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

Elevated prolactin during pregnancy drives a phenotypic switch in mouse hypothalamic dopaminergic neurons

Summary: Altered physiological states require neuronal adaptation. In late pregnancy and lactation, a sub-population of the mouse hypothalamic tuberoinfundibular dopaminergic (TIDA) neurons alters their behavior to synthesize and release met-enkephalin rather than dopamine. These neurons normally release dopamine to inhibit prolactin secretion and are activated by prolactin in a short-loop feedback manner. In lactation, dopamine synthesis is suppressed in an opioid-dependent (naloxone-reversible) manner, meaning that prolactin secretion is disinhibited. Conditional deletion of the prolactin receptor in neurons reveals that this change in phenotype appears to be driven by prolactin itself, apparently through an alteration in intracellular signaling downstream of the prolactin receptor that favors enkephalin production instead of dopamine. Thus, prolactin effectively facilitates its own secretion, which is essential for lactation and maternal behavior. These studies provide evidence of a physiologically important, reversible alteration in the behavior of a specific population of hypothalamic neurons in the adult brain. : Pituitary prolactin secretion is inhibited by dopamine released by hypothalamic neurons. Yip et al. show that, during lactation, these TIDA neurons alter their response to prolactin and release enkephalin in place of dopamine. This mechanism promotes rather than inhibits prolactin secretion, supporting its elevation during lactation. Keywords: prolactin, prolactin receptor, dopamine, encephalin, hypothalamus, tuberoinfundibular dopaminergic neurons, neuronal plasticity, lactation, lactotroph

Arcuate Nucleus Transcriptome Profiling Identifies Ankyrin Repeat and Suppressor of Cytokine Signalling Box-Containing Protein 4 as a Gene Regulated by Fasting in Central Nervous System Feeding Circuits

The arcuate nucleus of the hypothalamus is a primary site for sensing blood borne nutrients and hormonal messengers that reflect caloric status. To identify novel energy homeostatic genes, we examined RNA extracts from the microdissected arcuate nucleus of fed and 48-h fasted rats using oligonucleotide microarrays. The relative abundance of 118 mRNA transcripts was increased and 203 mRNA transcripts was decreased during fasting. One of the down-regulated mRNAs was ankyrin-repeat and suppressor of cytokine signalling box-containing protein 4 (Asb-4). The predicted structure of Asb-4 protein suggested that it might encode an intracellular regulatory protein, and therefore its mRNA expression was investigated further. Reverse transcription quantitative polymerase chain reaction was used to validate down-regulation of Asb-4 mRNA in the arcuate nucleus of the fasted Sprague-Dawley rat (relative expression of Asb-4 mRNA: fed = 4.66 ± 0.26; fasted = 3.96 ± 0.23; n = 4, P < 0.01). Down-regulation was also demonstrated in the obese fa/fa Zucker rat, another model of energy disequilibrium (relative expression of Asb-4 mRNA: lean Zucker = 3.91 ± 0.32; fa/fa  = 2.93 ± 0.26; n = 5, P < 0.001). In situ hybridisation shows that Asb-4 mRNA is expressed in brain areas linked to energy homeostasis, including the arcuate nucleus, paraventricular nucleus, dorsomedial nucleus, lateral hypothalamus and posterodorsal medial amygdaloid area. Double in situ hybridisation revealed that Asb-4 mRNA colocalises with key energy homeostatic neurones. In the fed state, Asb-4 mRNA is expressed by 95.6% of pro-opiomelanocortin (POMC) neurones and 46.4% of neuropeptide Y (NPY) neurones. By contrast, in the fasted state, the percentage of POMC neurones expressing Asb-4 mRNA drops to 73.2% (P  <  0.001). Moreover, the density of Asb-4 mRNA per fasted POMC neurone is markedly decreased. Conversely, expression of Asb-4 mRNA by NPY neurones in the fasted state is modestly increased to 52.7% (P  <  0.05). Based on its differential expression, neuroanatomical distribution and colocalisation, we hypothesise that Asb-4 is a gene involved in energy homeostasis.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73490/1/j.1365-2826.2005.01317.x.pd

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

International audienc

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