Structural, Biochemical Characterization and Molecular Mechanism of Cerastokunin: A New Kunitz-Type Peptide with Potential Inhibition of Thrombin, Factor Xa and Platelets.

The current investigation focused on separating Cerastes cerastes venom to produce the first Kunitz-type peptide. Based on its anti-trypsin effect, Cerastokunin, a 7.75 kDa peptide, was purified until homogenity by three steps of chromatography. Cerastokunin was found to include 67 amino acid residues that were obtained by de novo sequencing using LC-MALDI-MSMS. Upon alignment with Kunitz-type peptides, there was a high degree of similarity. Cerastokunin's 3D structure had 12% α-helices and 21% ß-strands with pI 8.48. Cerastokunin showed a potent anticoagulant effect by inhibiting the protease activity of thrombin and trypsin as well as blocking the intrinsic and extrinsic coagulation pathways. In both PT and aPPT, Cerastokunin increased the blood clotting time in a dose-dependent way. Using Lys48 and Gln192 for direct binding, Cerastokunin inhibited thrombin, Factor Xa and trypsin as shown by molecular docking. Cerastokunin exhibited a dose-response blockade of PARs-dependent pathway platelet once stimulated by thrombin. An increased concentration of Cerastokunin resulted in a larger decrease of tail thrombus in the mice-carrageenan model in an in vivo investigation when compared to the effects of antithrombotic medications. At all Cerastokunin doses up to 6 mg/kg, no in vivo toxicity was seen in challenged mice over the trial's duration.

Blood Lead Levels in the Population Living in Algeria: A Cross-Sectional National Study.

Lead poisoning, is currently recognized as a real public health problem, The WHO classifies lead as one of 10 chemicals of serious public health concern. In Algeria and North Africa, to date, no study on the evaluation of lead impregnation has been carried out at the national level. The main objective of this work is to assess the exposure of the general Algerian population to lead. A cross-sectional study was carried out over the entire Algerian national territory, on a population aged between 3 and 74 years old. The survey lasted three years, A questionnaire, a clinical examination and a blood sample were carried out for each individual. Generalized linear regression models were used to determine the factors influencing lead levels measured in blood samples. The study population, spread over 39 wilayas and 121 districts, consists of 3674 individuals. The mean lead levels were 28.27 µg/L, the median was 22.22 µg/L, and the 95th percentile was 73.83 µg/L, Blood lead levels were influenced differently by age, gender, wilaya of residence, dietary habits such as consumption of canned food and the way in which water is conserved for daily consumption. The use of kohl has been confirmed as a potential source of lead exposure. In Algeria, a blood lead value of 75 µg/L serves as the Reference Exposure Value, guiding public health responses and risk management strategies, Recommendations have been issued to reduce the blood lead levels of the general population in Algeria in terms of limitation of lead in the sources of exposure, installation of an effective health monitoring system.

Factors associated with therapeutic non-adherence in renal transplant patients: a bicentric study in Algeria / Facteurs associés à la non-observance thérapeutique chez les patients greffés rénaux : une étude bicentrique en Algérie

Introduction: Medication non-adherence is a global concern, particularly in the context of renal transplantation, where it leads to graft failures, increased hospitalizations, diminished quality of life for patients, and higher healthcare costs. The aim of this study was to assess the level of therapeutic adherence among Algerian kidney transplant recipients and identify potential influencing factors. Methods: A descriptive, cross-sectional bicenter study was conducted among kidney transplant patients receiving outpatient care at two specialized medical centers in Algeria: the Urology Department of the Hospital Establishment for Urology, Nephrology, and Renal Transplantation in Constantine, and the Nephrology and Renal Transplantation Department of the University Hospital Center (CHU) in Blida, spanning from January to December 2022. Therapeutic adherence was assessed using the 8-item Morisky questionnaire, while the level of knowledge was analyzed through a 12-item questionnaire. Logistic regression was used to identify factors associated with non-adherence to therapy. Results: This study included 130 patients with an average age of 47 years and a sex ratio of 1.7. The results revealed therapeutic non-adherence in 40.8% of the patients. Multivariate analysis identified several potentially associated factors, including residence, unemployment status, lack of affiliation with a health insurance fund, the use of a therapeutic regimen involving triple therapy, the occurrence of adverse effects, limited education level, and insufficient disease knowledge. Furthermore, non-adherence was associated with an increased risk of graft rejection. Conclusion: The findings of this study highlight concerning therapeutic adherence among kidney transplant recipients, emphasizing the crucial importance of therapeutic education to improve treatment adherence and underscoring the need to integrate these factors into clinical patient management.

Introduction: La non-observance thérapeutique est un problème mondial préoccupant, notamment dans le contexte de la transplantation rénale où elle entraîne des échecs de greffe, une augmentation des hospitalisations, une détérioration de la qualité de vie des patients et des coûts de santé accrus. Cette étude avait pour objectif d'évaluer le niveau d'observance thérapeutique chez les transplantés rénaux algériens et d'identifier les facteurs qui pourraient l'influencer. Méthodes: Une étude descriptive transversale bicentrique a été menée auprès de patients transplantés rénaux suivis en ambulatoire dans deux centres médicaux spécialisés en Algérie : le service d'urologie de l'Établissement hospitalier spécialisé (EHS) en urologie, néphrologie et transplantation rénale de Constantine ainsi que le service de néphrologie et transplantation rénale du Centre hospitalier universitaire (CHU) de Blida, sur une période allant de janvier à décembre 2022. L'observance thérapeutique a été évaluée à l'aide du questionnaire à 8 items de Morisky, tandis que le niveau de connaissance a été analysé à travers un questionnaire de 12 items. La régression logistique a été utilisée pour identifier les facteurs associés à la non-observance thérapeutique. Résultats: Cette étude a inclus 130 patients présentant un âge moyen de 47 ans et un sex ratio de 1,7. Les résultats ont révélé une non-observance thérapeutique chez 40,8 % des patients. L'analyse multivariée a permis d'identifier plusieurs facteurs potentiellement associés à cette non-observance, notamment le lieu d'habitation, le statut de chômage, l'absence d'affiliation à une caisse d'assurance maladie, l'utilisation d'un schéma thérapeutique incluant une trithérapie, la survenue d'effets indésirables, le niveau d'éducation limité et une connaissance insuffisante de la maladie. En outre, la non-observance a été associée à un risque accru de rejet de greffe. Conclusion: Les résultats de cette étude révèlent une observance thérapeutique préoccupante chez les transplantés rénaux, soulignant l'importance cruciale de l'éducation thérapeutique afin de l'améliorer et mettant en évidence la nécessité d'intégrer ces facteurs dans la gestion clinique des patients.

Validation of a simple spectrophotometric method for the rapid determination of salicylates in plasma.

INTRODUCTION: The determination of salicylate concentrations constitutes a critical aspect of medical diagnostics, particularly in emergency settings. High-performance liquid chromatography (HPLC) and spectrophotometry are efficient methods commonly utilized for this purpose. In emergency laboratories with limited resources, the validation of a cost-effective and reliable spectrophotometric method for salicylates in plasma becomes imperative. The present study aims to validate such a method, ensuring its applicability in toxicological emergencies within resource-constrained laboratories. MATERIALS AND METHODS: The proposed spectrophotometric analysis relies on detecting salicylic ions amidst the presence of ferric salts, resulting in the formation of a distinct purple chelate complex. To ascertain the method's credibility, the validation guidelines established by the European Medicines Agency (EMA) were employed as a benchmark. A comprehensive validation process was conducted over a three-day period, with three levels of validation standards being considered. RESULTS: Following the EMA protocol, the spectrophotometric method demonstrated commendable fidelity, accuracy, and linearity over a concentration range of 50 to 500 mg/L. The limit of detection and quantification was found to be 10 and 50 mg/L, respectively, and the correlation coefficient was determined to be R2 = 0.998. However, it is essential to acknowledge that interference with phenothiazines occurred at concentrations ranging from 50 to 100 mg/L. Despite this, the method's average sensitivity remains viable for practical use in cases of poisoning. The accuracy per concentration level proved satisfactory, with relative biases remaining below 15%, and the confidence intervals of mean recovery closely approximating the desired target value of 100%. CONCLUSION: In conclusion, the presented spectrophotometric method stands out as an economical, straightforward, and user-friendly approach, ideally suited for toxicological emergencies when resources are limited. The method delivers satisfying results, establishing its practical utility in critical medical scenarios. This validated method holds immense promise for emergency laboratories facing resource constraints.