PubMed Health⌕ Search

Biomedical subjects

M Chakir

Publications and source records attributed to M Chakir.

13 recordsLinked to original sources
PubMed2006

[Rat bite: an unusual cause of orbital cellulitis].

Rat bite is rarely reported in the literature. We report the case of a 33-year-old woman who was bitten by a rat on her upper eyelid. The clinical examination showed a large palpebral edema extending to the side of the face, associated with local signs of inflammation. Visual acuity was preserved and tomodensitometry showed a small exophthalmia that did not extend to the sinuses. This lesion led to a diagnosis of orbital cellulitis. Progression was favorable with antibiotics: amoxicillin, clavulanic acid, gentamicin, and metronidazole. The authors discuss the compromised prognosis of this disease and the necessity of rapid diagnosis and prompt therapeutic management.

Adult↗
PubMed2005

Male sterility at extreme temperatures: a significant but neglected phenomenon for understanding Drosophila climatic adaptations.

The thermal range for viability is quite variable among Drosophila species and it has long been known that these variations are correlated with geographic distribution: temperate species are on average more cold tolerant but more heat sensitive than tropical species. At both ends of their viability range, sterile males have been observed in all species investigated so far. This symmetrical phenomenon restricts the temperature limits within which permanent cultures can be kept in the laboratory. Thermal heat sterility thresholds are very variable across species from 23 degrees C in heat sensitive species up to 31 degrees C in heat tolerant species. In Drosophila melanogaster, genetic variations are observed among geographic populations. Tropical populations are more tolerant to heat induced sterility and recover more rapidly than temperate ones. A genetic analysis revealed that about 50% of the difference observed between natural populations was due to the Y chromosome. Natural populations have not reached a selection limit, however: thermal tolerance was still increased by keeping strains at a high temperature, close to the sterility threshold. On the low temperature side, a symmetrical reverse phenomenon seems to exist: temperate populations are more tolerant to cold than tropical ones. Compared to Mammals, drosophilids exhibit two major differences: first, male sterility occurs not only at high temperature, but also at a low temperature; second, sterility thresholds are not evolutionarily constrained, but highly variable. Altogether, significant and sometimes major genetic variations have been observed between species, between geographic races of the same species, and even between strains kept in the laboratory under different thermal regimes. In each case, it is easily argued that the observed variations correspond to adaptations to climatic conditions, and that male sterility is a significant component of fitness and a target of natural selection.

Adaptation, Physiological↗
PubMed2001

A synopsis of the clinical uses of argatroban.

Argatroban, a direct thrombin inhibitor, has been used in Japan since the early 1980's and was recently approved for use in the United States for patients with heparin-induced thrombocytopenia. However, its use has been studied in other clinical settings including, myocardial infarction, percutaneous coronary intervention and cerebral thrombosis. The doses used in the different clinical situations vary, but argatroban offers the advantage of not requiring renal adjustment. Because of its small molecular weight, argatroban has the ability to inhibit both clot bound and soluble thrombin. This paper provides a comprehensive review of both indicated and off label uses of argatroban. Pharmacology, pharmacokinetics, adverse events and drug interactions with argatroban are also discussed.

Antithrombins↗
PubMed1999

The blood vessel, linchpin of diabetic lesions.

The morbidity and mortality associated with diabetes mellitus are essentially related to the vascular lesions that develop over time in this condition. Both the macrocirculation and microcirculation are involved, and as a consequence, vital organs such as the brain, retina, heart, and kidney and the limbs become damaged. Because microalbuminuria represents the earliest and probably most sensitive indication of endothelial dysfunction in diabetes mellitus, the results of pharmacologic intervention with angiotensin-converting enzyme inhibitors, which treat glomerular hypertension were the first indication of potential beneficial effects in reducing diabetic nephroplasty. The nature of endothelial dysfunction related to diabetes is probably not homogeneous, since microcirculation networks are affected at different periods and with variable intensity. This appears to be the case for the aorta, the heart, segments of the digestive tract, the skin, and the skeletal muscle, the largest consumer of insulin. Although the aorta and large arteries contain a small portion of the total blood volume, their distribution of blood flow (pulse pressure) to peripheral organs may affect endothelial function in the microcirculation. Changes in the structure of conduit arteries, partly responsible for the alteration in compliance characteristics, could well be related to the way these arteries are fed by the vasa vasorum system. This report describes a new in vitro approach to examine capillary permeability in normal and alloxan-induced diabetic rabbits. Preliminary results indicate that the size of terminal arterioles of the vasa vasorum (increased diameter) and the capillary permeability to albumin (markedly enhanced) in this specialized network are profoundly affected in the thoracic aorta obtained from diabetic animals. Albumin extravasation into the interstitial fluid compartment of the aorta is likely to lead to structural and physicochemical changes: in fact, removal of interstitial macromolecules via lymphatic drainage is poor in the blood vessel wall of large arteries. This experimental approach is likely to be useful in the exploration of medications affecting the structure and function of conduit vessels.

Animals↗
PubMed1998

Reduction of capillary permeability in the fructose-induced hypertensive rat.

Impaired insulin transcapillary transport and the subsequent decrease in insulin delivery to target organs have been suggested to play a role in insulin resistance. These defects were studied in fructose-fed rats, an animal model with insulin resistance. For this study, male Sprague-Dawley rats were fed with either a 60% fructose enriched (F) or a standard chow diet (N) for a total of 2, 4, or 8 weeks. Capillary permeability to albumin was assessed at the end of each dietary period by quantifying the extravasation of albumin-bound Evans blue (EB) dye in different organs. Unanesthetized animals were injected with Evans blue dye (20 mg/kg) in the caudal vein 10 min before being killed and EB dye was extracted by formamide from selected organs collected after exsanguination. As expected, rats had an increase in blood pressure upon feeding with fructose at 4 and 8 weeks (F, 149 +/- 3 mm Hg; N, 139 +/- 3 mm Hg; P < .05). Using this technique, we showed a 56% and a 51% reduction in capillary permeability in skeletal muscles at 4 and 8 weeks of fructose feeding, respectively (4 weeks: N, 44.5 +/- 5.0 microg/g of dry tissue; F, 19.8 +/- 4.2 microg/g of dry tissue; P < .01 and 8 weeks: N, 23.3 +/- 3.7 microg/g of dry tissue; F, 11.3 +/- 4.0 microg/g of dry tissue; P < .05). Similar changes were observed at 4 weeks in the thoracic aorta (N, 82.8 +/- 8.8 microg/g of dry tissue; F, 53.0 +/- 5.1 microg/g of dry tissue; P < .02) and skin (N, 36.0 +/- 5.3 microg of dry tissue; F, 15.0 +/- 2.3 microg/g of dry tissue; P < .02) and at 8 weeks in the liver (N, 107.5 +/- 4.3 microg/g of dry tissue; F, 80.9 +/- 3.2 microg/g of dry tissue; P < .01). In conclusion, fructose feeding is accompanied by a significant and selective reduction of Evans blue leakage primarily in skeletal muscle and liver, and transiently in the skin and aorta, consistent with a role for decreased tissue insulin delivery in insulin resistance.

Animals↗
PubMed1996

Endothelial dysfunction in diabetes mellitus.

In the present study, we examined the pattern of Evan's blue (EB) extravasation over time and we verified the effect of two inhibitors of aldose reductase (sorbinil and ARI 509) as well as aminoguanidine, which modulate nitric oxide (NO) production, on streptozotocin-induced capillary extravasation abnormalities in the upper bronchi, heart, kidney, duodenum, pancreas, skeletal muscle and skin. Albumin extravasation was measured using the EB technique (20 mg/kg). On the third day, a transient decrease in EB leakage was observed in the lung (-49%), heart (-29%) and skeletal muscle (-64%). These early changes in EB were transient, and values returned to normal there after. Later on, EB extravasation was significantly enhanced in the skin (+358, +680, +580, +525 and +365, respectively, at 2, 4, 5, 6 and 7 weeks of diabetes), the duodenum (+101, +160, +92, +124 and +76%), the upper bronchus (+70, +113, +70, +41 and +25%) and the pancreas (+43, +102, +46, +15 and +78%). In the kidney, the increase of EB extravasation was significant at 2 weeks (26%), and from 5 to 7 weeks (+12, +22, +36%). The chronic treatment of diabetic rats with aminoguanidine normalized capillary permeability in most tissues, suggesting that NO is involved in the development of endothelium dysfunction in this streptozotocin-induced diabetic model. Treatment with aldose reductase inhibitors selectively normalized EB extravasation in the kidney.

Aldehyde Reductase↗
PubMed1996

Consequences of alteration in capillary permeability.

In this review paper, three aspects related to alteration in capillary permeability, based on a series of recent observations from this laboratory, are examined. Firstly, the determinants of capillary extravasation, which include pre- and post-capillary resistances in different microcirculation networks, as well as endothelial permeability per se, are described with particular reference to the heterogeneous character of both regulatory components, reported by this and other groups. Secondly, the endothelium-interstitium relationship, responsible in part for the maintenance of the interstitial compartment physicochemical characteristics, is introduced as an important factor in regulating the traffic of vital nutrients delivered to the cell mass, and the removal of waste products from the cellular compartment to the microcirculation, for ultimate excretion. Examined in this manner, it appears that modulation of capillary permeability is essential for the maintenance of cellular life, yet the neurohumoral mechanisms involved in the control of microcirculation networks are just starting to be identified. A number of morbid conditions characterized by multiorgan involvement exhibit a common pathophysiological denominator which involves endothelium-interstitium relationships, as illustrated in experimental animal models of arterial hypertension, diabetes mellitus, heart failure, and degenerative renal diseases. Enhanced capillary permeability associated with local interstitial edema in specific organs, such as the heart and the kidney, in arterial hypertension and diabetes mellitus, as well as decreased permeability in peripheral tissues, such as the skeletal muscle and the skin, in congenital cardiomyopathy, have been documented. It is likely that alteration in the characteristics of interstitial matrix composition contributes to target organ damage in these examples of systemic disorders from different etiologies. Thirdly, the recent identification of autocoids and hormones involved in the direct and indirect control of capillary permeability has led to the development of pharmacological tools capable of modulating pre- and post-capillary vascular tonus, as well as endothelial permeability. Angiotensin II antagonism, bradykinin B1-receptor inhibition, and modulation of eicosanoid production, in particular thromboxane A2, are associated in some of the above-described disorders, with normalization of capillary permeability defects, and occasionally with improvement in organ function. The eventual development of agents capable of directly controlling the physicochemical characteristics of the interstitial matrix should be of interest, not only for preventing the development of irreversible matrix structural alterations but also for facilitating the traffic of metabolites between capillaries and the cell mass of vital organs.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1995

Neutral endopeptidase inhibition, a new approach in the exploration of diabetic vasculopathy in rats.

Diabetic complications are mostly vascular and involve alteration in blood vessel reactivity and permeability. The contribution of the latter dysfunction to the development of target organ damage has not been thoroughly examined. In this study, we verify the acute effect of three peptidase inhibitors (phosphoramidon: N-(alpha-rhamnopyranosylhydroxyphosphinyl)-Leu-Trp, thiorphan: 3-mercapto-2-benzyl-propanoylglycine, and SQ 28,603: N-(2-mercaptomethyl)-1-oxo-3-phenylpropyl]- < or = b-alanine; each at a dose of 2 mg/kg), as well as captopril ([2S]-1-[3-mercapto-2-methyl-propionyl]-L-proline; 10 mg/kg), and an aminopeptidase inhibitor (amastatin: ([(2S,3R)-3-amino-2-hydroxy-5-methylhexanoyl]-Val-Val-Asp; 2 mg/kg) on capillary extravasation abnormalities in the streptozotocin-induced diabetic rat using the Evans blue method. Untreated diabetic rats exhibited a significant enhancement of Evans blue extravasation in the duodenum, upper bronchus, pancreas and skin (175 +/- 19, 94 +/- 4, 95 +/- 9 and 47 +/- 10 micrograms/g dry tissue respectively compared to 67 +/- 9, 44 +/- 5, 47 +/- 4, and 6 +/- 2 micrograms/g dry tissue). The three endopeptidase inhibitors normalized capillary permeability in all tissues. Also, treatment with captopril was associated with complete correction of capillary dysfunction in the skin and partially in the duodenum, upper bronchus, and pancreas. These findings indicate for the first time that the use of neutral endopeptidase inhibitors may be beneficial in preventing capillary abnormalities in this diabetic rat model.

Alanine↗
PubMed1995

Genetic basis of some morphological differences between temperate and equatorial populations of Drosophila melanogaster.

The genetic basis of three morphological traits (ovariole number, sternopleural bristle number and wing length) of Drosophila melanogaster has been investigated in natural populations that show great differences in these traits, i.e. Bordeaux (France) and Loua (Congo). F1 and F2 crosses, and chromosome substitutions between these two populations, were analysed. Maternal and/or X chromosome effects were found for sternopleural bristle number and wing length. For all traits, significant effects from each of the three chromosomes were found, but in general only one or two chromosomes had a major effect. Moreover, in all cases significant interactions between chromosomes were observed, suggesting the existence of epistatic effects. Our results are discussed and compared to those obtained from the analysis of selected laboratory strains.

Animals↗
PubMed1995

Disorders of body fluid balance: a new look into the mechanisms of disease.

OBJECTIVE: To review the mechanisms of disease on the basis of dysfunction in body fluid distribution secondary to abnormalities in capillary permeability and plasma membrane transport disorders, leading to quantitative and qualitative alterations of the interstitial space, a mainly strategic compartment positioned between the microcirculation and cell mass. DATA SOURCES: The recent literature on the mechanisms involved in the control of body fluid balance, with special reference to microcirculation and interstitial compartment physiology, as well as published and unpublished original data from the authors laboratory. DATA EXTRACTION AND SYNTHESIS: To illustrate the importance of capillary permeability dysfunction in the development of disease, animal (rat and dog) models of chronic renal failure, acute diuretic-induced fluid depletion, diabetes mellitus, arterial hypertension and ischemia-reperfusion of the kidney were used in an attempt to show that in all these experimental models, basic capillary permeability dysfunction (measured by the extravasation of Evans blue, a marker of albumin leakage) develops in specific microcirculation beds. As a consequence, tissue edema (interstitial and/or cellular) develops and likely impairs the traffic of nutrients and waste products to and from the cellular mass, and/or challenges the microcirculation, leading to organ damage. Kidney dysfunction is measured by conventional clearance methods (renal hemodynamics and tubular function). In some models, the eventual mediators of vascular abnormality are examined by use of pharmacological tools. CONCLUSIONS: The critical role of microcirculation dysfunctions, in particular capillary permeability, resulting in interstitial compositional changes is presented as the basis of disease. The apparent specificity of target organ damage may represent the nonspecific result of physicochemical alteration in the strategic interstitial fluid compartment.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1993

Adaptation to alcoholic fermentation in Drosophila: a parallel selection imposed by environmental ethanol and acetic acid.

Besides ethanol, acetic acid is produced in naturally fermenting sweet resources and is a significant environmental stress for fruit-breeding Drosophila populations and species. Although not related to the presence of an active alcohol dehydrogenase, adult acetic acid tolerance was found to correlate with ethanol tolerance when sensitive (Afrotropical) and resistant (European) natural populations of Drosophila melanogaster were compared. The same correlation was found when comparing various Drosophila species. Tolerance to acetic acid also correlated with the tolerance to longer aliphatic acids of three, four, or five carbons but did not correlate with the tolerance to inorganic acids (i.e., hydrochloric and sulfuric acids). These observations suggest that acetic acid is detoxified by the conversion of acetate into acetyl-CoA, a metabolic step also involved in ethanol detoxification. Future investigations on the adaptation of Drosophila to fermenting resources should consider selective effects of both ethanol and acetic acid.

Acclimatization↗
PubMedDate not supplied

[Role of neutral endopeptidases in capillary dysfunctions of diabetic origin in rats].

Among numerous complications associated with diabetes, the alterations of the normal properties of various microcirculation circuits lead to important dysfunctions which may contribute to target organ damage. As the endothelium plays a crucial role in the microcirculatory circuits, it is suggested that diabetes may influence both the physical and endocrine properties of that cell layer. In 1995, we reported an important increase in plasma extravasation in a model of diabetes in rats treated with streptozotocin. The increase of plasma extravasation was particularly significant in the pulmonary, skin and splanchnic areas. In that particular study, it was of interest that inhibitors of neutral endopeptidases, such as thiorphan, phosphoramidon and SQ 28,603 (specific inhibitor of the recombinant neutral endopeptidases2) corrected almost completely the increase of plasma extravasation induced by diabetes when compared with control rats. It is also worthy of note that the three above-mentioned inhibitors failed to normalize in any case the hyperglycaemia associated with the diabetes in these animals. The present document is a summary synthesis of the putative role of neutral endopeptidases and of the beneficial effects of the inhibitors of these enzymes in diabetes-induced plasma extravasation in the rat.

Animals↗