Microinjection of NMDA-neurotoxin into the superior salivatory nucleus of the rat: Short-term secretory and long-term drinking behavior effects.

The anatomical location of the superior salivatory nucleus (SSN), the site of origin of the parasympathetic preganglionic cell bodies that innervate the submandibular-sublingual salivary glands, is well established in rats. However, as of yet there is no functional data that convincingly shows the secretory nature of this region. Previous studies have not been able to differentiate between interventions on efferent or afferent fibers connected to the SSN versus interventions on the salivatory nucleus itself. Taking advantage of the fact that salivatory neurons express NMDA-receptors on their somas, in the present study SSN cell bodies were activated and lesioned sequentially by means of intracerebral application of NMDA-neurotoxin. In exp. 1 two effects, a short- and a long-term effect, were observed following NMDA administration. The first effect was high submandibular-sublingual saliva secretion during the hour following administration of the neurotoxin and the second was a profound change in drinking behavior once the animals recovered from the lesion. Thus, on post-surgery days 16, 17 and 18, the rats exhibited hyperdipsia in the presence of dry food but not in the presence of wet food. In expt. 2 results showed that saliva hypersecretion observed after NMDA-microinjection was completely blocked by the administration of atropine (a cholinergic blocker) but not after the administration of dihydroergotamine plus propranolol (α and ß-adrenergic blockers, respectively). From a functional perspective, these data suggest that the somata of the parvocellular reticular formation control the secretory activity of the submandibular-sublingual salivary glands and thus constitute the SSN.

Electron probe X-ray microanalysis of cisplatin-induced cell death in rat pheochromocytoma PC12 cells.

Several lines of evidence suggest that cisplatin-induced cell death is not always the result of apoptosis. A distinctive feature between apoptosis and necrosis is the alteration in cell volume regulation and ion homeostasis. Here we analyzed the changes in intracellular element content during cell death induced by exposure to therapeutic concentrations of cisplatin in the PC12 cell line. To quantitate Na, Cl and K content, electron probe X-ray microanalysis (EPXMA) was performed in whole freeze-dried cells. We also traced the alterations in morphological features with fluorescence and transmission electron microscopy. EPXMA demonstrated progressive derangement of the absolute intracellular Na, Cl and K contents. Cisplatin-treated cells showed two microanalytical patterns: 1) cells with alterations in elemental content typical of apoptosis, i.e., an increase in intracellular Na and a decrease in intracellular Cl and K, and 2) cells characterized by an increase in Na content and a decrease in K content, with no changes in Cl content. This intracellular profile for Na, Cl, and K was not typical of necrosis or apoptosis. Morphological analysis revealed two cellular phenotypes: 1) cells characterized by a phenotype typical of apoptosis, and 2) cells characterized by a hybrid phenotype combining variable features of apoptosis and necrosis. Taken together, our findings suggest that therapeutic concentrations of cisplatin may cause a hybrid type of cell death characterized by concurrent apoptosis and necrosis in the same individual PC12 cell.

Remote spatial memory and the hippocampus: effect of early and extensive training in the radial maze.

In a previous study we showed a temporally graded retrograde amnesia after hippocampal lesions when rats learned a spatial reference memory task in which two types of signals simultaneously indicated the goal arm (shape of the experimental room and extramaze landmarks). To investigate the effect that the navigational demands of the task have on remote memory expression, the same task was used in the present study as in our previous report, but on this occasion the shape of the surroundings was not predictive, which resulted in a highly demanding spatial task. Additionally, animals received extensive training in an early phase to ensure that the task was well learned. Results indicated a profound retrograde amnesia when dorsal hippocampal lesions were made 1 or 70 d after the end of the training (experiments 1 and 2). Using a long period of retraining, however, lesioned animals in the 70-d groups showed progressively more spared memory than the lesioned rats of the 1-d group. Experiments 3 and 4 showed that rats did not learn the above spatial task through an S-R association. Specifically, when animals acquired the task using a single cue (intra- or extramaze), hippocampal lesions did not produce retrograde amnesia. These findings support the possibility that in a highly demanding spatial task, hippocampal lesions produce a performance/navigational impairment that could interfere with the expression of spared remote spatial memory. The long period of retraining, however, seems to partially compensate for this deficit, but only when a long learning-surgery interval is employed.

Perirhinal cortex lesions produce retrograde amnesia for spatial information in rats: consolidation or retrieval?

Several lines of evidence in humans and experimental animals suggest that the hippocampus is critical for the formation and retrieval of spatial memory. However, although the hippocampus is reciprocally connected to adjacent cortices within the medial temporal lobe and they, in turn, are connected to the neocortex, little is known regarding the function of these cortices in memory. Here, using a reference spatial memory task in the radial maze, we show that neurotoxic perirhinal cortex lesions produce a profound retrograde amnesia when learning-surgery intervals of 1 or 50 d are used (Experiment 1). With the aim of dissociating between consolidation and retrieval processes, we injected lidocaine either daily after training (Experiment 2) or before a retention test once the learning had been completed (Experiment 3). Results show that reversible perirhinal inactivation impairs retrieval but not consolidation. However, the same procedure followed in Experiment 2 disrupted consolidation when the lidocaine was injected into the dorsal hippocampus. The results of Experiment 4 rule out the possibility that the deficit in retrieval is due to a state-dependent effect. These findings demonstrate the differential contribution of various regions of the medial temporal lobe to memory, suggesting that the perirhinal cortex plays a key role in the retrieval of spatial information for a long period of time.

Niveles de luz ultravioleta ambiental asociados con apoptosis y necrosis en fibroblstos humanos / Environmental levels of ultraviolet light associated with apoptosis and necrosis in human fibroblstos

La apoptosis involucra una serie de episodios altamente organizados y programados que tienen por objeto mantener la estabilidad genómica eliminando células huésped defectuosas. El propósito de este estudio fue determinar las dosis umbral y los tiempos de exposición a UV-A y UV-B medioambientales suficientes como para producir apoptosis y necrosis en la células normales de una línea celular de fobroblastos humanos. Se midieron dosis de UV-A y UV-B durante un período de seis años con un radiómetro UV de cuatro canales. Se irradiaron los fibroblastos una vez utilizando Simuladores Solar UV Oriel con seis dosis de UV basados en el medio ambiente. Las dosis correspondieron a 0, 11, 19, 23 y 45 minutos de radiación ambiental de UV-A y UV-B al sol del mediodía en Puerto Rico. Se utilizó en método de unión de la anexina-V para diferenciar entre los fibroblastos normales y fibroblastos apoptóticos o necróticos. La dosis umbral de la apoptosis a la necrosis se halló entre 24-28 KJ/m2, correspondiente a los 19 y 23 minutos de exposición ambiental a UV-A y UV-B. Este estudio proporciona los primeros datos que especifican las dosis de umbral medioambientales de UV-A y UV-B en las que los fibroblastos humanos experimentas apoptosis y necrosis. Estos resultados pueden proporcionar valiosos umbrales dosis-respuesta de apoptosis y necrosis para futuros estudios mecanicistas y datos de línea de base para programas de prevención de cáncer de piel.

DNA repair and breast carcinoma susceptibility in women.

BACKGROUND: Breast carcinoma is the most common cancer and the second leading cause of cancer-related deaths among women. The disease represents approximately 31% of all cancers in Puerto Rican women. Several DNA repair pathways are involved in preventing carcinogenesis. The current study evaluated the hypothesis that a reduced DNA repair capacity (DRC) is a susceptibility factor for breast carcinoma. METHODS: A retrospective case-control clinical study was performed to compare age-matched DRC in 33 women with histopathologically confirmed breast carcinoma (cases) and 47 cancer-free women (controls). DRC was measured using a host cell reactivation assay with a luciferase reporter gene and then transfected into human peripheral lymphocytes. A questionnaire was used to solicit breast carcinoma risk factors. RESULTS: Women with breast carcinoma had a mean DRC of 5.6% +/- 0.5 standard error of the mean (SEM). Cancer cases had a 36% reduction (P<0.001) in DRC when compared with the control group (DRC=8.7% +/- 0.7 SEM). Younger participants with breast carcinoma were found to have a more significant reduction in DRC when compared with age-matched controls. Family (odds ratio [OR]=4.1), maternal lineage (OR=5.5), and maternal (OR=12.4) history of breast carcinoma were found to be the only statistically significant (P<0.05) risk factors associated with the disease. CONCLUSIONS: The findings supported the hypothesis that a low DRC is a susceptibility factor for breast carcinoma. A 1% decrease in DRC corresponded to a 22% increase in breast carcinoma risk. To the authors' knowledge, the current study was the first to directly determine the DRC of women with breast carcinoma. Because DRC is an independent risk factor for breast carcinoma, the DRC of women may be a useful marker in predicting susceptibility.

DNA repair and nonmelanoma skin cancer in Puerto Rican populations.

BACKGROUND: UV radiation is a risk factor for nonmelanoma skin cancer (NMSC). The relation between DNA damage and oncogenesis suggests that diminished DNA repair capacity (DRC) is involved in tumorigenesis. OBJECTIVE: The purpose of this study was to test the hypothesis that a low DRC is a susceptibility factor for the development of NMSC in Puerto Rico. METHODS: A case-control retrospective clinical study was done to compare the age-adjusted DRC in participants with and without NMSC. DRC was measured using a host cell reactivation assay with a luciferase reporter gene irradiated with UV light and transfected into human peripheral lymphocytes. An epidemiologic questionnaire was used to solicit risk factors. RESULTS: The mean (+/-2 SE) DRC of 177 control patients without skin cancer was 8.6% +/- 0.7. Participants (280) with NMSC had a 42% lower DRC (5.0% +/- 0.3). CONCLUSION: A low DRC is a susceptibility factor for NMSC.

Amebiasis in the epidemiologic transition in Mexico: its morbidity and mortality trends in the Mexican Institute of Social Security

Amebiasis is one of the most common parasite-related diseases and one of those with the greatest impact on health. At the Instituto Mexicano del Seguro Social (Mexican Institute of Social Security-IMSS) approximately half a million cases per year are currently treated. Of these, more than 2500 correspond to the form wich invades the live. Within the process of epidemiologic transition which Mexico undergoing, a progressive reduction has been observed in incidence of, and mortality due to, invading amebiasis in all its clinical forms. In turn, there is a significant decrese in its fatality rate. The social and economic development and improved sanitary conditions observed in Mexico, particularly in the second half of this century, may have conditioned this process. The improvement in availability, accessibility and utilization of medical care services could also explain the reduction which has been noted in its fatality rate and mortality. The model for epidemiologic transition proposed by Omran and adapted for Mexico by Frenk, offers a plausible explanation for the changes observed in the occurrence and mortality of invanding amebiasis in Mexixo