Influence of lifestyle habits, nutritional status and insulin resistance in NAFLD

Non alcoholic fatty liver disease (NAFLD) is associated with obesity, diabetes and insulin resistance (IR). The aim of our study was to assess the relationship between IR, anthropometry, lifestyle habits, resting energy expenditure (REE) and degree of fatty liver at ultrasound in 48 overweight patients with NAFLD as compared to 24 controls without fatty liver, matched for age. Nutritional status, alcohol intake and physical activity were assessed by skinfold thickness measurements, a 7-day diary, and SenseWear armband (SWA). REE was assessed by both SWA (REE-SWA) and a Vmax metabolic cart (REE-Vmax). Fatty liver was measured by US and the Doppler Power Index was calculated. IR was assessed using the HOMA index. There was significant correlation between waist circumference, HOMA, Doppler power index and fatty liver grade at US. Multivariate analysis showed that alteration of waist circumference, Doppler power index, and HOMA were the major significant predictors of fatty liver. Our data demonstrated a significant association between NAFLD and central adiposity and IR

[acute Dapsone Exposure And Methemoglobinemia In Children: Treatment With Multiple Doses Of Activated Charcoal With Or Without The Administration Of Methylene Blue]

OBJECTIVE: To study the changes in methemoglobinemia of 17 children admitted with acute exposure to dapsone complicated by a methemoglobin concentration greater than 20% of the total hemoglobin. The children were treated with multiple doses of activated charcoal with or without the administration of methylene blue.PATIENTS AND METHODS: Seventeen patients (ages 1-13 y, median 3 y), were admitted 1-72 h after the ingestion of 100-1200 mg (median 350 mg, 10 patients) or an unknown amount of dapsone (7 patients). The methemoglobin blood concentrations upon admission ranged from 23.5%-49.7% (median 37.8%), and the main clinical features were cyanosis (17), tachycardia (17), vomiting (11) and tachypnea (8). All of the children received multiple doses of activated charcoal orally or via nasogastric tube (1g/kg, 10% solution, 4-6 times/day, 3-16 doses with a median of 8 doses). Twelve of the 14 patients with methemoglobin levels greater than 30% were also treated with a single dose of methylene blue (1-2% solution, 1-2 mg/kg) infused IV over 5 min.RESULTS: There was a progressive decrease in the methemoglobin levels after the beginning of both treatments (multiple doses of activated charcoal alone or associated with methylene blue), and only one dose of methylene blue was necessary. There were no significant statistical differences between the results of the two treatments according to the time-course decrease in methemoglobinemia (p=0.49 Wilcoxon test).CONCLUSIONS: Multiple doses of activated charcoal given when methemoglobin levels were greater than 20% can be considered as a possible treatment for pediatric patients, with or without the administration of methylene blue, after acute dapsone exposure.76290-

Hydrazones and Thiosemicarbazones Targeting Protein-Protein-Interactions of SARS-CoV-2 Papain-like Protease

The papain-like protease (PLpro) of SARS-CoV-2 is essential for viral propagation and, additionally, dysregulation of the host innate immune system. Using a library of 40 potential metal-chelating compounds we performed an X-ray crystallographic screening against PLpro. As outcome we identified six compounds binding to the target protein. Here we describe the interaction of one hydrazone (H1) and five thiosemicarbazone (T1-T5) compounds with the two distinct natural substrate binding sites of PLpro for ubiquitin and ISG15. H1 binds to a polar groove at the S1 binding site by forming several hydrogen bonds with PLpro. T1-T5 bind into a deep pocket close to the polyubiquitin and ISG15 binding site S2. Their interactions are mainly mediated by multiple hydrogen bonds and further hydrophobic interactions. In particular compound H1 interferes with natural substrate binding by sterical hindrance and induces conformational changes in protein residues involved in substrate binding, while compounds T1-T5 could have a more indirect effect. Fluorescence based enzyme activity assay and complementary thermal stability analysis reveal only weak inhibition properties in the high micromolar range thereby indicating the need for compound optimization. Nevertheless, the unique binding properties involving strong hydrogen bonding and the various options for structural optimization make the compounds ideal lead structures. In combination with the inexpensive and undemanding synthesis, the reported hydrazone and thiosemicarbazones represent an attractive scaffold for further structure-based development of novel PLpro inhibitors by interrupting protein-protein interactions at the S1 and S2 site

Enhancement of in-vitro activity of ofloxacin and gentamicin by rat serum

Normal rat serum shows antibacterial activity because of the presence of endogenous substances. The aim of this research was to study some aspects of the interaction between this biological fluid and some antibiotics, in order to demonstrate possible synergistic activity. Serum is able to lower the minimum inhibitory concentration of gentamicin and ofloxacin against some Gram-negative microorganisms. This can be explained by the presence of lysozyme, antibodies, beta-lysin and other complementary factors that are able to cooperate with these antibiotics