Early postnatal hyperthyroidism alters hippocampal circuitry and improves radial-maze learning in adult mice

Inbred mice show strain-specific differences in the hippocampal mossy fiber projection. These differences are most pronounced in the portion of the projection that forms synaptic connections with the basal dendrites of the CA3 pyramidal neurons [intra- and infrapyramidal mossy fiber (IIP-MF) projection]. We have previously demonstrated that the extent of the IIP-MF subfield is positively correlated with the capacity to perform a spatial radial-maze task and that an experimentally induced enlargement of the IIP-MFs, by means of postnatal thyroxine treatment, predicted the ability of adult two-way avoidance learning. In the present study, we tested whether this treatment would also influence radial-maze performance. Forty-five male mouse pups from the inbred strain DBA/2 (chosen because of scanty IIP-MF projection and poor radial-maze learning) were divided into three groups that received daily injections of either 2 micrograms L-thyroxine, an alkaline vehicle solution, or physiological saline. Treatment lasted from postnatal days 0 to 11. At the age of 3 months, these animals were tested in an eight-arm radial maze. The extent of their IIP-MF projections was measured by means of planimetry on Timm-stained sections. Thyroxine-treated animals made significantly fewer errors and had larger IIP-MF projections as compared to both control groups. Within each group, the individual variability of the IIP-MF projection was significantly and positively correlated with performance. We conclude that experimentally modified IIP-MF projections mediate processes underlying spatial working memory. It would appear that the hippocampal circuitry alterations induced by postnatal hyperthyroidism can counteract a hereditary lack of talent, albeit only partially and in selected populations.     

Enhanced Fluid Removal Guided by Blood Volume Monitoring During Chronic Hemodialysis

Fluid overload predisposes chronic hemodialysis patients to cardiovascular disease, a significant cause of morbidity and mortality in these patients. We evaluated the efficacy of monitoring changes in blood volume during routine hemodialysis to detect fluid overload. Intradialytic changes in blood volume were monitored by continuously measuring hematocrit in all 56 patients in a single dialysis unit over 7 weeks. After Week 1, patients were categorized into 2 separate groups depending on their maximum intradialytic decreases in blood volume. In Group 1, 46 of 56 or 82% had greater than a 5% decrease in blood volume while in Group 2, 10 of 56 or 18% had less than a 5% decrease in blood volume. During Weeks 2–7, dialytic fluid removal was intentionally increased in Group 2 patients by 0.80 ± 0.62 L (mean ± SD) or 47 ± 43%. This intervention resulted in a larger (p < 0.02) intradialytic decrease in body weight (2.7 ± 0.9 kg versus 2.0 ± 0.8 kg) and a larger (p < 0.02) intradialytic decrease in blood volume (15 ± 5% versus 4 ± 1%) than experienced during Week 1 with a low incidence of symptoms. We conclude that there is a significant percentage of chronic hemodialysis patients who can tolerate additional fluid removal without hypovolemic symptoms even though they are considered to be at dry weight by routine physical examination and that the identification of these patients can be facilitated by intradialytic blood volume monitoring.     

Biological mechanisms and cardiovascular effects of omega-3 fatty acids

The mechanisms and cardiovascular effects of omega-3 fatty acids are reviewed. Omega-3 polyunsaturated fatty acids are the major ingredient found in commercially available fish oil products. The incidence of many diseases, including coronary heart disease, diabetes mellitus, and psoriasis, is lower in Eskimos, who ingest diets rich in omega-3 fatty acids, compared with European controls. Potential mechanisms by which these fatty acids cause their many physiologic effects include competing with omega-6 fatty acids for prostaglandin and leukotriene pathways and enhancing cell membrane fluidity by virtue of the high degree of unsaturation. Numerous studies have documented longer bleeding times and decreased platelet aggregation in subjects ingesting omega-3 fatty acids. Omega-3 fatty acids may reduce serum cholesterol concentrations by decreasing the synthesis of very low density lipoprotein and, therefore, low-density lipoprotein. Blood viscosity is significantly and uniformly lower in subjects receiving omega-3 fatty acids compared with controls. Potential risks of supplementation with fish oils include hypervitaminosis A and D, vitamin E deficiency, increased bleeding times, decreased platelets, and ingestion of contaminated fish. Supplementation with moderate amounts of omega-3 fatty acids appears to be relatively safe. Possible adverse effects include nausea, diarrhea, and a "fishy" taste. Properly controlled, long-term clinical trials are needed to determine whether supplementation with omega-3 fatty acids would be therapeutically beneficial in various patient populations and disease states.     

Guidelines for a short-term therapy of a torture depression

Psychotherapeutic work with torture traumas and their aftereffects are made difficult through a number of factors. Six guiding principles are presented in this publication through which make it possible to influence the actual symptomatology within the limits of the short therapy, even under difficult conditions. Creative images, described in detail as process fantasies, are the focus of this short therapy. Situative experiences in the treatment process are not interpreted with reference to the subject or the concrete trauma. This leads to the intra-psychic patterns being unlinked from traumatic torture experience patterns. With the aid of a model which discusses the torture as a superinfection with psychogenic violence-viruses, the penetration and resistance to therapy towards the torture trauma can be illuminated so that a differentiation of social and psychological factors of the torture experience is made possible.     

Intraluminal Radiation for Esophageal Cancer: A Howard University Technique

The objective of radiotherapeutic management in esophageal cancer is to accomplish maximum tumor sterilization with minimal normal tissue damage. This sincere effort is most often countered by the differential in tumor dose response vs normal tissue tolerance. Intraluminal isotope radiation, with its inherent advantage of rapid dose falloff, spares the lungs, the spinal cord, and other vital structures, yet yields adequately high doses to esophageal tumor. Though in existence since the turn of the century, the method of intracavitary radium bougie application dropped out of favor due to technical difficulties imposed by the size of the radium source and radiation exposure to the personnel involved. The authors describe a simple “iridium 192 afterloading intraluminal technique” that eliminates technical problems and reduces radiation exposure considerably.     

Leukocyte apoptosis and its significance in sepsis and shock

Sepsis and multiple organ failure continue to be significant problems among trauma, burn, and the critically ill patient population. Thus, a number of laboratories have focused on understanding the role of altered apoptotic cell death in contributing to immune and organ dysfunction seen in sepsis and shock. Immune cells that undergo altered apoptotic changes include neutrophils, macrophages, dendritic cells, as well as various lymphocyte populations. Evidence of epithelial as well as endothelial cell apoptotic changes has also been reported. Although mediators such as steroids, tumor necrosis factor, nitric oxide, C5a, and Fas ligand (FasL) appear to contribute to the apoptotic changes, their effects are tissue- and cell population-selective. As inhibiting Fas-FasL signaling (e.g., gene deficiency, Fas fusion protein, or Fas short interfering RNA administration), caspase inhibition (caspase mimetic peptides), and/or the overexpression of downstream antiapoptotic molecules (e.g., Bcl-2, Akt) improve survival of septic mice, it not only demonstrates the pathological significance of this process but points to novel targets for the treatment of sepsis.     

Physical Factors affecting Maximum Precipitation of the BSA-AntiBSA Fowl System

Studies were made ascertaining the effects of temperature and length of incubation period on the amount of precipitate formed in the BSA-antiBSA fowl serum system. The specific factors considered were centrifugal temperature, temperature of incubation and length of incubation. Reactions were analysed for the entire precipitin curve, using doubling dilutions of antigen, and also for the region of equivalence using intervals of 1 μg. nitrogen.

Reactions mixtures were incubated at 37° for 3 hours and then centrifuged at 22° or at 4° and the precipitate was analysed for total N precipitated. In addition, secondary incubation periods, following this initial incubation treatment of 3 hours at 37°, were made. The secondary periods were either 18, 66 or 118 hours at 4° or 18 hours at 37° and were followed by centrifugation at either 22° or 4°.

Evaluation of the data showed centrifugation at 22° gave higher amounts of precipitate than at 4° in all cases and the differences were statistically significant in most of the instances. In eighteen of the twenty sera tested, precipitation was at a maximum after 3 hours' incubation at 37° and warm centrifugation in contrast to additional incubation periods and/or cold centrifugation.

     

Expression of interleukin-8 gene in inflammatory bowel disease is related to the histological grade of active inflammation.

Interleukin-8 (IL-8) is a potent cytokine for recruitment and activation of neutrophils. To visualize its distribution in the intestinal mucosa and to understand better its possible role in the induction and promotion of inflammatory bowel disease, expression of the IL-8 gene was analyzed in resected bowel segments of 14 patients with active Crohn's disease or ulcerative colitis. In situ hybridization with IL-8 anti-sense RNA probes revealed strong and specific signals in the histologically affected mucosa. The number of cells expressing IL-8 gene correlated with the histological grade of active inflammation. In accordance with the characteristic histological signs of active disease, IL-8-expressing cells were diffusely distributed over the entire affected mucosa in patients with ulcerative colitis, whereas in patients with Crohn's disease, IL-8-expressing cells showed a focal distribution pattern. Cells expressing IL-8 were mainly located at the base of ulcers, in inflammatory exudates on mucosal surfaces, in crypt abscesses, and at the border of fistulae. Analysis of semi-serial sections pointed to macrophages, neutrophils, and epithelial cells as possible sources of this cytokine in active inflammatory bowel disease. We consistently failed to detect IL-8 messenger RNA in the mucosa of uninvolved bowel segments and in normal-appearing control mucosa of patients with colon cancer. In contrast, tissue specimens from two patients with acute appendicitis displayed IL-8-expressing cells in the mucosa. These results support the notion that IL-8 plays and important but nonspecific role in the pathogenesis of inflammatory bowel disease and that the production of IL-8 messenger RNA is restricted to areas with histological signs of inflammatory activity and mucosal destruction.