Priming with a very low dose of DNA complexed with cationic block copolymers followed by protein boost elicits broad and long-lasting antigen-specific humoral and cellular responses in mice

Cationic block copolymers spontaneously assemble via electrostatic interactions with DNA molecules in aqueous solution giving rise to micellar structures that protect the DNA from enzymatic degradation both in vitro and in vivo. In addition, we have previously shown that they are safe, not immunogenic and greatly increased antigen-specific CTL responses following six intramuscular inoculations of a very low dose (1 μg) of the vaccine DNA as compared to naked DNA. Nevertheless, they failed to elicit detectable humoral responses against the antigen. To gain further insight in the potential application of this technology, here we show that a shorter immunization protocol based on two DNA intramuscular inoculations of 1 μg of DNA delivered by these copolymers and a protein boost elicits in mice broad (both humoral and cellular) and long-lasting responses and increases the antigen-specific Th1-type T cell responses and CTLs as compared to priming with naked DNA. These results indicate that cationic block copolymers represent a promising adjuvant and delivery technology for DNA vaccination strategies aimed at combating intracellular pathogens.     

Treatment of ABO Hemolytic Disease with Synthetic Blood Group Trisaccharides

Thirteen infants, 10 with A-O and 3 with B-O hemolytic disease of the newborn (ABO-HDN), were treated with synthetic A or B blood group trisaccharides (ATS, BTS) which cause dissociation of maternal antibody bound to infant red cells. The clinical outcome was compared with that of a control group of 21 infants treated with phototherapy during the preceding year. Exchange transfusion was required in 2 out of 13 infants in the experimental group and in 7 in the control group. A randomized prospective controlled study is necessary to confirm these results.     

High HIV prevalence and risk behaviors in men who have sex with men in Chennai, India

OBJECTIVE: To estimate HIV and sexually transmitted disease (STD) prevalence and behavioral risk characteristics of men who have sex with men (MSM) in Chennai, India. METHODS: A cross-sectional population-based random sample survey was conducted in 2001. Randomly selected residents of 30 slums in Chennai were interviewed for behavioral risk factors through face-to-face interviews. Sera and urine were examined for syphilis, HIV-1, gonorrhea, and chlamydia. Logistic regression analyses were used to assess associations between MSM status and HIV infection and to identify risk characteristics of MSM. RESULTS: Of 774 men, 46 reported (5.9%) sex with other men. MSM were more likely to be seropositive for HIV (odds ratio [OR] = 8.57; 95% confidence interval [CI]: 1.83, 40.23) and were more likely to have a history of STD (OR = 2.66; 95% CI: 1.18, 6.02) than non-MSM. Men who used illicit drugs in past 3 months (adjusted odds ratio [AOR] = 4.01; 95% CI: 1.92, 8.41), ever exchanged money for sex (AOR = 3.93; 95% CI: 1.97, 7.84), or were ever tested for HIV (AOR = 3.72; 95% CI: 1.34, 10.34) were significantly more likely to report sex with men. CONCLUSIONS: MSM in Chennai slums are at high risk for HIV. HIV prevention strategies aimed at changing unsafe drug and sexual practices should target the general population of men, with specific attention to areas with high rates of MSM.     

Aerobic exercise performance correlates with post-ischemic flow-mediated dilation of the brachial artery in young healthy men

In older healthy men, aerobic exercise capacity is related to postischemic flow-mediated dilation of the brachial artery (FMD), but corresponding data in a younger population is not available. In addition, whether submaximal aerobic exercise performance also correlates with this kind of vasomotor reactivity is not known. Therefore, in 15 nonsmoking young healthy men [age 27 (5) years; body mass index: 24 (2) kg/m²; mean (SD)] with different levels of ordinary physical activity, but not performing upper-extremity training, we measured FMD at 1 min after reactive hyperemia, and pulmonary oxygen uptake (O₂) at ventilatory anaerobic threshold (O₂AT) and at peak effort (peak O₂) during an incremental exercise on a treadmill. In our participants, FMD was 9.1 (3.4)%, O₂AT was 40.72 (5.92) ml/kg per min, and peak O₂ was 52.95 (8.13) ml/kg per min. Using bivariate Pearsons correlation, and in separate multivariate regression analyses, O₂AT and peak VO₂ showed a significant and reasonably good correlation with FMD (r=0.84, P<0.001 and r=0.77, P=0.001, respectively), independent of age, body mass index and serum total cholesterol (=0.77, P<0.001, R² of the overall model=0.79 and =0.70, P<0.005, R² of the overall model=0.69, respectively). Our data provide evidence suggesting that in young healthy men a higher submaximal and maximal aerobic exercise performance is associated with a greater FMD of peripheral conduit arteries.     

Profiles of HIV voluntary counseling and testing of clients at a district hospital,Chiang Mai Province,northern Thailand,from 1995 to 1999

Voluntary HIV counseling and testing (VCT) is a central component of comprehensive HIV prevention strategies targeting individual risk reduction. VCT data are essential for planning and improving HIV/AIDS intervention strategies. The objective of this study is to describe demographic profiles, reasons for seeking HIV counseling and testing, rate of declining HIV testing after pretest counseling, rate of failure to return for HIV test results, and HIV prevalence and associations among 3570 clients who sought VCT at Sansai Hospital in northern Thailand from 1995 to 1999. Data were abstracted retrospectively from client-level data recorded by the hospital counselors on a standard form. HIV prevalence was 29% and remained high throughout the study period. Reasons for seeking VCT for men and women were markedly different and highly correlated with rates of declining the test, failure to return for test results, and HIV prevalence. Declining VCT and failing to return were high among uneducated clients (p <.001). Failure to return among men was associated with HIV prevalence (OR = 1.72, p =.003), particularly for those who had risk behaviors (OR = 5.92, p <.001) and those who wanted to know their HIV serostatus (OR = 4.44, p =.002). Overall, VCT acceptance and returning for test results were high. VCT services at the community level can reach high-risk individuals, especially male partners of women tested as part of routine prenatal care.     

Migraine headaches and panic attacks

Migraine headache and panic attacks are two common conditions which first occur at an early age and appear to have a number of underlying physiologic abnormalities in common. In a population-based telephone interview survey examining headache occurrence in approximately 10,000 subjects, 12-29 years old, we assessed the prevalence of panic disorder (and a less severe entity designated as panic syndrome) using an abbreviated version of the National Institute of Mental Health Diagnostic Interview Survey. Subjects with panic disorder or panic syndrome reported more frequent occurrence of headaches during the preceding week, as well as headaches of longer duration and substantially more headaches with migraine symptoms than individuals without a history of panic attack. Males with panic disorder were 7 times more likely than those without this condition to report the occurrence of a migraine headache in the previous week. In addition, 5.5% of males and 9.5% of females with panic disorder or panic syndrome reported 25% of the total migraine headaches described by all study subjects in the one-week recall period.     

NO enhances presynaptic currents during cerebellar mossy fiber-granule cell LTP

Nitric oxide (NO) is a candidate retrograde messenger in long-term potentiation (LTP). The NO metabolic pathway is expressed in the cerebellar granule cell layer but its physiological role remained unknown. In this paper we have investigated the role of NO in cerebellar mossy fiber-granule cell LTP, which has postsynaptic N-methyl-d-aspartate (NMDA) receptor-dependent induction. Pre- and postsynaptic current changes were simultaneously measured by using extracellular focal recordings, and NO release was monitored with an electrochemical probe in P21 rat cerebellar slices. High-frequency mossy fiber stimulation induced LTP and caused a significant NO release (6.2 +/- 2.8 nM; n = 5) in the granular layer that was dependent on NMDA receptor as well as on nitric oxide synthase (NOS) activation. Preventing NO production by perfusing the NOS inhibitor 100 microM NG-nitro-l-arginine (L-NNA), blocking extracellular NO diffusion by 10 microM MbO2, or inhibiting the NO target guanylyl cyclase (sGC) with 10 microM 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-dione (ODQ) prevented LTP. Moreover, the NO donor 10 microM 2-(N,N-diethylamino)-diazenolate-2-oxide.Na (DEA-NO) induced LTP, which was mutually occlusive with LTP generated by high-frequency stimulation, prevented by ODQ, and insensitive to NMDA channel blockade (50 microM APV + 25 microM 7-Cl-kyn) or interruption of mossy fiber stimulation. Thus NO is critical for LTP induction at the cerebellar mossy fiber-granule cell relay. Interestingly, LTP manipulations were accompanied by consensual changes in the presynaptic current, suggesting that NO acts as a retrograde signal-enhancing presynaptic terminal excitability.