Influence of cytochrome P450 2D6*10/*10 genotype on the risk for tramadol associated adverse effects: a retrospective cohort study

Background: Tramadol is primarily metabolized by the highly polymorphic CYP2D6 enzyme, leading to a large spectrum of adverse events and clinical response. Ample evidence pointed a reduced CYPD26 activity score in individuals harboring the CYP2D6*10/*10 genotype, nevertheless, there is scarce studies on the impact of CYP2D6*10/*10 genetic polymorphism on long-term tramadol’s adverse effects.Aim: To test the correlation between CYP2D6*10/*10 expression and the risk for tramadol-associated adverse effects.Method: Using a database of Leumit Healthcare Services in Israel, we retrospectively assessed the occurrence of adverse events in patients who were prescribed tramadol. A binary logistic regression model was applied to model the relationship between CYP2D6*10/*10 genotype and the occurrence of adverse effects.Results: Data from four hundred ninety-three patients were included in this study. Only 25 (5.1%) patients were heterozygous for the CYP2D6*10 variant, while 56 patients (11%) were tested positive to the CYP2D6*10/*10 genotype. Compared to carriers of other variants, patients with the CYP2D6*10/*10 variant exhibited a higher occurrence of adverse events (odds ratio [OR] = 6.14, 95% confidence interval 3.18–11.83); the odds ratio for central nervous system adverse events and gastrointestinal adverse events were 5.13 (95% CI 2.84–9.28), and 3.25 (95% CI 1.78–5.93), respectively.Conclusion: Among the different CYP2D6 genotypes, CYP2D6*10/*10 genotype carries the higher risk of tramadol related adverse events. Appreciating the frequency of this specific allele it seems prudent to pharmacogenetically screen patients considered for long term tramadol treatment for better tolerability and efficacy outcomes

Prévalence du VIH chez la Femme Enceinte et Transmission Mère-Enfant du VIH à la Maternité de l’Hôpital Général de Douala, Cameroun

Nous rapportons ici une évaluation sommaire de nos activités de prévention transmission mère-enfant du VIH sur 6 ans (2002 à 2007). Il s’agissait d’une étude descriptive et rétrospective effectuée à l’Hôpital Général de Douala. Les enfants inclus étaient âgés d’au moins 18 mois. La technique d’ELISA GENSCREEN 3ème génération pour le VIH a été utilisée. Sur 5261 accouchements effectués pendant cette période, 138 étaient de mères VIH positifs (prévalence : 2,62%). Quatre de nos patientes étaient testées négatives au premier trimestre de gestation. Des 138 bébés, 87 seulement ont pu être testés (63%), dont 4 contaminés (prévalence de transmission : 4,6%). Des 4 enfants contaminés, un seul a reçu la prévention adéquate en grossesse, soit un taux de transmission sous prévention de 1,19%. Une meilleure organisation des stratégies de réduction de la transmission mèreenfant du VIH/SIDA, même dans un environnement à ressources limitées, peut conduire à des résultats similaires à ceux des pays du Nord. A la lumière de cette étude, nous recommandons fortement un deuxième test du VIH au 3ème rimestre de la grossesse afin de réduire davantage le risque de sa transmission périnatale.Mots Clés prévalence du VIH ; femme enceinte ; transmission mère-enfant du VI

Functional and bioactive properties of Bupleurum chinense DC. and Clematis chinensis osbeck mediated biogenic synthesized silver nanoparticles

The synthesis of novel metallic nanoparticles (NPs) using plant materials has emerged as a cost-effective alternative to synthetic NPs and has found wide application in biomedical, cosmetic, bioremediation, and health care technology. This study aimed to synthesize and characterize the morphologies, functional groups, and crystalline structures of silver nanoparticles (AgNPs) deduced using B. chinense (Bc) and C. chinensis (Cc). The biogenic AgNPs were appraised for their antioxidant content, radical scavenging activities, antimicrobial, anti-inflammatory, and anti-diabetic activities to understand their functional and health promoting properties. The AgNPs deduced from both plants were spherical in shape with the size of 20-30 nm and possessed face centered cubic phase arrangement. The total phenolic content (TPC) was high in Cc-AgNPs (166.2100 mgGAE/g) and exhibited strong hydroxyl (OH-) and ABTS+ radical scavenging activities. On the contrary, Bc-AgNPs with higher TFC (286.1438 mgQE/g) had greater nitric-oxide (NO), DPPH, Fe2+scavenging and anti-albumin denaturation activities. Minimum anti-α-amylase activity disparity was observed between Cc-AgNPs (EC50 = 0.2903 mg/mL) and Bc-AgNPs (EC50 = 0.2975 mg/mL) due to various inhibition mode contributed by bioactive compounds. Besides, Bc-AgNPs showed strongest inhibition towards Gram negative bacteria while Cc-AgNPs was more effective as an antifungal agent. In conclusion, biogenic AgNPs exhibited strong functional and bioactive properties which may be attributed to the presence of bioactive compounds on the surface of AgNPs and further in-depth analysis are required to be used for various biomedical applications

Strong neuroprotection with a novel platinum nanoparticle against ischemic stroke- andtissue plasminogen activator-related brain damages in mice

Reactive oxygen species (ROS) are major exacerbation factor in acute ischemic stroke, and thrombolytic agent tissue plasminogen activator (tPA) may worsen motor function and cerebral infarcts. The platinum nanoparticle (nPt) is a novel ROS scavenger, and thus we examined the clinical and neuroprotective effects of nPt in ischemic mouse brains. Mice were subjected to transient middle cerebral artery occlusion (tMCAO) for 60 min and divided into the following four groups by intravenous administration upon reperfusion, vehicle, tPA, tPA + nPt, and nPt. At 48 h after tMCAO, motor function, infarct volume, immunohistochemical analyses of neurovascular unit (NVU), in vivo imaging of matrix metalloproteinase (MMP), and zymography for MMP-9 activity were examined. Superoxide anion generation at 2 h after tMCAO was also examined with hydroethidine (HEt). As a result, administration of tPA deteriorated the motor function and infarct volume as compared to vehicle. In vivo optical imaging of MMP showed strong fluorescent signals in affected regions of tMCAO groups. Immunohistochemical analyses revealed that tMCAO resulted in a minimal decrease of NAGO and occludin, but a great decrease of collagen IV and a remarkable increase of MMP-9. HEt stain showed increased ROS generation by tMCAO. All these results became pronounced with tPA administration, and were greatly reduced by nPt. The present study demonstrates that nPt treatment ameliorates neurological function and brain damage in acute cerebral infarction with neuroprotective effect on NVU and inactivation of MMP-9. The strong reduction of ROS production by nPt could account for these remarkable neurological and neuroprotective effects against ischemic stroke

Human Neutrophil α-Defensins 1–3 Are Upregulated in the Microenvironment of Fibrotic Liver

Background and Objectives: Neutrophil infiltration is an established signature of Non-Alcoholic Fatty Liver Disease (NAFLD) and Steatohepatitis (NASH). The most abundant neutrophilic peptide, alpha-defensin, is considered a new evolving risk factor in the inflammatory milieu, intimately involved in lipid mobilization. Our objective is to assess for potential association between alpha-defensin immunostains and NAFLD severity. Materials and Methods: We retrospectively investigated the liver biopsies of NAFLD/NASH patients, obtained at Hillel Yaffe Medical center between the years 2012 and 2016. Patients’ characteristics were recorded, including relevant blood tests at the time of biopsy. Each biopsy was semi-quantitatively scored using NAFLD Activity Score (NAS) and NASH fibrosis stage. The biopsies were immunostained for alpha-defensin. The precipitation of alpha-defensin was correlated to NAS and fibrosis. Results: A total of 80 biopsies were evaluated: male ratio 53.2%, mean age 44.9 ± 13.2 years, 54 had fibrosis grades 0–2, and 26 were grade 3–4. Conventional metabolic risk factors were more frequent in the high-grade fibrosis group. Immunostaining for alpha-defensin disclosed higher intensity (a.u.) in grade 3–4 fibrosis relative to grades 0–2, 25% vs. 6.5%, p < 0.05, respectively. Moreover, alpha-defensin staining was nicely co-localized with fibrosis. Conclusions: In our group of NASH/NAFLD patients, higher metabolic risk profile was associated with higher fibrosis grade. Immunostaining for alpha-defensin showed patchy intense staining concordant with high fibrosis, nicely co-localized with histological fibrosis. Whether alpha-defensin is a profibrotic risk factor or merely risk marker for fibrosis must be clarified in future studies

SARS-CoV-2 Infection-Blocking Immunity Post Natural Infection: The Role of Vitamin D

Objective and Aim: The extent of the protection against SARS-CoV-2 conferred by natural infection is unclear. Vitamin D may have a role in the interplay between SARS-CoV-2 infection and the evolving acquired immunity against it. We tested the correlation between baseline 25(OH) D content and both the reinfection rate and the anti-spike protein antibody titer following COVID-19 infection. Methods A retrospective observational survey that included a large convalescent COVID-19 population of subjects insured by the Leumit HMO was recorded between 1 February 2020 and 30 January 2022. Inclusion criteria required at least one available 25(OH)D level prior to enlistment. The association between 25(OH)D levels, the rate of breakthrough infection, and the anti-spike protein antibody titer was evaluated. Results A total of 10,132 COVID-19 convalescent subjects were included, of whom 322 (3.3%) sustained reinfection within a one-year follow-up. In the first 8 months after recovery, the reinfected patients were characterized by a higher incidence of low 25(OH)D levels (<30 ng/mL, 92% vs. 84.8%, p < 0.05), while during the following three months, the incidence of low 25(OH)D levels was non-significantly higher among PCR-negative convalescent subjects compared to those reinfected (86% vs. 81.7, p = 0.15). By multivariate analysis, age > 44 years (OR-0.39, 95% CI: 0.173–0.87, p = 0.02) and anti-spike protein antibody titer > 50 AU/mL (0.49, 95% CI: 0.25–0.96, p = 0.04) were inversely related to reinfection. No consistent correlation with vitamin D levels was observed among the 3351 available anti-spike protein antibody titers of convalescent subjects. However, the median anti-spike protein antibody titers tended to increase over time in the vitamin D-deficient group. Conclusion Higher pre-infection 25(OH)D level correlated with protective COVID-19 immunity during the first 8 months following COVID-19 infection, which could not be explained by anti-spike protein antibody titers. This effect dissipated beyond this period, demonstrating a biphasic 25(OH)D association that warrants future studies

De Agenda XL: 12 09 15

Na een bewogen seizoen, met acht bijeenkomsten van De Agenda in 2015 - van Rotterdam tot Arnhem - en maar liefst 400 individuele deelnemers, wilden we gezamenlijk afsluiten waar we zijn begonnen, in Amsterdam. In een extra lange sessie maakten we de balans op, blikten we terug én vooruit. We vroegen ons af: wat is er het afgelopen jaar gebeurd? Welke veranderingen hebben plaatsgevonden? Hoe ervaren we de rol en waarde van kunst in de samenleving? Ook stonden we stil bij een thema dat de laatste tijd steeds explicieter naar voren treedt, de zogenaamde ‘uitholling van de sector’. Wij zien met trots en enthousiasme dat De Agenda is uitgegroeid tot een informele structuur van mensen, ideeën en mogelijkheden. De Agenda is een vanuit de sector zelf geïnitieerde reeks bijeenkomsten die moeten leiden tot een ander gesprek over de toekomst van de podiumkunsten in Nederland, gevoerd door allerlei generaties en vakgebieden. De Agenda is een plek van geëngageerde ‘zelfreflectie’, waar mensen voortdurend hun eigen denkbeelden kunnen vormen en ‘slijpen’ in gesprek met andere vakgebieden en generaties. Vanuit de agenda ontstaan op organische wijze kleinere allianties die het veld, diverse adviesraden, commissies en brancheorganisaties gevraagd en ongevraagd van advies voorzien