Lindane inhibition of [35S]TBPS binding to the GABAA receptor in rat brain.

The inhibition of [³⁵S]t-butylbicyclophosphorothionate ([³⁵S]TBPS) binding to the GABA_A receptor by the insecticide γ-hexachlorocyclohexane, lindane, was studied in several brain regions and using different membrane preparation methods, both in vitro and after dosing the animals with the chemical. In the latter studies, the amount of lindane remaining in the membrane suspensions used for binding assays was determined. In vitro data showed values of IC₅₀ from 150 to 1675 nM, varying in function of the membrane preparation method used. This may account for the discrepancies in IC₅₀ values found in the literature. IC₅₀ values within the range of 150–250 nM were determined using extensively washed membranes from several brain regions, so no evidence arose for brain regional differences in the affinity of lindane for the TBPS binding site. After different schedules of acute treatment with lindane, we found a manifest relationship between the extent of the observable inhibition of [³⁵S]TBPS binding and the lindane amount remaining in the membrane suspensions used for binding assays. This relationship was in good agreement with the in vitro data, so no support for an in vivo acute regulation of the binding site was obtained.     

Enhanced neurotoxicity of 3,3'-iminodipropionitrile following carbon tetrachloride pretreatment in the rat.

The consequences of 3,3'-iminodipropionitrile (IDPN) exposure in animals merits attention both because of its unique neurotoxic effects and as a potential model compound of human dyskinetic disorders. An important question that remains to be determined is whether IDPN itself or a putative active metabolite is responsible for the neurotoxic actions of the chemical in vivo. The present work tested the hypothesis that IDPN must be metabolized by the liver to an active metabolite to become neurotoxic. Thus a reduction in IDPN neurotoxicity would be expected when liver function is compromised. Male Long-Evans rats were given ip injections of saline, 100 (IDPN1) or 200 (IDPN2) mg/kg of IDPN for three days. Half of the animals in each IDPN dose group received corn oil po and the other half 1 g/kg of the hepatotoxicant carbon tetrachloride (CCl4) for three days, starting one day before IDPN administration. Body weights were obtained regularly after exposure. Horizontal and vertical motor activity, and acoustic startle response were monitored prior to, and 1,3,9 and 16 weeks after IDPN exposure. An observational rating score was obtained at 1, 3 and 9 weeks. Auditory thresholds for 5- and 40-kHz tones were estimated by reflex modification procedures at 10 weeks. Animals receiving IDPN2 alone displayed the overt behavioral signs characteristic of IDPN intoxication (postural disturbances, head dyskinesias, backward walking, circling, increased motor activity, and decreased startle response). They also showed weight loss, hyperactivity, a transient rearing deficit, decreased startle amplitudes and elevated auditory thresholds for low- and high-frequency tones. None of these symptoms were observed in the animals treated with CCl4 alone, and only a mild transient effect on the observational rating score was shown by the IDPN1 alone animals. In contrast, IDPN1/CCl4 resulted in the same or higher toxicity than the IDPN2 treatment. IDPN2/CCl4 resulted in severe toxicity (38% mortality over a two-week period) and enhanced body weight and behavioral effects compared to IDPN2 alone group. Impairment of xenobiotic biotransformation was confirmed by elevated pentobarbital sleeping time in animals under the same CCl4 dosing regimen. In conclusion, pretreatment with hepatotoxic dosages of CCl4 leads to increased toxicity of IDPN. This suggests that hepatic transformation of the chemical is not required for the manifestation of IDPN-induced neurotoxicity, but instead may be involved in the detoxification of this compound.     

P-fimbriae vaccines

To test for cross-protective capacity of two different P-fimbriae vaccines we vaccinated baboons with fimbriae purified from either Escherichia coli strain ER2 or strain JR1. The vaccinated animals showed elevated antibody titers to P-fimbriae from each of the E. coli strains used, suggesting cross-reactivity as was expected from the results of immunoprecipitation of the fimbriae. Enzyme-linked immunosorbent assay inhibition by heterologous P-fimbriae proved this to be true immunologic cross-reactivity.     

Changes in diastolic function in heart rejection: role of Doppler echocardiography]

In acute cardiac rejection, left ventricular diastolic function is altered. To study these abnormalities and their utility in cardiac allograft rejection, we studied 56 cardiac transplant recipients. All patients were assessed with endomyocardial biopsy and Doppler echocardiography done in the same day. A total of 163 Doppler studies were recollected. Cardiac transplant recipients were excluded during the early 6 weeks postoperative period. Totally, 100 biopsies were normal, 48 positive for mild rejection (Billingham Gde I-II) and 15 positive for moderate or severe rejection (Billingham Gde III-IV). Compared to negative biopsies, during acute rejection left ventricular wald thickness significantly increased (p < 0.05); isovolumic relaxation period and pressure half-time significantly decreased (p < 0.05, p < 0.001 respectively). Nevertheless, increase in peak early mitral flow velocity was only significantly associated with severe rejection (p < 0.001). Correlating only progressive shortening of isovolumic relaxation period parameter in the diagnosis of graft rejection, we forward a high sensibility (85%) and low specificity (57%). Thus, Doppler echocardiographic evaluation of left ventricular diastolic function provides a non-invasive tool for early detection of acute rejection monitoring after the early postoperative period.     

Determining the Alveolar Component of Nitric Oxide in Exhaled Air: Procedures and Reference Values for Healthy Persons

Nitric oxide (NO) production has been described using a 2-compartment model for the synthesis and movement of NO in both the alveoli and the airways. The alveolar concentration of NO (Ca_NO), an indirect marker of the inflammatory state of the distal portions of the lung, can be deduced through exhalation at multiple flow rates. Our objective was to determine reference values for Ca_NO. The fraction of exhaled NO (Fe_NO) was measured in 33 healthy individuals at a rate of 50 mL/s; the subjects then exhaled at 10, 30, 100, and 200 mL/s to calculate Ca_NO. A chemiluminescence analyzer (NIOX Aerocrine) was used to perform the measurements. The mean (SD) Fe_NO was 15 (6) ppb. The mean Ca_NO was 3.04 (1.30) ppb. These values of Ca_NO measured in healthy individuals will allow us to analyze alveolar inflammatory behavior in respiratory and systemic processes.     

Follow up of growth and steroids in premature adrenarche

In a follow up study of 34 patients with premature adrenarche we examined serum adrenal androgen levels and growth. The majority (28/34) showed an upward bend in the growth curve which, at the mean age of 2.3 years, preceded other signs of adrenarche on average by 3.8 years. Pubertal growth spurt was missing or reduced in 50% of the patients (8/16), however, final height did not differ from that expected from parental heights. Adrenal androgens did not remain elevated at adolescence. The mean age at menarche for all the girls was 0.5 years younger than in the general population.Conclusion Our findings imply that premature adrenarche may start earlier than previously recognized. Compared to ordinary growth these children seen to use a greater part of their potential for adult height already at that early age.     

Abuse liability of flunitrazepam among methadone-maintained patients

Abuse liability and acute subjective and psychomotor effects of flunitrazepam were assessed in ten methadone-maintained males with history of benzodiazepine and alcohol use, who voluntarily participated in a double-blind, controlled, cross-over, randomized clinical trial. There were six experimental sessions in which a single oral dose of flunitrazepam 1, 2, and 4 mg; triazolam 0.5 and 0.75 mg; and placebo was given. Evaluations included physiological measures; psychomotor performance tasks (simple reaction time, Digit Symbol Substitution Test, balance task, Maddox-wing device); and self-administered subjective effects questionnaires [Addiction Research Center Inventory (ARCI), Profile of Mood States (POMS), a series of visual analog scales (VAS)]. All drugs but flunitrazepam 1 mg caused an impairment of psychomotor tasks. Effects were more evident with the highest doses of both drugs. Only flunitrazepam 4 mg produced a significant decrease in balance time. Triazolam 0.75 mg induced increases in sedation measured by ARCI-PCAG, depression in POMS, and VAS-drowsiness scores. Flunitrazepam 4 mg caused euphoria-related effects as measured by increases in ARCI-MBG and “high” scores in the VAS. Our findings of flunitrazepam-induced euphoria in methadone-maintained subjects together with epidemiological evidence of flunitrazepam abuse by opioid dependents, suggest that it may be included in the group of benzodiazepines with a relatively high abuse potential. Received: 13 February 1998/Final version: 1 May 1998     

Regional distribution of a high-affinity enkephalin-degrading peptidase ('enkephalinase') and effects of lesions suggest localization in the vicinity of opiate receptors in brain.

The distribution of a high affinity enkephalin-dipeptidylcarboxypeptidase between regions of mouse brain is markedly heterogenous and parallels that of opiate receptors. Furthermore intrastriatal administration of kainic acid as well as interruption of the nigrostriatal dopaminergic pathway by 6-hydroxydopamine (6-OHDA) lead to similar decreases in this peptidase activity and in the number of opiate receptors. On the contrary, no correlation was found between low affinity enkephalin degrading enzymes and opiate receptors.     

Determinants of the Consumption of Regular Soda,Sport, and Energy Beverages in Spanish Adolescents

Increasing sugar-sweetened beverages (SSB) consumption and associated health impacts warrant health-policy action. We assessed associations of socioeconomic and lifestyle variables with adolescents’ consumption of regular soda (RSD), sport (SD), and energy (ED) drinks. Cross-sectional study of 3930 Spanish adolescents (2089 girls, 1841 boys) aged 13–18 years). We compared frequency of consuming each SSB type (European Food Safety Authority questionnaire) with sociodemographic and lifestyle variables (standardized questions). RSD, SD, and ED were consumed at least weekly by 72.7%, 32.3%, and 12.3% of participants, respectively, and more frequently (p < 0.001) by boys, compared to girls. Multivariate ordinal logistic regression showed inverse association between RSD, SD, and ED consumption and parental occupation-based socioeconomic status (p < 0.01). Daily smoking was associated (p < 0.001) with higher ED (OR 3.64, 95% CI 2.39–5.55) and RSD (OR 2.15, 95% CI 1.56–2.97) consumptions. SD intake was associated inversely with smoking (OR 0.60, 95% CI 0.40–0.89, p = 0.012) and directly with physical activity (OR 2.93, 95% CI 2.18–3.95, p < 0.001). School performance was lower among ED (OR 2.14, 95% CI, 1.37–3.35, p = 0.001) and RSD (OR 1.81, 95% CI 1.24–2.64, p = 0.002) consumers, compared to SD. Maleness and low socioeconomic status predicted SSB consumption. Smoking and low school performance were associated with higher ED and RSD intakes.