GABA and GAD-like immunoreactivity in the primate retina

GABA immunoreactivity was studied and compared with GAD immunoreactivity in the retinae of baboon, cynomolgus monkey and man. The central and peripheral parts of the retinae were investigated separately in cynomolgus monkey and in man. The same kinds of structures were stained with both antisera. Cells with a position corresponding to amacrine cells were stained, as well as processes in the inner plexiform layer and some cells in the ganglion cell layer. The outer plexiform layer and some cells with the position and configuration of horizontal cells also appeared immunoreactive. Staining was also observed in bipolar-like cells, in man most clearly when using the GABA antiserum in sections from the central parts of the retina. It is possible that horizontal cells, as well as bipolar-like cells, may play a previously unsuspected role in GABAergic transmission in the primate retina.     

The uptake of the GABA agonist, [H]isoguvacine, by the isolated retina of the rabbit

Previous autoradiographic studies aimed at showing neurones using GABA as their neurotransmitter have been hampered by the fact that the substance is a ubiquitous metabolite and therefore accumulated by a large variety of cells, including glia. Consequently, GABA uptake markers without this widespread uptake are desirable, and one, [³H]isoguvacine, has shown promising results in autoradiographic experiments. Its uptake has now been further studied with quantitative radiochemical techniques.

The uptake of the drug was slow compared to GABA uptake and reached a tissue/medium ratio of about 3 after 120 min. The uptake could be inhibited by GABA, beta-alanine or ouabain, and by incubating the retinas at 0°C. The uptake kinetics were complex but suggested a high affinity uptake system (K_m about 10⁻⁸ M) and perhaps one or several systems with lower affinities.

The results indicate that [³H]isoguvacine and [³H]GABA are accumulated and retained by the same neurones, which most likely use GABA as their neurotransmitter.     

GABA and GAD-like immunoreactivity in the primate retina

Summary GABA immunoreactivity was studied and compared with GAD immunoreactivity in the retinae of baboon, cynomolgus monkey and man. The central and peripheral parts of the retinae were investigated separately in cynomolgus monkey and in man. The same kinds of structures were stained with both antisera. Cells with a position corresponding to amacrine cells were stained, as well as processes in the inner plexiform layer and some cells in the ganglion cell layer. The outer plexiform layer and some cells with the position and configuration of horizontal cells also appeared immunoreactive. Staining was also observed in bipolar-like cells, in man most clearly when using the GABA antiserum in sections from the central parts of the retina. It is possible that horizontal cells, as well as bipolar-like cells, may play a previously unsuspected role in GABAergic transmission in the primate retina.     

Vascular Cellular Adhesion Molecule-1 (VCAM-1) Expression in Mice Retinal Vessels Is Affected by Both Hyperglycemia and Hyperlipidemia

Background

Inflammation has been proposed to be important in the pathogenesis of diabetic retinopathy. An early feature of inflammation is the release of cytokines leading to increased expression of endothelial activation markers such as vascular cellular adhesion molecule-1 (VCAM-1). Here we investigated the impact of diabetes and dyslipidemia on VCAM-1 expression in mouse retinal vessels, as well as the potential role of tumor necrosis factor-α (TNFα).

Methodology/Principal Findings

Expression of VCAM-1 was examined by confocal immunofluorescence microscopy in vessels of wild type (wt), hyperlipidemic (ApoE^−/−) and TNFα deficient (TNFα^−/−, ApoE^−/−/TNFα^−/−) mice. Eight weeks of streptozotocin-induced diabetes resulted in increased VCAM-1 in wt mice, predominantly in small vessels (<10 µm). Diabetic wt mice had higher total retinal TNFα, IL-6 and IL-1β mRNA than controls; as well as higher soluble VCAM-1 (sVCAM-1) in plasma. Lack of TNFα increased higher basal VCAM-1 protein and sVCAM-1, but failed to up-regulate IL-6 and IL-1β mRNA and VCAM-1 protein in response to diabetes. Basal VCAM-1 expression was higher in ApoE^−/− than in wt mice and both VCAM-1 mRNA and protein levels were further increased by high fat diet. These changes correlated to plasma cholesterol, LDL- and HDL-cholesterol, but not to triglycerides levels. Diabetes, despite further increasing plasma cholesterol in ApoE^−/− mice, had no effects on VCAM-1 protein expression or on sVCAM-1. However, it increased ICAM-1 mRNA expression in retinal vessels, which correlated to plasma triglycerides.

Conclusions/Significance

Hyperglycemia triggers an inflammatory response in the retina of normolipidemic mice and up-regulation of VCAM-1 in retinal vessels. Hypercholesterolemia effectively promotes VCAM-1 expression without evident stimulation of inflammation. Diabetes-induced endothelial activation in ApoE^−/− mice seems driven by elevated plasma triglycerides but not by cholesterol. Results also suggest a complex role for TNFα in the regulation of VCAM-1 expression, being protective under basal conditions but pro-inflammatory in response to diabetes.     

The impact of socio-demographic and religious factors upon sexual behavior among Ugandan university students

Introduction

More knowledge is needed about structural factors in society that affect risky sexual behaviors. Educational institutions such as universities provide an opportune arena for interventions among young people. The aim of this study was to investigate the relationship between sociodemographic and religious factors and their impact on sexual behavior among university students in Uganda.

Methods

In 2005, 980 university students (response rate 80%) were assessed by a self-administered questionnaire. Validated instruments were used to assess socio-demographic and religious factors and sexual behavior. Logistic regression analyses were applied.

Results

Our findings indicated that 37% of the male and 49% of the female students had not previously had sex. Of those with sexual experience, 46% of the males and 23% of the females had had three or more sexual partners, and 32% of the males and 38% of the females did not consistently use condoms. For those who rated religion as less important in their family, the probability of early sexual activity and having had a high number of lifetime partners increased by a statistically significant amount (OR = 1.7; 95% CI: 1.2–2.4 and OR = 1.6; 95% CI: 1.1–2.3, respectively). However, the role of religion seemed to have no impact on condom use. Being of Protestant faith interacted with gender: among those who had debuted sexually, Protestant female students were more likely to have had three or more lifetime partners; the opposite was true for Protestant male students.

Conclusion

Religion emerged as an important determinant of sexual behavior among Ugandan university students. Our findings correlate with the increasing number of conservative religious injunctions against premarital sex directed at young people in many countries with a high burden. of HIV/AIDS. Such influence of religion must be taken into account in order to gain a deeper understanding of the forces that shape sexual behavior in Uganda.     

The Invisible Suffering: Sexual Coercion,Interpersonal Violence,and Mental Health - A Cross-Sectional Study among University Students in South-Western Uganda

Background

Despite a history of conflicts and widespread human rights violation in sub-Saharan Africa, little is known about the prevalence of interpersonal violence among the population in this region. Evidence from high-income countries suggests that exposure to violence has mental health consequences and violence also has associations with experiences of sexual coercion.

Aims

This study sought to investigate the prevalence of physical and perceived threats of violence among university students in Uganda and to assess the possible relationship between such violence, sexual coercion, and symptoms of anxiety, depression, and psychoticism, respectively.

Method

In 2005, 980 Ugandan university students responded to a self-administered questionnaire (response rate 80%) that assessed socio-demographic factors, social capital, importance of religion, mental health, experience of violence and sexual coercion, and sexual behaviour factors. Logistic regression analysis was applied as the main analytical tool.

Results

Of those who responded, 28% reported perceived threats/threats of violence and 10% exposure to actual physical violence over the previous 12 months, with no significant gender differences in exposure history. Exposure to violence was significantly associated with the experience of sexual coercion among both males and females. Sexual coercion and threats/threats of violence were both significantly associated with poor mental health in males and females, but only males showed a strong association between exposure to physical violence and poor mental health.

Conclusion

The current study suggests that in terms of general exposure, both males and females in the study population are equally exposed to sexual coercion and interpersonal violence, and both male and female students show generally similar mental health effects of exposure to such violence. The prevalence of interpersonal violence found in our study population may have long-term negative health implications. Our findings may serve as a baseline for interventions and continuing research aimed at preventing interpersonal violence.     

HLA genes, islet autoantibodies and residual C-peptide at the clinical onset of type 1 diabetes mellitus and the risk of retinopathy 15 years later

Aims/Hypothesis

HLA genes, islet autoantibodies and residual C-peptide were studied to determine the independent association of each exposure with diabetic retinopathy (DR), 15 years after the clinical onset of type 1 diabetes in 15–34 year old individuals.

Methods

The cohort was identified in 1992 and 1993 by the Diabetes Incidence Study in Sweden (DISS), which investigates incident cases of diabetes for patients between 15 and 34 years of age. Blood samples at diagnosis were analyzed to determine HLA genotype, islet autoantibodies and serum C-peptide. In 2009, fundus photographs were obtained from patient records. Study measures were supplemented with data from the Swedish National Diabetes Registry.

Results

The prevalence of DR was 60.2% (148/246). Autoantibodies against the 65 kD isoform of glutamate decarboxylase (GADA) at the onset of clinical diabetes increased the risk of DR 15 years later, relative risk 1.12 for each 100 WHO units/ml, [95% CI 1.02 to 1.23]. This equates to risk estimates of 1.27, [95% CI 1.04 to 1.62] and 1.43, [95% CI 1.06 to 1.94] for participants in the highest 25^th (GADA>233 WHO units/ml) and 5^th percentile (GADA>319 WHO units/ml) of GADA, respectively. These were adjusted for duration of diabetes, HbA_1c, treated hypertension, sex, age at diagnosis, HLA and C-peptide. Islet cell autoantibodies, insulinoma-antigen 2 autoantibodies, residual C-peptide and the type 1 diabetes associated haplotypes DQ2, DQ8 and DQ6 were not associated with DR.

Conclusions

Increased levels of GADA at the onset of type 1 diabetes were associated with DR 15 years later. These results, if confirmed, could provide additional insights into the pathogenesis of the most common microvascular complication of diabetes and lead to better risk stratification for both patient screenings and DR treatment trials.     

Health Risks in Same-Sex Attracted Ugandan University Students: Evidence from Two Cross-Sectional Studies

Widespread discrimination across much of sub-Saharan Africa against persons with same-sex sexuality, including recent attempts in Uganda to extend criminal sanctions against same-sex behavior, are likely to have profound effects on this group’s health, health care access, and well-being. Yet knowledge of the prevalence of same-sex sexuality in this region is scarce. This study aimed to systematically examine prevalence of same-sex sexuality and related health risks in young Ugandan adults. We conducted two cross-sectional survey studies in south-western Uganda targeting student samples (n = 980, n = 1954) representing 80% and 72% of the entire undergraduate classes attending a university in 2005 and 2010, respectively. A questionnaire assessed items concerning same-sex sexuality (same-sex attraction/fantasies, same-sex sexual relations), mental health, substance use, experience of violence, risky sexual behavior, and sexual health counseling needs. Our findings showed that same-sex sexual attraction/fantasies and behavior were common among male and female students, with 10–25% reporting having sexual attraction/fantasies regarding persons of the same-sex, and 6–16% reporting same-sex sexual relations. Experiences of same-sex sexuality were associated with health risks, e.g. poor mental health (2010, AOR = 1.5; 95% CI: 1.0–2.3), sexual coercion (2010, AOR 2.9; CI: 1.9–4.6), and unmet sexual health counseling needs (2010, AOR 2.2; CI: 1.4–3.3). This first study of young adults in Uganda with same-sex sexuality found high levels of health needs but poor access to health care. Effective response is likely to require major shifts in current policy, efforts to reduce stigmatization, and reorientation of health services to better meet the needs of this vulnerable group of young people.