Do similar neural systems subserve aggressive and sexual behaviour in male rats? Insights from c-Fos and pharmacological studies

It is a common belief that male aggressive and sexual behaviour share many of the underlying neurobiological, neurological, pharmacological and neuroendocrine mechanisms. Therefore, we studied brain activation patterns in male rat after performance of aggressive and sexual behaviour and compared serotonergic pharmacology in the same paradigms to delineate possible similarities and differences. Patterns of Fos-immunoreactivity induced by aggressive and sexual encounters of Wild-type male Brown Norway rats were studied to localise the commonly activated (functionally shared) parts of the circuitry, and the specific (functionally different) parts of the neuronal circuitry. Some brain areas (caudal medial preoptic area and medial amygdala) were commonly activated, but other areas (e.g. posterodorsal parts of the medial amygdala, rostral preoptic and premammillary hypothalamus) showed remarkably specific differences in neural activation. 5-HT(1A) receptor agonists inhibit aggressive, but stimulate male sexual behaviour, whereas 5-HT(1B) receptor agonists inhibit both types of behaviour. Selective serotonin reuptake inhibitors share comparable inhibitory effects in aggression and sexual behaviour, although only at relatively high doses. We propose that separate hard-wired neural systems exist in the brain for aggressive and sexual behaviours, modulated via hierarchically 'higher-level' brain areas that are involved in the integration (gating) of the behavioural outcome of an organism.     

Flagella-mediated bacterial motility accelerates but is not required for Salmonella serotype Enteritidis invasion of differentiated Caco-2 cells

The relative contributions of the flagellum and the flagella-associated bacterial motility in the invasion of Caco-2 cells by Salmonella serotype Enteritidis were investigated using an fliC mutant defective in flagellin production and a motA mutant that carries flagella but is non-motile. Infection assays demonstrated that, at 1 h of infection, both the fliC and the motA mutants were severely impaired in bacterial invasion compared to the parental strain. Infection assays at 3 h infection demonstrated virtually equal invasion levels for both non-motile mutants and the parental strain. Together these data suggest that flagella-mediated bacterial motility accelerates the invasion of Salmonella but is not required for the invasion event per se.     

Is the Perceived Association between Chlamydia pneumoniae and Vascular Diseases Biased by Methodology?

Inter- and intralaboratory inconsistencies in detection rates of Chlamydia pneumoniae in vascular specimens have been demonstrated. In this study, 66 vascular tissue specimens from 66 patients with vascular disease were tested by three PCR assays: a 16S PCR-based reverse line blot (RLB) assay, a single-step PCR, and a nested PCR. Also, we explored the impacts of different DNA polymerase enzymes on the results based on gel electrophoresis and hybridization. The PCR results by gel electrophoresis in the single-step PCR depended on which DNA polymerase was used. All samples were negative with AmpliTaq Gold DNA polymerase, and 54.5% (36 of 66) were positive with the conventional Taq DNA polymerase. All samples were negative after hybridization with a C. pneumoniae-specific probe. In the nested PCR, all specimens were negative by gel electrophoresis and after hybridization. The RLB assay failed to detect C. pneumoniae in any specimen; however, 20 specimens were Chlamydia sp. positive. The sequence analysis of six of these samples demonstrated Chlamydia-like organisms. RLB detected Chlamydia sp. DNA in water and in the elution buffer after passage of the Qiagen columns (11 of 40). This study identified factors that may influence the detection of C. pneumoniae DNA in vascular tissues and consequently bias the perception of a link between C. pneumoniae and vascular diseases. The following are strongly recommended: to use DNA polymerases that have to be activated, to decontaminate with dUTP-uracil-DNA glycosylase, to hybridize with specific probes, to include sufficient controls, and to use molecular grade water.     

Intrahepatic CD8 T-lymphocytes and HBV core expression in relation to response to antiviral therapy for chronic hepatitis B patients

Recognition of HBV-infected hepatocytes by CD8 T-lymphocytes is important for viral clearance. Expression of hepatitis B core antigen (HBcAg) in HBV-infected hepatocytes can trigger this antiviral T-cell response. The intrahepatic CD8 T-lymphocytes and HBcAg expression were investigated in relation to response to antiviral therapy. Forty chronic HBeAg-positive patients treated with either lamivudine (n = 20) or interferon-alpha (n = 20) were investigated. Ten patients from each treatment group exhibited a response. Liver biopsies were carried out before and after therapy. CD8 T-lymphocytes and HBcAg expression were detected by immunohistochemistry. The number of pretreatment intrahepatic CD8 T-lymphocytes was significantly higher in responders (P = 0.008). In responders baseline nuclear HBcAg expression tended to be lower (P = 0.09). Cytoplasmic expression was not significantly different between responders and non-responders (P = 0.46). The number of CD8 T-lymphocytes correlated with cytoplasmic HBcAg (r(s) = 0.31; P = 0.04); CD8 T-lymphocytes were situated in clusters of hepatocytes with cytoplasmic HBcAg. Longitudinal analysis showed a significant reduction of CD8 T-lymphocytes after treatment in responders (P < 0.001). Multivariate analysis revealed pretreatment CD8 T-lymphocytes and age as independent prognostic factors for response (n = 40). The number of pretreatment CD8 T-lymphocytes was the only independent prognostic indicator for response to interferon-alpha (P = 0.03); it was of borderline significance for lamivudine therapy (P = 0.06). It is concluded that the number of pretreatment intrahepatic CD8 T-lymphocytes is an important predictor of response to HBV therapy with either interferon-alpha or lamivudine. Response to therapy led to a significant reduction of intrahepatic CD8 T-lymphocytes. Co-localisation of CD8 T-lymphocytes and HBcAg-positive hepatocytes suggests antiviral activity predominantly at the site of maximum HBV replication.     

Adenovirus types 5 and 35 seroprevalence in AIDS risk groups supports type 35 as a vaccine vector

The seroprevalence of adenovirus types 5 (Ad5) and 35 (Ad35) was investigated in patients at risk of AIDS. The seroprevalence of Ad5 was higher than Ad35 in HIV-infected patients from The Netherlands (60% versus 7%) and sub-Saharan Africa (90% versus 20%). The seroprevalence was similar among HIV-infected and uninfected individuals, and remained constant during progression to AIDS. Ad35 is less prone to neutralization than Ad5, encouraging the further development of Ad35 for vaccination against HIV.     

Smoking-dependent effects of the angiotensin-converting enzyme gene insertion/deletion polymorphism on blood pressure

BACKGROUND: Studies on the role of the angiotensin-converting enzyme (ACE) gene in the development of hypertension have yielded conflicting results. Recent studies suggested that this gene might have smoking-dependent effects on the development of cardiovascular disease. OBJECTIVE: To study the relationship between the ACE insertion/deletion (I/D) polymorphism, blood pressure and risk of hypertension in current, former and non-smokers in a population-based cohort. METHODS: We included 2412 non-smokers, 2794 former smokers and 1508 current smokers, all participants in the Rotterdam Study. In each group, we assessed the relationship between the ACE I/D polymorphism, systolic (SBP) and diastolic (DBP) blood pressures and risk of hypertension. Mean blood pressures and prevalence of hypertension were compared between carriers and non-carriers of the D allele. All analyses were adjusted for age, sex, body mass index, diabetes mellitus, high-density lipoprotein cholesterol, total cholesterol and use of antihypertensive medication. RESULTS: In non-smokers and former smokers, blood pressure and the risk of hypertension did not differ significantly between genotypes. In smokers, we found a significant increase in SBP in DD carriers (139.6 +/- 22.8 mmHg) compared with II carriers (136.0 +/- 22.7 mmHg) (P = 0.04). No effect of ACE genotype was observed for DBP. The risk of hypertension was significantly increased in smokers who carried one [odds ratio (OR) 1.4, 95% confidence interval (CI) 1.0 to 1.9; P = 0.05] or two (OR 1.5, 95% CI 1.1 to 2.2; P = 0.02) copies of the D allele. CONCLUSIONS: The D allele of the ACE polymorphism is associated with a significantly increased SBP and risk of hypertension in smokers. Our study underlines the importance of gene-environment interactions in the study of candidate genes for hypertension.     

Enhancement of effects of irradiation by gemcitabine in a glioblastoma cell line and cell line spheroids

Background and purpose To determine the cytotoxicity of, and radioenhancement by, gemcitabine on a glioma cell line grown as a monolayer and as spheroid cultures.Material and methods We used a human glioma cell line, Gli-6, which originated from a biopsy specimen of a patient with a glioblastoma multiforme. Spheroids of Gli-6 were prepared by seeding a single cell suspension on agarose-coated Petri dishes. Clonogenic and growth delay assays were used to determine radio-chemosensitivity of monolayer cultures. The growth delay assay was used to determine that of Gli-6 spheroid cultures.Results Spheroid cultures were found to be more resistant to irradiation with/or without gemcitabine than monolayer cultures. Whereas gemcitabine significantly enhances the radiation effect of exponentially growing Gli-6 monolayer cultures at minimal cytotoxic concentrations (10 nM, 24 h), no enhancement was seen in confluent monolayer cultures and in large spheroids at the same concentration. In small spheroids no enhancement was observed at a low-dose gemcitabine (10 nM for 24 h), but an enhancement was observed at higher concentrations (100 nM for 24 h).Conclusion Gemcitabine can lead to enhancement of the effects of X-irradiation in both monolayer as spheroid glioblastoma cultures. The lack of enhancement in confluent monolayer cultures supports the view that cell cycle distribution of cells is important in radiosensitisation by gemcitabine     

The same IkappaBalpha mutation in two related individuals leads to completely different clinical syndromes

Both innate and adaptive immune responses are dependent on activation of nuclear factor kappaB (NF-kappaB), induced upon binding of pathogen-associated molecular patterns to Toll-like receptors (TLRs). In murine models, defects in NF-kappaB pathway are often lethal and viable knockout mice have severe immune defects. Similarly, defects in the human NF-kappaB pathway described to date lead to severe clinical disease. Here, we describe a patient with a hyper immunoglobulin M-like immunodeficiency syndrome and ectodermal dysplasia. Monocytes did not produce interleukin 12p40 upon stimulation with various TLR stimuli and nuclear translocation of NF-kappaB was impaired. T cell receptor-mediated proliferation was also impaired. A heterozygous mutation was found at serine 32 in IkappaBalpha. Interestingly, his father has the same mutation but displays complex mosaicism. He does not display features of ectodermal dysplasia and did not suffer from serious infections with the exception of a relapsing Salmonella typhimurium infection. His monocyte function was impaired, whereas T cell function was relatively normal. Consistent with this, his T cells almost exclusively displayed the wild-type allele, whereas both alleles were present in his monocytes. We propose that the T and B cell compartment of the mosaic father arose as a result of selection of wild-type cells and that this underlies the widely different clinical phenotype.