy struggles with chronic illness and progressive hearing loss.

An international team of researchers who sequenced Beethoven's genome using authenticated locks of his hair may now have some answers.

Liver failure, or cirrhosis, was the likely cause of Beethoven's death, brought about by a number of factors, including alcohol consumption, they said.

“We looked at possible genetic causes of his three main symptom complexes — the progressive hearing loss, the gastrointestinal symptoms and the liver disease ultimately leading to his death due to liver failure,” said Markus Nothen of the Institute of Human Genetics at the University Hospital of Bonn.

Beethoven, Mr Nothen said, had a strong genetic disposition to liver disease and sequences of the hepatitis B virus were detected in his hair.

“We believe the disease arose from an interplay of genetic disposition, well-documented chronic alcohol consumption and hepatitis B infection,” Mr Nothen said.

The authors of a study on Beethoven's death, published in the Cell Press journal Current Biology on Wednesday, were unable to determine any genetic causes for the progressive hearing loss that eventually left the composer completely deaf by 1818.

"The researchers analysed eight locks of hair said to be from Beethoven and determined that five of them were almost certainly authentic,” said Tristan Begg, a doctoral student at the University of Cambridge and lead author of the study.

“Because we reconstructed the genome from ultra-short DNA fragments, we only confidently mapped about two thirds of it.”

Beethoven, who was born in Bonn in 1770 and died in 1827, battled gastrointestinal problems at various times of his life as well as jaundice.

“There were periods of acute illness where he was unable to work — for example, his month-long period of acute illness in the spring of 1825,” Mr Begg said.

The researchers, by studying Beethoven's DNA data and archival documents, also uncovered a discrepancy in his legal and biological genealogy.

They found an “extra-pair paternity event” — which appears in children resulting from an extramarital relationship — in Beethoven's direct paternal line, said Toomas Kivisild of the Institute of Genomics at the University of Tartu.

Mr Kivisild said it occurred sometime within seven generations that separate a common ancestor, Aert van Beethoven, at the end of the 16th century and Beethoven's birth in 1770.

“You cannot rule out that Beethoven himself may have been illegitimate,” Mr Begg said.

Beethoven had asked in an 1802 letter to his brothers that his health problems, particularly his hearing loss, be described after his death.

“He had the wish to be studied postmortem,” Mr Krause said.

“And it is kind of, basically, his wish that we are fulfilling to some degree with this project.”

Ludwig van Beethoven (baptised 17 December 1770 – 26 March 1827) was a German composer and pianist.

#Ludwig van Beethoven #Beethoven #classical music #music #AFP #Beethoven Haus #Bonn #Germany #Vienna #Austria

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viezec · 6 months ago

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What You Need To Know About Causes Of Liver Disease?

There are many different types of liver disease, each with their own unique set of causes. However, there are some commonalities among the various types of liver disease that are worth noting. Firstly, liver disease is often caused by excessive alcohol consumption. This can damage the liver cells and lead to scarring of the organ, known as cirrhosis. Obesity is another major risk factor for developing liver disease, as it can lead to fatty deposits building up in the liver and eventually causing inflammation. Viral infections such as hepatitis C are also a common cause of liver disease and can result in chronic inflammation of the organ.

https://shorturl.at/EhzqA

Email id- [email protected]

Ph no- +91 9650760803

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dr-smita-goel-homeopathy-clinic · 7 months ago

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*DR. SMITA GOEL HOMEOPATHY CLINIC*

www.thehomeopathyclinic.co.in

The liver is a largest, meaty organ. It has weight about 3 pounds, the liver is reddish-brown in colour and feels rubbery to the touch. Normally you can't feel the liver, because it's protected by the rib cage.

The liver has two large sections, called the right and the left lobes. The gallbladder sits under the liver, along with parts of the pancreas and intestines. The liver and these organs work together to digest, absorb, and process food.

The liver's main job is to filter the blood coming from the digestive tract, before passing it to the rest of the body. The liver also detoxifies chemicals and metabolizes drugs. As it does so, the liver secretes bile that ends up back in the intestines. The liver also makes proteins important for blood clotting and other functions.

There are following types of liver disease:

• Hepatitis: Inflammation of the liver, usually caused by viruses like hepatitis A, B, and C. Hepatitis can have non-infectious causes too, including heavy drinking, drugs, allergic reactions, or obesity.

• Cirrhosis: Long-term damage to the liver from any cause can lead to permanent scarring, called cirrhosis. The liver then becomes unable to function well.

• Liver cancer: The most common type of liver cancer, hepatocellular carcinoma, almost always occurs after cirrhosis is present.

• Liver failure: Liver failure has many causes including infection, genetic diseases, and excessive alcohol.

• Ascites: As cirrhosis results, the liver leaks fluid (ascites) into the belly, which becomes distended and heavy.

• Gallstones: If a gallstone becomes stuck in the bile duct draining the liver, hepatitis and bile duct infection (cholangitis) can result.

• Hemochromatosis: Hemochromatosis allows iron to deposit in the liver, damaging it. The iron also deposits throughout the body, causing multiple other health problems.

• Primary sclerosing cholangitis: A rare disease with unknown causes, primary sclerosing cholangitis causes inflammation and scarring in the bile ducts in the liver.

• Primary biliary cirrhosis: In this rare disorder, an unclear process slowly destroys the bile ducts in the liver. Permanent liver scarring (cirrhosis) eventually develops.

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aressida · 3 months ago

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Wrote a long one cos the in law family wanted him to take the flu shot, I said no.

"Dear Family, Friends, and Medical Professionals,

I am writing to share some thoughts and questions about vaccines, particularly in light of recent developments.

Do we believe that vaccines are the ultimate solution in medicine?

It is commonly known that influenza vaccines are reformulated each season due to the virus’s constant mutation, making it challenging to predict and protect against new strains accurately.

Is it true that these vaccines bypass the liver’s natural filtration system, potentially causing a shock to our bodies?

How should we classify these ingredients—as toxic or benign?

Here are just some vaccine ingredients, and these are being injected into your body and into your children’s bodies if you choose to vaccinate:

– Formaldehyde/Formalin – Highly toxic systemic poison and carcinogen.

– Betapropiolactone – Toxic chemical and carcinogen. May cause death or permanent injury after very short exposure to small quantities. Corrosive chemical.

– Hexadecyltrimethylammonium bromide – May cause damage to the liver, cardiovascular system, and central nervous system. May cause reproductive effects and birth defects.

– Aluminum hydroxide, aluminum phosphate, and aluminum salts – Neurotoxin. Carries risk for long-term brain inflammation/swelling, neurological disorders, autoimmune disease, Alzheimer’s, dementia, and autism. It penetrates the brain where it persists indefinitely.

– Thimerosal (mercury) – Neurotoxin. Induces cellular damage, reduces oxidation-reduction activity, cellular degeneration, and cell death. Linked to neurological disorders, Alzheimer’s, dementia, and autism.

– Polysorbate 80 & 20 – Trespasses the blood-brain barrier and carries with it aluminum, thimerosal, and viruses; allowing them to enter the brain.

– Glutaraldehyde – Toxic chemical used as a disinfectant for heat-sensitive medical equipment.

– Fetal Bovine Serum – Harvested from bovine (cow) fetuses taken from pregnant cows before slaughter.

– Human Diploid Fibroblast Cells – Aborted fetal cells. Foreign DNA has the ability to interact with our own.

– African Green Monkey Kidney Cells – Can carry the SV-40 cancer-causing virus that has already tainted about 30 million Americans.

– Acetone – Can cause kidney, liver, and nerve damage.

– E. Coli – Yes, you read that right.

– DNA from porcine (pig) Circovirus type-1

– Human embryonic lung cell cultures (from aborted fetuses)

You can view all of these ingredients on the CDC’s website. I encourage everyone to do their own research. Look up the MSDS on these chemicals. Read the thousands of peer-reviewed studies that have evaluated the biological consequences these chemicals can have on the body, especially when being injected.

Injecting foreign substances directly into the bloodstream—viruses, toxins, and proteins—has been linked to various diseases and disorders. These include conditions like atypical measles, cancer, leukemia, multiple sclerosis, and even SIDS (Sudden Infant Death Syndrome).

Conditions like Addison’s disease, anaphylactic shock, arthritis, asthma, asymptomatic COVID-19, Crohn’s disease, epilepsy, facial paralysis, fibromyalgia, fetal distress syndrome, foreign body embolism, genital herpes, hepatitis, hyperthyroidism, inflammatory bowel disease, jugular vein embolism, lung abscess, lupus, meningitis, MERS-CoV test positive, migraine-triggered seizures, multiple organ dysfunction syndrome, multiple sclerosis, multisystem inflammatory syndrome in children, pneumonia, stiff leg syndrome, stiff person syndrome, stillbirth, sudden heart attack, sudden respiratory failure, type 1 diabetes, uterine rupture, viral bronchitis—and much more.

This does not mean everyone will experience these reactions, but a significant number of test subjects have experienced one or more.

It is more than enough evidence to show that vaccine mandates are completely anti-scientific.

How can you make an informed decision if you do not have all the information?

We have also seen a shift where flu vaccines are now mRNA-based. But does a "vaccine" really prevent a virus or its recurrence as we expect it to?

The annual flu shot is, at best, a partial defense, aimed at last year’s strain. Does it truly help against the ever-mutating new flu, or is it just a temporary fix?

My concern is that this mindset—that a vaccine is a quick fix for everything—is flawed. The immune system may struggle to handle these types of agents, leading to breakthrough infections and potentially higher mortality rates.

For those who are vaccinated, I respect your choice. I simply ask for the same respect in return for my decision not to vaccinate. My reasons are personal and grounded in a belief that the government should not dictate my health choices and my family's.

Have you heard about Pfizer’s side effects?

Have you read the Pfizer documentation? Ask yourself if a drug with 32 pages of side effects is right for you.

The list of potential vaccine side effects released by Pfizer is alarming, ranging from autoimmune disorders to serious conditions like multiple organ dysfunction and sudden respiratory failure. Yet, this information was kept under wraps and only recently made public. Shouldn’t we be informed of the risks?

Do we even know the medium- or long-term effects of these vaccines?

Are they still in clinical trials? Is there a control group? What about Antibody-Dependent Enhancement (ADE) – has it been adequately tested? And why are ingredients like formaldehyde and mercury, known toxins, included in these vaccines?

Do you truly think this vaccine is 100% safe?

Transparency is crucial.

How can we make informed decisions if we are not given all the information?

We must ask ourselves, do we trust the pharmaceutical companies and their relationships with organizations like the CDC and FDA?

The FDA requested 75 years to release data on the Pfizer vaccine—why? Why did it take only 108 days to approve this vaccine, yet it supposedly requires decades to fully understand its effects?

Do you believe that SARS-CoV-2 has been isolated?

How well-informed are you about the CDC, FDA, pharmaceutical companies, and their donors? Do you think their qualifications are reliable?

These are important questions that deserve honest discussions. And, I believe it is crucial to acknowledge the existence of these alternative perspectives and engage in open discussions to gain a more comprehensive understanding.

Our health and freedom are at stake, and I urge everyone to think critically and seek out all the information before making decisions.

Thank you for taking the time to consider these points."

#vaccine questions #in laws family #we said no #stop using coercion #dont make me burn you #do your research people

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flyonthewallmedstudent · 11 months ago

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Disseminated Strongyloides and Hyperinfection

If you've ever rotated through any type of rotation that involves an immunocompromised host, your boss will have obsessed over the same few bugs. Including the parasite strongyloides. Aka threadworm.

They will never forget it, nor will they let you. They all seem to have that one case of disseminated disease that got missed and ended badly. Of all the bugs in the world to screen prior to starting significant immunosuppression, this is one of them, along side HIV, viral hepatitis and TB.

It's endemic to tropical environments in the developing world.

The concern is hyperinfection and disseminated disease in the case of the immunocompromised, in which case the mortality is 90%.

Hence the universal acceptance of screening for it in serology (I.e. IgG) in patients about to be immunocompromised on long term or high dose steroids. I.e. solid organ transplants, BMTs, rheumatology patients needing strong long term immunosuppression etc.

image source: NEJM, Case report ssx: rash and diarrhoea after starting steroids for malignant spinal cord compression (common practice), preceded by intermittent eosinophilia (the WCCs that are directed against parasites etc.)

The how: As part of it's infective lifestyle, the larva penetrate the skin, and via skin & the mucosal layers, it enters the blood stream, travels to the right heart and into the lungs. As the host coughs, they swallow the larvae and it enters the GI. Does that sound completely skin crawling and eerie?

Clinical manifestations: Pulmonary - eosinophilic pneumonitis (the WCCs directed at parasites increase and are the sources of inflammation in the lungs), alveolar bleeding from larval damage (yikes). On CT imaging, essentially you just see ground glass changes - non specific findings of inflammation (which can be caused by a huge array of things, of which, disseminated strongyloides would actually be the last on your list if you're not in an endemic area...). classic presentation in any GG inflammation is SOB, sometimes cough.

GI: larvae mature, embed into the intestinal mucosa and produce eggs. The eggs perpetuate the lifecycle and the host gets diarrhoea, abdominal pain etc.

Skin - rash, from dissemination of the larvae but also at the penetration site (may go unnoticed).

So then what's hyperinfection? T cell mediated immunity is suppressed in immunosuppression either by broadly suppresive steroids (dexamethasone, prednisolone etc.) Or transplant patients on therapy directed at the T cells, in order to prevent them rejecting their organs (maybe I'm still doing this, I'll make a blog on rejection).

Hyperinflation...wait.. hyperinflation..freudian slip but equally bad.

I mean hyperinfection results from the immune system leaving the worms to proliferate unchecked. "Excessive" worms are seen in usual affected organs - skin, lungs and gut. So expect an excess in clinical presentation, bloody diarrhoea, weight loss, malabsorption etc.

Disseminated disease occurs when it spreads outside the 'usual' routes of skin, lungs, gut and the numbers lead to catastrophic damage. Respiratory failure, AKI, shock, DIC, meningitis. Can spread widely to liver, heart, etc.

As added flavour, it can also lead to gut bugs causing bacteraemia. E.g. Ecoli, strep bovis (so look for malignancy as well as Strongyloides).

Given how devastating severe disease is, it's common practice for any immunocompromised host with eosinophilia and who's traveled to the subtropics/tropics to be screened. I've seen some really paranoid ones will send off serology on seeing eosinophilia.

As the bug can autoinfect a host, expect it to be there for a lifetime once infected.

Chronic/mild forms of the disease present as well, chronic GI symptoms (heart burn, anorexia, reflux, abdo pain, diarrhoea) and is often mistaken for IBD. Hence the importance of scopes and biopsies given therapy for IBD is immunosuppression.

investigations: easy pick up on biopsy if scoped or bronch'd. otherwise, serology. Suspect it on seeing eosinophilia. Stool mCS also an option. in chronic disease - mildly elevated eosinophilia and elevated IgE

Treatment of strongyloides vs hyperinfection: ivermectin or albendazole. Ivermectin is so infamous now post pandemic.

Issues: serology can take time to return, if in doubt, I've see some consultants/attendings empirically treat with ivermectin because the risk of mortality in hyperinfection is so high. But only in cases where patients are from or travelled to endemic areas. It's considered low risk if they have done neither.

Sources (will always aim for free ones)

Gastroenterology & Hepatology Journal 2011

NEJM Case report

BMJ Case reports

CDC

Give me a shout if you've treated this!

#medblr #medblrs #nematodes #strongyloides #infectious diseases

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medchemexpressinhibitor-blog · 11 months ago

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Understanding the Deadly Toxin Found in Certain Mushroom Species

Introduction

Mushrooms are a diverse group of organisms, and while many are safe and edible, some species contain poisonous compounds. β-Amanitin is one such toxin found in certain mushroom species belonging to the genus Amanita. This article aims to explore factual evidence regarding the properties, effects, and potential dangers associated with β-Amanitin.

Understanding β-Amanitin

β-Amanitin is a cyclic peptide toxin produced by various species of mushrooms, including Amanita phalloides (death cap) and Amanita virosa (destroying angel). It is highly stable and resistant to heat, making it a potent toxin even after cooking[¹^]. Once ingested, β-Amanitin targets specific cellular processes, leading to severe liver damage and potentially fatal consequences.

Mechanism of Action

Inhibition of RNA Polymerase II: β-Amanitin specifically inhibits RNA polymerase II, an essential enzyme responsible for transcribing messenger RNA (mRNA) in eukaryotic cells. By binding to RNA polymerase II, β-Amanitin prevents mRNA synthesis, disrupting important cellular processes and ultimately leading to cell death[²^].

Factual Evidence Regarding β-Amanitin

Toxicity and Poisoning: Ingestion of mushrooms containing β-Amanitin can cause acute liver failure, often with delayed symptoms. The initial phase may include gastrointestinal distress, followed by a symptom-free period lasting up to 24 hours. Subsequently, liver damage manifests, characterized by jaundice, hepatic encephalopathy, and potentially progressing to multi-organ failure[³^].

Treatment Challenges: β-Amanitin poisoning is considered a medical emergency, and prompt recognition and appropriate treatment are crucial. Unfortunately, there is no specific antidote for β-Amanitin poisoning. Current management involves supportive care, liver protection measures, and potentially liver transplantation in severe cases[⁴^].

Forensic Toxicology: Due to the potent effects of β-Amanitin and its presence in lethal mushroom species, its detection plays a significant role in forensic toxicology. Analytical techniques such as high-performance liquid chromatography (HPLC) and mass spectrometry (MS) are employed to identify and quantify β-Amanitin in biological samples[⁵^].

Prevention and Awareness

Mushroom Identification: The primary preventive measure is accurate mushroom identification. Proper training and knowledge are crucial for distinguishing edible mushrooms from poisonous species, especially those containing β-Amanitin.

Education and Public Awareness: Raising awareness about the dangers of consuming wild mushrooms without expert guidance is essential. Public education campaigns can help reduce the incidence of β-Amanitin poisoning by promoting safe mushroom foraging practices.

Conclusion

β-Amanitin, a toxic compound found in certain species of mushrooms, poses a significant threat to human health. Its inhibition of RNA polymerase II leads to severe liver damage and potential fatality. Timely recognition of symptoms, along with supportive care and appropriate medical intervention, is vital for managing β-Amanitin poisoning.

To prevent β-Amanitin poisoning, it is crucial to exercise caution when consuming wild mushrooms and rely on expert identification. Public awareness campaigns can play an important role in educating the general population about the risks associated with consuming unknown mushrooms. Please visit MedChemExpress

(Note: This article is for informational purposes only and should not replace professional medical advice. If there is a suspicion of mushroom poisoning, seek immediate medical attention or contact a poison control center.)

#biochemistry #business #chemistry

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dominafamiliar · 1 year ago

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DC universe story arc idea (may have been done, but I'm not aware of this particular setup)

Batman is still goth Sherlock Stark. He is reviled by society, with the police actively hunting him or feeding him false tips to lure him into mob ambushes. In-universe Superman reacts to big, flashy crises when they arise, and he's loved for his quick response times. By contrast, Batman roots out the causes of crime, seeking to scrape out the cancer and sluice out the corruption, until every last dreg, every ounce of bribery and lies, is laid bare to the public... A rogue's gallery of inmates from Arkham asylum keep getting let out to keep Batman busy, off the mob, and off the state officers who want him gone.

Arkham is a city-funded asylum, and there's local ordinances and state laws that prohibit the asylum from receiving funding from charities or charitable persons, barring Bruce Wayne from having an impact on the asylum on that front. He's actively sponsoring various legislators who aim to tear down those restrictions, but they've all got other priorities too, and the opposition is still stronger.

The Night Wing is an organization of Robinsonas and Batsonas who are largely orphans and the homeless. Some of them wear costumes. Most of them don't. Informants, smugglers, and a few combat-trained veterans make up the bulk of their organization, but there's a few others with specialized skills. One Batgirl is a hacker who calls herself Oracle. Her dad was on track for commissioner of the Gotham police before he walked into an ambush during a drug bust. Gordon never got to see his daughter grow up. Barbara lost her mom to racketeers a few years after. At 16, she was living on couches, bouncing around, trying to finish school. Her computer lab teacher caught on and decided to teach her the ins and outs of coding, hacking, troubleshooting, etc. So she could support herself by getting a job fixing broken code for health insurance companies, or something.

Instead, she became a tech vigilante, and uses her know-how to jailbreak tech, hack software, and erase her own footprint with a forged footprint that leads investigators somewhere else.

Joker has it out for Batman, knows that Batman is Bruce Wayne, but won't tell a soul because that would spoil the fun.

Harvey Dent knows who Bruce Wayne became, because he saw what losing Thomas and Martha did to the child, saw what Bruce became when his parents' killer was finally found, and saw how when Bruce returned from abroad, the Batman started to show up. NOBODY else knows it's Bruce in the Bat Suit until Bane shows up and rips the bat mask off.

In this version, Bane isn't a Luchador, or quite Tom Hardy's version. Rather, he's a former wrestling federation Heel who got into the drug trade, and eventually became a cartel boss. He's not a member of the League of Assassins, but Talia al Ghul is his primary problem-solver, and she is one of the few surviving members of the League.

Riddler:

Poison Ivy is a chemist who concocts several toxic plant compounds into serums and cosmetics that she uses to keep herself inoculated to their effects. She's at a high enough dose she'll eventually develop hepatic and renal failure, but in the interim, she's so deadly that any kind of bodily fluid exchange with someone else is likely to kill them.

Sometimes that's a kiss. Sometimes she spits in someone's eye. Sometimes, well... you get the idea. Skin-to-skin contact can cause anything from mild euphoria, discomfort, pain, etc. But direct fluid exchange is almost guaranteed fatal. Harleen Quinzel has a natural immunity to nearly every poison Pamela Isley uses, as do Selena Kyle and Richard Grayson.

Selena Kyle is a bast-worshipping vigilante who survived a near-fatal fall when she found evidence of corporate malfeasance. Together with Dr. Pamela Isley and Dr. Harleen Quinzel, the three of them are probably the most villainous of the vigilantes, but they only go after demonstrably evil people. Abusers, torturers, people who litter...

Joker is usually the most deadly of rogues' gallery villains, as he kills to seal the punchline of his jokes. But the most murderous and evil villains are government employees. Officers in Gotham police, judges, attorneys. Not all. Not even most. But the few who are evil shield themselves under the cloak and pretext of righteousness by rule of law.

The stories revolve around Bruce Wayne growing from a boy who lost his parents to a rich man bent on saving the world, to recognizing just how small a part he plays in real world solutions to the ongoing problems.

The series would run for approximately 4 books or 4 season's worth of material, where Bruce would grow less and less the focus of the story, and by the end of season 3, full blown revolution is underway with certain members of society's elite pitching their support for the common folk, or digging in their heels about it.

One poignant scene in Season 2 has Bruce getting it in his head that he should fire Alfred, dissolve Wayne Enterprises, and give up his vast sums of fortune to the poor, and while Alfred affirms that giving money to help the poor would be a good start, he doesn't think dissolving Wayne Enterprises would be a good idea. When Bruce inquires about Alfred's opinion on leaving the business, he just shrugs and says he loved Thomas ever since they served together. Carried each other to the med tent, survived ambushes and mines together. Had Thomas had a mind for it, he would have gone AWOL just to be with him. Had it been legal, he would have married the man.

But Thomas Wayne was as straight as they come, and while he respected Alfred and loved him as a brother, did not reciprocate romantic interest. So Alfred had prepared to move on with his life when Thomas hired him on as a butler. It was only after their deployment that Alfred realized that his beloved friend was extremely rich. Of course, he accepted the job. He was there to help Martha throughout the pregnancy. He was there to help Thomas calm down when she went into labor prematurely with hypertension. He held both of their hands throughout the process, and he'd always seen Bruce as a surrogate son. He just... didn't dare say so until now.

What had he to lose? His "job"? So Alfred suggests Bruce take a different track. Build charitable organizations that provide employment to the under-employed, but also serve as watchtowers throughout the city. Nerve centers for the Night Wing. And in so doing, Bruce ingratiates himself to the public, gradually spending down his own wealth into an organization whose end-goal objective by the final season, is to have broken the corruption of the mob, shaken the police departments down to spare parts and built up new community support structures. Not perfect, but better.

Decriminalization of drugs, sex work, and other poverty-survival tools, while increasing penalties for embezzlement, bribery, and other crimes of power. Arkham gets closed, demolished, and turned into a memorial park to the victims of the Joker and the other villains. Arkham's patients get permanent residencies in much more modernized hospitals. Therapists with adequate training, minimal use of meds, except where absolutely necessary. The last episode shows Bruce stopping in to walk with Jack, the man who went as Joker for so many years.

The show ends on a hopeful note, leaving room for a better future without promising perfection.

#The Bat Man #Batman #Gotham #Rant #long post

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