Effect of active immunization against growth hormone releasing factor on concentrations of somatotropin and insulin-like growth factor I in lactating beef cows

Two experiments were conducted to determine the effects of immunoneutralization of growth hormone-releasing factor [GRF(1–29)-NH2] on concentrations of somatotropin (ST) and insulin-like growth factor I (IGF-I) in lactating beef cows. In Experiment 1, multiparous Hereford cows were immunized against 2 mg GRF(1–29)-(Gly)4-Cys-NH2 conjugated to human serum albumin (GRFi, n=3) or 2 mg human serum albumin (HSAi, n=3) at 52 ± 1 d prior to parturition. Boosters (1 mg) were administered on days 12, 40 and 114 postpartum (pp). Serum samples were collected at 15-min intervals for 5 hr on days 18, 46 and 120 pp, followed by administration (IV) of an opioid agonist (FK33-824; 10 μg/kg) and an antagonist (naloxone; .5 mg/kg) at hours 5 and 7, respectively. A GRF-analog ([desamino-Tyr1, D-Ala2, Ala15] GRF (1–29)-NH2; 3.5 μg/kg) and arginine (.5 g/kg) were administered at hour 10 on days 47 and 121, respectively. Percentage binding of [125I]GRF (1:100 dilution of serum) 28 d after primary immunization was greater in GRFi (14.3 ± 4.9) than in HSAi (.7 ± .3) cows. Binding increased to 29.3 ± 6.5% after first booster in GRFi cows. Episodic release of ST was abolished by immunization against GRF; concentration and frequency of release of ST were lower (P125I]GRF, absence of pulsatile release of ST, low concentrations of ST and IGF-I and failure of ST to increase after IV opioid agonist or arginine

Differences in risk behaviours and HIV status between primary amphetamines and opioid injectors in Estonia and Russia

Background and objective People who inject drugs (PWID) account for over half of new HIV infections in Eastern Europe and central Asia, where opioids continue to be the dominant illicit drugs injected. Stimulants including amphetamines (ATS) have been associated with HIV infection risk in several settings. We sought to examine whether primary ATS injection was associated with greater HIV risk, compared to opioid injection in two European locales with significant HIV epidemics. Methods PWID in Kohtla-Järve and St. Petersburg were recruited using respondent-driven sampling in 2012–2013. Survey data on demographic characteristics, service use, injecting and sexual risk behaviours and HIV-status (and HCV in Kohtla-Järve) were compared between primary opioid and ATS injectors using logistic regression models. Results Of 591 injectors recruited in Kohtla-Järve and 811 in St. Petersburg, 195 (33%) and 27 (4%) primarily injected ATS in each city. In both cities, ATS injectors were younger than opioid injectors, initiated injection later, injected less frequently and were more likely to have been paid for sex. In both cities, PWID had high levels of multiple sex partners. In Kohtla-Järve, ATS-injectors had lower odds of back-loading and greater odds of polydrug use than opioid-injectors. In St. Petersburg, where over half of PWID reported unsafe sharing practices, ATS-injectors were less likely to report these practices. ATS-injection was negatively associated with being HIV positive in Kohtla-Järve (aOR = 0.6; 95%CI: 0.5–0.8) and St. Petersburg (aOR = 0.3; 95%CI: 0.1–0.7). ATS-injection was negatively associated with HCV-reactivity in Kohtla-Järve (aOR = 0.5; 95%CI: 0.3–0.6). Conclusions In both locations, primary ATS injection was associated with lower injecting risk behaviours, lower odds of HIV and being paid for sex compared to opioid injection. Interventions targeting the characteristics and needs of ATS injectors are needed to increase contact with services and reduce sexual and injecting risk. Harm reduction services, including sexual risk reduction, need to be expanded for all PWID in St. Petersburg

Psychosocial and contextual correlates of opioid overdose risk among drug users in St. Petersburg, Russia

<p>Abstract</p> <p>Background</p> <p>Opioid overdose in Russia is a problem that has grown more severe as heroin abuse expanded over the past decade, yet few studies have explored it in detail. In order to gain a clearer understanding of the situation, 60 drug users, both in and out of drug treatment in St. Petersburg, were interviewed concerning their overdose experience and knowledge about overdose recognition and prevention.</p> <p>Methods</p> <p>Using a semi-structured interview, we sought to identify and describe local attitudes, knowledge and experience (both self-sustained and witnessed) of opioid overdose. Bi-variate and multiple logistic regressions were performed in order to identify the relationship between overdose experience and sociodemographic factors, risk behaviors, and clinical psychiatric measures.</p> <p>Results</p> <p>We found that having experienced or witnessed an opioid overdose within the previous year was common, overdose knowledge was generally high, but nearly half the participants reported low self-efficacy for effectively intervening in an overdose situation. In bivariate analyses, self-reported family problems (i.e., perceived problematic family interactions) were positively associated with both experiencing (t₅₆= 2.49; p < 0.05) and with witnessing a greater number of overdoses in the previous year (rho_s= 0.31; p < 0.05). Having previously overdosed [Adjusted Risk Ratio (ARR) 1.7, 95% Confidence Interval (CI) 1.1–2.6] and higher SCL-90-R somatization scores (ARR 1.2, 95% CI 0.96 – 1.5) were independently associated in multivariable analyses with self-sustained overdose experience in the past year. Greater perceived likelihood of experiencing a future overdose and concern about medical problems were independently associated with witnessing a higher number of overdoses within the previous year. Over two thirds of the participants expressed interest in receiving training in overdose prevention and response.</p> <p>Conclusion</p> <p>Opioid overdose experience is very common among drug users in St. Petersburg, Russia, and interest in receiving training for overdose recognition and prevention was high. Future research should target the development of effective overdose recognition and prevention interventions, especially ones that include naloxone distribution and involve drug users' families.</p

Ontogeny of synaptophysin and synaptoporin in the central nervous system

The expression of the synaptic vesicle antigens synaptophysin (SY) and synaptoporin (SO) was studied in the rat striatum, which contains a nearly homogeneous population of GABAergic neurons. In situ hybridization revealed high levels of SY transcripts in the striatal anlage from embryonic day (E) 14 until birth. In contrast. SO hybridization signals were low, and no immunoreactive cell bodies were detected at these stages of development. At E 14, SY-immunoreactivity was restricted to perikarya. In later prenatal stages of development SY-immunoreactivity appeared in puncta (identified as terminals containing immunostained synaptic vesicles), fibers, thick fiber bundles and ‘patches’. In postnatal and adult animals, perikarya of striatal neurons exhibited immunoreaction for SO; ultrastructurally SO antigen was found in the Golgi apparatus and in multivesicular bodies. SO-positive boutons were rare in the striatum. In the neuropil, numerous presynaptic terminals positive for SY were observed. Our data indicate that the expression of synaptic vesicle proteins in GABAergic neurons of the striatum is developmentally regulated. Whereas SY is prevalent during embryonic development, SO is the major synaptic vesicle antigen expressed postnatally by striatal neurons which project to the globus pallidus and the substantia nigra. In contrast synapses of striatal afferents (predominantly from cortex, thalamus and substantia nigra) contain SY

Fiber-Flux Diffusion Density for White Matter Tracts Analysis: Application to Mild Anomalies Localization in Contact Sports Players

We present the concept of fiber-flux density for locally quantifying white matter (WM) fiber bundles. By combining scalar diffusivity measures (e.g., fractional anisotropy) with fiber-flux measurements, we define new local descriptors called Fiber-Flux Diffusion Density (FFDD) vectors. Applying each descriptor throughout fiber bundles allows along-tract coupling of a specific diffusion measure with geometrical properties, such as fiber orientation and coherence. A key step in the proposed framework is the construction of an FFDD dissimilarity measure for sub-voxel alignment of fiber bundles, based on the fast marching method (FMM). The obtained aligned WM tract-profiles enable meaningful inter-subject comparisons and group-wise statistical analysis. We demonstrate our method using two different datasets of contact sports players. Along-tract pairwise comparison as well as group-wise analysis, with respect to non-player healthy controls, reveal significant and spatially-consistent FFDD anomalies. Comparing our method with along-tract FA analysis shows improved sensitivity to subtle structural anomalies in football players over standard FA measurements

Drug choice, spatial distribution, HIV risk, and HIV prevalence among injection drug users in St. Petersburg, Russia

Abstract Background The HIV epidemic in Russia has been driven by the unsafe injection of drugs, predominantly heroin and the ephedrine derived psychostimulants. Understanding differences in HIV risk behaviors among injectors associated with different substances has important implications for prevention programs. Methods We examined behaviors associated with HIV risk among 900 IDUs who inject heroin, psychostimulants, or multiple substances in 2002. Study participants completed screening questionnaires that provided data on sociodemographics, drug use, place of residence and injection- and sex-related HIV risk behaviors. HIV testing was performed and prevalence was modeled using general estimating equation (GEE) analysis. Individuals were clustered by neighborhood and disaggregated into three drug use categories: Heroin Only Users, Stimulant Only Users, and Mixed Drug Users. Results Among Heroin Only Users, younger age, front/backloading of syringes, sharing cotton and cookers were all significant predictors of HIV infection. In contrast, sharing needles and rinse water were significant among the Stimulant Only Users. The Mixed Drug Use group was similar to the Heroin Only Users with age, front/back loading, and sharing cotton significantly associated with HIV infection. These differences became apparent only when neighborhood of residence was included in models run using GEE. Conclusion The type of drug injected was associated with distinct behavioral risks. Risks specific to Stimulant Only Users appeared related to direct syringe sharing. The risks specific to the other two groups are common to the process of sharing drugs in preparation to injecting. Across the board, IDUs could profit from prevention education that emphasizes both access to clean syringes and preparing and apportioning drug with these clean syringes. However, attention to neighborhood differences might improve the intervention impact for injectors who favor different drugs

Spatial distribution of HIV prevalence and incidence among injection drugs users in St Petersburg: implications for HIV transmission

The HIV/AIDS epidemic in St Petersburg, as in much of Russia, is concentrated among injection drug users (IDU) in whom prevalence reached 30% in 2003. Understanding the dynamics of the epidemic is important in developing appropriate responses in the resource-constrained context of Russian cities such as St Petersburg

Consistency and diversity of spike dynamics in the neurons of bed nucleus of Stria Terminalis of the rat: a dynamic clamp study

Neurons display a high degree of variability and diversity in the expression and regulation of their voltage-dependent ionic channels. Under low level of synaptic background a number of physiologically distinct cell types can be identified in most brain areas that display different responses to standard forms of intracellular current stimulation. Nevertheless, it is not well understood how biophysically different neurons process synaptic inputs in natural conditions, i.e., when experiencing intense synaptic bombardment in vivo. While distinct cell types might process synaptic inputs into different patterns of action potentials representing specific "motifs'' of network activity, standard methods of electrophysiology are not well suited to resolve such questions. In the current paper we performed dynamic clamp experiments with simulated synaptic inputs that were presented to three types of neurons in the juxtacapsular bed nucleus of stria terminalis (jcBNST) of the rat. Our analysis on the temporal structure of firing showed that the three types of jcBNST neurons did not produce qualitatively different spike responses under identical patterns of input. However, we observed consistent, cell type dependent variations in the fine structure of firing, at the level of single spikes. At the millisecond resolution structure of firing we found high degree of diversity across the entire spectrum of neurons irrespective of their type. Additionally, we identified a new cell type with intrinsic oscillatory properties that produced a rhythmic and regular firing under synaptic stimulation that distinguishes it from the previously described jcBNST cell types. Our findings suggest a sophisticated, cell type dependent regulation of spike dynamics of neurons when experiencing a complex synaptic background. The high degree of their dynamical diversity has implications to their cooperative dynamics and synchronization