Kinetics of permeation of 2,3-butanediol on isolated perfused rat kidney model assessed by proton nuclear magnetic resonance spectroscopy.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to G Benoit.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Several arguments exist in various animal species and man for the presence of a sympathetic component in the pelvic nerve, classically regarded as parasympathetic. We tested this hypothesis in the male rat. Nerve bundles issued from the sacral region of the paravertebral sympathetic chain and reaching the S1 spinal nerve were identified. Neurons in the sacral parasympathetic nucleus of the L6-S1 spinal cord and in the L2-S1 paravertebral sympathetic chain were retrogradely labeled from the pelvic nerve. Radioautography evidenced labeling of unmyelinated fibers in the pelvic nerve following in vitro incubation with 3H-noradrenaline. A population of sympathetic fibers issued from the lumbosacral sympathetic chain exists in the pelvic nerve of the male rat. This qualitative study provides a morphological basis to uncover the role of the sympathetic outflow present in the pelvic nerve.
The role of peripheral parasympathetic and sympathetic pathways was explored in erectile responses elicited by hypothalamic medial preoptic area (MPOA) stimulation in adult male anesthetized rats. Under control conditions, MPOA stimulation reliably elicited erectile responses evidenced by an increase of the intracavernous pressure-to-blood pressure ratio. The erectile response was abolished by 1) acute bilateral section of cavernous or pelvic nerves or cauda equina and 2) chronic lesions of pelvic nerves or cauda equina. Acute section of the hypogastric nerve did not significantly decrease the erectile response. The erectile response was significantly depressed after acute or chronic sections of the paravertebral sympathetic chain at the L4-L5 level or chemical sympathectomy with 6-hydroxydopamine. The decrease due to acute sympathetic chain lesion was reversed by bilateral ligation of the external iliac arteries. Accordingly MPOA stimulation elicits erectile responses via 1) activation of the parasympathetic outflow conveyed by the pelvic and cavernous nerves and 2) activation of neural fibers conveyed by the sympathetic pathways. We propose that sympathetic fibers running in the paravertebral sympathetic chain are responsible for vasoconstriction of nonpenile areas to divert blood to the penis, allowing the dramatic increase of penile arterial inflow required for erection.
A total of 6889 cadaver kidney grafts carried out in the French transplant network from 1 January 1989 to 31 December 1992 were analyzed using single and multifactorial methods in order to evaluate the impact on graft survival of matching for sex and age between donors and recipients. The mean graft survival rate was 75% at 3 yr with donors between 10 and 50 yr of age compared to 65% for donors under 10 yr of age and 67% at 3 yr for donors over 50 yr of age (p < 0.000001). For child recipients there were no significant differences in graft survival whatever the difference in age with the donor (+/- 10 yr). For young adults (17-49 yr of age) the prognosis at 3 yr was the same (75%) whether the donor was in the same age category or older than the recipient. For older adults (> 50 yr of age) a poorer prognosis was obtained when the donor was 10 yr or more older than the recipient (61% at 1 yr, p = 10(-4)). The grafts performed with male donors had a better prognosis (76% at 3 yr) than those using female donors (71% at 3 yr, p < 0.0002). The poorest results were obtained with female donors when the recipient was male (70% at 3 yr). The results of the multivariate analysis of seven parameters involved in graft survival show that the main parameters significantly controlling graft survival are preimmunization before the graft (p = 10(-6)), HLA-DR incompatibility (p = 0.004), retransplantation (p = 0.008), donor sex (p = 0.003), and matching for age between donor and recipient (p = 0.1). These results suggest that age and sex should be considered as criteria in the choice of donors and recipients in organ allocation.
Relaxation of arterial and cavernous smooth muscle fibers, leading to the filling of the sinusoidal spaces with blood, are the local mechanisms of erection. Smooth muscle relaxation results from activation of parasympathetic neural pathway and probably simultaneous inhibition of the sympathetic outflow. Reflexive erection elicited by recruitment of penile afferents conveyed by the dorsal penile nerve involves both autonomic and somatic efferents. This reflex is mediated at the spinal cord level and modulated by supraspinal influences. Serotonergic pathways originating in the raphe nuclei mediate inhibitory control on reflexive erection. Several hypothalamic areas such as the medial preoptic area and the paraventricular nucleus are the source of descending pathways and/or represent important integrating centers. Dopamine acting at the medial preoptic area level may regulate penile erection. Neuroendocrine regulation may vary depending on the context in which erection occurs, for example, coitus, in response to extrinsic or psychogenic stimuli, and rapid eye movement sleep.
The peripheral control of local mechanisms of erection and detumescence has now been more clearly elucidated. This knowledge has been acquired as a result of the recent development of pharmacological research designed to study the regulation of erectile smooth muscle tone. Smooth muscle fibres of the corpora cavernosa and arteries supplying the penis relax in response to a reduction of intracellular calcium. This relaxation allows both an increase of the blood flow to the penis and opening of sinusoid spaces. Cyclic nucleotides, cAMP and cGMP, are intracellular messengers of the mediators acting on smooth muscle fibres and regulating these intracellular calcium movements. Gap-junctions, greatly facilitating rapid ion exchanges between smooth muscle fibres, make erectile tissue a real functional syncytium. Nonadrenergic, noncholinergic neurotransmitters, mainly nitric oxide (NO), are synthesized by parasympathetic neurons present in cavernous nerves and act directly on smooth muscle fibres. NO increases the intracellular cGMP concentration. Other proerectile mediators, such as acetylcholine, CGRP or substance P, act via endothelial cells by promoting the synthesis and release of NO by these cells. In contrast, neurotransmitters of the sympathetic nervous system, norepinephrine and neuropeptide Y, and endothelin, secreted by endothelial tissues, induce contraction of cavernous smooth muscle fibres, thereby opposing erection. Oxygenation of the cavernous tissue is also an important factor in the regulation of local mechanisms of erection. Poor oxygenation prevents the synthesis of cGMP and predisposes to cavernous fibrosis due to increased synthesis of collagen via TGF beta. A better understanding of the peripheral pharmacology of erection opens the way to new pathophysiological and therapeutic prospects in the broad symptomatic context of erectile dysfunction.
It has been suggested that tacrine (THA) induced hepatotoxicity was related to its metabolic pathway involving cytochrome P4501A2 (CYP1A2). Using a model of genetically modified cells we have demonstrated that THA induced a marked decrease in cell viability and a strong inhibition of RNA and protein synthesis. However, these cytotoxic effects did not differ in parental Chinese hamster V79 cells and variant cells expressing human or rat CYP1A2 as well in human HepG2 and Chang Liver cells despite their notable metabolism ability to metabolize THA to hydroxylated metabolites. These results strongly suggest that THA-induced cytotoxicity is not mediated by CYP1A2 indicating that THA could be toxic by direct inhibition at the ribosomial level.
Penile erection can be elicited by various stimuli integrated in the spinal cord and/or higher central nervous structures. The medial preoptic area (MPOA) of the hypothalamus is known to play a key role in the regulation of the male sexual behavior. In anesthetized male rats we performed MPOA stimulation via stereotaxically implanted electrodes or canulae delivering L-glutamate. An erectile response, assessed by an increase of intracavernous pressure (ICP), was recorded during electrical stimulation of the MPOA. Stimulating the posterior region of the MPOA elicited a greater erectile response than stimulation applied to the anterior region. Microinjections of L-glutamate also elicited an ICP increase. Stimulation of MPOA neurons therefore elicits activation of neural pathways controlling penile erection.
We have generated mouse models of human Tay-Sachs and Sandhoff diseases by targeted disruption of the Hexa (alpha subunit) or Hexb (beta subunit) genes, respectively, encoding lysosomal beta-hexosaminidase A (structure, alpha) and B (structure, beta beta). Both mutant mice accumulate GM2 ganglioside in brain, much more so in Hexb -/- mice, and the latter also accumulate glycolipid GA2. Hexa -/- mice suffer no obvious behavioral or neurological deficit, while Hexb -/- mice develop a fatal neurodegenerative disease, with spasticity, muscle weakness, rigidity, tremor and ataxia. The Hexb -/- but not the Hexa -/- mice have massive depletion of spinal cord axons as an apparent consequence of neuronal storage of GM2. We propose that Hexa -/- mice escape disease through partial catabolism of accumulated GM2 via GA2 (asialo-GM2) through the combined action of sialidase and beta-hexosaminidase B.
95% of renal transplantations performed in France use cadaver donor kidneys. Two donor nephrectomy techniques are proposed: a beating heart technique and an arrested heart technique. In the very great majority of cases (80%), donor nephrectomy can be performed during multi-organ removal, performed according to bioethical regulations: unrelated, anonymity between donor and recipient, security, traceability and evaluation. The urologist has a role to play at each step of organ donation, in which he is the main protagonist. The first steps are performed in close collaboration with the intensive care unit which established the diagnosis of brain death of the potential donor. The following steps, guided by the French transplant establishment, are the urologist's responsibility: He is responsible for abdominal exploration looking for a tumour or any other abnormality. A strictly aseptic technique is essential to prevent contamination of the organ. He is responsible for removing kidneys in such a way as to ensure the shortest possible warm ischaemia time, the best storage solution, and the best preservation of their anatomical structure. He must be familiar with the outcome of transplants in order to adapt his technique to the results of transplants.
Twenty five double kidney-pancreas transplantations were performed according to the total pancreas transplantation technique with drainage of exocrine secretions into the bladder via a vesicoduodenostomy. 72% of kidney-pancreas grafts were functional at one year and 59% were functional at four years. The authors observed a slightly higher rejection rate (0.56 versus 0.34) and a higher incidence of urinary tract infection (60% versus 35%) following double pancreas and renal transplantation than after isolated renal transplantation. Complications were rare: two venous thromboses and two cases of urethritis requiring of rediversion of the duodenum into the intestine. These good results, comparable to those reported in the international registry, reflect the value of the pancreatic and renal transplantation technique using a total pancreas drained into the bladder. It would probably be preferable to transplant patients earlier, when chronic renal failure secondary to insulin-dependent diabetes induces end-stage renal failure and the need for haemodialysis.
The neurophysiology of erection remains poorly elucidated, particularly at the spinal cord level. We studied variation of intracavernous pressure (ICP) in rats. Tactile stimulation of the prepuce in conscious rats induces the appearance of sequences of reflex erectile responses affecting the corpora cavernosa and/or corpus spongiosum and glans. During this test, implantation of a telemetric pressure transducer allowed us to record ICP increases occurring simultaneously to erectile responses. These increases were characterized by brief suprasystolic peaks preceded by an infrasystolic plateau. Each type of reflex erectile response was accompanied by a characteristic profile of ICP increase. Participation of the corpora cavernosa was demonstrated, particularly during erections of the glans. In anaesthetised rats, electrical stimulation of the dorsal nerve of the penis induces an increase of intracavernous pressure which tends to reach blood pressure values. This erectile response of the corpora cavernosa is abolished by proximal section of the dorsal nerve of the penis, markedly decreased by section of the homolateral pelvic nerve, and abolished after bilateral section of the two pelvic nerves. Striated muscle paralysis does not abolish the erectile response. These data help to define the neurophysiology of the reflex erection. In particular, they provide a clearer explanation of the spinal integration of reflex erection.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
In a series of 1500 patients transplanted between 1976 and 1992, 12 patients presented urinary calculi. The symptoms presented included obstructive anuria in 3 patients and abdominal pain in 1 patient. There were 8 asymptomatic patients. The risk factors were mainly hyperparathyroidism and non-absorbable sutures. The occurrence of renal graft calculi is now ten times less frequent than in the 1980s. In all, 5 of the patients were treated using incisional surgery, 5 with ESWL and 4 using ureteroscopy; a double J stent was inserted for the 3 cases of obstructive anuria. Nine patients are currently calculus-free and 2 have relapsed. One asymptomatic patient was not treated. The renal function of these 12 patient was not modified and no hypertension was noted after treatment. Calculi are generally asymptomatic when they are diagnosed by ultrasonography and in our experience they can be treated using ESWL or by ureteroscopy. In our opinion all patients can be treated successfully but with a high rate of relapse if the causal factors are not treated.
PURPOSE: Urologists successfully use ureteral stents to protect the ureterovesical anastomosis in nontransplant patients. MATERIALS AND METHODS: We determined the value of ureteral stents in transplant patients. The frequency of urological complications (leaks, obstructions and urinary tract infections) was compared in a prospective randomized series of 194 kidney transplantations (97 with and 97 without a double pigtail ureteral stent). RESULTS: In the stent group 1 patient had a urinary leak and 35 had urinary tract infections (including 2 cases of Corynebacterium cystitis). In the no stent group 6 patients had urinary leaks, 4 had obstructions and 32 had urinary tract infections. The 1-year patient and graft survival rates were similar in both groups, and renal function at 1 year was also similar (229 versus 208 mumol./l. creatinine in the stent and no stent groups, respectively). A small number of stent related complications occurred (2 stent breakages and 1 stent migration). No stones formed in any case. CONCLUSIONS: Ureteral stent insertion significantly decreases the rate of vesicoureteral leakage and obstruction in renal transplantation.
OBJECTIVES: In order to prolong the cold ischaemia time and to improve the quality of donor kidneys, we have designed and developed a renal perfusion machine allowing the control of perfusion parameters (temperature, pressure, flow rate, resistance) during the various phases of a kidney perfusion and storage protocol at -4 degrees C. ANIMALS, MATERIALS AND METHODS: Twenty four rat kidneys were removed and the effects of perfusion and storage at -4 degrees C were studied using a perfusion/storage machine allowing the controlled addition of 2,3 butanediol in University of Wisconsin (UW solution). The kidneys were stored for 96 hours at -4 degrees C and were studied in terms of perfusion parameters (pressure, resistance) and according to their histological appearance. RESULTS: The machine allows controlled perfusion of a cryoprotective agent and preservation of kidneys at -4 degrees C for 96 hours. CONCLUSION: In animals, it is possible to store kidneys at a temperature of -4 degrees C for 96 hours by using a vecor solution (UW solution) and a cryoprotective agent (2,3 butanediol). The perfusion and storage of organs under these conditions must be performed by a computer-assisted machine, allowing monitoring and control of the various steps of perfusion/storage.