The Effects of Prenatal Exposure to Cocaine on the Dopaminergic Cells in the Rat Retina. An Immunocytochemical and Neurochemical Study

There is a growing consensus that the development of the eye is affected by prenatal exposure to cocaine. Considering that the retina is affected by prenatal cocaine exposure, that this drug affects the dopaminergic systems, that the dopaminergic cells in the retina show a well-defined pattern of development and that they can be specifically stained in wholemounts by the antibody anti-tyrosine hydroxylase (TH), this study was undertaken to evaluate the effects of in utero cocaine exposure on the dopaminergic cells of the rat retina. Pregnant Wistar rats were given 60mg (kg body weight)⁻day⁻¹of cocaine hydrochloride, subcutaneously, from gestational days 8 to 22. Control groups of pregnant rats were pair-fed. At PND14, 30 and 90, male offspring from different litters were perfused with fixative and the retinas processed as wholemounts and immunostained with the antibody anti-TH. Rats from other groups were decapitated at the same post-natal ages, the retinas dissected and processed by neurochemical techniques to measure the concentrations of dopamine, its metabolites and the turnover of dopamine. There was a significant increase of the retina surface area between PND14–30 in the control group, which was not found in the cocaine group. The density of the immunostained small TH cells was lower in the cocaine groups. No drug-effects were detected in the density of the large TH cells. The densities of the total large and small cells in the superior, inferior and nasal hemiretinas were similar to those found in the whole retinas; however, in the temporal hemiretinas of the cocaine groups, the density of the large TH cells was higher and of the small TH cells was lower than in controls, resulting in an absence of effects on the total density of TH-cells in this hemiretina. A transient increase in the level of dopamine metabolite (DOPAC) and of the turnover of dopamine at PND14 was detected in the cocaine groups. All quantitative parameters reached normal values, in all groups, at PND90. These results show that, during the critical periods in which catecholamines can influence the development of neurons, cocaine transiently affects the pattern of dopaminergic neurons in the retina. This may have functional importance due to the role of this neurotransmitter as a regulatory and/or trophic factor in developing neuronal circuitries.     

Measuring quality of life in oncology: is it worthwhile? II. Experiences from the treatment of cancer

This is the second part of the paper on quality of life in cancer patients which appeared in this journal (Montazeri et al., 1996a). In this part experiences from the treatment of cancer are given and relevant literature is reviewed. Several topics have been covered, including new directions and methods in assessing quality of life. It is argued that in a chronic condition, adding life to years instead of years to life is an important task. Adding years to life may prolong survival, but whether this is to the benefit of patients is debatable. Considering patients' views, their values and preferences may improve the quality of care and at the same time, reduce the psychological distress and physical discomfort in patients with cancer. It is concluded that quality of life measures have considerable potential in this challenging issue.     

Variable species and stage specificity of schistosomulum surface epitopes recognized by mice vaccinated with highly irradiated cercariae

Antibodies from mice vaccinated with highly irradiated Schistosoma mansoni or S. haematobium cercariae were used to characterize schistosomulum surface epitopes which were found to be diverse in their species and stage specificities. The epitopes recognized on the Mr greater than 200,000 and 15,000 schistosomulum surface antigens of S. mansoni and the Mr greater than 200,000 schistosomulum surface antigen of S. haematobium were found to be cross-specific whereas those on the Mr 38,000, 32,000 and 20,000 schistosomulum surface antigens of S. mansoni and the Mr 35,000, 30,000 and 24,000 schistosomulum surface antigens of S. haematobium were only immunoprecipitated by homologous antibody and are thus possible targets of the protective species-specific immunity stimulated by highly irradiated cercariae. The epitopes recognized on the Mr greater than 200,000 and 38,000 antigens of S. mansoni were shown to cross-react with both the egg and the adult worm whereas those on the Mr 32,000 and 20,000 antigens only cross-reacted with the adult worm, and those on the Mr 15,000 antigen cross-reacted with neither the adult worm nor the egg. In addition the epitopes on the Mr 38,000 and 32,000 antigens were demonstrated to be polypeptide in nature. Those on the Mr greater than 200,000, 20,000 and 15,000 antigens, on the other hand, could not be conclusively defined.     

PLASMA CONCENTRATIONS AND CLINICAL EFFECTS OF LORAZEPAM AFTER ORAL ADMINISTRATION

The relation between plasma concentrations and properties oflorazepam administered orally as premedication was studied inpatients undergoing minor surgery. The drug was found to bereliably absorbed in most subjects producing plasma concentrationssimilar to those reported after injection. Effective concentrationswere obtained within 30–60 min, maintained for 4–6h and were closely related to the action of the drug on memoryand its sedative and anxiolytic properties. Its kinetics weredescribed in about half the subjects by a one-compartment model,but in others two compartments were required. Variable half-liveswere found (range 9.3–32.1 h, mean about 20h). Sufficientdrug remains after 24h to suggest that residual c.n.s. effectsmay still be present.     

EFFECT OF METHIONINE ON THE FATTY ACID COMPOSITION OF CELLULAR MEMBRANES IN RATS WITH CHRONIC ETHANOL CONSUMPTION AND JEJUNOILEAL BYPASS

The objective of this study was to investigate the effect ofalcohol administration on jejunoileal bypass (JIB)-induced liverdysfunction in rats resulting in abnormalities of fatty acidcomposition of cell membranes, and whether methionine is ableto reverse these changes. Male Wistar rats were subjected toa jejunoileal bypass operation. For 12 weeks, all groups werepair-fed either an alcohol-containing (36% of total calories)liquid diet or a liquid diet in which alcohol was replaced isocaloricallyby starch. Methionine supplementation in three control groupswas 0, 32 and 160 mg/kg body weight/day and the rats in thefour alcohol feeding groups received 0, 32, 160 and 224 mg/kgbody weight/day. In the alcohol group without any methioninesupplementation, higher proportions of oleic and linoleic acidand lower proportions of docosahexaenoic and arachidonic acidbecame evident in tissue samples of liver and jejunum, in comparisonwith the other alcohol group A possible explanation for thisreduction in tissue polyunsaturated fatty acid (PUFA) may bea decrease in the activities of 6-and 5-desaturases, and subsequentlya displacement of PUFA from lipid fractions by other fatty acids.Interestingly, in the alcohol group with the highest methioninesupplementation, compared to all other alcohol groups, lowerproportions of oleic acid, and higher proportions of docosahexaenoicacid, appeared. A possible explanation for this increase ofPUFA in tissue may be increased activities of 6-and 5-desaturases.     

Characterization of Disulfoton-Induced Behavioral and Neurochemical Effects Following Repeated Exposure

These experiments examined the relationship between behavioralalterations and neurochemical changes in rats exposed repeatedlyto disulfoton, an organophosphate cholinesterase inhibitor.Male Long-Evans rats were injected ip for 30 days with 0, 0.5,1, or 2 mg/kg of disulfoton in corn oil. Clinical signs andmotor activity were measured during the course of repeated exposure.Cognitive function, as measured in the Morris water maze, andpassive avoidance procedures were assessed near the end of thedosing regimen. Regional brain acetylcholinesterase (AChE) activitywas measured during the course of dosing while the total numberof muscarinic receptors was measured at the end of the dosingregimen. Tolerance developed rapidly to the clinical signs producedby disulfoton, but not to the disulfoton-induced decrease inmotor activity. Disulfoton affected the acquisition of watermaze performance, but had no effect on passive avoidance acquisitionor retention. Repeated exposure to disulfoton decreased brainAChE activity and the number of [³H]quinuclidinyl benzilatebinding sites. These data indicate that, in spite of muscarinicreceptor down-regulation that followed repeated exposure todisulfoton, animals become tolerant to only some of the functionaleffects produced by this chemical.     

Programming Antitachycardia Pacing for Primary Prevention in Patients With Implantable Cardioverter Defibrillators: Results From the PROVE Trial

Programming ATP for ICD Patients. Objectives: The PROVE trial was designed to determine if antitachycardia pacing (ATP) is clinically beneficial for primary prevention in patients who have implantable cardioverter defibrillators (ICDs) or cardiac resynchronization therapy defibrillators (CRT‐Ds). Background: Use of ICDs and CRT‐Ds reduces mortality in patients with ventricular dysfunction and mild to moderate heart failure. However, in studies of the primary prevention population, shock‐only ICDs are predominantly used, without ATP programming for less painful termination of ventricular tachycardia (VT). Methods: We conducted a prospective, nonrandomized, multicenter study using market‐released ICDs and CRT‐Ds. Patients received devices programmed to deliver ATP for VT cycle lengths of 270–330 ms. Follow‐up evaluation was performed at 3, 6, and 12 months. The incidence of VT and the rate of successful termination by ATP were analyzed. Results: Of 830 patients in the study population (men, 73%; mean age, 67.3 ± 12 years), 32% received single‐chamber ICDs, 44% dual‐chamber ICDs, and 24% CRT‐Ds. ATP was attempted for 112 VT episodes in 71 patients, and 103 (92%) of the VT episodes were successfully terminated. Three VT episodes were accelerated by ATP and required termination by ICD shock; 6 episodes terminated spontaneously or by ICD shock. Conclusions: VT is common in patients without a history of this arrhythmia who have received ICDs or CRT‐Ds for primary prevention indications. Programming ICDs for ATP therapy at the time of implantation could potentially terminate most VT episodes and reduce the number of painful shocks for these patients. (J Cardiovasc Electrophysiol, Vol. 21, pp. 1349‐1354, December 2010)