Effect of age and caloric restriction on insulin receptor binding and glucose transporter levels in aging rats

We report on the effect of age and chronic caloric restriction (CR) on insulin binding and glucose transporter content in both diaphragm and heart muscle membrane of young (11 months), mid-age (17 months), and old (29 month) ad libitum fed and CR Brown-Norway rats. The control animals received rat chow ad lib and CR animals were allowed 60% of ad libitum food. The CR regimen was initiated at four months of age and the animals were maintained on their respective diets until necropsy. There was no effect of age on insulin binding for either ad libitum or CR animals at each age evaluated. Caloric restriction significantly lowered insulin levels at each age studied when compared to the ad libitum-fed rats. However, CR animals were noted to have increased insulin binding (p < 0.001) compared to ad libitum-fed animals at each age for diaphragm muscle. For the heart, there appeared to be a decreased binding, particularly at higher insulin concentrations, in CR-fed animals. There was no net change in Glut-1 or Glut-4 levels for heart muscle membrane, or Glut-4 levels for diaphragm muscle membrane between ad libitum or CR animals. This data indicates that caloric restriction may have tissue-specific effects for insulin receptor binding, and that the improved insulin sensitivity in CR states is not a result of altered glucose transporter protein content.     

Safety and immunogenicity of Haemophilus type b-tetanus protein conjugate vaccine, mixed in the same syringe with diphtheria-tetanus-pertussis vaccine in young infants

As new vaccines are developed there is increasing interest in reducing the number of injections given to children by combining vaccines in one syringe. We studied the safety and immunogenicity of Haemophilus influenzae type b-tetanus protein conjugate vaccine (PRP-T) administered at ages 2, 4 and 6 months mixed in the same syringe with DTP vaccine and its effects on the seroresponse to DTP vaccine. A group of 112 healthy 2-month-old infants received DTP-PRP-T or DTP-placebo mixed immediately before immunization in the same syringe. The addition of PRP-T to DTP did not increase the rate of local or systemic reactions. After the first, second and third dose, the PRP-T recipients showed a geometric anti-PRP antibody mean of 0.13, 2.31 and 6.40 micrograms/ml vs. 0.07, 0.05 and 0.05 micrograms/ml among the DTP-placebo recipients, respectively. Of the PRP-T recipients, 94 and 98% attained antibody concentration of greater than or equal to 0.15 micrograms/ml protein after the second and third dose, respectively, and 65 and 94% attained a concentration of greater than or equal to 1.0 micrograms/ml after the second and third dose, respectively. At the age of 1 year 94 and 52% of the DTP-PRP-T recipients vs. 12% and 0% of the placebo recipients still maintained titers of greater than or equal to 0.15 and greater than or equal to 1.0 micrograms/ml, respectively. The administration of DTP in the same syringe with PRP-T did not affect significantly the antibody response to diphtheria and tetanus toxoid and to pertussis agglutinins. It is concluded that PRP-T vaccine could be administered in the same syringe as DTP.     

Brain protection at the blood-cerebrospinal fluid interface involves a glutathione-dependent metabolic barrier mechanism.

The choroid plexuses (CPs) form a protective interface between the blood and the ventricular cerebrospinal fluid (CSF). To probe into the pathways by which CPs provide brain protection, we sought to evaluate the efficiency of glutathione conjugation in this barrier as a mechanism to prevent the entry of blood-borne electrophilic, potentially toxic compounds into the CSF, and we investigated the fate of the resulting metabolites. Rat CPs, as well as human CPs from both fetal and adult brains, displayed high glutathione-S-transferase activities. Using an in vitro model of the blood-CSF barrier consisting of choroidal epithelial cells cultured in a two-chambered device, we showed that glutathione conjugation can efficiently prevent the entry of 1-chloro-2,4-dinitrobenzene (CDNB) into the CSF, a model for electrophilic compounds. The duration of this enzymatic protection was set by the concentration of CDNB to which the epithelium was exposed, and this barrier effect was impaired only on severe epithelial intracellular glutathione and cysteine depletion. The conjugate was excreted from the choroidal cells in a polarized manner, mostly at the blood-facing membrane, via a high-capacity transport process, which is not a rate-limiting step in this detoxification pathway, and which may involve transporters of the ATP-binding cassette c(Abcc) and/or solute carrier 21 (Slc21) families. Supplying the choroidal epithelium at the blood-facing membrane with a therapeutically relevant concentration of N-acetylcysteine sustained this neuroprotective effect. Thus, glutathione conjugation at the CP epithelium coupled with the basolateral efflux of the resulting metabolites form an efficient blood-CSF enzymatic barrier, which can be enhanced by pharmacologically increasing glutathione synthesis within the epithelial cells.     

Risk factors of influenza transmission in households.

BACKGROUND: Influenza transmission in households is a subject of renewed interest, as the vaccination of children is currently under debate and antiviral treatments have been approved for prophylactic use. AIMS: To quantify the risk factors of influenza transmission in households. DESIGN OF STUDY: A prospective study conducted during the 1999 to 2000 winter season in France. SETTING: Nine hundred and forty-six households where a member, the index patient, had visited their general practitioner (GP) because of an influenza-like illness were enrolled in the study. Five hundred and ten of the index patients tested positive for influenza A (subtype H3N2). A standardised daily questionnaire allowed for identification of secondary cases of influenza among their household contacts, who were followed-up for 15 days. Of the 395 (77%) households that completed the questionnaire, we selected 279 where no additional cases had occurred on the day of the index patient's visit to the GP. METHODS: Secondary cases of influenza were those household contacts who had developed clinical influenza within 5 days of the disease onset in the index patient. Hazard ratios for individual clinical and demographic characteristics of the contact and their index patient were derived from a Cox regression model. RESULTS: Overall in the 279 households, 131 (24.1%) secondary cases occurred among the 543 household contacts. There was an increased risk of influenza transmission in preschool contacts (hazard ratio [HR] = 1.85, 95% confidence interval [CI] = 1.09 to 3.26) as compared with school-age and adult contacts. There was also an increased risk in contacts exposed to preschool index patients (HR = 1.93, 95% CI = 1.09 to 3.42) and school-age index patients (HR = 1.68, 95% CI = 1.07 to 2.65), compared with those exposed to adult index cases. No other factor was associated with transmission of the disease. CONCLUSION: Our results support the major role of children in the dissemination of influenza in households. Vaccination of children or prophylaxis with neuraminidase inhibitors would prevent, respectively, 32-38% and 21-41% of secondary cases caused by exposure to a sick child in the household.     

Gender differences in condom-related behaviors and attitudes among Mexican adolescents living on the U.S.-Mexico border.

Adolescents are at increasing risk for HIV infection in Mexico. Research on gender differences in risk behaviors and determinants is needed to develop effective HIV prevention interventions targeting Mexican adolescents. This study examined gender differences in the likelihood of unprotected sex and theoretical correlates among high school students in the border city of Tijuana. Three hundred seventy high-school students completed a face-to-face interview and a self-administered survey. Differences in sexual initiation, condom use, intentions to use condoms in the future, and attitudes towards condoms in this population were assessed. Although male students initiated sexual practices earlier than females, females were more likely to have unprotected sex. Females perceived themselves as more likely to avoid unprotected sex in the future and held more favorable attitudes about condoms. The results suggest that stereotypical gender roles and communication barriers place Tijuana female high school students at higher risk for HIV infection than their male peers.     

Increased circulating interleukin-7 levels in HIV-1-infected women

Sex-based differences in CD4 T-cell (CD4) counts are well recognized, but the basis for these differences has not been identified. Conceivably, homeostatic factors may play a role in this process by regulating T-cell maintenance and repletion. Interleukin (IL)-7 is essential for normal T-cell production and homeostasis. We hypothesized that differences in IL-7 might contribute to sex-based differences in CD4 counts. Circulating IL-7 levels were analyzed in 299 HIV-1-infected women and men. Regression analysis estimated that IL-7 levels were 40% higher in women than in men (P = 0.0032) after controlling for CD4 count, age, and race. Given the important role of IL-7 in T-cell development and homeostasis, these findings suggest that higher IL-7 levels may contribute to higher CD4 counts in women.