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Voxelotor (GBT440, OXBRYTA®) appeared recently as one of the possible treatments for sickle cell disease. This molecule, by binding the alpha globin of hemoglobin, causes hyperaffinity of the latter for oxygen and reduces its polymerization properties. Several therapeutic trials have been able to show its effectiveness on certain aspects of sickle cell disease; thus, the french HAS (High Authority of Health) college issued an early access authorization and, since 2021, this treatment can be offered to patients under a temporary authorization for use. Consequently, the laboratories that carry out the biological monitoring of sickle cell patients will be confronted with new profiles characteristic of the presence of hemoglobin combined with GBT440. This work presents a collection of images obtained by different techniques: HPLC, capillary electrophoresis, isoelectrofocusing, alkaline gel and acid agar gel electrophoresis in transfused or non-transfused sickle cell disease patients. The ability to observe the presence of GBT440 by these analyzes could be useful in order to characterize the therapeutic follow-up of patients.

The medical and university department of biology pathology at Henri Mondor hospital in Créteil has been engaged in an NF EN ISO 15189 accreditation process since 2014. One of the elements of this process concerns the quality of handling of samples and their transportation to laboratories, including the implementation place requires fighting against pre-examination non-conformities, which are the source of many dysfunctions. The pre-examination group has implemented several actions in a targeted care service. Thanks to these, the rate of non-conformities has halved in 18 months. In parallel, a work project targeting student nurses on internship was born to follow up on the results of a statistical study carried out by the pre-examination group on non-conformities. The objective of the project was to include nursing students on internship in a full support course on good sampling practices and pre-analytical non-conformities. This was based on the realization of two knowledge quizzes (before and after training), theoretical training, and visits to several laboratories. This study lasted 10 months with the participation of 37 students. The results showed a marked improvement in knowledge of pre-analytics as well as total satisfaction of all students. Our approach has helped to better understand the needs of laboratories and demonstrates the usefulness of training students in good sampling practices in order to ensure better patient care as well as an improvement in their comfort and well-being.

Leptin and adiponectin are two adipokines currently used as biomarkers for diagnostic orientation and phenotyping in syndromes of lipodystrophy and severe insulin resistance. The level of these biomarkers also has an impact on the therapeutic management of the patients. These aspects, as well as our experience as a reference center, are described in this brief overview.

The identification of leptin allowed the discovery of a new endocrine system. This major adipokine controlling energy homeostasis is also involved in the regulation of neuroendocrine function and fertility. Unfortunately, leptin is not able to treat common obesity, which associates hyperleptinemia and resistance to the hormone. Conversely, treatment with recombinant leptin is effective in situations of leptin deficiency. Several pathophysiological situations associated with adipose tissue dysfunctions and abnormal regulation of leptin secretion are discussed in this review. The advantage of the potential use of the leptin assay in some pathophysiological conditions is proposed.

Adiponectin is a major adipokine involved in energy homeostasis that exerts insulin-sensitizing properties. The level of adiponectin is reduced in situations of insulin resistance and is negatively associated with several pathophysiological situations including abdominal obesity, metabolic syndrome, steatosis and non-alcoholic steatohepatitis, type 2 diabetes, some cancers and cognitive diseases. These aspects are discussed in this review.

Leptin and adiponectin are two adipokines. Their circulating concentrations, high for leptin and low for adiponectin, are predictive of insulin resistance and of an unfavorable cardiometabolic evolution in patients with obesity, metabolic syndrome or type 2 diabetes. In addition, recently, the adiponectin/leptin ratio has been proposed as an index of adipose tissue dysfunction together with threshold values for cardiometabolic risk for this index. The relevance and potential applications of the adiponectin/leptin and leptin/adiponectin ratios are discussed in the light of recent literature in this brief update.

Elevated circulating leptin levels have been associated with an increased cardiovascular risk in humans. However, recent meta-analyses show that certain epidemiological studies did not find this association, suggesting distinct effects of leptin depending on the pathophysiological context. Studies performed in mice deficient in leptin or in leptin receptors are often contradictory, showing both protective and deleterious effects of leptin. These effects appear to vary depending on the genetic background of the animal and the doses of leptin administered, making interpretation of the results difficult. In humans, elevated adiponectinemia is associated with a favourable cardiovascular risk profile. Adiponectin exerts protective effects at all stages of development of atherosclerotic plaque. However, our knowledge of the pathophysiological mechanisms involved in these protective effects has been established from cellular models, which do not necessarily reproduce the pathology in all its complexity. In addition, mouse models have a very different lipoprotein metabolism from humans, which does not always allow extrapolation of results to humans. Finally, epidemiological studies evaluating adiponectin as a marker of cardiovascular risk show paradoxical results since a high serum adiponectin concentration has not been associated with a reduction in the number of cardiovascular events but with an increase of cardiovascular and all causes mortality in healthy subjects and coronary patients. These observations illustrate the paradox of adipokines actions and show the complexity to use these biomarkers in cardiovascular diseases. Resistance to the action of these adipokines is one of the hypotheses put forward to explain these discrepancies.

As part of the laboratory accreditation process, it may be required to determine the laboratory's own reference values. Thus, we have accredited in our laboratory, the serum amyloid A (SAA) assay for which the supplier gave the usual values. However, we did not have a reference population to check them., Materials and Methods: We extracted from our laboratory information management system, the values of all SAA and C-reactive protein (CRP) assays performed simultaneously from 2014 to 2018. We selected all SAA-CRP couples with a CRP <5 mg/L and <3 mg/L assuming that these subjects were comparable to the general population. For each of the selected CRP thresholds, we quantified the number of subjects with SAA ≤6.4 mg/L (provider's data), then SAA ≤10 mg/L (threshold below which the risk of kidney complications is low). We compared annual averages of SAA-CRP couples (2014-2018) by analysis of variance (ANOVA)., Results and Discussion: For subjects with CRP <5 mg/L, we found SAA value ≤6.4 mg/L in 84.6% and ≤10 mg/L in 92.8% of cases. These results were respectively 89.6% et 95.6% when considering CRP <3 mg/L. Similar thresholds were observed for adults and children. The ANOVA analysis did not show any difference per year from 2014 to 2018 for both SAA and CRP in children, adults and the total population., Conclusion: Our reference values were comparable to those given in the supplier's record and those issued from the literature both for children and adults. The analysis of the evolution of the biomarker average level as a function of time could be an additional relevant element.

Adipose tissue is now recognized as an endocrine organ involved in regulating physiologic and pathologic processes including inflammation. It synthesizes and secretes hormones such as leptin and adiponectin. It can secrete other products namely adipokines including cytokines and chemokines. The release of adipokines by either adipocytes or adipose tissue-infiltrated macrophages leads to a chronic sub-inflammatory state that likely plays a major role in cardiovascular complications linked to obesity and insulin resistance.

White adipose tissue is the main site of energy storage, but it is now recognized as an active participant in regulating physiologic and pathologic processes including immunity and inflammation. It has an endocrine function by secreting at least two main hormones, leptin and adiponectin. It can secrete other products, named adipokines, including cytokines and chemokines, involved in inflammation process. The release of adipokines by either adipocytes or adipose tissue infiltrated macrophages lead to a chronic sub-inflammatory state that could play a central role in cardiovascular complications linked to obesity and insulin resistance, a risk factor to develop type-2 diabetes.

Lipodystrophic syndromes regroup a heterogeneous group of genetic or acquired diseases. Lipodystrophy, an altered development and/or repartition of body fat, is associated with alterations of lipid and glucose metabolism with insulin resistance. Genetic forms, rare, can be generalized and recessive resulting from mutations in the seipin or AGPAT2 gene. Partial lipodystrophies are dominant and observed in patients mutated in the gene encoding PPAR-gamma or lamin A/C, a gene seen also mutated in patients with syndromes of premature aging. Acquired forms are common and regroup the highly prevalent Metabolic Syndrome, hypercorticism together with lipodystrophy related to antiretroviral treatment of HIV-infected patients.

HIV infection requires the continuous administration of antiretroviral molecules. Individual molecules belonging to the two main classes, protease inhibitors (PIs) and nucleoside analogues inhibitors of the viral reverse transcriptase (NRTIs) have been shown to be involved in deleterious side effects collectively called the lipodystrophy syndrome. This syndrome associates altered body fat repartition (peripheral lipoatrophy and visceral fat hypertrophy) and metabolic alterations (dyslipidemia, insulin resistance and diabetes). The pathophysiology of these alterations is complex but different studies argue for adipose tissue being a target of some PIs and NRTIs acting through different mechanisms. NRTIs are able to induce mitochondrial dysfonction and to modify adipocyte phenotype and adipose tissue pattern of secretion of cytokines (TNFalpha, IL-6) and other adipokines (adiponectin, leptin) probably through the production of reactive oxygen species. Some PIs also act on adipocyte, alter its differentiation and insulin sensitivity and also the pattern of secretion of adipokines by adipose tissue. These hypotheses could explain the loss of adipose tissue, while the mechanisms of visceral fat hypertrophy remain speculative. Since some adipokines and the free fatty acids released by adipocytes play a major role in the control of liver and muscles insulin sensitivity, these alterations are probably involved in the metabolic alterations seen in the patients. In addition, lipodystrophic adipose tissue could be involved in the increased lesions of atherogenesis and steatohepatitis presented by these patients. The treatment of lipodystrophy remains difficult and, at present, privileges the switch of the more deleterious drugs towards new molecules less aggressive for adipose tissue.

Obesity is a risk factor for type 2 diabetes and cardiovascular diseases. The hypothesis that cytokines could play a role in the pathophysiology of obesity and insulin resistance is suggested in the last few years. We showed a positive correlation between circulating interleukin (IL-6) levels and obesity and insulin resistance suggesting that IL-6 could be involved in insulin resistance in humans. We showed a decrease of both circulating and adipose tissue IL-6 levels in non-diabetic obese subjects after a very low calorie diet program inducing weight loss. This suggests that adipose tissue could be involved in the regulation of circulating IL-6 levels in these subjects. Adipose tissue is also involved in lipodystrophies particularly in HIV patients on antiviral therapy. We showed an alteration of the SREBP-1 transcription step in subcutaneous abdominal adipose tissue from HIV patients. We found an inverse correlation between circulating adiponectin levels and both insulin resistance and cardiovascular risk factors such as CRP levels and apolipoprotein B/A1 ratio. These findings suggest that adipose tissue is involved in insulin resistance in humans particularly via adipocytokine secretion., (Copyright John Libbey Eurotext 20003.)

Immunoglobulin D (IgD) multiple myeloma is rare, accounting for less than 2% of all patients with multiple myeloma. The main presenting features are bone pain in 70% of patients. Extramedullary involvement is less common. We report a case of Ig D lambda multiple myeloma in a 74-year-old man that was revealed by pleural effusion and dyspnea. This effusion was found to be caused by multiple myeloma after electrophoretic and cytologic assays. The patient received a course of chemotherapy with melphalan and prednisone. The patient died one month later with signs of septic shock. Pleural effusion as a first sign of Ig D multiple myeloma is rarely described and the prognosis associated with such a localisation is very poor.

Recent advances in human, bacterial and viral genome projects and the development of quantitative real-time reverse transcription-polymerase chain reaction methods offer the possibility of analysing a large number of gene transcripts. These molecular developments represent an important advancein the field of genetics, cancer, virology, bacteriology and hematology. A limiting step remains the isolation of high quality mRNA purified from biological samples. This review describes the different methods used to isolate mRNA from biological samples and to verify RNA integrity and gives precise details about RNA storage conditions.

Unlabelled: OBJECTIVES AND JUSTIFICATION: To describe facilitated diffusion glucose transporters (GLUT) in humans, and particularly the regulation of GLUT4 expression since it is predominantly responsible for insulin-mediated glucose transport in muscle and adipose tissue, and plays a crucial role in whole-body glucose homeostasis., Main Points: Numerous studies have shown abnormal expression of GLUT4 in insulin responsive tissues in diabetes mellitus and other insulin resistant states. The recent development of transgenic mice that overexpress GLUT4 in muscle, adipose tissue, or both has also emphasized the importance of GLUT4 in glucose homeostasis., Perspectives and Projects: The studies performed in transgenic mice suggest that strategies to increase GLUT4 transporters in insulin responsive tissues may lead to new therapeutic possibilities to improve insulin sensitivity in insulin resistant states such as non-insulin-dependent diabetes mellitus., Conclusions: Glucose transport is a crucial process in mammals, which needs specific transmembrane hexose transporters. Each transporter is important in the regulation of glucose homeostasis. Advances in the knowledge of both the action and the regulation of the glucose transport system may provide new insights for the development of therapeutic interventions in diseases such as obesity or diabetes mellitus.