Membrane depolarization of isolated rat liver mitochondria attenuates permeability transition pore opening and oxidant production

It has been suggested that one key feature of mitochondrial permeability transition (PT) regulation is its control by the proton electrochemical gradient and that depolarization favors pore opening, swelling, and reactive oxygen species (ROS) production. Moreover, ROS have been suggested to facilitate the process of mitochondrial PT pore opening. The aim of this study was to show that collapsing the mitochondrial membrane potential with the mitochondrial uncoupler, carbonyl cyanide p-(trifluoromethoxy) phenylhydrazone (FCCP), at concentrations of up to 10 microM, does not induce mitochondrial swelling and, in fact, stabilizes mitochondria exposed to oxidant, protecting them from tert-butyl hydroperoxide (TBH)-induced high-amplitude swelling. FCCP decreased polyethylene glycol-induced mitochondrial contraction following exposure to TBH, indicating closing of the PT mega-channel. In the presence of the calcium uniporter inhibitor ruthenium red, FCCP induced PT due to suppression of calcium efflux. Under PT-favorable conditions, ROS production was evaluated in mitochondria following treatments with TBH, inorganic phosphate, or FCCP (with or without ruthenium red). FCCP alone and in combination with ruthenium red attenuated mitochondria-derived ROS production. FCCP also decreased the augmented ROS production induced by inorganic phosphate. It is concluded that mitochondrial depolarization protects and prevents high-amplitude swelling and PT-derived ROS production.     

Incomplete Administration of Intravenous Vancomycin Prophylaxis is Common and Associated With Increased Infectious Complications After Primary Total Hip and Knee Arthroplasty

BackgroundVancomycin is often used as antimicrobial prophylaxis in patients undergoing total hip or knee arthroplasty. Vancomycin requires longer infusion times to avoid associated side effects. We hypothesized that vancomycin infusion is often started too late and that delayed infusion may predispose patients to increased rates of surgical site infections and prosthetic joint infections.MethodsWe reviewed clinical data for all primary total hip arthroplasty (THA) and total knee arthroplasty (TKA) patients at our institution between 2013 and 2020 who received intravenous vancomycin as primary perioperative gram-positive antibiotic prophylaxis. We calculated duration of infusion before incision or tourniquet inflation, with a cutoff of 30 minutes defining adequate administration. Patients were divided into two groups: 1) appropriate administration and 2) incomplete administration. Surgical factors and quality outcomes were compared between groups.ResultsWe reviewed 1047 primary THA and TKA patients (524 THAs and 523 TKAs). The indication for intravenous vancomycin usage was allergy (61%), methicillin-resistant staphylococcus aureus colonization (17%), both allergy and colonization (14%), and other (8%). 50.4% of patients began infusion >30 minutes preoperatively (group A), and 49.6% began infusion <30 minutes preoperatively (group B). Group B had significantly higher rates of readmissions for infectious causes (3.6 vs 1.3%, P = .017). This included a statistically significant increase in confirmed prosthetic joint infections (2.2% vs 0.6%, P = .023). Regression analysis confirmed <30 minutes of vancomycin infusion as an independent risk factor for PJI when controlling for comorbidities (OR 5.22, P = .012).ConclusionLate infusion of vancomycin is common and associated with increased rates of infectious causes for readmission and PJI. Preoperative protocols should be created to ensure appropriate vancomycin administration when indicated.     

Increased intracellular concentration of an initiator protein markedly reduces the minimal sequence required for initiation of DNA synthesis.

One of the most common sites used for cloning in the filamentous phages f1, fd, and M13 lies within the phage "functional origin," a sequence of 140 nucleotides that is required for phage replication. Even small insertions (four nucleotides) at this location severely reduce origin function. Secondary trans-acting mutations in the phage genome are necessary to restore efficient replication. One of these mutations, present in one of our cloning vectors, R218, has been fully characterized. It consists of a regulatory mutation within gene V that leads to a marked increase in the intracellular level of the phage gene II protein, the "initiator" of viral replication. Increased gene II protein production is sufficient to reduce the minimal sequence required for a functional origin to only 40 nucleotides, while the remaining 100 (containing the cloning site) become entirely dispensable. The general implications of these findings are discussed.     

An outbreak of Molluscum contagiosum in a kibbutz

Summary Molluscum contagiosum is a viral disease that presents in a primary care setting as single or multiple wart-like lesions. We have seen an outbreak of Molluscum contagiosum in a small rural community, affecting 34 individuals. The most infected were children two-to nine-years-old. The diagnosis was made on clinical grounds. Spread appeared to be as a result of direct contact and by fomites. There was no evidence, in our study, of spread via swimming pool. Cryosurgery was used to treat our patients with Molluscum contagiosum.

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Ausbruch von Molluscum contagiosum in einem Kibbuz

Zusammenfassung Molluscum contagiosum ist eine virale Erkrankung, die bei Fällen, die in der Allgemeinpraxis beobachtet werden, mit einzelnen oder zahlreichen warzenähnlichen Läsionen auftritt. Wir haben in einer kleinen ländlichen Gemeinde einen Ausbruch von Molluscum contagiosum mit 34 Fällen beobachtet. Betroffen waren vor allem Kinder im Alter von zwei bis neun Jahren. Die Diagnose wurde klinisch gestellt. Die Übertragung erfolgte offensichtlich durch direkten Kontakt und kontaminierte Materialien. Für eine Übertragung im Swimming Pool ergab sich kein Anhalt. Zur Behandlung der Molluscum contagiosum-Läsionen wurde bei unseren Patienten Kryochirurgie eingesetzt.

     

Effect of nitric oxide synthase inhibitor on experimentally induced burn wounds

BACKGROUND: Nitric oxide (NO) may have an important role in the healing of burn wounds. This study investigated the effect of NO on experimentally induced burn wounds by preventing NO synthesis. METHODS: A total of 40 mice weighing 25 to 30 g were used in this study. The shaved skin on the back of the mice was immersed in 100 degrees C water for 10 seconds to achieve a partial-thickness scald burn. The mice were divided into two groups of 20. In group I (control group), 17.5 mg/kg of serum physiologic (placebo) was injected intraperitoneally two times a day for 15 days. In group II (study group), 17.5 mg/kg of aminoguanidine (NO synthase inhibitor) was injected intraperitoneally two times a day for 15 days. On day 15 of the burn, the animals were killed and the burn areas were investigated histologically. Histologic changes such as epithelial proliferation, abscess, collagen, and granulation tissue were evaluated. RESULTS: Epithelial proliferation, formation of collagen, and granulation tissue with rich capillaries observed in the control group were statically significantly higher than those observed in the study group (z = -2.022, p < 0.05; z = -2.02, p < 0.05; and z = -2.022, p < 0.05; respectively). CONCLUSION: We concluded that healing of the burn wound is delayed by preventing NO synthesis.     

Celiac disease diagnosed in the elderly

BACKGROUND AND AIMS: In the past 20 years, a growing proportion of new cases of celiac disease (CD) are diagnosed in adults and in patients with extraintestinal manifestations. Our understanding of the extremely wide spectra of manifestations and the profound effects on elderly patients is improving. Nevertheless, CD is still underdiagnosed in elderly patients. In this study, we describe a case series of CD patients diagnosed after the age of 60. METHODS: A retrospective chart review was preformed in cases of CD diagnosed after the age of 60. Patients were included if they had positive serology and histologic findings compatible with CD. Eligible patients were reinterviewed, and demographic, clinical, and laboratory information were recorded. RESULTS: During the study period, 7 patients with CD diagnosed after the age of 60 were identified. The most common presenting findings were weight loss, iron deficiency anemia, and diarrhea. Two patients suffered from severe early osteoperosis and 2 additional patients had elevated liver function tests. Neurologic manifestation was suspected in 3 cases. Two female patients presented with cognitive decline that was attributed to Alzheimer dementia but ameliorated after the initiation of gluten-free diet. The third patient had peripheral neuropathy that completely resolved after the initiation of gluten-free diet. Median lag in diagnosis was 8 years. Diet treatment led to complete resolution of symptoms in most cases and a significant weight gain (median 7.75 kg, range 5 to 11). One patient developed a fatal intestinal T-cell lymphoma. CONCLUSIONS: In this case series, we have described several cases of CD in patients over the age of 60 with a varied spectrum of manifestations. We have also found a significant lag in diagnosis and treatment. We believe that it is important to promote the identification of CD as a possible culprit in varied clinical conditions in the elderly population.     

Methimazole Slows Hepatocyte Streaming in Rats

Hepatocytes are hypothesized to continuallystream from the portal tract to the terminal hepaticvein. By this model, when a cell divides, one of itsprogeny replaces the dividing ancestor and the other is displaced into a more remote location. Thepresent experiment aims to demonstrate thathypothyroidism affects liver cell turnover. Thirty maleadult rats were divided into two groups. One receivedmethimazole for two weeks and the other served as control.Each rat was injected intraperitoneally with 18.5 KBq[³H]thymidine/g body weight. Rats were killedafter 1 hr and two and four weeks. Autoradiography was done. The distance of the labeled cells fromthe portal tract was measured. The mean TSH levels ofthe methimazole-treated group and controls were 1.45 and0.25 mM/liter, respectively (P < 0.01). Hepatocyte streaming was lower in hypothyroid (1.8m/day) than in untreated rats (2.5 m/day) (P< 0.01). The respective labeling indices 1 hr afterlabeling were 0.9% and 1.24% (P < 0.05). We concludethat hypothyroidism diminishes hepatocyte and littoral cellturnover and slows down their streaming.