GAYET WERNICKE'S ENCEPHALOPATHY AFTER COVID-19 IN ELDERLY SUBJECTS IN TROPICAL ENVIRONMENTS: STUDY OF SIX (6) OBSERVATIONS IN CONAKRY.

In sub-Saharan Africa, the COVID-19 pandemic has caused severe malnutrition in elderly populations with the appearance of vitamin deficiencies, in particular thiamine responsible for Gayet Wernicke's encephalopathy (EGW). We present a series of six (6) patients hospitalized in the Neurology Department of the CHU Ignace Deen for the management of a brain syndrome with vigilance disorders after recovery from COVID-19, including oculomotor disorders, motor incoordination on a course of severe weight loss. The six patients underwent an evaluation of malnutrition by determining the WHO body mass index, the Detsky index, the serum albumin assay, the thiamine assay and a neuroradiological assessment (MRI) and an electroencephalogram (EEG) examination although this does not seem necessary for diagnosis. Study of nutritional status: weight loss greater than 5%, patients in Desky group B and C, plasma albumin<30 g/l, lowered thiamine and MRI neuroradiological data: by the existence of hypersignals in certain regions of the neocortex, certain gray nuclei, the mammillary bodies the thalamic nuclei close to the wall of the 3rd ventricle and the regions bordering the 4th ventricle sign Gayet Wernicke's encephalopathy syndrome. This study shows a stereotyped clinical, biological, neuroradiological and evolutionary profile of Gayet Wernicke's encephalopathy in elderly subjects recovered from Covid-19 with proven malnutrition. These results are useful for the therapeutic and prognostic discussion.

Maternal exposure to organophosphate flame retardants alters locomotor and anxiety-like behavior in male and female adult offspring.

Endocrine disrupting chemicals (EDCs) are chemicals found in our environment that interrupt typical endocrine function. Some flame retardants (FRs) are EDCs as shown in their interaction with steroid and nuclear receptors. Humans are consistently exposed to flame retardants as they are used in everyday items such as plastics, clothing, toys, and electronics. Polybrominated diphenyl ethers were used as the major FR until 2004, when they were replaced by organophosphate flame retardants (OPFRs). Previous research in rodent models utilizing a commercial flame retardant mixture containing OPFRs reported alterations in anxiety-like behavior in the elevated plus maze (EPM) for rodents perinatally exposed to OPFRs. In the present study we utilize wild-type mice maternally exposed (gestational day 7 to postnatal day 14) to either an OPFR mixture of tris(1,3-dichloro-2-propyl), triphenyl phosphate, and tricresyl phosphate or a sesame seed oil vehicle. These mice were evaluated for anxiety-like behavior in adulthood on the open field test (OFT) and the light/dark box (LDB) as well as the EPM. Outcomes from the OFT and LDB indicate that males and females maternally exposed to OPFRs exhibit altered locomotor activity. Results of the EPM were sex-specific as we did not observe an effect in females; however, effects in males differed depending on exposure condition. Males maternally exposed to OPFRs exhibited an anxiolytic-like phenotype in contrast to their vehicle counterparts. This effect in perinatally OPFR-exposed males was not due to alterations in locomotor activity. Our research illustrates that there are sex- and exposure-dependent effects of perinatal OPFR exposure on adult locomotor and anxiety-like behaviors in a mouse model.

Transmissible arthritis in a man from Guinea.

We report the case of a 32-year-old man with septic arthritis and Neisseria gonorrhoeae tenosynovitis, diagnosed after joint fluid culture treated with ceftriaxone. It is one of the most frequent causes of purulent septic arthritis in young people in undeveloped countries. Early diagnosis is important to avoid complications.

Late-onset spondyloarthritis: a study of 133 patients in Dakar, Senegal.

Reports of late-onset spondyloarthritis in sub-Saharan Africa are sparse. This series allows us to describe the characteristics of this disease in Senegal. This is a retrospective study conducted in the Rheumatology Department of the Dantec University Hospital (Dakar) where we reviewed records of spondyloarthritis cases. Its diagnosis met the modified ASAS and New York criteria. Late-onset was defined as after the age of 55 years. During the study period, the department managed 133 late-onset patients, or 38% of all spondyloarthritis cases (350). Age ranged from 65 to 74 years, with a mean of 66. HLA B 27 phenotyping was performed in 89 patients; 39 patients were HLA B27 positive (29%). The treatments were based on DMARDs (salazopyrin and methotrexate).

Delayed catabolism of apoB-48 lipoproteins due to decreased heparan sulfate proteoglycan production in diabetic mice.

We used wild-type (WT) mice and mice engineered to express either apoB-100 only (B100 mice) or apoB-48 only (B48 mice) to examine the effects of streptozotocin-induced diabetes (DM) on apoB-100- and apoB-48-containing lipoproteins. Plasma lipids increased with DM in WT mice, and fat tolerance was markedly impaired. Lipoprotein profiles showed increased levels and cholesterol enrichment of VLDL in diabetic B48 mice but not in B100 mice. C apolipoproteins, in particular apoC-I in VLDL, were increased. To investigate the basis of the increase in apoB-48 lipoproteins in streptozotocin-treated animals, we characterized several parameters of lipoprotein metabolism. Triglyceride and apoB production rates were normal, as were plasma lipase activity, VLDL glycosaminoglycan binding, and VLDL lipolysis. However, beta-VLDL clearance decreased due to decreased trapping by the liver. Whereas LRP activity was normal, livers from treated mice incorporated significantly less sulfate into heparan sulfate proteoglycans (HSPG) than did controls. Hepatoma (HepG2) cells and endothelial cells cultured in high glucose also showed decreased sulfate and glucosamine incorporation into HSPG. Western blots of livers from diabetic mice showed a decrease in the HSPG core protein, perlecan. Delayed clearance of postprandial apoB-48-containing lipoproteins in DM appears to be due to decreased hepatic perlecan HSPG.

Regulation of apolipoprotein B-containing lipoproteins by dietary soluble fiber in guinea pigs.

Dietary soluble-fiber sources such as pectin, guar gum, or psyllium decrease plasma concentrations of low-density-lipoprotein (LDL) cholesterol in guinea pigs by distinct mechanisms, including increases in LDL apolipoprotein (apo) B turnover and/or decreases in LDL apo B flux (J Lipid Res 1995; 36:2394-404). The present studies were undertaken to test whether changes in the rates of very-low-density lipoprotein (VLDL) apo B secretion, VLDL conversion to LDL, and hepatic uptake of VLDL were related to the cholesterol-lowering actions of these soluble fibers. Guinea pigs were fed (by wt) 12.5% pectin, 12.5% guar gum, 7.5% psyllium, or a control diet containing cellulose as the fiber source. Plasma cholesterol concentrations were significantly lower in guinea pigs fed pectin, guar gum, and psyllium by 42%, 46%, and 35%, respectively (P < 0.001), compared with those animals fed the control diet, whereas plasma triacylglycerol concentrations were lower only with guar gum intake. The secretion rate of triacylglycerol, determined after Triton was injected to block VLDL catabolism, was not different among dietary treatment groups whereas the secretion rate of apo B was lower with pectin, guar gum, and psyllium intakes (P < 0.01). In addition, pectin, guar gum, and psyllium significantly altered the composition of newly secreted VLDLs by increasing the number of triacylglycerol and phospholipid molecules in the secreted lipoprotein, indicating the presence of larger nascent VLDLs. In contrast, the average particle diameter of mature VLDLs as determined by electron microscopy was smaller in the dietary soluble-fiber groups in the following order: pectin < psyllium < guar gum. Plasma lecithin-cholesteryl acyltransferase and cholesteryl ester transfer protein activities were lower with intake of pectin, guar gum, and psyllium (P < 0.01). Injection of radiolabeled lipoproteins indicated that pectin, guar gum, and psyllium intakes resulted in more rapid VLDL and LDL apo B turnover and lower LDL apo B flux in guinea pigs fed guar gum and psyllium. These results suggest that the secretion rate of apo B, compositional changes in lipoproteins occurring in the intravascular compartment, and up-regulation of LDL receptors-associated with faster LDL apo B turnover rates-are secondary metabolic responses induced by dietary fiber that contribute to the lowering of plasma cholesterol concentrations.

Hypocholesterolemic effects of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors in the guinea pig: atorvastatin versus simvastatin.

Male Hartley guinea pigs were fed a hypercholesterolemic diet rich in lauric and myristic acids with 0, 10, or 20 mg/kg of simvastatin or atorvastatin for 21 days. Atorvastatin and simvastatin resulted in a lowering of plasma low-density lipoprotein (LDL) cholesterol in a dose-dependent manner by an average of 48 and 61% with 10 and 20 mg/kg, respectively. Both statins were equally effective in lowering plasma LDL cholesterol and apolipoprotein B (apo-B) levels. Atorvastatin and simvastatin treatments yielded LDL particles that differed in composition from the control. Due to the relevance of LDL oxidation and cholesteryl ester transfer in plasma to the progression of atherosclerosis, these parameters were analyzed after statin treatment. Atorvastatin and simvastatin treatment decreased the susceptibility of LDL particles to oxidation by 95% as determined by the formation of thiobarbituric acid reactive substances. An 80% decrease in the transfer of cholesteryl ester between high-density lipoprotein (HDL) and the apo-B-containing lipoproteins was observed after simvastatin and atorvastatin treatment. In addition, statin effects on plasma LDL transport were studied. Simvastatin- and atorvastatin-treated guinea pigs exhibited 125 and 175% faster LDL fractional catabolic rates, respectively, compared with control animals. No change in LDL apo-B flux was induced by either treatment; however, LDL apo-B pool size was reduced after statin treatment. Hepatic microsomal free cholesterol was lower in the atorvastatin and simvastatin groups. However, only atorvastatin treatment resulted in an 80% decrease of acyl-CoA:cholesterol acyltransferase activity (P < 0.001). In summary, atorvastatin and simvastatin had similar LDL cholesterol lowering properties, but these drugs modified LDL transport and hepatic cholesterol metabolism differently.

Atorvastatin and simvastatin have distinct effects on hydroxy methylglutaryl-CoA reductase activity and mRNA abundance in the guinea pig.

The effects of atorvastatin and simvastatin on hydroxy methylglutaryl (HMG)-CoA reductase activity and mRNA abundance were studied in guinea pigs randomized to three groups: untreated animals and those treated with 20 mg/kg of atorvastatin or simvastatin. Guinea pigs were fasted for 0, 6, 12, or 18 h in an attempt to remove the drug from their systems. Reductase activity and mRNA levels were analyzed after each time point. Reductase inhibitor treatment resulted in 50-62% lower cholesterol concentrations compared to untreated guinea pigs (P < 0.0001), while plasma triacylglycerol (TAG) concentrations did not differ among groups. Plasma cholesterol and TAG were 50-70% lower after 18 h fasting in the three groups (P < 0.001). In the nonfasting state, simvastatin and atorvastatin treatment did not affect HMG-CoA reductase activity compared with untreated animals. However, after 6 h of fasting, simvastatin-treated guinea pigs had higher HMG-CoA reductase activity than untreated animals (P < 0.01), suggesting that the drug had been removed from the enzyme. In contrast, atorvastatin-treated guinea pigs maintained low enzyme activity even after 18 h of fasting. Further, HMG-CoA reductase mRNA abundance was increased by sevenfold after atorvastatin treatment and by twofold after simvastatin treatment (P < 0.01). These results suggest that simvastatin and atorvastatin have different half-lives, which may affect HMG-CoA reductase mRNA levels. The increase in reductase activity by simvastatin during fasting could be related to an effect of this statin in stabilizing the enzyme. In contrast, atorvastatin, possibly due to its longer half-life, prolonged inhibition of HMG-CoA reductase activity and resulted in a greater increase in mRNA synthesis.

[Neurological complications of chronic alcoholism: study of 42 observations in Guinea]. / Complications neurologiques de l'alcoolisme chronique : étude de quarante-deux observations en Guinée.

Neurologic disorders related to chronic alcoholism in traditional areas of Guinea are frequent, but reports about them are rare. We conducted the first study in Guinea on this subject and retrospectively collected 42 cases of neurologic manifestations related to alcoholism over a 7-year period. The standard findings of the literature were confirmed in our population: peak frequency after the age of 40 years (82.8%) and clear male overrepresentation (M/F sex ratio: 13/1). All the standard signs and symptoms are reported, with a clear predominance of alcoholic polyneuropathy and hepatic encephalopathy. The study of nutritional status by both body mass index (BMI) and the Detsky criteria showed that these patients were severely malnourished. The brain MRI was a crucial contribution for diagnosing the standard central nervous system complications of alcoholism: Gayet Wernicke encephalopathy, Marchiafava-Bignami disease, Korsakoff syndrome, central pontine myelinolysis, and cerebellar degeneration.

[Neurological disorders related to vitamin B12 deficiency in prisons in Guinea: a 22-case study]. / Manifestations neurologiques associées à la carence en vitamine B12 en milieu carcéral en Guinée : étude de 22 observations.

Neurological disorders related to vitamin B12 deficiency are common in prisons of tropical Africa. We collected 22 cases (20 men and 2 women). They all showed vitamin B12 deficiency associated with neurological signs that were represented by sclerosis combined with bone marrow (n = 9), peripheral neuropathy (n = 6), cerebellar syndrome (n = 2), a pyramidal syndrome of the lower limbs (n = 4) and optic neuropathy (n = 1). Laboratory tests showed a mean hemoglobin concentration of 7.2 ± 1.5 g/dl, mean 104 ± 28 fl, macrocytic anemia in 10 patients. Biermer's disease was identified in 9 patients, 3 patients showed the syndrome of non dissociation of vitamin B12, a gastrectomy in 2 patients and no etiology was identified in 8 patients.

Dietary carbohydrate type and fat amount alter VLDL and LDL metabolism in guinea pigs.

The effects of low/high fat diets and simple/complex carbohydrate intake on specific aspects of plasma VLDL and LDL metabolism were evaluated. Guinea pigs were fed for 4 wk two different fat/carbohydrate concentrations: 2.5/58 (g/100 g) or 25/29 (g/100 g) with either sucrose or cornstarch as the sole carbohydrate source. Intake of high fat diets resulted in higher plasma cholesterol (P < 0.001), whereas sucrose intake resulted in higher plasma triacyglycerol (TAG) concentrations (P < 0.03). Intake of starch increased apolipoprotein (apo) B secretion rates (P < 0.001), and nascent VLDL were smaller and contained less TAG/apo B than particles from the sucrose-fed group (P < 0.01). Guinea pigs fed the starch diets had higher plasma VLDL apo B flux and faster VLDL apo B clearance than those fed sucrose diets (P < 0.01). In addition, more rapid VLDL removal from plasma in guinea pigs fed complex carbohydrate/high fat diets was associated with less conversion of VLDL to LDL and lower plasma cholesterol concentrations compared with the high fat/sucrose group (P < 0.01). Low fat compared with high fat intake resulted in 60% more rapid plasma LDL apo B fractional catabolic rates (FCR). The LDL apo B fractional catabolic rate of all dietary groups was inversely correlated with plasma cholesterol concentrations (r = -0.83, P < 0.001). These results demonstrate that in guinea pigs, low fat diets decrease plasma LDL cholesterol concentrations by increasing LDL turnover rates, and complex carbohydrates reduce plasma TAG by affecting the composition of nascent VLDL particles and by increasing VLDL apo B catabolism.

Hypocholesterolemic actions of atorvastatin are associated with alterations on hepatic cholesterol metabolism and lipoprotein composition in the guinea pig.

Guinea pigs were fed 15% (w/W) fat, high in lauric and myristic acids, a diet known to produce hypercholesterolemia in these animals. The diet was given alone or in combination with four doses of atorvastatin equivalent to 1, 3, 10, and 20 mg/kg per day. Atorvastatin reduced plasma LDL cholesterol concentrations by 46, 50, 53, and 70%, respectively (P < 0.001). Plasma apoB concentrations were reduced by atorvastatin (P < 0.001) and compositional changes occurred in VLDL and LDL with reductions of the relative proportion of cholesteryl ester and increases in triacylglycerol. A reduction in hepatic cholesteryl ester (66%) was observed only with the highest atorvastatin dose (20 mg/kg per day) while microsomal cholesterol was reduced by 30% with 3-20 mg/kg per day. Hepatic ACAT activity was down-regulated and apoB/E receptor number was increased by atorvastatin. In contrast, HMG-CoA reductase activity and cholesterol 7 alpha-hydroxylase were not affected by the drug. VLDL apoB secretion rates were decreased by atorvastatin treatment 59 and 76% with 3 and 20 mg/kg per day, respectively. Nascent VLDL particles were larger after drug treatment, showing an increased number in triacylglycerol molecules. These results support the hypothesis that the plasma LDL lowering induced by atorvastatin is due to a decreased secretion of apoB in combination with an increase of hepatic apoB/E receptors.

Hamsters and guinea pigs differ in their plasma lipoprotein cholesterol distribution when fed diets varying in animal protein, soluble fiber, or cholesterol content.

There were two objectives to these studies: 1) to compare the lipoprotein cholesterol distribution in two animal models in response to different dietary treatments and 2) to assess whether the hypercholesterolemia induced by high cholesterol intake could be reversed by consumption of vegetable-protein and/or dietary fiber. Guinea pigs, which carry the majority of plasma cholesterol in LDL, and hamsters, with a higher distribution of cholesterol in HDL, were evaluated in three different studies. In Study 1, animals were fed semi-purified diets for 4 wk with proportions of 60:40, 20:80 or 0:100 (w/w) of casein/ soybean protein. Hamsters and guinea pigs that consumed 100% soybean protein had lower plasma total cholesterol (TC) than those fed diets containing casein (P < 0.01). In Study 2, three doses of dietary pectin (2.7, 5.4, or 10.7 g/100g) added in place of cellulose were tested. Intake of 10.7 g/100 g pectin resulted in the lowest plasma TC concentrations for both species (P < 0.01). Although the TC lowering was similar in studies 1 and 2, the lipoprotein cholesterol distribution differed. Whereas the differences in plasma cholesterol were in LDL in guinea pigs, hamsters exhibited differences in both non-HDL and HDL cholesterol. In study 3, animals were fed 100% soybean protein, 10.7 g/100 g pectin, and three doses of dietary cholesterol: 0.04, 0.08, or 0.16 g/100 g, which is equivalent to 300, 600, or 1,200 mg/d in humans. Guinea pigs and hamsters had the highest plasma LDL and hepatic cholesterol concentrations when they consumed 0.16 g/100 g of cholesterol (P < 0.01). However, intake of 0.08 g/100 g of cholesterol resulted in lower plasma LDL cholesterol concentrations than did consuming high animal protein (60:40 casein/ soy) or low soluble fiber (2.7 g/100 g). Relatively high levels of dietary cholesterol combined with vegetable protein and soluble fiber resulted in desirable lipoprotein profiles in animal models that significantly differ in their lipoprotein cholesterol distribution.

Hypolipidemic mechanisms of pectin and psyllium in guinea pigs fed high fat-sucrose diets: alterations on hepatic cholesterol metabolism.

Studies were conducted to determine whether pectin (PE) or psyllium (PSY) could reverse the high plasma cholesterol and triacylglycerol (TAG) concentrations induced by high fat (HF) or high sucrose (HS) diets and which are the mechanisms involved. Male guinea pigs were fed either a low fat (LF) or a HF diet with 80% of the carbohydrate energy derived from sucrose. Cellulose was used as control. Plasma LDL cholesterol, TAG, apolipoprotein B, and hepatic cholesteryl ester were lower in guinea pigs fed PE and PSY compared to the control group (P < 0.03). In addition, a 45% higher number of hepatic apoB/E receptors was observed by PE and PSY intake. Hepatic ACAT, HMG-CoA reductase, and cholesterol 7alpha-hydroxylase (C7H) activities were higher in the HF compared to the LF groups (P < 0.01). PSY intake with HF resulted in up-regulation of C7H and HMG-CoA reductase activities (P < 0.05). Additional studies measuring the effects of PE and PSY on low density lipoprotein (LDL) transport and very low density lipoprotein (VLDL) secretion were conducted in the HF groups. ApoB secretion was reduced by pectin and psyllium (P < 0.01) intake while LDL fractional catabolic rates were 100% faster in guinea pigs fed PE or PSY. In these studies the extent of the hypolipidemic response was specific to each fiber type and associated with the amount of sucrose. In addition, PSY altered the activity of hepatic enzymes of cholesterol homeostasis in the HF group. These additional effects of PSY might explain the more dramatic changes in plasma lipid levels associated with PSY consumption.