Coenzyme Q10 and vitamin D interventions could ameliorate COVID-19 related cellular bioenergetic dysfunction and cytokine storms

The immune response to SARS-CoV-2 varies from asymptomatic or mild symptoms of high temperature, muscle aches and coughs lasting 7 to 14 days to lower respiratory tract infections leading to pneumonia and serious respiratory distress as well as long COVID-19. Complications occur due to an abnormal immune response which involves upregulation of multiple cytokines leading to sustained inflammation which results in the spread of infection to vital organs. The double vaccine roll out has been rapid however vaccine mediated antibodies are not 100% effective against future coronavirus variants which may become increasingly more resistant and easily transmissible to overcome host immunity. Invariably supportive therapies will be needed. Research has shown that coenzyme Q10 and vitamin D deficiencies can have detrimental effects on immune cell defence, function and cytokine secretion promoting inflammation and sepsis especially against microbes. Early interventions including supplementation of these factors could mitigate cellular dysfunction especially in relation to mitochondria bioenergetics and help maintain cell immunity. This is particularly important as chronically ill COVID-19 patients seem to display abnormal immune cell phenotypes in infected organs indicating this could contribute to disease progression. The immune response and proposed roles of Vitamin D and Coenzyme Q10 in COVID-19 are discussed

Macrophage derived platelet activating factor implicated in the resolution phase of gouty inflammation

Human blood derived in vitro differentiated monocytes or macrophages are a population of cells which have been investigated over the years to determine the role these cells play in the resolution phase of gout. Macrophages are able to phagocytose monosodium urate monohydrate (MSU) crystals without releasing inflammatory factors. This study analysed macrophage platelet activating factor secretion and its possible role in the pathway of gout resolution. Analysis of sunatants from in vitro differentiated macrophages stimulated with MSU crystals revealed the secretion of platelet activating factor (PAF) mean ± SEM; ng/mL per 106 cells. This secretion was absent in immature monocytes treated similarly. When these monocytes were pretreated with recombinant human PAF-acetylhydrolase (rhuPAF-AH) and MSU crystals resulted in TNFα suppression. Addition of WEB2086, a platelet activating factor (PAF) antagonist, to differentiated macrophages with MSU crystals unmasked TNFα secretion mean ± SEM; ng/mL per 106 cells. This study identifies a role for PAF and the PAF receptor antagonist in the pathway by which macrophages ingest MSU crystals and resolve the concomitant inflammation

Urate crystals induce macrophage PAF‑AH secretion which is differentially regulated by TGFβ1 and hydrocortisone

The aim of the present study was to establish the role of platelet‑activating factor acetyl hydrolase (PAF‑AH) in the resolution phase of gout using an established in vitro mononuclear cell model. The effects of signalling pathway inhibitors on PAF‑AH secretion, as well as the effects of the common treatments hydrocortisone and colchicine, an antibody against the anti‑inflammatory cytokine transforming growth factor β1 (TGFβ1), and the transcriptional inhibitor actinomycin D, were also investigated. The effect of recombinant PAF‑AH on cytokine secretion by these cells was also determined. Human peripheral blood‑derived monocytes were isolated and differentiated into macrophages. Monocytes and macrophages were stimulated with monosodium monohydrate urate (MSU) crystals or lipopolysaccharide in the presence or absence of AEG3482 [a c‑Jun N‑terminal kinase (JNK) inhibitor], MG132 (a proteasome inhibitor), hydrocortisone or colchicine. Cultures were then analysed for PAF‑AH secretion using ELISA. A 6‑fold upregulation of PAF‑AH secretion was observed following macrophage exposure to MSU crystals for 24 h (29.3±6 vs. 5.4±0.3 ng/ml unstimulated; P<0.05). Following 72 h, PAF‑AH levels decreased significantly (11.1±1.8; P<0.01). Secretion was further enhanced following pre‑treatment with the JNK protein kinase inhibitor AEG3482 prior to MSU crystal stimulation (P<0.05) and was abrogated when cells were preincubated with actinomycin D or the proteasome inhibitor MG132 (50, 100 and 200 µM). The addition of recombinant PAF‑AH (2.5‑10 ng/ml) to MSU crystal‑stimulated immature monocyte cultures significantly decreased pro‑inflammatory interleukin (IL)‑1β (unstimulated 687±124 vs. stimulated 113±30 pg/ml) and IL‑6 secretion (unstimulated 590±50 vs. stimulated 182±19 pg/ml). Treatment of MSU crystal‑stimulated macrophages with hydrocortisone (2 µM) also significantly decreased PAF‑AH release (P<0.05). Neutralising anti‑TGFβ1 addition decreased PAF‑AH dose‑dependently with the highest inhibition observed at 1 µg/ml (P<0.05). The results implicated that PAF‑AH may have an anti‑inflammatory role in the resolution phase of gout

Type II perforation of the body of the gallbladder in acalculous cholecystitis: a rare complication of enteric fever

Gallbladder perforation is a rare but potentially life-threatening complication of acute cholecystitis with or without gallstones. Enteric fever leading to small bowel perforation is rare, and gallbladder perforation is extremely rare. It requires early and accurate diagnosis. If left untreated, it is associated with high mortality. Clinical diagnosis is often difficult. The most common site of perforation is the fundus; perforation in the body is rare. We report a case of gallbladder perforation as a complication of enteric fever, which presented as acute abdomen and responded very well after cholecystectomy. Although rare and unusual, this case report shows that gallbladder perforation should be considered in patients presenting with acute abdomen and a history of enteric fever.Keywords: Enteric fever; Acalculous cholecystitis; Perforation; Cholecystectom

Antibacterial apple cider vinegar eradicates methicillin resistant Staphylococcus aureus and resistant Escherichia coli

Methicillin-resistant Staphylococcus aureus (MRSA) and resistant Escherichia coli (rE.coli) infections can spread rapidly. Further they are associated with high morbidity and mortality from treatment failure. Therapy involves multiple rounds of ineffective antibiotics alongside unwanted side effects, alternative treatments are crucial. Apple cider vinegar (ACV) is a natural, vegan product that has been shown to have powerful antimicrobial activity hence we investigated whether ACV could ameliorate these resistant bacteria. The minimum dilution of ACV required for growth inhibition was comparable for both bacteria (1/25 dilution of ACV liquid and ACV tablets at 200 µg/ml were effective against rE. coli and MRSA). Monocyte co-culture with microbes alongside ACV resulted in an increase in monocyte phagocytosis by 21.2% and 33.5% compared to non-ACV treated but MRSA or rE. coli stimulated monocytes, respectively. Label free quantitative proteomic studies of microbial protein extracts demonstrated that ACV penetrated microbial cell membranes and organelles, altering the expression of key proteins. This resulted in significant reductions in total protein expression, moreover we could only detect ribosomal proteins; 50 s 30 s, enolase, phosphenol pyruvate and the ATP synthase subunit in rE. coli. Elongation factor iNOS and phosphoglycerate kinase OS were the only proteins present in MRSA samples following ACV treatment

Antimicrobial activity of apple cider vinegar against Escherichia coli, Staphylococcus aureus and Candida albicans; downregulating cytokine and microbial protein expression

The global escalation in antibiotic resistance cases means alternative antimicrobials are essential. The aim of this study was to investigate the antimicrobial capacity of apple cider vinegar (ACV) against E. coli, S. aureus and C. albicans. The minimum dilution of ACV required for growth inhibition varied for each microbial species. For C. albicans, a 1/2 ACV had the strongest effect, S. aureus, a 1/25 dilution ACV was required, whereas for E-coli cultures, a 1/50 ACV dilution was required (p < 0.05). Monocyte co-culture with microbes alongside ACV resulted in dose dependent downregulation of inflammatory cytokines (TNFα, IL-6). Results are expressed as percentage decreases in cytokine secretion comparing ACV treated with non-ACV treated monocytes cultured with E-coli (TNFα, 99.2%; IL-6, 98%), S. aureus (TNFα, 90%; IL-6, 83%) and C. albicans (TNFα, 83.3%; IL-6, 90.1%) respectively. Proteomic analyses of microbes demonstrated that ACV impaired cell integrity, organelles and protein expression. ACV treatment resulted in an absence in expression of DNA starvation protein, citrate synthase, isocitrate and malate dehydrogenases in E-coli; chaperone protein DNak and ftsz in S. aureus and pyruvate kinase, 6-phosphogluconate dehydrogenase, fructose bisphosphate were among the enzymes absent in C.albican cultures. The results demonstrate ACV has multiple antimicrobial potential with clinical therapeutic implications

Laparoscopic colorectal cancer surgery - a prospective study of short-term outcomes of consecutive cases over 3 years

This study was carried out with the objectives to study the feasibility of laparoscopic colorectal cancer resection, to observe short term outcome such as recovery parameters, oncologic safety, morbidity and mortality, and to analyze the experience of laparoscopic colorectal surgery in a teaching hospital. Between January 2007 and July 2009, all consecutive adult cases admitted to our department for colorectal cancer were assessed for eligibility. The ethical committee approved the protocol at the Sterling Hospital. Out of 31 patients,17 were males and 14 females. The mean age was 59 years. The most common clinical presentation was weight loss and altered bowel habits. Rectum (51.61%) was the most commonly involved organ followed by cecum (22.58%). - median time to liquid diet was two days (range 1-22), and a solid diet was three days (range 3-30). The median time to first flatus was two days (range 1-5), and the first stool was five days (range 3-7). The postoperative stay was eight days (range 6-30) median time to mobilization was 2.5 days. The postoperative stay is cumulative and includes patients who underwent reoperation for the anastomotic leak. The median operating time was 240 mins (range 116 – 520). The median length of incision was 6 cm (range 4 – 10 cm). The median blood loss was 170 ml. Blood loss was higher in patients with hemorrhage and tumor adhesions, and both of them were converted to open. These patients incidentally had a more extended hospital stay. The laparoscopic technique for colorectal cancer is feasible and safe. Laparoscopic colorectal surgery (LCS) is associated with short term benefits like the earlier return of gastrointestinal function and shorter length of hospital stay. From the oncologic point of view, tumor resections are adequate, taking into context numbers of lymph nodes retrieved and resectional margins in context to oncologic safety. The decreased postoperative wound infections and early recovery facilitate appropriate adjuvant therapy. Advanced laparoscopic surgery requires a team approach with proper case selection. Transvaginal delivery of specimens can give scar-less surgery and the option for assisted natural orifice surgery

Lipemic serum: A quick clue to diagnose hyperlipidemic acute pancreatitis

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