[Efficacy and tolerance of Latanoprost given as a first intention in the treatment of primitive open angle glaucoma in African melanoderm]. / Efficacité et tolérance du Latanoprost donné en première intention dans le traitement du glaucome primitif a angle ouvert chez le mélanoderme africain.

OBJECTIVE: To assess the reduction in IOP and ocular symptoms in patients newly diagnosed with POAG and treated with latanoprost as monotherapy. PATIENTS AND METHOD: A multicentric, cross-sectional, descriptive study was conducted. We included adults newly diagnosed with POAG. All patients received one drop of preserved latanoprost 0.005% in each eye every night for 12 weeks. Changes in IOP and ophthalmic signs and symptoms were assessed during and at the end of treatment. RESULTS: A total of 524 patients were included, with a participation rate of 93% at 12 weeks. The mean age was 52.79±17.33 years, and the sex ratio M/F was 1.39. At inclusion, the mean IOP was 21.68±9.72mmHg. After 2 weeks of treatment, the mean IOP was 15.49±5.81mmHg, for a reduction of 28.55%. After 12 weeks of treatment, the mean IOP was 13.16±3.54mmHg, for a reduction of 39.30%. The main symptom recorded was a gritty foreign body sensation, the frequency of which was 4.72% at W2 and 2.45% at W12. The main sign was hyperemia (4.33% at W2 and 1.84% at W12). CONCLUSION: Latanoprost given as first-line monotherapy in POAG in blacks considerably reduces IOP. The incidence of side effects remains low; it is higher at the start of treatment.

[Problem Of Diabetic Foot Amputations]. / ProbléMatique Des Amputations Du Pied Diabétique.

INTRODUCTION: The diabetic foot wound is a real public health problem, 10% of the reasons for hospitalization. The risk of amputation is 10 to 30 times higher in diabetics than the general population. OBJECTIVE: To study the problem of amputations of the diabetic foot. METHOD: This was a descriptive and cross-sectional study that took place in the Department of Medicine and Endocrinology of the Mali Hospital from July 1st, 2016 to June 30th, 2017. RESULTS: Twenty-five (25) diabetic patients were enrolled in our study. The sex ratio was 0.66. At admission, 100% of our patients had arterial disease, 96% neuropathy, and mixed foot in 80%. Poor glycemic control in 64% of patients; osteitis in 52% of cases; 92% of the patients had a 100% amputation risk according to the University of Texas classification. Nearly half or 46% of patients had amputations in the leg. We recorded 1 death case that is 4%. CONCLUSION: The problem of amputation of diabetic feet is a function of the poor equilibrium and progressive neurological and vascular complications of diabetes.

INTRODUCTION: La plaie du pied diabétique constitue un réel problème de santé publique, 10% des motifs d'hospitalisation. Le risque d'amputation est de 10 à 30 fois plus élevé chez les diabétiques que la population générale. OBJECTIF: Etudier la problématique des amputations du pied diabétique. MÉTHODE: II s'agissait d'une étude descriptive et transversale qui s'est déroulée dans le service de médecine et d'endocrinologie de l'hôpital du Mali du 1er Juillet 2016 au 30 Juin 2017. RÉSULTATS: Vingt-cinq (25) patients diabétiques ont été recrutés dans notre étude. Le sex ratio était de 0,66. A l'admission, 100% de nos patients avaient une artériopathie, 96% une neuropathie, et un pied mixte dans 80%. Un mauvais équilibre glycémique chez 64% des patients ; l'ostéite dans 52% des cas; 92% des patients avaient un risque d'amputation à 100% selon la classification de l'université du Texas. Près de la moitié soit 46% des patients ont été amputé au niveau de la jambe. Nous avons enregistré 1 cas de décès soit 4%. CONCLUSION: La problématique de l'amputation des pieds diabétiques est fonction du mauvais équilibre et des complications évolutives neurologiques et vasculaires du diabète.

Effects of a high-fat diet on superoxide anion generation and membrane fluidity in liver mitochondria in rats.

BACKGROUND: Obesity is a primary factor of lifestyle-related diseases, and the age of its onset has decreased. The reactive oxygen species (ROS), the superoxide anion, is generated in the mitochondrial electron transport chain and the damage it induces in cells may be a contributing factor to obesity-related lifestyle diseases. In the present study, the influence of the ingestion of a high-fat diet (HFD) on superoxide anion generation in rat liver mitochondria (Mt) and membrane fluidity was investigated. METHODS: Male Wistar rats were fed a normal diet (ND, n = 6) or HFD (n = 6). Liver Mt were isolated and oxygen consumption, superoxide anion production (the adrenaline method), and membrane fluidity (the spin label method) were measured. RESULTS: After 11 weeks, body weights and abdominal circumferences were higher in the HFD group than in the ND group. Mt oxygen consumption was higher in the HFD group than in the ND group. Superoxide anion production was significantly lower in the HFD group than in the ND group, while no significant changes were observed in membrane fluidity. CONCLUSION: Although rats developed diet-induced obesity, it did not reach the level of disease development. The promotion of lipid metabolism appeared to reduce superoxide anion production, but did not influence membrane fluidity. While superoxide anion damages cells as an oxidative stress, ROS and superoxide dismutase are essential signaling molecules in the body. The present results suggest that the continuous ingestion of a HFD impairs Mt and induces disease development.

Protein kinase C-dependent and -independent mechanisms of dense granule exocytosis by human platelets.

We examined the mechanisms of ATP release by human platelets using Ro-31-7549, a specific inhibitor of protein kinase C. Ro-31-7549 almost completely inhibited TPA-induced platelet aggregation and ATP release at 5-10 microM in washed platelets and in platelet-rich plasma. However, it suppressed thrombin- and U46619-induced ATP release by only 48% and 21%, respectively, and had little effect on aggregation in washed platelet suspensions containing serum or in platelet-rich plasma. The addition of GRGDS to prevent aggregation inhibited this residual thrombin-induced release by 53% and the residual U46619 release by 100% in the presence of Ro-31-7549. In washed platelet suspensions free of serum or plasma, Ro-31-7549 almost completely inhibited the ATP release and partially suppressed the aggregation induced by these agonists. These results suggested that there are protein kinase C-dependent and -independent mechanisms for ATP release by human platelets and that activation of the latter mechanism may depend on aggregation and plasma factors.

Ca2+ entry pathways activated by the tumor promoter thapsigargin in human platelets.

Thapsigargin-activated Ca2+ entry into platelets was examined in the presence of S-145, a thromboxane A2 receptor antagonist, to inhibit indirect effects by endogenously formed prostaglandin H2/thromboxane A2. With external Ca2+ present, 0.2 microM thapsigargin caused a prompt increase in intracellular Ca2+ concentration ([Ca2+]i) followed by a gradual increase. Pretreatment with 6 microM wortmannin, a specific inhibitor of myosin light chain kinase, partly inhibited the increase in [Ca2+]i. In Ca(2+)-free EGTA buffer, thapsigargin induced a smaller increase in [Ca2+]i, and subsequent addition of Ca2+ to the buffer caused a further prompt increase in [Ca2+]i, demonstrating external Ca2+ entry. Wortmannin only partly inhibited this entry of external Ca2+. The wortmannin-insensitive Ca2+ entry pathway remained open for more than 6 min in Ca(2+)-free buffer. On the other hand, when receptor agonists such as thrombin and U46619 were substituted for thapsigargin, activation of the wortmannin-insensitive Ca2+ entry was transient (Hashimoto et al., J. Biol. Chem (1992) 267, 17078-17081). In the presence of S-145 and wortmannin, thapsigargin stimulated phosphorylation of neither the 20-kDa myosin light chain nor the 47-kDa protein, a substrate of protein kinase C. These results suggest that thapsigargin induces external Ca2+ entry by two mechanisms: (1) a mechanism involving myosin light chain kinase; (2) a mechanism, not activated by receptor agonists, that is independent of the major protein kinases of platelets.

Roles of myosin light-chain kinase in platelet shape change and aggregation.

We examined the roles of myosin light-chain kinase in platelet responses to ADP using wortmannin, which almost completely inhibited myosin light-chain kinase at 3-6 microM. This concentration of wortmannin did not affect ADP-induced changes in the shape of the platelets, but it markedly inhibited aggregation in platelet-rich plasma and washed platelets. ML-9, another inhibitor of myosin light chain kinase, elicited similar effects on the platelet responses to wortmannin. Electron microscopic studies showed that there was no wortmannin effect on the ADP-induced spheration of discoid platelets, pseudopod formation, or granule centralization. Wortmannin at concentrations which prevented myosin light-chain kinase also inhibited platelet aggregation induced by ADP in the presence of U46619, an analogue of thromboxane A2, which is a prerequisite for ADP-induced irreversible aggregation. Although wortmannin partially inhibited protein kinase C, the protein kinase C inhibitor Ro-31-7549 (5 microM) prevented neither ADP- or ADP/U46619-induced changes in the shape of the platelets nor aggregation. These results suggest that myosin light-chain kinase activation is a prerequisite for ADP-induced platelet aggregation, but not for changes in their shape.

Protein kinase C plays a key role in the cross-talk between intracellular signalings via prostanoid receptors in a megakaryoblastic cell line, MEG-01s.

In a previous study, we characterized prostanoid and thrombin receptors expressed on a megakaryoblastic cell line, MEG-01s (Blood 78, 2328-2336, 1991). In this study, we examines the mechanism of cross-talk between intracellular Ca2+ ([Ca2+]i) and cAMP signalings through prostanoid and thrombin receptors. Addition of a thromboxane (TX)A2 mimetic (U46619 or STA2) or thrombin stimulated the formation of inositol phosphates and dose-dependently augmented a prostaglandin (PG)I2 mimetic (iloprost)- or forskolin-induced cAMP formation. 12-O-tetradecanoylphorbol-13-acetate (TPA) and ionomycin, to lesser extent, also augmented iloprost-induced cAMP formation. The enhancing effect of U46619 or TPA on cAMP formation was inhibited by prolonged pretreatment of the cells with TPA (2.5 microM, 24 h), but not with calmodulin-antagonists; W-7, W-5, or KN-62. The elevation of [Ca2+]i induced by thrombin, STA2 or PGE2 was significantly suppressed by pretreatment of the cells with TPA (100 nM) as well as cAMP mimetics such as dibutyryl cAMP (5 mM), forskolin (5 microM) and iloprost (1 microM). These results suggest the key role of PKC on the cross-talk between [Ca2+]i and cAMP signalings through prostanoid and thrombin receptors; PKC, which is activated with TXA2 or thrombin, concomitantly suppress further [Ca2+]i elevation and enhances the PGI2 receptor-mediated cAMP formation, which, in turn, suppress [Ca2+]i elevation.

[Envenomation accidents caused by snakebites in the surgical emergency unit of Gabriel-Touré Hospital, Bamako, Mali (1998-1999)]. / Les accidents d'envenimation par morsure de serpent dans le service des urgences chirurgicales de l'hôpital Gabriel-Touré, Bamako, Mali (1998-1999).

This study aimed at assessing envenomations caused by snakebite in the Gabriel Touré hospital between January 1998 and December 1999. We included in total 112 victims of snakebites proved by the identification of the snake, the fangs traces and envenomation signs. The bites concerned 34 women (30.36%) versus 78 men (69.64%) from the Bamako district, while 66.7% were from a rural environment. The farmers were the most affected category (35.1%). The bite concerned the lower limb in 83.3% of the cases. Snakes such as Echis ocellatus, Bitis arietans, Naja nigricollis and N. katiensis caused the envenomations. The viperine syndrome dominated the clinical picture; its severity depended on the bleeding stage and the delay of administration of the antivenom serum (AVS) after the envenomation: 19 hours for Echis sp. and 2 hours for Naja sp. This study shows that the envenomation accidents caused by snakes are frequent with a lethality rate of 9.8%.

Effects of a single local administration of cilostazol on neointimal formation in balloon-injured rat carotid artery.

To elucidate if locally administered cilostazol, an inhibitor of cyclic AMP phosphodiesterase III, suppresses neointimal formation in balloon-injured carotid artery of the rat, 20 mg of cilostazol was topically applied using pluronic gel at the time of balloon injury. Rats were sacrificed 14 days after balloon injury to measure the extent of neointimal formation. Plasma and tissue concentrations of cilostazol were also measured at 1, 3, 7 and 14 days after topical application. The 5-bromo-2'-deoxyuridine (BrdU, a thymidine analogue) was given intraperitoneally to detect proliferation of smooth muscle cells in the injured media at 3 days after balloon injury. At 1 day after injury, plasma and tissue concentrations were 0.147+/-0.043 microg/ml and 1380 microg/g tissue. Although the plasma concentration of cilostazol was undetectable ( < 0.02 microg/ml), a significant amount of cilostazol (46 microg/g tissue) was still detected in the tissue at the site of application even after 2 weeks. The intimal area of the injured carotid after 2 weeks was significantly smaller in the cilostazol-treated group than in the gel-treated control group (0.06+/-0.01 vs 0.15+/-0.02 mm2, P<0.001). BrdU-positive smooth muscle cells in the injured media after 3 days were also significantly fewer in the cilostazol-treated group than in the gel-treated control group (4.3+/-0.5 vs 9.1+/-0.9% of total cells, P < 0.001). These results suggest that local administration of cilostazol using pluronic gel maintains a high concentration of the drug at the application site, has an anti-proliferative effect on smooth muscle cells, and may have potential for clinical therapeutic use for the prevention of restenosis following arterial intervention.

Inducible stx2 phages are lysogenized in the enteroaggregative and other phenotypic Escherichia coli O86:HNM isolated from patients.

We characterized two Shiga toxin-producing Escherichia coli (STEC) O86:HNM isolates from a patient with hemolytic uremic syndrome (HUS) or bloody diarrhea. Both of them did not possess the eaeA gene. However, the isolate from a HUS patient carried genetic markers of enteroaggregative E. coli (EAEC) and showed aggregative adherence pattern to HEp-2 cells. The other isolate from bloody diarrhea, which was negative with EAEC markers, was diffusely adhered to HEp-2 cells. The stx2 gene in both E. coli O86:HNM strains was encoded in each infectious phage, which was partially homologous to that of strain EDL933, a STEC O157:H7. These results will help to explain the genotypic divergences of STEC.

Characteristics of protein kinase C-independent exocytosis in human platelets.

We evaluated the characteristics of the protein kinase C (PKC)-independent mechanism for ATP release in platelet-rich plasma. When ADP (10 microM) and U46619 (1 microM) were both added as agonists, a significant release was observed immediately after stimulation. The PKC inhibitor, Ro-31-7549 (10 microM), or a cyclooxygenase inhibitor, aspirin (400 microM) or indomethacin (20 microM), partially inhibited ATP release with little effect on platelet aggregation. The ATP release observed in the presence of Ro-31-7549 was abolished by a cyclooxygenase inhibitor or by preventing aggregation without stirring. In the nonstirred condition, thromboxane B2 formation was reduced by 93%. When sodium arachidonate (1 mM) rather than U46619 was used with ADP, ATP release in the presence of Ro-31-7549 was abolished by stopping the stirring with no effect on thromboxane B2 formation. In contrast, ADP/U46619-induced ATP release observed in the presence of aspirin was only partially inhibited when the stirring was stopped. This release was also inhibited dose-dependently by Ro-31-7549 at concentrations between 1 and 10 microM. These results suggest that PKC-independent ATP-release in this system requires aggregation and is inhibited by a cyclooxygenase inhibitor, while PKC-dependent exocytosis is insensitive to aggregation and a cyclooxygenase inhibitor.

Relationship of fat mass and fat distribution to blood pressure.

The relationship of fat mass, lean body mass (LBM), and fat distribution to blood pressure was examined in Japanese adult men and women. Percent body fat was estimated using two skinfold thicknesses, and fat mass and LBM were then calculated. Correlation coefficients showed that fat mass, fat distribution, and age were weakly associated with blood pressure levels, and that the correlation coefficients of LBM to blood pressure levels were nearly zero. Stepwise regression analysis revealed that fat mass and age contributed significantly to the variations in blood pressure levels. In addition, only in the case of men, trunk-extremity skinfolds ratio was also entered into the model for diastolic and mean arterial blood pressure. It thus has been concluded that fat mass may be the more predictive determinant of blood pressure level than LBM in the Japanese population, and that the independent correlation of fat distribution to blood pressure is rather small.

Electron microscopic localization of acridine orange chromatin interaction products in rat pheochromocytoma PC12 cells.

The purpose of the present study is to examine the distribution pattern of acridine orange (AO) binding to DNA in rat adrenal pheochromocytoma PC12 cells that respond to nerve growth factor (NGF). PC12 cells were incubated in a medium containing 100 ng/ml of NGF for 1-14 days for AO ultracytochemistry. Electron microscopic studies revealed that AO binds to DNA exclusively within the euchromatin portion of the cell nucleus. About 35% of the untreated PC12 cells showed characteristic electron-dense interaction products within the nuclei. The average numbers of AO chromatin interaction products per cell nucleus and per micron 2 nuclear area were 45 and 1.6, respectively. In the presence of NGF, cell proliferation was suppressed. The cells gradually extend neurite-like cell processes. Mean 3H-labeling index was 40.0 +/- 2.2% in untreated cells and 13.0 +/- 2.3% in PC12 cells with NGF for 6 days after incubation for 30 min. With increasing the cellular differentiation percentages of AO positive cells and average numbers of AO chromatin interaction products per cell nucleus and per micron 2 nuclear area showed a progressive decrease. The results of the present and previous studies suggest that AO chromatin interaction products may be indicative of cell proliferation and differentiation.

The use of an enzyme-linked immunosorbent assay for estimation of the immune status of chickens artificially immunized against coccidiosis.

Nine thousand commercial breeder chicks (Chankee) reared in a floor pen were exposed to restricted numbers of Eimeria tenella and E. necatrix oocysts to confer immunity. Antibody induction in these chicks was examined by the enzyme-linked immunosorbent assay (ELISA) with antigen prepared from E. tenella oocysts. The oocyst excretion pattern demonstrated recycled infections which continued in these chicks for greater than or equal to 22 days after exposure. Antibody levels in their sera, as determined by the mean absorbence values in ELISA, increased gradually up to 38 days post-inoculation. Mean absorbence values of sera from control chicks remained at a low level. When infected and control chicks were challenged with the two species of coccidia, the test chicks were protected against both species. The antibody level did not change for 8 days in the challenge groups, while in the control chicks, absorbence in ELISA rose significantly and the mean absorbence value was higher than that in immunized chicks. Some factors which influence the results of ELISA are considered and the applicability of this method to measuring immunity against coccidiosis in chickens is discussed.

Relationship between glycosylated hemoglobin and the prevalence of proteinuria in Japanese men.

A total of 5,174 Japanese men were included in a cross-sectional study to examine the relationship between the glycated hemoglobin (HbA1C) level and the prevalence of proteinuria as determined using a reagent strip. The prevalence of proteinuria rose significantly at HbA1C levels above 5.9%, whereas no relationship was observed at HbA1C levels below 5.9%. Multiple logistic regression analysis showed that blood pressure and a family history of diabetes were independent factors associated with proteinuria in subjects with a HbA1C below 5.9% who were not under medication for diabetes. In contrast, HbA1C, obesity and smoking were associated with proteinuria in subjects who were under medication for diabetes and/or have a HbA1C above 5.9%. These findings suggest that maintaining a HbA1C level below 5.9%, non-smoking and a standard body weight may reduce the prevalence of proteinuria in Japanese men. Healthy life-style and standard body weight are especially important for subjects with a family history of diabetes.

Nutritional assessment of a group of Japanese elementary school children in Tokyo: with special emphasis on growth, anemia, and obesity.

Anthropometric data, nutrient intake data, and blood biochemical parameters were analyzed for 66 elementary school children living in Tokyo, Japan, and their nutritional status was evaluated focusing on three problems: (1) zinc nutriture and growth, (2) anemia with iron deficiency, and (3) lipid nutriture and obesity. The subjects' mean energy and protein intakes met the recommended levels for Japanese children. However, their zinc intake levels were inadequate at 7.2, 8.3, and 8.5 mg in grades 2 (mean age: 8 yr), 4 (10 yr), and 6 (12 yr), respectively. Mean serum zinc concentration was 0.82 +/- 0.15 microgram/ml; the percentages of subjects who showed serum zinc concentration lower than 0.68 microgram/ml, the lower limit of the normal serum zinc concentration, were 28.6, 15.4, and 5.0% in grades 2, 4, and 6, respectively. These serum zinc concentrations indicated the existence of marginal zinc deficiency in some children, particularly in grade 2, though it was not severe enough to retard growth. Their iron intake levels (8.2, 10.2, and 10.2 mg for grades 2, 4, and 6, respectively) in combination with the proportion of iron intake from animal foods (37%) were judged to be adequate because no children showed serum ferritin, serum iron, or transferrin saturation levels lower than the criteria levels recommended for iron deficiency. Moreover, no definitely anemic children were found. Daily lipid intakes were 65.7, 74.5, and 78.3 g in grades 2, 4, and 6, respectively, and the mean percentage of energy intake from lipid to total energy intake, 32%, exceeded the level recommended. Mean serum total cholesterol concentrations and the percentage of subjects with elevated cholesterol levels (greater than or equal to 200 mg/dl) were high compared with the reported values. Means of the body mass index (BMI) and Rohrer Index (RI) for the subjects were slightly higher than Japanese standards. With these parameters for obesity, triglycerides and atherogenic index were positively correlated and HDL cholesterol and HDL cholesterol percentage to total cholesterol were negatively correlated.

[Pharmacokinetics and clinical studies on cefminox in the field of obstetrics and gynecology].

Cefminox (CMNX, MT-141), a new cephamycin antibiotic, was studied in the field of obstetrics and gynecology, and the following results were obtained. The absorption and the penetration of CMNX into pelvic dead space exudate were good. The mean peak serum level after single intravenous injection was 190.8 micrograms/ml. The level in pelvic dead space exudate reached a peak of 36.6 micrograms/ml 4 hours after an intravenous injection of 1 g and 6.5 micrograms/ml after 12 hours, thus the level over MIC against main pathogenic organisms was maintained for a long time. CMNX was administered against gyneco-obstetrical infections such as intrauterine, intrapelvic, adnexal infections and postoperative wound infections with daily dose of 2 g and was effective in 11 cases out of 12 cases (91.7%), and 81.8% of bacteriological effect was obtained. No side effect was observed. From the above results the usefulness of CMNX in the field of obstetrics and gynecology was suggested.

[Clinical studies on cefoxitin in the field of obstetrics and gynecology].

Clinical studies were done on cefoxitin (CFX), the first cephamycin antibiotic, in the field of obstetrics and gynecology and following results were obtained. CFX was administrated by intravenous drip infusion for average 6.9 days at a daily dose of 2--6 g to 58 patients; 15 with intrauterine infections, 5 with intrapelvic infections, 11 with adnexitis, 3 with mastitis, 5 with urinary tract infections, 2 with other infections and 17 for prophylaxis of postoperative infections. The clinical results were excellent in 8 cases, good in 39 cases, fair in 4 cases, poor in 6 cases and unknown in 1 case, with the efficacy of 82.5%. Total bacteriological effective rate was 88.9%. As to side effects, eruption was observed only in 1 case. From the results of the present study, the usefulness of CFX was demonstrated in the field of obstetrics and gynecology.

[Clinical application of latamoxef during the perinatal period].

Pharmacokinetic studies and clinical evaluations of latamoxef (LMOX) were carried out in perinatal mothers and infants. LMOX was promptly absorbed after intravenous injection and intravenous drip infusion in pregnant women, producing dose-related peak blood levels. Placental transference to the fetus was favorable. After intravenous injection and intravenous drip infusion of 1.0--2.0 g of LMOX, drug concentration of the cord blood, amniotic fluid and fetal blood exceeded MICs of the main pathogenic organisms. By administration of the dose of 1.0--2.0 g twice a day, it is possible to successfully prevent or treat uterine infections. LMOX was effective in the prophylaxis or therapy of perinatal infections. Moreover, newborn infants delivered from mothers receiving LMOX treatment having drug concentrations exceeded MICs of main pathogenic organisms however not remained more than 12 hours after birth, and did not exhibit any laboratory test abnormalities. The above results demonstrated that LMOX is a clinically useful antibiotic for the prophylaxis and treatment of perinatal infections.