CD81-induced behavioural changes during chronic cocaine administration: in vivo gene delivery with regulatable lentivirus

CD81, a tetraspanin transmembrane protein involved in cell adhesion, is up-regulated in the mesolimbic dopaminergic pathway 24 h following acute administration of high doses of cocaine [Brenz-Verca et al., (2001) Mol. Cell. Neurosci., 17, 303-316]. Further evidence consecutive with this observation and based on microarray analysis are presented here. In addition, a regulatable lentivirus was developed bearing the rat CD81 gene under the control of a tetracycline inducible system. This lentivirus vector was stereotaxically injected into the ventral tegmental area (VTA) of two groups of animals, one fed water (expressing CD81) and the other Doxycycline solution (which down-regulates CD81 expression) and locomotor activity after chronic cocaine administration (10 mg/kg daily) was monitored. After 2 weeks, the groups were inverted, animals receiving water were placed on Doxycycline and the second group was placed on water. In all cases highly a significant increase (3.2-fold) in locomotor activity was observed in animals expressing CD81 in the VTA vs. animals placed on Doxycycline. Similar studies where CD81 was delivered into the nucleus accumbens (NAcc) resulted in significantly higher effects (30%), in accordance with microarray data and our previous reports, yielding a 4.2-fold increase in locomotor activity. No change was observed under similar conditions in control animals, which were injected a regulatable lentivirus expressing GFP. These findings suggest that CD81 expression in the mesolimbic dopaminergic pathway contributes to behavioural changes associated with cocaine sensitization. This study provides a powerful approach for evaluating a gene function in vivo in a single animal under various paradigms, even on gene candidates, which display small changes of expression.     

Long-term nutritional and digestive consequences of pelvic radiation

OBJECTIVE: To study long-term changes in nutritional status and gastrointestinal (GI) functions of 15 women previously treated with radiotherapy for gynecological cancer. Two years prior to this research, these patients had been assessed twice: before external radiotherapy and 5 weeks later, at the completion of the external dose (45-50 Gy). METHODS: Each patient was given complete clinical evaluation, consisting of dietary, physical activity and digestive symptoms questionnaires. Blood was drawn for routine clinical laboratory tests (hemoglobin, white blood cell count, creatinine, lipoproteins, glucose, total proteins, albumin, and C reactive protein). Body composition was assessed by classical anthropometric indicators and double beam X-ray absorptiometry (DEXA), while muscle strength was measured through a hand dynamometer. Resting energy expenditure (REE), obtained by indirect calorimetry, was subtracted from energy ingestion, derived from dietary records, to calculate energy balance. RESULTS: This third evaluation included fifteen patients. A significant increase in body mass index (BMI), % body fat and waist circumference were observed in comparison to earlier evaluations. The lean compartment decreased significantly, and REE descended in parallel. Meanwhile, total energy, fat and protein intake increased, compared to previous measurements. The changes in bowel habits observed during radiotherapy persisted at this third evaluation, with the exception of diarrhea, which was less reported. Abdominal bloating and rectal symptoms were the most prevalent complaints. CONCLUSIONS: After radiation treatment for gynecological cancer, patients gained more body fat than expected in Chilean women around menopause. In spite of high protein ingestion, the loss of fat-free mass observed during radiation treatment was not recovered along with weight increase. This is probably associated with infrequent physical activity, both during and after treatment, and hyperphagia.     

Do oral contraceptives improve vocal quality? Limited trial on low-dose formulations

OBJECTIVE: To evaluate the effect of low-dose monophasic oral contraceptives on female vocal quality. METHODS: Acoustic voice parameters of six women who use oral contraceptives and six women who do not were evaluated repeatedly during the menstrual cycle. Frequency and amplitude variations were measured using a computerized voice analysis program. Repeated-measures analysis of variance was performed to test differences between groups for each acoustic voice parameter. RESULTS: Vocal stability among the women who use oral contraceptives was significantly better than among those who did not use oral contraceptives (P <.05). Specifically, amplitude and frequency variations between successive vocal cycles were smaller in women using oral contraceptives in comparison with the control group (.24 dB versus.37 dB and.86% versus 1.27% for amplitude and frequency variations, respectively). CONCLUSION: Contrary to the reports of adverse effects that high-dose pills have on voice, low-dose oral contraceptives show a favorable influence on voice in young women.     

Ovarian response to gonadotropin stimulation in repeated IVF cycles after unilateral salpingectomy

Purpose : This study aimed to examine ovarian response to gonadotrpoin stimulation after repeated IVF treatment cycles in patients who underwent previous unilateral salpingectomy for tubal pregnancy. Methods : The study group included 26 patients who underwent unilateral salpingectomy for tubal pregnancy 1–9 years prior to starting IVF treatment. A control group of 52 patients with anatomically intact pelvis was treated during the same time period by ICSI. The two groups were matched for age, number of gonadotropin ampules, and length of stimulation. End point measurements included number of follicles, oocytes, and cleaved embryos in consecutive treatment cycles of each group. Results : There were 98 cycles in the study group and 154 cycles in the control group. The mean number of follicles, retrieved oocytes, and cleaved embryos were not different in the two groups, and no reductions in these parameters were noted up to 10 cycles of treatment. The mean number of follicles ipsilateral to the operated side was similar to the number of follicles of the contralateral ovary and was not different whether salpingectomy was by laparoscopy or laparotomy. Conclusions : Unilateral salpingectomy does not affect ipsilateral ovarian response to gonadotropin stimulation even after repeated IVF treatment cycles.     

Supplementing with beta-hydroxy-beta-methylbutyrate (HMB) to build and maintain muscle mass: a review

Beta-hydroxy-beta-methylbutyrate, more commonly referred to as HMB, is derived from the amino acid, leucine, and its keto acid, alpha-ketoisocaproate. In several studies combining HMB supplementation and resistance exercise, researchers have concluded that HMB may play an important role in reducing protein degradation and/or increasing recovery of damaged muscle cells. These actions could be advantageous to all individuals participating in exercise programs and improve the lives of many by overcoming weakness or frailty.     

The antinociceptive effect of amisulpride in mice is mediated through opioid mechanisms

Antinociceptive effects of various neuroleptics in animal acute pain-models have been described, mediated trough different pathways including the opioid system. In this study, we assessed the antinociceptive effects of the atypical neuroleptic drug amisulpride, which acts as a selective blocker of dopamine D2 and D3 receptors. Furthermore, at low doses amisulpride has a selective preference for presynaptic dopamine autoreceptors, while at high doses it manifests a preferential action at post-synaptic dopamine receptors. We found amisulpride to be a potent antinociceptor agent in the mouse tail-flick assay, with an ED50 of 36.6 mg/kg. This effect was antagonized by naloxone (P<0.05), indicating an involvement of opioid mechanisms as mediators of the antinociceptive effect of amisulpride. Beta-funaltrexamine (mu1- and mu2-opioid receptor antagonist), naloxonazine (selective mu1-opioid receptor antagonist), naltrindole (selective delta-opioid receptor antagonist), Nor-binaltorphamine (kappa1-opioid receptor antagonist) reversed amisulpride antinociception at the same dose that they antagonized morphine's antinociceptive effect (all P<0.005). We found that the sensitivity of amisulpride-induced antinociception is mediated through selective involvement of all three opioid receptor subtypes. Based on previous studies with risperidone, clozapine and olanzapine we tend to attribute this global interaction with the opioid system to amisulpride's action at the dopamine D2 receptor sites.     

Complete Freund's adjuvant immunization prolongs survival in experimental prion disease in mice

We recently reported that immunization of mice with certain self-prion protein peptides induced specific T-cell and B-cell immune responses; importantly, this immunization was associated with a decrease in the number of protease-resistant PrP(Sc) particles recoverable in a transplanted, scrapie-infected syngeneic tumor. The present study was carried out to determine whether immunization with the immunogenic PrP peptides might influence the natural history of experimental scrapie in mice. We immunized C57BL/6 mice with self-prion peptides in complete Freund's adjuvant (CFA) or with CFA alone as a control and then infected the mice with mouse-adapted scrapie by injection either intraperitoneally or intracerebrally. We report here that immunization with CFA, irrespective of whether prion peptides were present in the inoculum, resulted in marked prolongation of survival of the mice, whether the challenge was intracerebral or intraperitoneal. Mice in the immunized and control groups that died contained equivalent amounts of PrP(Sc). Thus, CFA immunization has a therapeutic effect in experimental scrapie in mice, possibly by reducing the rate of PrP(Sc) accumulation in the brain.