Effects of MK-801 and Phenytoin on Flurothyl-Induced Seizures During Development

Summary We determined the effects of the N-methyl-Daspartate (NMDA) receptor blocker MK-801 (0.05, 0.1, and 0.5 mg/kg intraperitoneally, i.p.) and phenytoin (PHT, 5, 10, and 20 mg/kg i.p.) on flurothyl-induced clonic and tonic-clonic seizures in 9-, 1 5, 30-, and 60-day-old male rats. Both agents had seizure-, age-, and dose-specific effects. The highest dose of MK-801 was anticonvulsant against clonic flurothyl-induced seizures only in 9- and 60-day-old rats, but suppressed tonic-clonic seizures in all ages. The lowest dose of MK-801 (0.05 mg/kg) produced significant anticonvulsant effects only in 15 day old rats. PHT did not have any effect on clonic seizures throughout development. Both doses of PHT (10 and 20 mg/kg) were anticonvulsant against tonic-clonic seizures in adult rats but not in any other age group. The results indicate that NMDA receptors play an important role in tonic-clonic flurothyl-induced seizures throughout development (especially in 15-day-old rats) and that the anticonvulsant effects of PHT may vary at different stages of brain development.     

INVOLVEMENT OF PHOSPHOPROTEIN PHOSPHATASE 1 IN COLLAGEN-PLATELET INTERACTION

The binding of type I collagen to its receptor initiates platelet aggregation, but the relationship of the receptor to other signal transduction components is not yet established. Correlation of platelet aggregation and anti-type I collagen receptor antibody immunoprecipitation of type I collagen treated [³²PO4]-labeled platelets showed that there are two phosphoproteins (M_r 53 kDa and 21 kDa) that coprecipitated with the 65 kDa platelet type I collagen receptor. In the present investigation, we have identified one of the phosphoproteins. A soluble component the 100,000×g supernatant fraction of 53 kDa protein is recognized by polyclonal anti-PP1 antibody. The activity of the precipitated phosphatase is inhibited by okadaic acid and inhibitor 1, suggesting that it is protein phosphatase 1 (PP 1). Phosphorylation decreases PP 1 activity as was found with [³²PO4]-phosphorylase b as the substrate. The immunocoprecipitation of the type-1 collagen receptor and PP 1 inot the result of cross reactivity of the anti-type I collagen receptor antibody with the PP I protein. These results indicate that the platelet type I collagen receptor, PP 1, and unidentified 21 kDa protein are in close association with the platelet type I collagen receptor upon the binding of type I collagen by the receptor. Copyright © 1996 Elsevier Science Ltd     

Age-Specific Effects of Baclofen on Pentylenetetrazol-Induced Seizures in Developing Rats

Summary: Purpose : To determine whether seizures have age-specific features, we studied the role of γ-aminobutyric acid, (GABAB) transmission in rats of various ages (9, 15, 30, and 60 postnatal days). Methods: We used a GABA, receptor agonist baclofen (2 or 5 mg/kg intraperitoneally, i.p.) and a GABA_B receptor antagonist CGP 35348 (100 or 600 mg/kg i.p.) in the pentylenetetrazol (PTZ)-induced model of clonic and tonic-clonic seizures (100 mg/kg subcutaneously, s.c.).
Results : Whereas baclofen was anticonvulsant and CGP 35348 proconvulsant in most animals, there were distinct age-related differences in the effectiveness of these drugs and the antagonist had some anticonvulsant activity in adults. Furthermore, the two drugs acting at GABA_B receptors had a different profile of action in clonic seizures as compared with tonic-clonic seizures.
Conclusions : The differences in the age-specific action of the GABA_B agonist and antagonist suggest that different GABA_B receptor subsets may mediate the drug effects. The results indicate that putative antiepileptic drugs (AEDs) must be tested during development because it may not be possible to extrapolate age-specific anticonvulsant effects from studies in adult animals.     

Impact of Social Confrontation on Rat CD4 T Cells Bearing Different CD45R Isoforms

The impact of social defeat on lymphocyte subpopulations and T helper subsets was investigated in Long Evans rats. CD4 T helper cell subsets with distinct functional properties and different cytokine profiles can be distinguished by using the mAbs OX-22 (anti-CD45RC) and OX-7 (anti-CD90, Thy1.1). Male intruders were exposed for 2, 6, or 48 h to aggressive resident pairs. All intruders were attacked upon introduction and were defeated as indicated by frequent display of full submissive postures. After 2 and 48 h of confrontation, drastic but differential effects on blood leukocyte numbers, CD4 and CD8a cells, and CD4 subsets were evident. However, after 6 h of confrontation most lymphocyte subset numbers corresponded to baseline levels. Focusing on CD4 subsets after 2 h of confrontation, we demonstrated that only the number of the CD45RC⁻CD90⁻subset declines, whereas neither the number of the CD45RC⁺CD90⁻subset nor the number of the CD45RC⁻CD90⁺subset (recent thymic emigrants) was influenced. Con A stimulation of sorted subsets identified the CD45RC⁻CD90⁻as a poor producer of IFN-γ. The data clearly demonstrate that social factors might differentially influence not only T cell subsets but also T helper cell subsets with distinct cytokine profiles in a possibly time-dependent manner. Such a stress-induced shift toward a CD45RC⁺CD90⁻-dominated milieu may have important consequences in interpreting results obtained from mitogenic stimulation of blood lymphocytes and cytokine production profiles measured after such a stimulation. In addition, a shift toward a CD45RC⁺CD90⁻dominance may modify the type and magnitude of immune response, at least temporarily.     

Combat-related posttraumatic stress disorder among second-generation Holocaust survivors: preliminary findings

The authors assessed the impact of the Nazi Holocaust on the course and symptoms of posttraumatic stress disorder (PTSD) among Israeli combat stress reaction casualties. They examined a sample of 96 such casualties of the 1982 Lebanon War whose parents had gone through the Nazi Holocaust and compared them to casualties who did not have such family history for 3 consecutive years beginning 1 year after their participation in the war. Results showed that 2 and 3 years after their participation in the 1982 Lebanon War, the children of Holocaust survivors, i.e., "second-generation" casualties, had higher rates of PTSD than did the control subjects, as well as a somewhat different clinical picture. Clinical and methodological implications of the findings are discussed.     

Malignant pleural effusions: pleurodesis using a small-bore percutaneous catheter

This study describes our experience using a percutaneously placed small-bore catheter for drainage of malignant pleural effusions and subsequent instillation of a sclerosing agent to obliterate the pleural space. We treated 15 consecutive patients with known metastatic cancer and a symptomatic pleural effusion. Twelve patients survived for more than four weeks after the procedure; 11 of these 12 patients had a successful objective clinical response. The procedure was well tolerated, with little or no discomfort during catheter placement and the maintenance period. No serious complications were encountered. We conclude that the use of a small-bore percutaneously placed "pneumothorax" catheter in the management of malignant pleural effusions is an effective and more comfortable alternative to large-bore closed-tube thoracostomy.     

Self-reported urogenital symptoms in postmenopausal women: Women's Health Initiative

OBJECTIVE: To examine the prevalence and correlates of self-reported urogenital symptoms (dryness, irritation or itching, discharge, dysuria) among postmenopausal women aged 50-79. DESIGN: A cross-sectional analysis based on n=98,705 women enrolled in the US-based Women's Health Initiative observational study and clinical trials. Urogenital symptoms, symptom severity (mild, moderate, severe), and all covariates were self-reported through questionnaires at enrollment. Prevalence rates of each urogenital symptom were examined and logistic regression was used to identify potential correlates. RESULTS: Prevalence rates for each symptom were: dryness, 27.0%; irritation or itching, 18.6%; discharge, 11.1%; and dysuria, 5.2%. Four factors were correlated with two or more symptoms: Hispanic ethnicity (adjusted odds ratio (AOR)=2.1-3.1 versus white women across all symptoms), obesity (AOR=2.2 severe discharge versus none, AOR=3.6 severe irritation/itching versus none), treated diabetes (pills or shots) compared to no diabetes (AOR=2.4 severe dysuria versus none, AOR=3.2 severe irritation/itching versus none), and vaginal cream HRT/ERT compared to those who never used HRT/ERT (AOR=4.4 severe dryness versus none, AOR=4.6 severe irritation/itching versus none). Factors not associated with the symptoms included sexual activity, age, years since menopause, current smoking, marital status, gravidity, and natural versus surgical menopause. CONCLUSIONS: This is the first report to document urogenital symptoms by race/ethnicity among an exclusively postmenopausal population. We found an elevated prevalence of urogenital symptoms among women who are Hispanic, obese, and/or diabetic. Confirmation of our findings in these subgroups, and, if confirmed, analysis on why these populations are at greater risk, are areas for future research.     

Two novel paradigms for the simultaneous assessment of conditioned taste aversion and food intake effects of anorexic agents

The conditioned taste aversion (CTA) is routinely used to assess the aversive consequences of anorexic agents, including potential pharmacological therapies for obesity. In a typical CTA paradigm, rats briefly sampling a novel tastant (e.g., saccharin) are acutely administered with toxin (e.g., lithium chloride, LiCl). After as few as one taste-toxin pairing, rats will reliably avoid the novel tastant. This paradigm is frequently used for the assessment of possible aversive consequences of drugs that are candidates for pharmacological therapies. The degree to which the drug supports development of a CTA is interpreted as an index of its aversive properties. Difficulties with previous work include the inability to assess affects on food intake and CTA simultaneously, particularly during chronic drug administration. We report here two novel CTA paradigms for the assessment of appetitive and aversive consequences of anorexic agents, simultaneously. In the first experiment, animals receive an intraoral infusion of a novel and highly palatable tastant immediately prior to administration of increasing doses of LiCl. In the second experiment, rats were implanted intraperitoneally with osmotic minipumps that chronically delivered a low dose of LiCl for 7 days. LiCl did not affect short or long term food intake in either experiment. However, LiCl did support the development of a CTA in both paradigms. These results suggest that both the appetitive and aversive consequences of anorexic agents can be assessed simultaneously during either acute or chronic drug administration.     

Combined Administration of Meningococcal Serogroup B Outer Membrane Vesicle Vaccine and Conjugated Serogroup C Vaccine Indicated for Prevention of Meningococcal Disease Is Safe and Immunogenic

MenBvac and Menjugate are safe and efficacious vaccines. The purpose of this study was to evaluate safety and immunogenicity of the combination (MenB/C) of the lyophilized active components of the conjugated group C vaccine Menjugate when reconstituted with the full liquid group B outer membrane vesicle vaccine MenBvac compared to MenBvac and Menjugate given separately. At 6-week intervals, healthy adults were given one dose of MenB/C followed by two doses of MenBvac (MenB/C group), three doses of MenBvac (MenB group), or one dose of Menjugate and two doses of placebo (MenC group). Injection site reactions were frequent in all groups. However, most reactions were short lasting and mild or moderate in intensity, and the vaccines were found to be well tolerated, with no vaccine-related serious adverse events. MenB/C was immunogenic with regard to both serogroup B and C meningococci. Both the serum bactericidal assay and the enzyme-linked immunosorbent assay analyses showed that the immune responses of the combination vaccine were similar to the immune responses of its separate components MenBvac and Menjugate for both serogroup B and C. In conclusion, the combined MenB/C vaccine is safe and immunogenic. The two vaccines do not interact negatively with each other and can easily be administered in the same syringe. The induced immune responses suggest that the combined vaccine is likely to confer protection against systemic group B disease caused by the vaccine strain as well as against group C meningococcal disease.