Quantitative stereological studies of a ''selection'' protocol of hepatocarcinogenesis following initiation in neonatal male and female rats

Understanding the reasons for infertility and the development of new techniques for its treatment is one of the fields within medicine which has undergone a dramatic development during the last two decades. In the past, gynecologists seemed more successful in the treatment of female problems than urologists and andrologists on the male side, while in the last couple of years this scenario has changed due to the development of both operative procedures to harvest spermatozoa from the epididymis and the testis and the ability to micro-inject single spermatozoa (ICSI) or even spermatides directly into metaphase II oocytes. It should, however, be emphasized that the successful development of in vitro fertilization (IVF) and other assisted reproduction technologies (ART), could not have taken place without the development of diagnostic innovations, such as immunoassays of hormones, high resolution ultrasound and various endoscopic techniques. Today, treatment of the infertile couple is less of a medico-technical problem and more a socio-economic dilemma. This communication is an attempt to summarize the more prominent steps in reproductive medicine during the last decades and one more general conclusion of global relevance which can be drawn, is that less money must be spent on diagnosis and more resources transferred to treatment options.     

An AP-2 binding sequence within exon 1 of human and porcine choline acetyltransferase genes enhances transcription in neural cells

It has been established that GABAA and GABAB receptors can exist separately and/or co-exist in the membrane of dorsal root ganglion neurons. In our previous investigation it has been shown that co-existence of these two kinds of receptors is about 80% of the neurons examined (20/25). The present study was aimed to explore whether the activation of these two kinds of receptors could interact with each other using intracellular and whole-cell patch-clamp recordings. Baclofen, a specific GABAB receptor agonist, was found to exert negative modulatory effects on the responses mediated by GABAA receptor. In experiments with intracellular recording, GABA (0.3-1000 microM)- and muscimol (100-1000 microM)-induced depolarization was attenuated markedly and reversibly by preapplication of baclofen (100 microM) (15/21 and 17/21, respectively). In whole-cell patch-clamp recordings GABA (100 microM) and two specific GABAA receptor agonists, muscimol (10 microM) and isoguvacine (50 microM), activated currents were inhibited markedly by preapplication of baclofen 30 s or more and the inhibition was concentration dependent (1-100 microM baclofen) and reversible. The possible mechanisms underlying the inhibition by baclofen of the responses mediated by GABAA receptor and the physiological significance implicated are discussed.     

Testosterone worsens endothelial dysfunction associated with hypercholesterolemia and environmental tobacco smoke exposure in male rabbit aorta

OBJECTIVES: To assess the effects of interaction of sex hormones, hypercholesterolemia (HC) and environmental tobacco smoke (ETS) exposure on endothelium-dependent relaxation, we examined vascular reactivity in vitro in an animal model of atherogenesis. BACKGROUND: Animal and human studies indicate the presence of interactions between classic coronary artery disease risk factors and endothelium-dependent relaxation. Sex hormones have also been shown to influence release of endothelium-derived relaxing factor. METHODS: New Zealand White rabbits were randomized to receive either an HC diet (n = 8) or ETS exposure plus HC diet (n = 8). Eight rabbits receiving a normal diet, without exposure to ETS, served as the control group. The HC diet consisted of 3% soybean oil and 0.3% cholesterol by weight over 13 weeks. The source of ETS was sidestream smoke of 4 cigarettes/15 min, 6 h/day, 5 days/week over 10 weeks in a smoking chamber. Rabbits were killed, and fresh aortic rings were harvested and maintained in oxygenated Krebs solution in an organ bath at 37 degrees C. Rings were precontracted with norepinephrine and exposed to acetylcholine in increasing doses, and isometric tension was recorded. Rings were also exposed to physiologic concentrations (1 nmol/liter) of either 17-beta-estradiol, testosterone or progesterone before pre-contraction with norepinephrine and relaxation with acetylcholine. Endothelium-independent relaxation was studied using nitroglycerin. The surface area of the ring covered by lipids was measured by Sudan IV staining. RESULTS: HC and ETS significantly reduced endothelium-dependent relaxation (p = 0.01 and p < 0.0005, respectively) and caused atherogenesis (p < 0.0005 and p = 0.047, respectively) but did not affect endothelium-independent relaxation. Incubation with estradiol and estradiol plus progesterone did not influence endothelium-dependent relaxation. Testosterone reduced endothelium-dependent relaxation (p = 0.049) and augmented the endothelial dysfunction associated with ETS exposure and HC (p = 0.03). CONCLUSIONS: Both HC and ETS are atherogenic and impair endothelial function but do not affect endothelium-independent relaxation. Physiologic levels of estradiol and estradiol plus progesterone do not affect endothelium-dependent relaxation. Physiologic levels of testosterone impair relaxation and augment the endothelial dysfunction associated with ETS exposure and HC.     

A concussive-like brain injury model in mice (II): selective neuronal loss in the cortex and hippocampus

The modeling of human concussive brain injury (CBI) in the laboratory has been challenging. In the present study, we developed an experimental CBI model in mice using a novel weight-drop device. Various injury levels were examined by adjusting the height of the falling weight (diameter 10 mm, length 20 cm, weight 21 g). At a height of 50 cm, the impact resulted in a mortality rate of 46.7% with a skull fracture rate of 28.6%. At a height of 25 cm, however, the impact produced a concussive-like brain injury (CLBI) to the mice without skull fracture. A series of pathophysiological and neurobehavioral responses was evaluated at this injury level. The CLBI mice lost muscle tone and righting reflex response immediately following the trauma and recovered from the latter within a short duration of 1.6 +/- 0.32 min (mean +/- SE). Brain edema formation started at 12 h, reached a maximum at 24 h and recovered 48 h. Typically edema was found in the neocortex, hippocampus, and cerebellum, but not in the brain stem. Deficits in the feeding behaviors lasted for 2 days, accompanied by lower body weight persisting for 5 days. The body weight growth rate for 24 h returned to the control levels by the third day postinjury. Learning and memory were evaluated at the end of 1-3 weeks after the trauma using a water-finding task. At 1 week, exploratory behaviors were slightly inhibited while learning and memory were profoundly impaired. Interestingly, the learning and memory deficits lasted for 2 weeks while recovering to the control levels by 3 weeks. No motor disability was found in the CLBI mice during the 3-week evaluations. These results indicate that the weight-drop impact produced graded injury to the brain, and at the injury level of 25 cm it produced a CLBI in the mice in which the characteristics of transient loss of neurobehavioral responses, short duration of brain edema, and long-lasting learning and memory deficits are similar to those of human CBI.     

Cohort analyses of the treatment of smear-positive pulmonary tuberculosis patients under programme conditions in Korea, 1983-1994

The authors previously reported that male offspring of mothers rats given alkaline ionized water (AKW) showed a significantly higher body weight by day 14 after birth than did offspring of mother rats given tap water (TPW); furthermore, marked myocardial necrosis and fibrosis were observed particularly in the former male offspring at the age of 15 weeks. In the present experiment we looked for differences in bioparameters, namely the milk yield of mothers and suckled milk volume of the offspring, between the AKW- and the TPW-treated groups in order to reveal the factors which cause the unusual body weight gain in the offspring. Even though we were able to repeat our previous observation (the body weight of the male offspring of the AKW group increased significantly more by day 14 and 20 after birth and of the female by day 20 after birth than did that of the TPW group (p < 0.05), no significant difference was noted in any of the bioparameters, including those related to milk production and consumption. It is thus suspected that the water-hydrated cation, which was transferred either to the fetus through the placenta or to the offspring through the milk, might be the cause of the unusual body weight increase. Since calcium plays an important role in skeletal formation, it is tentatively concluded that the higher calcium concentration of AKW enriched the mother, serum calcium which was transferred to the fetus through the placenta and to the offspring through the milk.     

Tumor cells cultured in vivo in diffusion chambers induce hematological alterations

We have studied in BALB/c mice the hematological alterations of the host induced by the growth of tumor cells in diffusion chambers (DC) In this model, host-tumor interactions are only mediated by soluble factors. Tumor cells proliferate and grow in DC up to 15 days after implant. Our results show a reversal of the granulocyte-lymphocyte ratio in peripheral blood, with lymphopenia and a relative increase of myeloid progenitors in the bone marrow of mice bearing DC with M3 tumor cells (M3TC).