The effects of a single memantine treatment on behavioral alterations associated with binge alcohol exposure in neonatal rats

Background

The third trimester in human fetal development represents a critical time of brain maturation referred to as the “brain growth spurt”. This period occurs in rats postnatally, and exposure to ethanol during this time can increase the risk of impairments on a variety of cognitive and motor tasks. It has been proposed that one potential mechanism for the teratogenic effects of ethanol is NMDA receptor-mediated excitotoxicity during periods of ethanol withdrawal. In neonatal rats, antagonism of NMDA receptors during ethanol withdrawal, with drugs such as MK-801 and eliprodil, has been shown to mitigate some of the behavioral deficits induced by developmental ethanol exposure. The current study examined whether memantine, an NMDA receptor antagonist and a drug used clinically in Alzheimer's patients, would attenuate impairments associated with binge ethanol exposure in neonatal rats.

Methods

On postnatal day 6, rats were exposed to 6 g/kg ethanol via intubation with controls receiving an isocaloric maltose dextrin solution. Twenty-one hours following the ethanol binge, rats received intraperitoneal injections of memantine at 0, 10, 15, or 20 mg/kg. Ethanol's teratogenic effects were assessed using multiple behavioral tasks: open field activity, parallel bars and spatial discrimination reversal learning.

Results

Ethanol-treated rats were overactive in the open field and were impaired on both reversal learning and motor performance. Administration of 15 or 20 mg/kg memantine during withdrawal significantly attenuated ethanol's adverse effects on motor coordination, but did not significantly alter activity levels or improve the spatial learning deficits associated with neonatal alcohol exposure.

Conclusion

These results indicate that a single memantine administration during ethanol withdrawal can mitigate motor impairments but not spatial learning impairments or overactivity observed following a binge ethanol exposure during development in the rat.     

Thyroid dysfunction after mantle irradiation of Hodgkin's disease patients

Thyroid dysfunction can develop in patients with Hodgkin's disease who are treated with mantle irradiation. During the period 1970-89, the records of 320 patients who received mantle irradiation and who had thyroid function tests (TFT) were retrospectively reviewed. The median age was 30 years (range, 7-69 years). The median mantle and thyroid dose was 36 Gy (range, 30-40 Gy) and 39.8 Gy (range, 32-65 Gy), respectively. Overall thyroid dysfunction was present in 39% of the patients. Clinical hypothyroidism was seen in 10% and biochemical hypothyroidism was noted in 25%. Hyperthyroidism was found in 4% of patients. Thyroid nodules had developed in six patients (2%), of which those in four patients were malignant. Age, sex, histological subtype, stage of disease, dose, lymphangiogram and treatment with chemotherapy were not significant factors in the development of thyroid dysfunction. The narrow dose range prevented adequate analysis of dose effect. The results indicate that the incidence of thyroid abnormalities is high enough to warrant regular TFT assessment with pre-irradiation levels and follow-up testing for life because the development of abnormalities can occur many years later. Thyroid examination should form part of the routine follow-up examination and any abnormality should be promptly investigated.     

Insulin-like growth factor-I mitigates motor coordination deficits associated with neonatal alcohol exposure in rats

Prenatal alcohol exposure can affect brain development, leading to behavioral problems, including overactivity, motor dysfunction and learning deficits. Despite warnings about the effects of drinking during pregnancy, rates of fetal alcohol syndrome remain unchanged and thus, there is an urgent need to identify interventions that reduce the severity of alcohol's teratogenic effects. Insulin-like growth factor-I (IGF-I) is neuroprotective against ethanol-related toxicity and promotes white matter production following a number of insults. Given that prenatal alcohol leads to cell death and white matter deficits, the present study examined whether IGF-I could reduce the severity of behavioral deficits associated with developmental alcohol exposure. Sprague-Dawley rat pups received ethanol intubations (5.25 g/kg/day) or sham intubations on postnatal days (PD) 4-9, a period of brain development equivalent to the third trimester. On PD 10-13, subjects from each treatment received 0 or 10 microg IGF-I intranasally each day. Subjects were then tested on a series of behavioral tasks including open field activity (PD 18-21), parallel bar motor coordination (PD 30-32) and Morris maze spatial learning (PD 45-52). Ethanol exposure produced overactivity, motor coordination impairments, and spatial learning deficits. IGF-I treatment significantly mitigated ethanol's effects on motor coordination, but not on the other two behavioral tasks. These data indicate that IGF-I may be a potential treatment for some of ethanol's damaging effects, a finding that has important implications for children of women who drink alcohol during pregnancy.     

Uroscopy in the 21st century: high-field NMR spectroscopy

From the experiments described, it can be seen that there are different research approaches that can be taken and these are summarized in Table 1. Whereas much scientific research is principally hypothesis led, there remains, nevertheless, an important place for exploratory research. High resolution NMR can measure, directly and simultaneously, a wide range of endogenous metabolites in biological fluids and has the unique capability of providing structural information on the metabolites detected. It has proved to be a powerful research tool with which to study inherited metabolic diseases, renal disease, drug metabolism, and toxicity, and can be used to monitor the effects of drug therapy. For instance, by using a library of experimental toxins one can map the metabolic profile of site-specific nephron injury. With this approach in man one could eventually take an unknown disease such as Balkan nephropathy and predict the initial site of tubular injury, the mode of injury and therefore the kind of toxin capable of producing that injury. NMR spectroscopic techniques are still advancing rapidly, with ever increasing sensitivity and sophistication of NMR pulse sequences to enhance structural elucidation in complex mixtures. Given the advances in directly coupled HPLC-NMR and even HPLC-NMR-mass spectroscopy it is likely that these technologies in conjunction with pattern recognition will make major contribution to our understanding of renal processes and provide new diagnostic insights in the 21st century.      

Effect of Aerobic Exercise Training on Maternal Weight Gain in Pregnancy: A Meta-Analysis of Randomized Controlled Trials

Background

Weight gains in pregnancy within the recommended guidelines are associated with healthy fetal and maternal outcomes; higher weight gains are associated with fetal macrosomia. This study was a systemic review of randomized controlled trials on the effect of aerobic training on maternal weight in pregnancy.

Methods

The study data source was publications through May 2012 in the MEDLINE (PubMed) database. The citation lists of randomized controlled trials on the effect of aerobic training and maternal weight were extracted. Data on participants'' characteristics, study quality, population, intervention, treatment outcome (maternal weight gain) were collected and analyzed.

Results

There were 11 randomized controlled studies using body weight (kg) as measure of treatment outcome. A total of 1177 subjects were recruited in the 11 studies. The mean± SD weight gain (kg) for the exercise (11.31± 7.44kg) and control (14.42± 6.60kg) groups; Meta-analysis result indicated significant effect of aerobic training on maternal weight (t= -7.580, p= .000) at p< 0.05.

Conclusion

It was concluded that aerobic training is an effective tool in maternal weight gain control in pregnancy. More randomized controlled trials are warranted.