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Biomedical subjects

S Benchetrit

Publications and source records attributed to S Benchetrit.

At least 19 recordsLinked to original sources

Somatostatin treatment attenuates proteinuria and prevents weight loss in NZB/W F1 mice.

Somatostatin, a naturally occurring neuropeptide, is an immunomodulator which inhibits humoral and cell mediated immunity as well as secretion of proinflammatory cytokines. The objective of this study was to examine the effects of a somatostatin analogue on the severity of glomerulonephritis in the female NZB/W F1 murine model of systemic lupus erythematosus (SLE). Twenty female NZB/W F1 mice were treated at 23 weeks of age with 10 mg/kg of the somatostatin analogue Sandostatin- LAR, IM every four weeks. Ten control mice received IM injection of vehicle. Mice were assessed at four-week intervals for weight change, proteinuria, anti-DNA antibodies and splenocyte cytokine profile. The mice were sacrificed at age 34.5 weeks. Kidneys were collected and evaluated by light and immunofluorescence (IF) microscopy. Spleens were collected and splenocyte intracellular cytokines were measured by FACS analysis. In the treatment group significantly less proteinuria was observed four weeks after the second somatostatin analogue injection (dipstik scale: +2.07 +/- 0.95 versus. +3.5 +/- 1.08, P = 0.0002). The treated mice did not lose weight while the control group lost weight over time (P = 0.016). No differences were noted between the groups in anti-DNA antibody titres, cytokine profile or the severity of lupus nephritis as assessed by light and IF microscopy. Somatostatin analogue treatment attenuated proteinuria and prevented weight loss in NZB/W F1 mice, suggesting a possible beneficial effect on renal parameters and systemic manifestations of the disease. Further studies will be needed to assess the value of somatostatin analogue treatment in lupus nephritis, utilizing higher doses, at different stages of the disease, for longer periods.

Animals↗

Intraperitoneal treatment of incisional and umbilical hernias using an innovative composite mesh: four-year results of a prospective multicenter clinical trial.

Intraperitoneal positioning of conventional parietal mesh provides efficient reconstruction but causes visceral adhesion formation in 80-100% of the cases. The purpose of this clinical trial was to assess the performance and tolerance of a new generation of polyester mesh protected by a hydrophilic resorbable film. Eighty patients were included in a prospective multicenter clinical trial. Patients were treated for ventral hernia via an open approach (64%) or laparoscopically (36%). All meshes were implanted in a midline intraperitoneal location. The main objective was to evaluate the anti-adhesive capability of the mesh in relation to the viscera. In order to assess the absence of visceral adhesion objectively, an ultrasound (US) specific examination was initially validated (pre-operative prediction vs. per-operative findings) and then used during the follow-up. The usual clinical parameters were also collected to follow the patients on a period up to 4 years. Pre-operative US prediction vs. per-operative macroscopic findings: sensitivity 79%, overall accuracy 76%, negative predictive value 85%. After 12 months, 86% of the patients were ultrasonically adhesion free. Early post-operative complications were: seroma/hematoma (16%), subcutaneous infection (4%), cutaneous necrosis (1%) and occlusions (outside the mesh) (2.5%). No mortality was reported. Clinically, after 12-month follow-up, no complication related to post-operative adhesions to the mesh was noted: (occlusion 0%, fistula 0%). Late complications were: mesh sepsis (1%), new defects (4%) and recurrence (2.5%). Finally, 56 patients (75.7%) were clinically evaluated with a mean follow-up of 48+/-6 months. One direct recurrence was noted while six patients experienced new defect outside the mesh. No long-term severe complication such as occlusion or enterocutaneous fistula was observed. Based on a mean clinical follow-up of 4 years, the results of this prospective multicenter clinical trial demonstrate the safety and the efficiency of this composite mesh in the intraperitoneal treatment of incisional and umbilical hernia. In particular there was no early or long-term main complication due to the intraperitoneal location of the mesh.

Cicatrix↗

Early endothelial dysfunction following renal mass reduction in rats.

BACKGROUND: Endothelial dysfunction has been previously described in severely hypertensive rats with renal mass reduction (RMR) receiving large dietary Na loads. Because hypertension and Na loading reduce endothelium-dependent vasodilation, the effect of renal failure per se is unclear. METHODS: Responses to acetylcholine in noradrenaline-contracted isolated perfused mesenteric arteries were studied. Vessels were obtained from RMR rats kept on a normal diet, 3 and 10 days after surgery, and the results were compared with those from sham-operated rats (SN). The role of three putative mediators of endothelium-dependent vasodilation was assessed using: L-NAME (10(-4) mol L(-1)); indomethacin (INDO, 10(-5) mol L(-1)); and a mixture of charybdotoxin and apamin (C/A, both 10(-7) mol L(-1)), inhibitors of Ca-activated K-channels to mediate the effects of endothelium-derived hyperpolarizing factor (EDHF). RESULTS: Response to acetylcholine but not that to nitroprusside (endothelium-independent) was decreased in RMR. L-NAME reduced further acetylcholine relaxations in SN but not in RMR. By contrary, INDO decreased acetylcholine vasodilation in RMR but had no effect in SN. C/A had similar effects in the SN and RMR rats. The levels of 6-keto prostaglandin F1alpha were elevated in the urine of the RMR rats and were perfusate from the RMR vessels. CONCLUSION: Endothelial dysfunction occurs early after RMR, even when systolic blood pressure is only minimally elevated and Na intake is normal. This alteration may be because of decreased availability of nitric oxide, partially compensated by increased prostacyclin production.

6-Ketoprostaglandin F1 alpha↗

Low molecular weight heparin reduces proteinuria and modulates glomerular TNF-alpha production in the early phase of adriamycin nephropathy.

BACKGROUND/AIM: Heparin has been shown to be renoprotective in a number of experimental nephropathies. The inflammatory component in the early phase of Adriamycin (ADR) induced nephropathy has been established. A microdose of low molecular weight heparin (Fragmin; F) has been noted to exert immunomodulatory effects independent of its anticoagulant activity. We assessed the effects of microdoses of F on daily proteinuria and glomerular production of tumor necrosis factor alpha (TNF-alpha) and prostaglandins 8 and 15 days after induction of ADR nephropathy. METHODS: Following intravenous injection of ADR (7 mg/kg) to Wistar rats weighing 200 +/- 20 g, F 20 microg/day/rat s.c. was administered for 8 and 15 days (groups F8 and F15). The respective control groups (C8 and C15) received normal saline subcutaneously. Proteinuria, serum albumin, and creatinine clearance were evaluated on days 8 and 15. The production of TNF-alpha and prostaglandins from glomerular supernatants was measured by radioimmunoassay on days 8 and 15. RESULTS: F significantly reduced proteinuria (mg/day) on day 8: 13.6 +/- 1.2 in F8 versus 40.3 +/- 2.7 in C8 (p = 0.008). The glomerular production of TNF-alpha (pi/ml) was significantly lower on day 8 in rats treated with F: 356 +/- 33 in F8 versus 764 +/- 81 in C8 (p = 0.006). A decrease in the prostaglandin E2/thromboxane B2 ratio was noted in the F group between 8 and 15 days (1.1 in F8 vs. 0.9 in F15, p = 0.005) which principally reflects an increase of thromboxane B2. The antiproteinuric effect of F shown after 8 days was no longer present after 15 days (354 +/- 91 mg/day in F15 vs. 499 +/- 69 mg/day in C15, p = 0.33). The same trend was seen for the glomerular production of TNF-alpha. Light microscopy and immunohistochemistry for interstitial and glomerular macrophages were negative. CONCLUSION: The lowering effect of microdoses of F on the proteinuria seen during the early phase of ADR nephropathy may be mediated by a decreased production of glomerular TNF-alpha, supporting the anti-inflammatory action of low molecular weight heparin.

Animals↗

Effect of methyldopa on renal function in rats with L-NAME-induced hypertension in pregnancy.

BACKGROUND: Pregnancy-induced hypertension is characterized by an increased sympathetic activity and probably by a decreased synthesis/activity of nitric oxide. The aim of the present study is to evaluate whether the beneficial action of the sympathetic antagonist methyldopa (a first-choice hypotensive agent in the treatment of PIH) may be associated to changes in nitric-oxide synthesis. METHODS: Forty pregnant Wistar rats received L-NAME (NO synthase inhibitor, 9-10 mg/kg/day) from mid-pregnancy (day 11) through to term. Some rats were treated with daltroban (TxA receptor antagonist, 60 mg/kg/day), diltiazem (calcium channel blocker, 30 mg/kg/day), methyldopa (central adrenergic antagonist, 400 mg/kg/day) or L-arginine (260 mg/kg/day) from mid-pregnancy. The effect of the different treatments on systolic blood pressure (SBP), creatinine clearance (CCR), urine protein excretion (UP) and urinary nitrate excretion (UNO(3), representing urine NO metabolite) were evaluated and the results compared with those found in normal pregnancy. Normal pregnant rats receiving similar treatment were used as controls. RESULTS: In normal pregnant (P) rats, SBP values decreased from 94 +/- 2 to 83 +/- 3 mm Hg at the end of pregnancy (p < 0.01) and CCR augmented significantly. Drug treatment had no significant effect. In NAME-treated rats, at the same period, the SBP augmented from 92 +/- 1 to 129 +/- 1.8 mm Hg (p < 0.01). At the end of pregnancy, NAME rats had significantly lower CCR values and higher UP excretion when compared with P rats. UNO(3) increased significantly in P and in P rats treated with methyldopa. As expected, in NAME rats UNO(3) excretion was significantly reduced. Treatment with methyldopa normalized SBP, improved CCR and proteinuria and was associated with an increase in UNO(3). Similar results were obtained with L-arginine treatment. Diltiazem lowered SBP significantly but had no effect on renal function or UNO(3) and daltroban had no effect. CONCLUSION: The increased UNO(3) found in NAME rats treated with methyldopa suggests that the vasoconstriction secondary to chronic NO inhibition may be partially related to an increased sympathetic activity. The efficient action of the sympathetic antagonist methyldopa may be due not only to its antihypertensive effects but also by its stimulating effect on NO synthesis leading also to an improvement of renal function.

Animals↗

Laparoscopic gastric banding with Lap-Band for morbid obesity: two-step technique may improve outcome.

BACKGROUND: Laparoscopic placement of an adjustable gastric band is an attractive alternative for patients who can benefit from a restrictive bariatric procedure. Creation of the retrogastric tunnel (RGT) may, however, be a considerable challenge early in the surgeon's learning curve. Recent reports described up to 10% band slippage and occasional gastric perforation associated with RGT. The two-step (TS) technique involves a crural dissection towards the angle of His through a gastrohepatic ligament approach. It facilitates passage of the band's tubing posteriorly with no wide posterior gastric wall dissection. PATIENTS AND METHODS: Prospective data were registered for the 109 patients (92 females, 17 males) who underwent laparoscopic adjustable gastric banding from December 1998 to May 2000. In 11 patients the standard RGT approach was used, and in 98, the TS technique. The two groups were demographically similar. Mean age was 37 years (18-59); mean preoperative weight was 120 kg (90-165). RESULTS: All procedures were completed laparoscopically. The mean operative time was 59 minutes (31-150) and the mean hospital stay 1.2 days (1-5). Complications in the TS group were gastric wall hematoma in one patient, 3 days of intubation postoperatively in one patient, damage to a band demonstrated in a postoperative contrast study in one patient, and a port-site hernia in one patient. There was no band slippage in the TS group. Among the 11 patients undergoing RGT, there was band slippage in three (27%), immediately postoperatively in one and after 3 and 11 months in the other two. In a mean follow-up of 7 months (1-18), similar weight loss was found in both groups. The mean BMI decreased from 44 kg/m2 (36-61) preoperatively to 40, 38, 36, 34 kg/m2 at 1, 3, 6 and 9 months respectively. 52 patients required band adjustment; of these, 12 required two adjustments. CONCLUSION: Our experience with both the RGT and TS techniques indicates that the latter may offer better results, particularly in the early experience period. It is recommended that in their initial experience with the adjustable band, surgeons should become familiar with this approach.

Adolescent↗

Chronic exogenous hyperinsulinaemia-induced hypertension in pregnant rats: effect of chronic treatment with l-arginine.

Recent studies have shown that maternal hyperinsulinaemia is a risk factor for the development of hypertension in pregnancy. Experimentally, pregnant rats with chronic exogenously induced hyperinsulinaemia (P-INS rats) have increased blood pressure at the end of gestation. This is associated with a blunted elevation of the excretion of the urinary metabolites of nitrate (UNO(x)). In the present study, we aimed to evaluate the mechanism(s) of the increase in blood pressure in this model. Four groups were studied: normal pregnant rats (P rats), P-INS rats, P-INS rats treated with L-arginine (2 g/l in the drinking water) (L-ARG rats) and hyperinsulinaemic virgin rats (V-INS rats). Systolic blood pressure (SBP), UNO(x) excretion (on ingestion of a controlled low-nitrate diet), urine noradrenaline (norepinephrine) and plasma endothelin levels were evaluated. Rats were killed on day 22 of pregnancy. Five P-INS rats were not killed at this time, in order to measure SBP 30 and 60 days after delivery. Fetal number and fetal body weight were evaluated. At the end of pregnancy, a 10+/-3% increase in SBP was found in P-INS rats, contrasting with a fall of -15+/-4% in P rats (P<0.01). In the L-ARG group at the end of pregnancy, SBP values had fallen by -14+/-2%, to values comparable with those of P rats. The increase in UNO(x) excretion was 175+/-38% in P rats, 106+/-12% in L-ARG rats and 41+/-8% in P-INS rats (P<0.01 compared with P and L-ARG groups). No differences were found in the urinary excretion of noradrenaline or in the plasma levels of endothelin-1 between the pregnant groups. Fetal number was similar in all groups, but fetal body weight was lower for P-INS rats compared with P and L-ARG rats. Thus the blood pressure response to L-arginine strongly suggests that a decrease in NO availability may be the main pathogenic mechanism involved in the development of hypertension in this model.

Animals↗

Altered vascular reactivity following partial nephrectomy in the rat: a possible mechanism of the blood-pressure-lowering effect of heparin.

BACKGROUND: This study was designed to assess whether the antihypertensive effect of heparin in rats after renal mass reduction (RMR) is related to changes in nitric oxide activity, and to study in vitro the altered behaviour of resistance-sized arteries induced by chronic administration of heparin. METHODS: Male Wistar rats were assigned to one of two experimental protocols. In the first protocol, RMR rats received heparin (250 units/day s.c.) and tail systolic blood pressure (SBP) was measured weekly for 4 weeks. In a subgroup, urinary nitrate excretion (UNO3) and in vitro vascular reactivity of isolated perfused mesenteric arterial beds were measured 2 weeks after RMR. The second protocol assessed whether inhibition of NO synthesis with L-NAME (70 mg/l added to the drinking water) prevents the blood-pressure-lowering effect of heparin. RESULTS: In untreated RMR rats SBP increased from 111+/-3 mmHg to 127+/-5 mmHg at 2 weeks and 139+/-5 mmHg at 4 weeks. In contrast, in RMR rats treated with heparin, SBP was 114 +/-3 mmHg at 2 weeks and 115+/-4 mmHg at 4 weeks (P<0.05 for both). Treatment with L-NAME increased SBP both in untreated and heparin-treated RMR groups. Two weeks after nephrectomy daily urinary nitrate increased significantly more in RMR rats treated with heparin than in untreated RMR rats (22+/-2 vs 14.2+/-2.3 micromol/day, P<0.05). In vitro studies performed at 2 weeks showed that vessels of untreated RMR rats had a blunted vasodilator response to acetylcholine that was restored to levels similar to that of controls in the heparin-treated group. CONCLUSIONS: These results suggest that, in rats after renal ablation, heparin may exert its antihypertensive effect, at least in part, by affecting the altered behaviour of resistance vessels during the development phase of hypertension. Increased NO production may contribute to this effect.

Animals↗

[Time off of work after inguinal hernia repair. Results of a multicenter prospective study].

A multicentre prospective study was conducted to evaluate the effective duration of time off work following inguinal hernia repair. From 1st October to 30 November 1997, 14 surgeons repaired 459 hernias in 359 patients, corresponding to 28.8% of salaried workers, 10.9% self-employed and 4.8% civil servants. 46% of patients were retired. Only 6.9% of patients were treated by reconstruction of the inguinal floor without mesh, 59.6% were operated by laparoscopy and a conventional prosthesis repair was performed in 33.2%. There were 0.6% of complications or modifications of the postoperative course. The mean effective time off work was 17.5 days after unilateral repair and 24.7 days after bilateral repair. For unilateral repairs, no significant difference was observed between occupational groups in terms of effective time off work, in the absence of complications. In contrast, patients of these occupational groups presented a shorter time off work following an uncomplicated TAPP repair than after plug-Lichtenstein repair. In the group of salaried workers, a significant difference was observed between patients undergoing TAPP or TEP repair and those undergoing plug-Lichtenstein repair.

Adult↗

Nitric oxide and vascular reactivity in pregnant rats with adriamycin nephropathy.

1. In previous studies we have shown that, after the administration of adriamycin, hypertension developed in rats who became pregnant (adriamycin-pregnant rats), whereas virgin animals remained normotensive. Subsequently, we showed that this hypertension was prevented by administration of L-arginine, suggesting that deficient synthesis of nitric oxide may be pathogenetic in this model. 2. To further assess the role of nitric oxide in this model, we measured mean arterial blood pressure after administration of L-arginine to adriamycin-pregnant rats or of NG-nitro-L-arginine-methyl ester (L-NAME) to normal pregnant rats. In other experiments, we assessed the response of isolated perfused arterial mesenteric vessels, precontracted with noradrenaline, to acetylcholine, L-arginine or L-NAME. 3. Blood pressure was decreased in normal pregnant rats, whereas it was elevated in adriamycin-pregnant rats. L-NAME treatment increased blood pressure in normal pregnant rats and L-arginine decreased it in adriamycin-pregnant rats. 4. Mesenteric vessels of adriamycin-pregnant rats exhibited an exaggerated vasoconstrictory response to noradrenaline, when compared with the blunted response observed in normal pregnancy. The addition of L-NAME in vitro induced a further contraction, significantly greater in normal pregnant rats. The vasodilatory response to acetylcholine and L-arginine was greater in vessels from adriamycin-pregnant rats. In contrast, responses to either nitroprusside or diazoxide were similar in all groups. 5. The results suggest a state of reduced nitric oxide synthesis in rats with adriamycin nephropathy, leading to vascular maladaption and hypertension in pregnancy.

Acetylcholine↗

[Treatments of biliary fistulas following the removal of a Kehr tube after orthotopic liver transplantation].

Biliary tract complications are a major source of morbidity after liver transplantation. From October 1990 to September 1992, 77 patients, including 13 children and 64 adults, received 80 liver transplants. Biliary reconstruction was performed using a choledochocholedochostomy with a T-tube in 40 recipients. We report the management of bile leaks following T tube removal in 6 patients. In all cases, bile leak was diagnose by ultrasound examination requested for abdominal pain. In the first 2 patients, a surgical treatment was applied: Roux-en-Y choledochojejunostomy was performed on the first patient and simple suture of the fistula in the second patient. Two patients were managed nonoperatively using endoscopic and radiological procedures allowing placement of bile duct prosthesis and abdominal drainage. In 2 patients with small localized sub-hepatic collection, no surgical or radio-endoscopic treatment was attempted; spontaneous resolution of the collections was achieved in 2 months on ultrasound examination. All patients are alive, although, the patient who was operated on with a roux-en-Y choledochojejunostomy developed thrombosis of the right hepatic artery and biliary anastomotic stenosis which required further operations. We advocate endoscopic placement of endobiliary prosthesis and percutaneous biliary drainage as first-line therapy for significant fistula after T-tube removal. The use of choledochocholedochostomy without a T-tube when possible for biliary reconstruction in liver transplantation could be an effective procedure, but requires further evaluation.

Adult↗