CONSUMPTION ANALYSIS OF METFORMIN, SULFONYLUREAS, AND OTHER ANTIDIABETICS DRUGS IN MOROCCO (1991-2005)

Objective: Type 2 Diabetes is one of the chronic diseases with a high prevalence and consequently a substantial socio-economic burden in Arab countries. In this paper, we evaluated the antidiabetic drugs consumption in Morocco during the period of 1991 to 2005, drug classes used and the effect of major studies on the consumption of the biguanides.Methods: We used sales data from the subsidiaries of the Intercontinental Marketing Service Health. The consumption volume was converted to Defined Daily Dose (DDD).Results: During 1991-2005 antidiabetic drugs consumption increased from 1.37 to 4.22 DDD/1000 inhabitants/day. In 2005 the sulfonylureas were the most consumed 2.96 DDD/1000 inhabitants/day) followed by the Biguanides (1.06 DDD/1000 inhabitants/day) and glinides 0.1 DDD/1000inhabitants/day. The largest consumption share in volume was held by sulfonylureas 72.22%, followed by the biguanides 22.22%.Conclusion: This study documents progressive changes in the consumption of antidiabetic's between 1991-2005 in Morocco. However, the significant increase in the utilization of antidiabetic's drugs is not the result of increased adherence but of increased patient number, since the use of metformin as first line therapy was still suboptimal and influenced by different studies as the Campbell and UKPDS study.Â

SIMPLE HPLC-UV METHOD FOR DETERMINATION OF METFORMIN IN HUMAN PLASMA AND ERYTHROCYTES APPLICATION TO THERAPEUTIC DRUG MONITORING

Objective: The aim of this study was to develop a simple, rapid, efficient, cost effective and reproducible, stability indicating reverse phase high performance liquid chromatography method (RP-HPLC) for dosage of metformin in human plasma and erythrocytes. Methods: In this method, the plasma or erythrocyte proteins were precipitated using Perchloric acid: acetonitrile (50 % v/v) mixture and the supernatant liquid were injected into the HPLC system. The separation was achieved with a symmetry C8 column with the mobile phase containing 10 % water and 90 % sodium dihydrogen phosphate buffer (5.8 mM), the pH was adjusted to 3.8 with Phosphoric acid. The temperature was elevated to 25 °C. The detection was done by a UV detector at 232 nm. Results: The retention time was observed at around 4.412 min for metformin and 6.022 for lansoprazole an internal standard (IS). The response was linear over a range of 2-32µg ml-1, the coefficient of determination (r²) was found to be (r² =0. 9988). The lowest limit of quantification and detection was 0.1 µg/ml and 0.3 µg/ml respectively. No endogenous substances were found to interfere with the peaks of the drug. The intra-day and inter-day coefficient of variations was 2.1 % or less for all the selected concentrations. The relative errors at all the studied concentrations were 3.5 % or less. Conclusion: The HPLC method described in this article was simple, selective, reproducible, linear, and precise, it can be applied for therapeutic drug monitoring of metformin in human plasma and erythrocytes

Interrelations entre neuromediateurs dans des systemes neuroniques centraux : la serotonine, la substance P et le GABA dans le raphe et ses projections spinales et olfactives, approche radioautographique et immunocytochimique chez le rat

SIGLECNRS T Bordereau / INIST-CNRS - Institut de l'Information Scientifique et TechniqueFRFranc

Impact of aflatoxin B1 on hypothalamic neuropeptides regulating feeding behavior

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Effect of food deprivation on the hypothalamic gene expression of the secretogranin II-derived peptide EM66 in rat

International audienceEM66 is a peptide derived from the chromogranin, secretogranin II (SG-II). Recent findings in mice indicate that EM66 is a novel anorexigenic neuropeptide that regulates hypothalamic feeding behavior, at least in part, by activating the POMC neurons of the arcuate nucleus. The present study aimed to investigate the mechanism of action of EM66 in the control of feeding behavior and, more specifically, its potential interactions with the NPY and POMC systems in rat. We analyzed by Q-PCR the gene expression of the EM66 precursor, SG-II, in hypothalamic extracts following 2, 3, or 4 days of food deprivation and compared it with the expression levels of the two major neuropeptidergic systems, that is, POMC and NPY, modulating feeding behavior. Our results show that fasting for 2 and 3 days has no effect on SG-II mRNA levels. However, 4 days of food deprivation induced a significant alteration in the expression levels of the three genes studied, with a significant increase in SG-II and NPY mRNAs, and conversely, a significant decrease in POMC mRNA. These data indicate that the EM66 gene expression is modulated by a negative energy status and suggest interactions between EM66 and NPY to regulate food intake through the POMC system

Immunohistochemical distribution of the secretogranin II-derived peptide EM66 in the rat hypothalamus: A comparative study with jerboa

International audienceEM66 is a 66-amino acid peptide derived from secretogranin II, a member of granin acidic secretory protein family, by proteolytic processing. EM66 has been previously characterized in the jerboa (Jaculus orientalis) hypothalamus and its potential implication in the neuroendocrine regulation of feeding behaviour has been demonstrated. In the present study, an immunohistochemical analysis of the localization of EM66 within hypothalamic structures of rat was performed and compared to the distribution of EM66 in the jerboa hypothalamus. In the rat hypothalamus, as in the jerboa, EM66 immunostaining was detected in the parvocellular paraventricular, preoptic and arcuate nuclei, as well as the lateral hypothalamus which displayed an important density of EM66-producing neurones. However, unlike jerboa, the suprachiasmatic and supraoptic nuclei of the rat hypothalamus were devoid of cellular EM66-immunolabeling. Thus, the novel peptide EM66 may exert common neuroendocrine activities in rat and jerboa, e.g. control of food intake, and species-specific roles in jerboa such as the regulation of biological rhythms and hydromineral homeostasis. These results suggest the existence of differences between jerboas and rats in neuroendocrine regulatory mechanisms involving EM66

EM66-containing neurones in the hypothalamic parvicellular paraventricular nucleus of the rat: No plasticity related to acute immune stress

International audienceOBJECTIVES AND METHODS: Neuropeptides, as the main neuroendocrine system effectors, regulate notably the response to different stressors via a secretory plasticity within their respective hypothalamic neuronal populations. The aim of the present study was to explore by immunocytochemistry the occurrence and the potential expression plasticity of the novel neuropeptide EM66 in the CRH neurones of stressed rats. RESULTS: The secretogranin II (SgII)-derived peptide EM66 is strongly expressed within hypothalamic neuroendocrine areas such as the parvocellular aspect of the paraventricular nucleus (pPVN) as well as the median eminence, suggesting a probable hypophysiotropic effect of this peptide. As a first approach to investigate such a role, we evaluated by immunohistochemistry EM66 expression within the pPVN following acute immune stress induced by lipopolysaccharide (LPS) or interleukin-1β (IL-1β) injection in rat. This study showed that EM66 is present in the pPVN but the number of EM66 immunolabeled cells did not fluctuate in this structure following LPS peripheral injection. In line with this observation, an intracerebroventricular injection of IL-1β did not provoke any significant variation of the number of intraparaventricular EM66 neurones. CONCLUSION: The present data revealed for the first time that EM66 expression would be insensitive to the central and peripheral cytokines within the neurose-cretory hypothalamic pPVN. This result indicates that EM66 does not participate to the phenotypic plasticity of hypothalamic parvicellular neurones in response to acute inflammatory stress

Emotion processing in Parkinson’s disease: a blood oxygenation level-dependent functional magnetic resonance imaging study

Parkinson’s disease is a neurodegenerative disorder caused by loss of dopamine neurons in the substantia nigra pars compacta. Tremor, rigidity, and bradykinesia are the major symptoms of the disease. These motor impairments are often accompanied by affective and emotional dysfunctions which have been largely studied over the last decade. The aim of this study was to investigate emotional processing organization in the brain of patients with Parkinson’s disease and to explore whether there are differences between recognition of different types of emotions in Parkinson’s disease. We examined 18 patients with Parkinson’s disease (8 men, 10 women) with no history of neurological or psychiatric comorbidities. All these patients underwent identical brain blood oxygenation level-dependent functional magnetic resonance imaging for emotion evaluation. Blood oxygenation level-dependent functional magnetic resonance imaging results revealed that the occipito-temporal cortices, insula, orbitofrontal cortex, basal ganglia, and parietal cortex which are involved in emotion processing, were activated during the functional control. Additionally, positive emotions activate larger volumes of the same anatomical entities than neutral and negative emotions. Results also revealed that Parkinson’s disease associated with emotional disorders are increasingly recognized as disabling as classic motor symptoms. These findings help clinical physicians to recognize the emotional dysfunction of patients with Parkinson’s disease