Rare metabolic disease mimicking COL4A1/COL4A2 fetal brain phenotype.

Pathogenic variants of collagen type IV alpha 1 and 2 (COL4A1/COL4A2) genes cause various phenotypic anomalies, including intracerebral hemorrhage and a wide spectrum of developmental anomalies. Only 20% of fetuses referred for COL4A1/COL4A2 molecular screening (fetuses with a suspected intracerebral hemorrhage) carry a pathogenic variant in these genes, raising questions regarding the causative anomaly in the remaining 80% of these fetuses. We examined, following termination of pregnancy or in-utero fetal death, a series of 113 unrelated fetuses referred for COL4A1/COL4A2 molecular screening, in which targeted sequencing was negative. Using exome sequencing data and a gene-based collapsing test, we searched for enrichment of rare qualifying variants in our fetal cohort in comparison to the Genome Aggregation Database (gnomAD) control cohort (n = 71 702). Qualifying variants in pyruvate dehydrogenase E1 subunit alpha 1 (PDHA1) were overrepresented in our cohort, reaching genome-wide significance (P = 2.11 × 10-7 ). Heterozygous PDHA1 loss-of-function variants were identified in three female fetuses. Among these three cases, we observed microcephaly, ventriculomegaly, germinolytic pseudocysts, agenesis/dysgenesis of the corpus callosum and white-matter anomalies that initially suggested cerebral hypoxic-ischemic and hemorrhagic lesions. However, a careful a-posteriori reanalysis of imaging and postmortem data showed that the observed lesions were also consistent with those observed in fetuses carrying PDHA1 pathogenic variants, strongly suggesting that these two phenotypes may overlap. Exome sequencing should therefore be performed in fetuses referred for COL4A1/COL4A2 molecular screening which are screen-negative, with particular attention paid to the PDHA1 gene. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Prevalence of COL4A1 and COL4A2 mutations in severe fetal multifocal hemorrhagic and/or ischemic cerebral lesions.

OBJECTIVE: To establish the prevalence of COL4A1 and COL4A2 gene mutations in fetuses presenting with a phenotype suggestive of cerebral injury. METHODS: This was a single-center retrospective analysis of all cases of fetal cerebral anomalies suggestive of COL4A1 or COL4A2 gene mutation over the period 2009-2018. Inclusion criteria were: (1) severe and/or multifocal hemorrhagic cerebral lesions; (2) multifocal ischemic-hemorrhagic cerebral lesions. These anomalies could be of different ages and associated with schizencephaly or porencephaly. Between fetuses with and those without a mutation, we compared gestational age at the time of diagnosis, parity and fetal gender. RESULTS: Among the 956 cases of cerebral anomaly diagnosed in our center during the 10-year study period, 18 fetuses were identified for inclusion. A pathogenic COL4A1 gene mutation was found in five of these cases, among which four were de-novo mutations. A variant of unknown significance was found in four fetuses: in the COL4A1 gene in one case and in the COL4A2 gene in three cases. No COL4A1 or COL4A2 mutation was found in the remaining nine fetuses. The median (interquartile range) gestational age at diagnosis was significantly lower in cases with a mutation (24 (22-26) weeks) than in cases without a mutation (32 (29.5-34.5) weeks) (P = 0.03). CONCLUSIONS: A phenotype suggestive of cerebral injury was found in 18 of the 956 (1.9%) cases in our population, in 28% of which there was an associated COL4A1 or COL4A2 mutation. COL4A1 and COL4A2 gene mutations should be sought systematically in cases of severe and/or multifocal hemorrhagic or ischemic-hemorrhagic cerebral lesions, with or without schizencephaly or porencephaly. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Incidence and surgical treatment of synthetic mesh-related infectious complications after laparoscopic ventral rectopexy.

BACKGROUND: Prosthetic-related infection and erosion occurring after a laparoscopic ventral rectopexy (LVR) are rare complications, and their importance is often underestimated. The aim of this study was to compare the incidence rate and surgical management of these complications in LVR patients with polyester (PE) or polypropylene (PP) prostheses. METHODS: From January 2004 to June 2012, 149 patients underwent LVR with PE and 176 underwent LVR with PP. Surgical management and rate of infectious and erosive prosthesis-related complications, depending on the type of prosthesis, were described and compared. Functional results after complications were assessed. RESULTS: Five patients from the PE prosthesis group (3.3 %), compared with two patients from the PP prosthesis group (1.1 %), experienced prosthesis-related infection or erosion (p = 0.16). The rate of erosion alone was 3.3 % in patients with a PE prosthesis, and 0.55 % in patients with a PP prosthesis (p = 0.06). The average time until clinical diagnosis of a prosthesis-related complication was identical for both groups: 31 months (range 3-62 months). All patients underwent surgical removal of the prosthesis: For the five patients from the PE group, complete removal was performed by laparoscopy associated with a transanal procedure. For the two patients in the PP mesh group, laparoscopy was ineffective in removing the mesh which was partially removed through a subsequent transanal procedure. None of the patients had a protective stoma, and in all patients the complication had resolved 12 months after removal. Only one patient had worsening functional symptoms (fecal incontinence) after prosthesis removal. CONCLUSIONS: When a prosthesis-related infection or erosion occurs, treatment consists in the surgical removal of the prosthesis by laparoscopy/and/or a transanal procedure. Functional symptoms do not routinely recur after prosthesis removal.

Decentralising tuberculosis case management in two districts of Burkina Faso.

SETTING: In West Africa, national tuberculosis programmes (NTPs) face many problems due to the low performance of health care delivery systems and patients' social and cultural environment. OBJECTIVE: To improve the case management of TB in Burkina Faso. DESIGN: Using the operational research process as a tool, TB case management was decentralised from the district hospital to eight primary health care centres in 2003. RESULTS: Twelve months after decentralisation, the quality of case detection remained satisfactory. The delay between the identification of TB suspects with chronic cough and the confirmation of TB was reduced from 13 to 6 days. The detection rate of TB suspects during the study (30%) was twice as high as for 2001 and 2002 (15%). However, the detection rate for smear-positive TB cases decreased from 32.3% in 2001 and 2002 to 6.5% during the year of the study. CONCLUSION: Sufficient time and commitment are essential to obtain a case management system that is decentralised and effective. Efforts therefore need to continue to obtain more information and better results.

C-peptide, Na+,K(+)-ATPase, and diabetes.

Na+,K(+)-ATPase is an ubiquitous membrane enzyme that allows the extrusion of three sodium ions from the cell and two potassium ions from the extracellular fluid. Its activity is decreased in many tissues of streptozotocin-induced diabetic animals. This impairment could be at least partly responsible for the development of diabetic complications. Na+,K(+)-ATPase activity is decreased in the red blood cell membranes of type 1 diabetic individuals, irrespective of the degree of diabetic control. It is less impaired or even normal in those of type 2 diabetic patients. The authors have shown that in the red blood cells of type 2 diabetic patients, Na+,K(+)-ATPase activity was strongly related to blood C-peptide levels in non-insulin-treated patients (in whom C-peptide concentration reflects that of insulin) as well as in insulin-treated patients. Furthermore, a gene-environment relationship has been observed. The alpha-1 isoform of the enzyme predominant in red blood cells and nerve tissue is encoded by the ATP1A1 gene. A polymorphism in the intron 1 of this gene is associated with lower enzyme activity in patients with C-peptide deficiency either with type 1 or type 2 diabetes, but not in normal individuals. There are several lines of evidence for a low C-peptide level being responsible for low Na+,K(+)-ATPase activity in the red blood cells. Short-term C-peptide infusion to type 1 diabetic patients restores normal Na+,K(+)-ATPase activity. Islet transplantation, which restores endogenous C-peptide secretion, enhances Na+,K(+)-ATPase activity proportionally to the rise in C-peptide. This C-peptide effect is not indirect. In fact, incubation of diabetic red blood cells with C-peptide at physiological concentration leads to an increase of Na+,K(+)-ATPase activity. In isolated proximal tubules of rats or in the medullary thick ascending limb of the kidney, C-peptide stimulates in a dose-dependent manner Na+,K(+)-ATPase activity. This impairment in Na+,K(+)-ATPase activity, mainly secondary to the lack of C-peptide, plays probably a role in the development of diabetic complications. Arguments have been developed showing that the diabetes-induced decrease in Na+,K(+)-ATPase activity compromises microvascular blood flow by two mechanisms: by affecting microvascular regulation and by decreasing red blood cell deformability, which leads to an increase in blood viscosity. C-peptide infusion restores red blood cell deformability and microvascular blood flow concomitantly with Na+,K(+)-ATPase activity. The defect in ATPase is strongly related to diabetic neuropathy. Patients with neuropathy have lower ATPase activity than those without. The diabetes-induced impairment in Na+,K(+)-ATPase activity is identical in red blood cells and neural tissue. Red blood cell ATPase activity is related to nerve conduction velocity in the peroneal and the tibial nerve of diabetic patients. C-peptide infusion to diabetic rats increases endoneural ATPase activity in rat. Because the defect in Na+,K(+)-ATPase activity is also probably involved in the development of diabetic nephropathy and cardiomyopathy, physiological C-peptide infusion could be beneficial for the prevention of diabetic complications.

[Genetics of diabetic complications: peripheral neuropathy]. / Génétique des complications du diabète: neuropathie périphérique.

Diabetic neuropathy is a common complication of type 1 and 2 diabetes mellitus. Chronic hyperglycaemia and/or insulin deficiency in the peripheral nerve lead to metabolic and vascular disturbances, responsible for the functional alterations and the characteristic histological abnormalities observed in the nerve fibre. Recently, genetic factors have been described, suggestive of a predisposition and/or a protective effect for diabetic neuropathy in certain patients. The search for these genetic factors through the study of polymorphism of gene involved in the various metabolic and vascular pathways, is currently increasing, but with contradictory results. The main studies and data are reviewed in this Article. The identification of candidate-genes should allowed, in the future, to better identify and manage diabetic patients at-risk for peripheral neuropathy.

Physicochemical properties of lipids: new strategies to manage fatty acid bioavailability.

Fatty acid bioavailability can be managed through the physicochemical properties of lipid such as lipid-droplet size, lipid-droplet ultrastructure (lipids organization between core and surface), structure of triglycerides and of phospholipids. The lipid-droplet size exhibits a major effect on lipase activity during lipid digestion. The lipid-droplet ultrastructure is a dynamic factor controling lipase interaction at the lipid interface via the surface phospholipid layer, and also lipase activity via the proportion of triglyceride molecules able to locate at the surface. Triglyceride structure affects in a strong manner digestion, absorption and fatty acid metabolism. Finally, optimal fatty acid transport to specific tissues is dependent on the vehicle molecule (triglyceride or ethyl ester or phospholipid). All these aspects provide convincing support for the possibility of using biotechnologically remodeled lipids with specific physicochemical properties for health benefits.

Peripheral diabetic neuropathy and polyunsaturated fatty acid supplementations: natural sources or biotechnological needs?

The two essential fatty acids linoleic and alpha-linolenic acids, precursors of the n-6 and n-3 PUFA family, respectively, are known to play a strong regulatory function on cells via their incorporation into membrane phospholipids, and also on microcirculation by the production of eicosanoids. Moreover, diabetes mellitus induces impairment in PUFA metabolism due to an inhibition of desaturases, the enzymes involved in their synthesis. The decrease in PUFA bioavailability will conduct to marked alterations in membranes as well as impairment of the microcirculation. Those metabolic perturbations are involved in part in the degenerative complications of diabetes such as neuropathy. Nutritional supplementations with PUFA have given very interesting results in experimental diabetic neuropathy but also in human diabetic neuropathy. The gamma linolenic and arachidonic acids, members of the n-6 family, prevent the physiological abnormalities associated to neuropathy. The results obtained with the n-3 family PUFA are more discordant, probably because of the simultaneous use of eicosapentaenoic and docosahexaenoic acids. Nevertheless, the use of docosahexaenoic acid-enriched phospholipids produced positive results in the treatment of experimental diabetic neuropathy. These PUFA are available from natural sources but a biotechnological demand exists to provide these PUFA in different structural forms.

Dose dependent accretion of docosahexaenoic acid (DHA) in cardiac membranes of rats fed egg yolk powder enriched in DHA.

We tested the hypothesis that enrichment of the diet with docosahexaenoic acid (DHA) enriched egg yolk powder could modify specifically the (n-3) fatty acids content of rat plasma, red blood cells and heart membranes. Dose-dependent effect of DHA was studied in rats supplemented during 4 weeks. Three groups of adult male rats, DHA10, DHA35 and DHA60 (n = 5 each), had their diet supplemented with 10 mg, 35 mg or 60 mg DHA/kg body weight/day, respectively. Fatty acid composition of membranes and plasma lipids were determined. A significant dose-dependent increase in DHA was observed in all three types of samples. Arachidonic acid (AA) levels did not change in heart and red blood cell membranes whereas it increased significantly in plasma with the DHA35 diet. These results contrast with that previously reported for fish oil supplementation where a decrease in AA levels was reported. Hence, DHA enriched egg yolk supplementation leads to a specific accretion of DHA without competition on AA status.

Docosahexaenoic acid-enriched egg phospholipids supplementation induces accretion of arachidonic acid in rat blood lipids.

Animal and humans studies have shown that supplementation with triacylglycerides containing omega3 fatty acids, mainly docosahexaenoic acid (DHA) and eicosapentaenoic acid, can induce a decrease in arachidonic acid (AA) in blood lipids. Interestingly, we observed in a previous work that a supplementation with DHA enriched eggs in a healthy elderly population induced an accretion of AA in their blood lipids. The present study investigates whether purified DHA enriched egg phospholipids could be responsible for this effect. Four groups of rats were supplemented daily, for eight weeks, with DHA phospholipids (10, 30 or 60 mg/kg) or with soybean phospholipids. Red blood cell membranes and plasma fatty acid levels were compared with that of rats without supplementation. Soybean phospholipids supplementation increased the level of AA in blood lipids but decreased that of DHA. The doses of DHA phospholipids, 30 and 60 mg/kg, induced greater amounts of AA without affecting significantly DHA levels. In contrast, DHA phospholipids supplementation, 10 mg/kg, in which there was the greatest amount of AA, induced only a slight increase in AA levels. Moreover, DHA levels were decreased by this supplementation. These results demonstrate that specific increases in AA levels are preferentially associated with DHA phospholipids levels in supplementation.

Differential effect of omega3 PUFA supplementations on Na,K-ATPase and Mg-ATPase activities: possible role of the membrane omega6/omega3 ratio.

Several functional properties of Na,K-ATPase are strongly dependent on membrane fatty acid composition, but the underlying mechanism is still not well defined. We have studied the effects of two types of supplementations enriched in the w3 polyunsaturated fatty acids on the Na,K-ATPase and Mg-ATPase activities in sciatic nerve (SN) and red blood cells (RBC). Eight groups of rats, controls and diabetics, received a standard diet, supplemented or not with 30 or 60 mg/kg/day of docosahexaenoic acid (DHA) or with soybean for eight weeks. Diabetes induced significant decrease of Na,K-ATPase activity in SN (-23%) and RBC (-25%), without affecting Mg-ATPase activity. In RBC, soybean and DHA supplementations caused significant increases in Na,K-ATPase activity (in various range, +13% to +145%) in all groups, and in Mg-ATPase activity in control soybean (+65%), control and diabetic DHA high dose (+39%, +53%) and diabetic DHA low dose (+131%) groups. In SN, the soybean caused a significant decrease in Na,K-ATPase activity (-26%) and still more in the diabetic group (-53%). The DHA diet induced a slight decrease in activity in control groups, whilst during diabetes, at high dose, we noted an aggravation of this decrease (-36%). Mg-ATPase activity was not modified by supplementations except for the low dose of DHA where the activity was slightly decreased in the control group (-16%). The supplementations induced multiple tissue-specific modifications in the membrane fatty acid composition of RBC and of SN homogenates. Several specific correlations have been found between variations in fatty acids amounts and Na,K-ATPase activity in these tissues but only in RBC for Mg-ATPase activity. Indeed, we observed that the variations in Na,K-ATPase activity are positively and significantly correlated with changes in the omega6/omega3 ratio in SN as well as in RBC. These data clearly show, for the first time, that the diet could modulate the Na,K-ATPase activity via the omega6/omega3 ratio in the membranes. A similar correlation was observed with Mg-ATPase activity in RBC, suggesting also a dietary regulation of the enzyme; but for the SN, this activity might be regulated by a different omega6/omega3 ratio or by another pathway.

Genetic and environmental regulation of Na/K adenosine triphosphatase activity in diabetic patients.

Even if the pathogenesis of diabetic neuropathy is incompletely understood, an impaired Na/K adenosine triphosphatase (ATPase) activity has been involved in this pathogenesis. We previously showed that a restriction fragment length polymorphism (RFLP) of the ATP1-A1 gene encoding for the Na/K ATPase's alpha 1 isoform is associated with a low Na/K ATPase activity in the red blood cells (RBCs) of type 1 diabetic patients. We thus suggested that the presence of the variant of the ATP1A1 gene is a predisposing factor for diabetic neuropathy, with a 6.5% relative risk. Furthermore, there is experimental evidence showing that lack of C-peptide impairs Na/K ATPase activity, and that this activity is positively correlated with C-peptide level. The aim of this study was to evaluate the respective influence of genetic (ATP1-A1 polymorphism) and environmental (lack of C-peptide) factors on RBC's Na/K ATPase activity. Healthy and diabetic European and North African subjects were studied. North Africans were studied because there is a high prevalence and severity of neuropathy in this diabetic population, and ethnic differences in RBC's Na/K ATPase activity are described. In Europeans, Na/K ATPase activity was significantly lower in type 1 (285 +/- 8 nmol Pi/mg protein/h) than in type 2 diabetic patients (335 +/- 13 nmol Pi/mg protein/h) or healthy subjects (395 +/- 9 nmol Pi/mg protein/h). Among type 2 diabetic patients, there was a significant correlation between RBC's Na/K ATPase activity and fasting plasma C-peptide level (r = 0.32, P <.05). In North Africans, we confirm the ethnic RBC's Na/K ATPase activity decrease in healthy subjects (296 +/- 26 v 395 +/- 9 nmol Pi/mg protein/h, r < 0.05), as well as in type 1 diabetic patients (246 +/- 20 v 285 +/- 8 nmol Pi/mg protein/h; P <.05). However, there is no relationship between the ATP1A1 gene polymorphism and Na/K ATPase activity. ATP1A1 gene polymorphism could not explain the ethnic difference. We previously showed that Na/K ATPase activity is higher in type 1 diabetic patients without the restriction site on ATP1A1 than in those heterozygous for the restriction site. This fact was not observed in healthy subjects. In type 2 diabetic patients, association between ATP1A1 gene polymorphism and decreased enzyme activity was found only in patients with a low C-peptide level. Therefore, the ATP1-A1 gene polymorphism influences Na/K ATPase activity only in case of complete or partial C-peptide deficiency, as observed in type 1 and some type 2 diabetic patients, without any correlation with hemoglobin A1c (HbA1c). Correlation observed between C-peptide levels and RBC's Na/K ATPase suggests that the deleterious effect of C peptide deficiency on Na/K ATPase activity is worse in the presence of the restriction site. This may explain the high relative risk of developing the neuropathy observed in type 1 diabetic patients bearing the variant allele.

Gamma-linolenic acid restores renal medullary thick ascending limb Na(+),K(+)-ATPase activity in diabetic rats.

In diabetes, the activity of Delta-6 desaturase, which converts linoleic acid (LA) into gamma-linolenic acid (GLA), the first step of arachidonic acid (AA) synthesis, is decreased, leading to alterations in membrane phospholipid composition. On the other hand, 12 wk after the onset of diabetes, Na(+),K(+)-ATPase activity is reduced in many organs, including the kidney. The medullary thick ascending limb (MTAL) reduced Na(+),K(+)-ATPase activity, whereas the sodium load secondary to glomerular hyperfiltration was increased. The aim of our study was to examine whether the changes in membrane fatty acid composition resulting from the inhibition of Delta-6 desaturase may be involved in the decreased Na(+),K(+)-ATPase activity observed in the outer MTAL after 12 wk of diabetes. GLA is a fatty acid that by-passes the Delta-6 desaturase step. We measured the membrane fatty acid composition and the Na(+),K(+)-ATPase activity in the renal outer medulla of control and streptozotocin (STZ)-induced diabetic rats 12 wk after the induction of diabetes. Measurements were performed after supplementation of control rats with sunflower oil (SO) or GLA for 12 wk, and supplementation of 12 wk diabetic rats with SO for 12 wk or with GLA for 6 or 12 wk. Supplementation with GLA not only prevented the decrease in Na(+),K(+)-ATPase activity observed after 12 wk of diabetes but also time dependently stimulated Na(+),K(+)-ATPase activity in the outer medulla. The changes in Na(+),K(+)-ATPase activity were related to parallel changes in the amount of Na(+),K(+)-ATPase alpha(1) subunit protein. In addition, in diabetic rats only, Na(+),K(+)-ATPase activity was positively correlated with the amount of AA present in cell membranes (r = 0.92, P < 0.05). Our results indicate that nutritional GLA supplementation increases Na(+),K(+)-ATPase activity and expression in diabetic rats. In addition, the positive correlation between AA content and Na(+),K(+)-ATPase activity suggests that in diabetic rats, alterations in membrane fatty acid composition contribute to the decreased Na(+),K(+)-ATPase activity in outer medulla.

APACC, a French prospective study on aspirin efficacy in reducing colorectal adenoma recurrence: design and baseline findings.

UNLABELLED: Colorectal cancer is the second most frequent cause of death from cancer in western countries. Many lines of evidence suggest that non-steroidal anti-inflammatory drugs (NSAIDs) may offer chemoprevention against colorectal cancer. A multicentre, double-blind, randomized, controlled trial is underway to determine the efficacy of regular aspirin intake (160 or 300 mg/day) in reducing colorectal adenoma recurrence. We now report the baseline characteristics of subjects enrolled into the trial. RESULTS: A total of 618 polyps were excised from 274 patients at the baseline colonoscopy. Men had on average (+/-SD) 2.5 +/- 1.8 polyps per subject and women had 1.7 +/- 1.2. Ninety-one (33.7%) had three or more adenomas and 183 (67.8%) had more than one adenoma measuring 10 mm or more in diameter. The mean (+/-SD) age of the subjects was 57.7 (+/- 9.4) years. Sixty-seven (24.9%) reported that they had previously had adenoma(s), 95 (35.2%) reported a family history of colorectal cancer and 41 (15.2%) a family history of colorectal adenomas. PERSPECTIVE: All subjects will undergo a one-year clearance colonoscopy by February 2001. Clinical, molecular biological and dietary data will enable us to investigate other factors influencing the recurrence of adenomas in this group of high-risk subjects.

Evidence of time-dependent changes in renal medullary Na,K-ATPase activity and expression in diabetic rats.

The medullary thick ascending limb (MTAL) of the kidney displays structural changes during long term diabetes. After twelve weeks of diabetes, there is controversy over the changes in Na,K-ATPase activity. To observe the long-term changes, we studied MTAL Na,K-ATPase activity and protein expression in diabetic animals 6 (6W) and 12 weeks (12W) after induction of diabetes with streptozotocin. Three groups were studied, one control group, one group 6W after, and one group 12W after induction of diabetes. Membrane fractions from the inner strip of the outer medulla representing MTAL were isolated. Na,K-ATPase activity and western blottings of alpha1- and beta1-subunits were carried out. 6W diabetes resulted in an increase, and 12W in a decrease in the MTAL Na,K-ATPase activity versus the control group (respectively 63.3 +/- 21.2; 7.5 +/- 2.4 and 31.6 +/- 11.4; micromol Pi/mg prot/hr +/- SEM). The Na,K-ATPase subunit expression was increased at 6W, and decreased after 12W, resulting in amounts below control values for both alpha1- and beta1-subunits. Our results confirm a diabetes-induced biphasic time-dependent alteration MTAL Na,K-ATPase activity, supported by similar changes in alpha1 and beta1 Na,K-ATPase subunits-expression.

Na,K-atpase alterations in diabetic rats: relationship with lipid metabolism and nerve physiological parameters.

Type 1 diabetes induces several metabolic and biochemical disturbances which result in the alteration ofNa,K-ATPase, an enzyme implicated in the physiopathology of neuropathy Several fatty acid supplementations lessen this alteration. The aims of this study were to determine the possible relationships between Na,K-ATPase activity in nerves and red blood cells (RBCs) and, on one hand, the fatty acid alterations induced by diabetes in these tissues and plasma and on the other, on nerve physiological parameters. Two groups of rats, control and diabetic (n = 15), were sacrified 8 weeks after induction of diabetes with streptozotocin. Nerve conduction velocity (NCV), nerve blood flow (NBF), Na,K-ATPase activity and membrane fatty acid composition of sciatic nerves, red blood cells (RBCs) and plasma were measured. NCV, NBF and Na,K-ATPase activity in RBCs and in sciatic nerves were significantly decreased in diabetic rats. We revealed a positive correlation between Na,K-ATPase activity in sciatic nerves and both NBF and NCV and between Na,K-ATPase activity in RBCs and NBF and the same activity in sciatic nerve. Diabetes induced major changes in plasma fatty acids and RBC membranes and less important changes in sciatic nerve membranes. Na,K-ATPase activity correlated negatively with C20: 4 (n-6) and C22: 4 (n-6) levels in nerves and with C18: 2 (n-6) levels in RBCs. During diabetes, changes in the membrane fatty acid composition suggest the existence of a tissue-specific regulation, and the decrease in Na,K-ATPase activity correlates with the alteration in the level of specific fatty acids in RBCs and sciatic nerves. Modifications in the lipidic environment of Na,K-ATPase would be involved in the alteration of its activity. Na,K-ATPase activity seems to be implicated in the decrease of both NCV and NBF during diabetes.

[Hepatitis C virus contamination of endoscopes and biopsy forceps]. / Contamination des endoscopes et des pinces à biopsies par le virus de l'hépatite C.

BACKGROUND: Procedures such as digestive endoscopy may explain some unclear contaminations by HCV. AIMS: The aims of this study were to detect HCV genome on endoscopes and biopsy-forceps used in patients with known chronic HCV infection and to determine its presence in their gastric juice and saliva. METHODS: A gastroscopy with antral biopsies was performed in 48 patients with non-treated replicative chronic hepatitis C. Samples were obtained after pushing 10 mL of sterile water through the biopsy-suction channel and after immersing the brush used to clean this channel. The biopsy-forceps were also immersed and their tips brushed in 10 mL of sterile water. This sampling technique was repeated three times: immediately after the endoscopic procedure (T0), after washing with a detergent (T1) and after immersion for 20 minutes in a 2% glutaraldehyde solution (T2). The HCV genome was detected by polymerase chain reaction (PCR, Amplicor - Roche Diagnostics Systems). For the last 15 patients, samples of gastric juice and saliva were obtained before antral biopsies and used to detect HCV genome. RESULTS: HCV genome was detected in the biopsy-suction channel in 13 cases (27%) at T0 and in one case (2%) at T1. It was undetectable after completion of the disinfection procedure (T2). Three biopsy-forceps (6%) were PCR positive immediately after the endoscopy but none at T1 and T2. HCV genome was found in the gastric juice in three cases. In all of them, it was also found at T0 in the biopsy-suction channel but not on the biopsy-forceps. When saliva contained HCV genome (4 cases), it was present in the biopsy-suction channel in only one case. In this case, the gastric juice was also PCR positive. CONCLUSIONS: HCV genome is detected in 27% of cases in the biopsy-suction channel after an endoscopic procedure performed on patients with chronic HCV infection. The biopsy-forceps are PCR positive in 6% of cases. The infected gastric juice may play a role in the contamination of the endoscopes. The complete disinfection procedure seems effective to eliminate HCV.