Sexual behaviour and Chlamydia trachomatis infections in German female urban adolescents, 2004.

This ad-hoc observational study, conducted in the metropolitan area of Berlin during 2004, revealed that the prevalence of Chlamydia trachomatis (CT) infections in female urban adolescents self-presenting at their gynaecologist without (n=397) or with (n=124) symptoms of CT infection was 5.5% (95% CI 3.7-8.2%) and 9.7% (95% CI 5.6-16.2%), respectively. The prevalence of CT infection was significantly dependent on the number of lifetime sexual partners. Condom use was inconsistent, and lack of knowledge about CT infections and associated health risks predominated in this cohort. The data indicated a need for health education concerning CT to be targeted at female adolescents.

2,9-Dimethyl-beta-carbolinium, a neurotoxin occurring in human brain, is a potent inducer of apoptosis as 1-methyl-4-phenylpyridinium.

The causes of neurodegeneration are not well understood. However, the role of environmental and endogenous toxins is receiving much attention. In this study, we compared the synthetic neurotoxin 1-methyl-4-phenyl-pyridinium with beta-carbolines occurring in human brain. Methylation of both nitrogens is necessary to convert a beta-carboline into a potent inhibitor of mitochondrial complex I. The respective beta-carboline, 2,9-dimethyl-beta-carbolinium ion is neurotoxic in rats. To investigate the underlying mechanisms, we incubated mouse neuroblastoma 2A cells with 2,9-dimethyl-beta-carbolinium ion, and compared the findings with effects of norharman, the precursor beta-carboline of methylated derivatives, and with 1-methyl-4-phenyl-pyridinium. 2,9-Dimethyl-beta-carbolinium ion caused a significant increase of reactive oxygen species (higher efficiency than 1-methyl-4-phenyl-pyridinium) and of mitochondrial membrane potential within the first minutes. After 60 min, the membrane potential dissipated. Concomitantly, the levels of glutathione increased in 2,9-dimethyl-beta-carbolinium ion but not in 1-methyl-4-phenyl-pyridinium treated cells. After 24 h effector caspases 3 and 7 were activated and the number of apoptotic cells increased as revealed by fluorescence-activated cell sorting cytometry. When incubated longer (48 h), cells underwent late apoptosis/secondary necrosis as shown by fluorescence-activated cell sorting analysis and confirmed qualitatively by an electron microscopy study. The effects of 2,9-dimethyl-beta-carbolinium ion on apoptotic changes were similar to those induced by 1-methyl-4-phenyl-pyridinium(,) while norharman showed only a weak potency at the very high doses. To investigate whether 2,9-dimethyl-beta-carbolinium ion is neurotoxic under in vivo conditions and whether only dopaminergic neurones are affected we conducted a dose-response study. Three weeks after injection of 2,9-dimethyl-beta-carbolinium ion in the substantia nigra we found a dose-dependent decrease of dopamine and its metabolites in the striatum of rats. The levels of 5-hydroxytryptamine were diminished although the decrease was less. The levels of noradrenaline increased after some doses. The findings strongly suggest an important role of endogenous beta-carbolines in neurodegeneration with apoptosis as the predominant mechanism.

Cabergoline protects dopaminergic neurons against rotenone-induced cell death in primary mesencephalic cell culture.

In the present study, primary mesencephalic cell cultures prepared from embryonic mouse mesencephala were used to investigate the neuroprotective effect of cabergoline, an ergoline D2 receptor agonist, against the pesticide and neurotoxin rotenone relevant to Parkinson disease (PD). Treatment of cultures with cabergoline alone significantly increased the number of tyrosine hydroxylase immunoreactive (THir) neurons and reduced the release of lactate dehydrogenase (LDH) into the culture medium compared to untreated controls. Against rotenone toxicity, cabergoline significantly rescued degenerating THir neurons, reduced the release of LDH into the culture medium and improved the morphology of surviving THir neurons. The neuroprotective effects afforded by cabergoline were independent of dopaminergic stimulation as blocking of dopamine receptors by the dopamine receptor antagonist sulpiride did not prevent them. Furthermore, rotenone-induced formation of reactive oxygen species (ROS) was significantly reduced by cabergoline. Although cabergoline increased the glutathione (GSH) content in the culture, the protective effect for dopaminergic neurons seemed not to be predominantly mediated by increasing GSH, as depletion of GSH by L-buthionine-(S,R)-sulfoximine (BSO), a GSH biosynthesis inhibitor, did not prevent cabergoline-mediated neuroprotection of THir neurons in rotenone-treated cultures. Moreover, cabergoline significantly increased the ATP/protein ratio in primary mesencephalic cell cultures when added alone or prior to rotenone treatment. These results indicate a neuroprotective effect of cabergoline for dopaminergic neurons against rotenone toxicity. This effect was independent of dopamine receptor stimulation and was at least partially mediated by reducing ROS production and increasing the ATP/protein ratio.

Oxidative stress to dopaminergic neurons as models of Parkinson's disease.

The effects of exogenous toxins (MPP(+), rotenone) and potentially neurotoxic properties of levodopa (L-DOPA) on the survival rate of dopaminergic neurons in dissociated primary culture are presented. Dopamine agonists show a capacity to counteract MPP(+)-toxicity. Moreover, a preserving potential of the antioxidant and bioenergetic coenzyme Q(10) (CoQ(10)) on the activities of tyrosine hydroxylase (TH), complexes I and II of the respiratory chain, and hexokinase activity in striatal slice cultures against MPP(+) is demonstrated.

Practical importance of neuroprotection in Parkinson's disease.

Consensus could be reached that there is overwhelming evidence of preclinical neuroprotection. However, the evidence of neuroprotection/neurorescue under clinical conditions is limited. Lessons from clinical trials designed to show neuroprotection (selegiline, amantadine, dopamine agonists) demonstrate that with the drugs available neuroprotection/neurorescue has to start as early as possible. A PET-controlled clinical trial with ropinirole shows that there seems to be a good chance for neuroprotection in the early phase of Parkinson's disease in patients treated from the very beginning of the disease while there is no such benefit in patients with a late start of a neuroprotective therapeutic strategy. Also long-term clinical neuroprotection cannot be reached. Complicating factors to demonstrate clinical neuroprotection are discussed.

Coenzyme Q10 reduces the toxicity of rotenone in neuronal cultures by preserving the mitochondrial membrane potential.

Defects in mitochondrial energy metabolism due to respiratory chain disorders lead to a decrease in mitochondrial membrane potential (DeltaPsim) and induce apoptosis. Since coenzyme Q10 (CoQ10) plays a dual role as an antioxidant and bioenergetic agent in the respiratory chain, it has attracted increasing attention concerning the prevention of apoptosis in mitochondrial diseases. In this study the potential of CoQ10 to antagonize the apoptosis-inducing effects of the respiratory chain inhibitor rotenone was explored by video-enhanced microscopy in SH-SY5Y neuroblastoma cells. The cationic fluorescent dye JC-1 which exhibits potential-dependent accumulation in mitochondria was used as an indicator to monitor changes in DeltaPsim. The relative changes in fluorescence intensity after incubation with rotenone for 15 minutes were calculated. Pre-treatment with CoQ10 (10 or 100 microM) for 48 h led to a significant reduction of rotenone-induced loss of DeltaPsim. These results suggest, that cytoprotection by CoQ10 may be mediated by raising cellular resistance against the initiating steps of apoptosis, namely the decrease of DeltaPsim. Whether these data may provide new directions for the development of neuroprotective strategies has to be investigated in future studies.

Oxidative stress and living cells.

The review deals with the effects of reactive oxygen species, both radical and nonradical (e.g. hydrogen peroxide), on cells and organisms. The chemical and biochemical aspects include description of individual reactive oxygen species, chemical reactions giving rise to them, their interconversions and interactions with metals (Fe2+, Cu2+, Cu+) and other substances (scavengers, antioxidants). The biological aspects concern the specific features and locations of cellular enzyme systems involved in radical production and/or removal. Major harmful effects of the species on the molecular (protein oxidation, lipid peroxidation, damage to DNA) and cellular level (effect on signal transduction, on cell membrane functions and on gene expression) are surveyed. Methods whereby cells and organisms cope with the onslaught of these reactive species are reviewed as well as implications for plant, animal and human health.

Stability and refractoriness of the high catalase activity in the oxidative-stress-resistant fission yeast Schizosaccharomyces pombe.

Effect of oxygen and metabolic substrates (glucose, ethanol) on the catalase activity of anaerobically grown Schizosaccharomyces pombe cells was assessed and compared with that of Saccharomyces cerevisiae in order to determine the catalase activity regulation in S. pombe. In contrast to S. cerevisiae, the total catalase activity of permeabilized S. pombe anaerobically grown cells is higher than that found in aerobically grown cells, is stable and constant under all circumstances (i.e. it is not induced by oxygen and/or substrates), and only a negligible part (3-5%) of it is contributed by de novo protein synthesis during aeration with or without substrates. The patent catalase activity of intact cells rises 2-fold during 6-h aeration without substrate and 7-8-fold in the presence of glucose or ethanol. The increase is not inhibited by cycloheximide and is thus not due to de novo catalase synthesis, but may reflect enhanced transport of catalase to the cell surface or a permeabilization of the plasma membrane during the aeration.

Effect of hydrogen peroxide on sugar transport in Schizosaccharomyces pombe. Absence of membrane lipid peroxidation.

Stationary unaerated cells of S. pombe containing endogenous substrates but not energized by any exogenous ones take up 2-deoxy-D-glucose, 6-deoxy-D-glucose, D-xylose and D-arabinose actively over diffusion equilibrium. The active uptake is inhibited by 20-100 mmol/L H2O2 which causes an increase in KT but has no effect on Jmax. This "competitive inhibition" indicates that H2O2 affects directly the sugar binding sites of the transporters. The ATP-binding site of the plasma membrane H(+)-ATPase is also affected by 100 mmol/L H2O2; the KT decreases 7-fold, Jmax about 2.5-fold. These effects are not likely to be mediated by membrane lipid peroxidation which appears to be lacking in S. pombe, and this lack may be one of the reasons for the high resistance of this yeast to H2O2. Because of this S. pombe represents a suitable system for studying direct effects of oxidants on membrane proteins.

Inactivation of the plasma membrane ATPase of Schizosaccharomyces pombe by hydrogen peroxide and by the Fenton reagent (Fe2+/H2O2): nonradical vs. radical-induced oxidation.

In the absence of added Fe2+, the ATPase activity of isolated Schizosaccharomyces pombe plasma membranes (5-7 mumol P(i) per mg protein per min) is moderately inhibited by H2O2 in a concentration-dependent manner. Sizable inactivation occurs only at 50-80 mmol/L H2O2. The process, probably a direct oxidative action of H2O2 on the enzyme, is not induced by the indigenous membrane-bound iron (19.3 nmol/mg membrane protein), is not affected by the radical scavengers mannitol and Tris, and involves a decrease of both the K(m) of the enzyme for ATP and the V of ATP splitting. On exposing the membranes to the Fenton reagent (50 mumol/L Fe2+ + 20 mmol/L H2O2), which causes a fast production of HO. radicals, the ATPase is 50-60% inactivated and 90% of added Fe2+ is oxidized to Fe3+ within 1 min. The inactivation occurs only when Fe2+ is added before H2O2 and can thus bind to the membranes. The lack of effect of radical scavengers (mannitol, Tris) indicates that HO. radicals produced in the bulk phase play no role in inactivation. Blockage of the inactivation by the iron chelator deferrioxamine implies that the process requires the presence of Fe2+ ions bound to binding sites on the enzyme molecules. Added catalase, which competes with Fe2+ for H2O2, slows down the inactivation but in some cases increases its total extent, probably due to the formation of the superoxide radical that gives rise to delayed HO. production.

[Consultation hours for adolescent males: because men's health begins in adolescence]. / Jungensprechstunde : Weil Männergesundheit bei Jungengesundheit anfängt.

BACKGROUND: Young men are underrepresented in terms of offers concerning primary and secondary prevention in medicine. As a consequence, urologists often only see boys and young men from the perspective of missed prevention. AIM: What should an offer for boys and young men look like in a urologist's practice that focuses on the physical, social and sexual health of boys and young men? The author draws analogies for the establishment of consultation hours for young men in a urologist's practice based on her successful establishment of consultation hours for girls in a gynecologist's practice. RESULTS: Due to acceleration, boys also enter puberty early today. Because of their lack of knowledge about the changes in their body, they can be described as overnewsed and underinformed, despite their intense media consumption. This mixture of half-knowledge, coolness, sexual curiosity and lack of ability for predictive planning and action prevents boys and young men from having the knowledge they need to adequately and responsibly deal with their physical, social and sexual health care. CONCLUSION: If boys and young men had the opportunity to learn, appreciate, and protect their bodies at an early stage through competent preventive offers in the urologist's practice, then they would also experience less stress and powerlessness. In addition, it is almost certain that solid, fundamental understanding concerning their health will also lead to specific effects in male health competence. Only in this manner can young men be made ​​aware of the preventive services in a urological practice and can be a partner in other medically necessary decision-making processes.