Modulatory effects of phosphatidylserine on the binding of muscarinic cholinergic receptor ligands

The modulation of the binding of muscarinic cholinergic receptor ligands by phosphatidylserine purified from bovine cerebral cortex (BC-PS) was examined in vitro and in vivo. The enrichment of bovine cerebral cortical synaptosomal membranes with BC-PS, using a fusion technique, produced a concentration-dependent decrease in the affinity (increase in K _d ) of [³H]quinuclidinyl benzylate (³H-QNB) specific binding to muscarinic acetylcholine receptors (mAChR), without changes in their maximal number (Bmax). Similar results were observed when [³H]oxotremorine (³H-OXO) was used to label a high affinity subpopulation of mAChR. On the other hand, preincubation of BC-PS liposomes with synaptosomal membranes in a nonoptimum fusion condition (at pH 7.4) did not alter the binding properties of both radioligands. Fusion experiments using a pure phosphatidylserine preparation from spinal cord revealed a similar decrement in the affinity of³H-QNB specific binding. Five day’s intraperitoneal (i.p.) administration of 15 mg/kg of BC-PS liposomes in rats increased the maximal number of cerebral cortical binding sites for³H-OXO. Scatchard analysis revealed no changes in the apparent dissociation constant. This modification is selective in relation to the neural structure studied. Thus, BC-PS treatment did not modify³H-OXO binding in the hippocampal formation and cerebellum. In contrast, parallel experiments using the muscarinic antagonist³H-QNB showed no alteration in the binding properties of mAChR. Five day’s i.p. administration of 15 mg/kg/d of phosphatidylcholine from bovine cerebral cortex (BC-PC) liposomes produced quite similar results to those obtained with BC-PS. These results indicate that mAChR are under the modulatory action of phosphatidylserine (PS) and phosphatidylcholine (PC), and suggest that this endogenous phospholipids may play a regulatory role on the mAChR. The possible implications of these findings on the effects of PC or PS treatment in neurological disorders involving a decrease in central cholinergic functions are discussed.     

Effects of acetylcholine, carbachol, and mannitol on rabbit corneal endothelial function as assessed by corneal deturgescence

Background: Anterior chamber miotic solutions are widely used in ophthalmic surgery to induce pupillary contraction. We investigated whether the acetylcholine, carbachol, or mannitol present in perfusing solutions can affect corneal endothelial function. Methods: Freshly dissected deepithelized rabbit corneas were mounted in a Dikstein-Maurice chamber at 36 °C. The endothelial sides were perfused with six solutions: (A) 55 mM (1%) acetylcholine Cl plus modified balanced salts; (B) control for A, with acetylcholine Cl replaced by sucrose; (C) 0.55 mM (0.01%) carbachol Cl plus balanced salts; (D) balanced salts solution (BS; control for C); (E) 3% mannitol plus modified balanced salts; and (F) modified balanced salts (control for E, with mannitol replaced by sucrose). Corneal thickness was followed for 3 h in each experiment. The effect of solution E did not differ from that of solution F. Results: The carbachol-containing solution produced a small increase in corneal thickness compared to the control solution, while the acetylcholine-containing solution resulted in corneal thickness lower than that in control preparations. Conclusion: From these data, acetylcholine is harmless to the endothelium, and may actually stimulate its fluid pump mechanism. Carbachol, on the other hand, appears to have a detrimental effect.     

Health care delivery system. Effects on surgical education: The Mexican panorama

Health care delivery in Mexico is divided in three groups: a social sector that covers approximately 53% of the population and is financed by the labor force, the state and the employer; a public, or open, sector that covers 33% of the population and is financed by federal and state funds; and a private sector that covers about 5% of the population and has two categories, the not-for-profit hospitals and the profit-oriented institutions. Most medical practitioners can work in any of the three groups or in several. Nine percent of Mexico's population, because of extreme ignorance, poverty, or isolation, have no or limited access to medical care. Mexico has 58 medical schools, which graduate about 7800 new physicians annually, awarding them the title Medico cirujano (Physician Surgeon). There are more than 160,000 physicians in Mexico, 20,000 of whom are unemployed. Each year, approximately 12,000 physicians compete for the 4306 places in the official residency training programs for all specialties. Of those taking the examination, 2000 try to get one of the 625 slots available for training in general surgery. Most of the surgical training programs in Mexico have a 3-year duration. The Mexican Academy of Surgery, the Mexican Society of General Surgery, and the Mexican Board of Surgery, as well as private individuals and organizations, are working to improve the quality of medical education and trying to establish a 5-year training program in surgery. The rapid movement toward modernization that is sweeping the country must include the improvement of surgical education as well.

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Resumen La atención de la salud en México está dividida en tres grupos: el Sector Social que cubre approximadamente el 53% de la población y que está financiado por la fuerza laboral, el Estado y el empleador; un Sector Público o Abierto que cubre el 33% de la población y que es financiado con fondos federales y estatales; y un Sector Privado que cubre el 5% de la población y que posee dos categorías: la de los hospitales sin ánimo de lucro y la de las instituciones con ánimo de lucro. La mayoría de los médicos pueden trabajar en cualquiera de los 3 grupos, o en combinación. El 9% de la población mexicana, por extrema ignorancia, pobreza y aislamiento no posee acceso alguno, o sólo lo tiene mínimo, a la atención médica.México posee 58 facultades de medicina, las cuales gradúan alrededor de 7.800 nuevos médicos anualmente, a quienes se les expide el título de médico cirujano.Hay más de 160.000 médicos en México, 20.000 de los cuales se encuentran desempleados. Cada año aproximadamente 12.000 médicos compiten por las 4.306 plazas en los programas oficiales de adiestramiento en las diferentes especialidades. De aquellos que presentan examen, 2.000 tratan de obtener uno de los 625 lugares disponibles para adiestramiento en círugía general.La mayoría de los programas de adiestramiento quirúrgico en la nación son de tres años de duración. La Academia Mexicana de Cirugía, la Asociación Mexicana de Cirugía General y el Consejo Mexicano de Cirugía, así como individuos y organizaciones privadas, trabajan en pro del mejoramiento de la calidad de la educación médica y tratan de establecer un programa de adiestramiento en cirugía de cinco años de duración. Los rápidos cambios de modernización que ocurren en el país deben incluir también el mejoramiento de la educación quirúrgica.

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Résumé L'administration des soins au Mexique est repartie entre trois secteurs: 1) Le secteur social qui couvre environ 53% de la population et qui est financé par la caisse des ouvriers, celle de l'état et celle du patronat; 2) un secteur public ou ouvert, qui couvre environ 33% de la population et qui est financé par des fonds fédéraux et gouvernementaux et enfin 3) un secteur privé, qui ne couvre que 5% environ de la population et qui comprend deux catégories, les hôpitaux à but non-lucratif et les institutions à but lucratif. La plupart des médecins peuvent exercer dans un ou plusieurs de ces trois groupes. Neuf pourcent de la population, en raison d'une extrême pauvreté, de son ignorance ou de son éloignement, a peu ou pas d'accés à des soins structurés.Il y a 58 écoles de Médecine au Mexique, produisant environ 7800 nouveaux médecins par an. Ils reçoivent le titre de Medico Cirujano littéralement, Médecin chirurgical. Il existe plus de 160000 médecins au Mexique, dont 20000 sont sans travail. Chaque année, environ 12000 médecins sont en compétition pour obtenir un des 4306 postes officiels de résidents, toutes spialités confondues. Parmi ceux qui se présentent, 2000 sont candidats pour un poste en chirurgie. La plupart des programmes d'enseignement durent trois ans. L'Académie de Chirurgie Mexicaine, La Société Mexicaine de chirurgie Générale et le comité d'accréditation chirurgicale, tout en accord avec les institutions privées et leur dirigeants oeuvrent pour un programme de cinq ans. La vague de progrès, ressentie dans tous les domaines, qui traverse actuellement le pays doit aussi intéresser l'amélioration de l'enseignement en chirurgie.

     

Single forebrain ventricle without prosencephaly: agenesis of the corpus callosum with dehiscent fornices

Coalescence of the cerebral ventricles with formation of a single forebrain ventricle is described in an unusual case of agenesis of the corpus callosum with dehiscent fornices and severe hydrocephalus. The cerebral hemispheres were fully cleaved. The detached fornices were widely separated from the thalami. The membrana tectoria was retroverted over the midbrain and cerebellum, where it joined the fornices and merged with a curved membranous ependymal dome which, at a great distance, circumvented the thalami as it extended toward the anterior commissure. Other anomalies included arhinencephaly, multiple subependymal heterotopias, and Dandy-Walker malformation. Similar malformations have been described as interhemispheric cysts, as (holo)prosencephaly, or as midline telencephalic dysgenesis. The basic features of prosencephaly and agenesis of the corpus callosum are reviewed and compared to the present case.     

Virtual Changes of the Shape of the Lips

Many of the unsatisfactory results in cosmetic surgery are due not to the technique employed itself but to the virtual changes that our work has imposed in other areas. These changes are especially evident in the face, due to the small dimensions of its organs. The surgeon should do a thorough evaluation of the area to be treated prior to the surgery and make her/him notice not only the usual existing asymmetries, but also the modifications which probably will be noticed in the neighboring parts after surgery, to avoid later problems. The surgeon will discover then the many irregularities a patient may have, which have not been noticed by the patient before. These, if not detected in time, are weapons that may act as a boomerang against the surgeon later.     

Urodynamic Evaluation in Simultaneous Insulin-Dependent Diabetes Mellitus and End Stage Renal Disease

Purpose

We evaluated the urodynamic changes produced by insulin-dependent diabetes mellitus with end stage renal disease.

Materials and Methods

A urodynamic evaluation was performed on 51 young patients (mean age plus or minus standard deviation 35 plus/minus 6 years) with long-term diabetes mellitus (average 21 plus/minus 6 years) and end stage renal disease (86 percent on dialysis).

Results

The urodynamic study was abnormal in 84 percent of the patients. The bladder was hypersensitive in 39 percent and hyposensitive in 30 percent of the cases, and maximum vesical capacity was greater than 600 ml. in 33 percent. An acontractile detrusor was noted in 6 percent of the patients, while 4 percent had detrusor hyperreflexia and 35 percent had bladder outlet obstruction.

Conclusions

A high frequency of vesical alterations was observed, which were modified by association of progressive vesical dysfunction and diabetes mellitus. In diabetes mellitus dialysis protects against detrusor hypocontractility but predisposes the patients to have bladder obstruction.     

Paramagnetic changes in cancer: growth of Walker 256 carcinoma studied in frozen and lyophilized tissues.

Samples of Walker 256 carcinoma grown in muscles of Sprague-Dawley rats were studied at low temperatures before and after lyophilization. The effects of lyophilization on the ESR spectra were different for tumours and normal muscle. Prior to lyophilization of a tumour sample, there was a decrease in free radicals, while after the lyophilization, there was an "increase". The "increase" was due to the lyophilized tumour having a narrower line, producing a greater peak-peak height measurement than in muscle, without an increase in the total number of spins. Exposure of lyophilized samples to air produced an increase in the intensity of the spectra and a change in line shape; also these effects differed for tumour and muscle. Mn++ levels were lower in tumour than in muscle, a difference eliminated by lyophilization. Poor growth conditions in tumours increased the occurrence of ESR spectra due to NO complexes with both heme and non-heme iron proteins. These results may help to resolve the principal controversies about experimental findings in ESR of tumours. At least part of the signals seen after lyophilization do not reflect free radicals in vivo. The signals after lyophilization reflect biochemical differences between tumour and muscle; spectroscopic data indicate that it is feasible to determine the molecular basis of these differences.     

Left ventricular hypertrophy in hypertensive patients with autosomal dominant polycystic kidney disease: influence of blood pressure and humoral and neurohormonal factors

Left ventricular hypertrophy (LVH) is a common finding in hypertensive autosomal dominant polycystic kidney disease (ADPKD) patients. There are few studies on the influence of blood pressure (BP) and nonhemodynamic factors on LVH in these patients. The aim of this study was to evaluate the relationship between BP, humoral and neurohormonal factors and left ventricular mass (LVM) in hypertensive ADPKD patients. In 20 hypertensive ADPKD patients, ambulatory BP was monitored for 24 h, left ventricular dimensions were estimated by echocardiography, and plasma renin activity (PRA), plasma noradrenaline (NA), angiotensin II (Ang II), aldosterone, atrial natriuretic peptide (ANP) and insulin-like growth factor I (IGF-I) were also determined. Twenty age- and sex-matched essential hypertensive subjects served as controls. Ambulatory BP and LVM index were similar in the two groups, although male ADPKD patients had higher LVM indices than their matched controls. Eight ADPKD patients (40%) and 6 essential hypertensives (30%) showed LVH. PRA, Ang II, aldosterone, ANP and IGF-I levels were similar in the two groups, but plasma NA levels were higher in ADPKD patients than in controls (281 +/- 158 vs. 160 +/- 62 pg/ml, p = 0.004). ADPKD patients with LVH did not differ from those without LVH with regard to humoral and neurohormonal parameters, but had higher ambulatory BP levels. In ADPKD patients, correlation analysis revealed a significant association between LVM index and 24-hour systolic and diastolic BP, but not with any of the hormonal factors evaluated. On multiple regression analysis, 24-hour diastolic BP was the only independent variable linked to LVM index. In conclusion, ambulatory BP is one of the most important determinants of LVM in hypertensive ADPKD patients. Further studies are warranted to elucidate the role of nonhemodynamic factors in the pathogenesis of LVH in this population.     

Phase II study of denileukin diftitox for relapsed/refractory B-Cell non-Hodgkin's lymphoma.

PURPOSE: Denileukin diftitox is a fusion protein combining diphtheria toxin and interleukin-2 (IL-2) that targets tumor cells expressing the IL-2 receptor. Its efficacy has been shown in CD25+ cutaneous T-cell lymphoma, but not in B-cell non-Hodgkin's lymphoma (NHL). A phase II study was performed to evaluate the efficacy and tolerability of denileukin diftitox for relapsed or refractory B-cell NHL. PATIENTS AND METHODS: Patients with relapsed or refractory B-cell NHL were eligible. Tumor CD25 expression was determined by immunohistochemistry or flow cytometry. Denileukin diftitox was administered intravenously at a dose of 18 microg/kg once daily for 5 days every 3 weeks, up to eight cycles. RESULTS: Of the 45 patients assessable for response, 32 (71%) were refractory to the last chemotherapy treatment, and all were previously treated with rituximab. Three complete responses (6.7%) and eight partial responses (17.8%) were observed, for an overall response rate of 24.5%. Nine patients (20%) had stable disease. Objective response rates were similar in CD25+ (22%) and CD25- histologies (29%), as were stable disease rates (22% and 18%, respectively). For responding patients, the median time to treatment failure was 7 months, with a median follow-up in survivors of 18 months (range, 9 to 28 months), and the projected progression-free survival at 20 months was 24% (95% CI, 0% to 60%). Most toxicities were low-grade and transient. CONCLUSION: Denileukin diftitox seems to be effective in relapsed or refractory, CD25+ and CD25- B-cell NHL and is well-tolerated at the dosage evaluated. Evaluation of denileukin diftitox in combination with other agents may be warranted.