Protection of both auditory hair cells and auditory neurons from cisplatin induced damage

Knowledge about body composition is important in metabolic and nutritional studies. In this cross-sectional study the body composition of 403 healthy white Dutch children and adolescents was evaluated by using dual-energy X-ray absorptiometry (DXA). Possible determinants of body composition were analyzed. In 85 subjects the results of bioelectrical impedance analysis (BIA) were compared with DXA. Fat mass, lean tissue mass, and bone mineral content were greater in older boys and girls. Percentage body fat was greater in older girls but not in boys and it was higher in girls than in boys at all ages. From the age of 14 y boys had higher lean tissue mass and bone mineral content than girls. Tanner stage had a significant relation with body composition in both sexes. Percentage body fat was lower in boys in stage 4 than in stage 3 and was higher in consecutive Tanner stages in girls. After adjustment for age, Tanner stage was significantly positively related to lean tissue mass and bone mineral content in boys and girls and to percentage body fat and fat mass in girls. The profession of the parents and the education of the father had a significant negative correlation with percentage body fat and fat mass in girls (P < 0.01). Physical activity was related to lean tissue mass (P = 0.001) but not to fat mass in boys after adjustment for age. A high correlation and a small difference was found between lean body mass by BIA and lean tissue mass by DXA. Body composition in healthy Dutch children and adolescents is related to age, sex, Tanner stage, socioeconomic status, and physical activity.     

Nitric oxide inhibits apoptosis by preventing increases in caspase-3-like activity via two distinct mechanisms

Nitric oxide (NO) has emerged as an important endogenous inhibitor of apoptosis, and here we report that NO prevents hepatocyte apoptosis initiated by the removal of growth factors or exposure to TNFalpha or anti-Fas antibody. We postulated that the mechanism of the inhibition of apoptosis by NO would include an effect on caspase-3-like protease activity. Caspase-3-like activity increased coincident with apoptosis due to all three stimuli, and treatment with the caspase-3-like protease inhibitor N-acetyl-Asp-Glu-Val-Asp-aldehyde inhibited both proteolytic activity and apoptosis. Endogenous or exogenous sources of NO prevented the increase in caspase-3-like activity in hepatocytes. Exposure of purified recombinant caspase-3 to an NO or NO+ donor inhibited proteolytic activity. Dithiothreitol (DTT), but not glutathione, reversed the inhibition of recombinant caspase-3 by NO. When lysates from cells stimulated to express inducible NO synthase or cells exposed to NO donors were incubated in DTT, caspase-3-like activity increased to about 55% of cells not exposed to a source of NO. Similarly, administration of an NO donor to rats treated with TNFalpha and D-galactosamine also prevented the increase in caspase-3-like activity as measured in liver homogenates. The effect of the NO donor was reversed by about 50% if the homogenate was incubated with DTT. TNFalpha-induced apoptosis and caspase-3-like activity were also reduced in cultured hepatocytes exposed to 8-bromo-cGMP, and both effects were inhibited by the cGMP-dependent kinase inhibitor KT5823. The suppression in caspase-3-like activity in hepatocytes exposed to an NO donor was partially blocked by an inhibitor of soluble guanylyl cyclase, 1H-[1,2,4]oxadiazolo[4,3, -a]quinoxalin-1-one, (ODQ), while the incubation of these lysates in DTT almost completely restored caspase-3-like activity to the level of TNFalpha-treated controls. These data indicate that NO prevents apoptosis in hepatocytes by either directly or indirectly inhibiting caspase-3-like activation via a cGMP-dependent mechanism and by direct inhibition of caspase-3-like activity through protein S-nitrosylation.     

The effects of macrolides on the expression of bacterial virulence mechanisms

Human erythrocytes in the circulation undergo dynamic oxidative damage involving membrane lipid peroxidation and protein aggregation during aging. The present study was undertaken to determine the effect of n-3 fatty acid supplementation on lipid peroxidation and protein aggregation in the circulation and also the in vitro susceptibility of rat erythrocyte membranes to oxidative damage. Wistar male rats were fed a diet containing n-6 fatty acid-rich safflower oil or n-3 fatty acid-rich fish oil with an equal amount of vitamin E for 6 wk. n-3 Fatty acid content in erythrocyte membranes of rats fed fish oil was significantly higher than that of rats fed safflower oil. The degree of membrane lipid peroxidation and protein aggregation of rats fed fish oil was not significantly higher than that of rats fed safflower oil when the amounts of phospholipid hydroperoxides, thiobarbituric acid-reactive substances, and detergent-insoluble protein aggregates were measured. When isolated erythrocytes were oxidized under aerobic conditions in the presence of Fe(III), the degree of membrane lipid peroxidation of erythrocytes from rats fed fish oil was increased to a greater extent than that of rats fed safflower oil, whereas the degree of membrane protein aggregation of both groups was increased in a similar extent. Hence, n-3 fatty acid supplementation did not affect lipid peroxidation and protein aggregation in membranes of circulating rat erythrocytes, and the supplementation increased the susceptibility of isolated erythrocytes to lipid peroxidation, but not to protein aggregation, under the aerobic conditions. If a sufficient amount of vitamin E is supplied, n-3 fatty acid supplementation may give no undesirable oxidative effects on rat erythrocytes in the circulation.     

Dynamics of spontaneous beating of cardiomyocytes in vitro depend on the number of involved cells

The hypothalamic suprachiasmatic nucleus (SCN) is the predominant pacemaker of the mammalian brain that generates and controls circadian rhythms of various endocrine and behavioral processes. Different lines of evidence suggest that stress interferes with the maintenance of such rhythms. As a first approach to investigate whether the neuropeptide arginine vasopressin (AVP), which shows circadian rhythms of synthesis and release within the SCN, might contribute to this stress-induced alterations in circadian rhythms, we monitored acute effects of swim stress on the intra-SCN release of AVP in male rats by means of the microdialysis technique. A 10-min forced swimming session triggered a marked but relatively short-lasting increase in the intranuclear release of AVP (to approx. 440%). This effect was restricted to the area containing predominantly somata and dendrites of vasopressinergic neurons, since no changes in AVP release could be measured in one of their major projection areas, the nucleus of the dorsomedial hypothalamus. Our data provide evidence that the amount of AVP released within the SCN can vary widely not only in accordance with AVP's intrinsically regulated circadian rhythm but also in response to a physiologically relevant stressor. In this way, the neuropeptide may contribute to the regulation of endocrine and behavioral rhythms particularly in challenging situations associated with resettings of the endogenous clock.     

Narrowband UV-B produces superior clinical and histopathological resolution of moderate-to-severe psoriasis in patients compared with broadband UV-B

OBJECTIVE: To compare the therapeutic effectiveness of daily exposure to narrowband (NB) UV-B vs broadband (BB) UV-B with and without tar. DESIGN: Half-body exposures to NB UV-B or BB UV-B were given daily for 4 weeks in this comparative treatment study. Narrowband UV-B was delivered from TL-01 fluorescent bulbs and BB UV-B from conventional bulbs in the same phototherapy cabinet. Narrowband UV-B was compared using a paired treatment approach to BB UV-B above the waist and to BB UV-B with tar (Goeckerman treatment) below the waist. SETTING: General clinical research center of a university hospital inpatient unit. PATIENTS: Twenty-two patients with moderate-to-severe plaque-type psoriasis completed the study. MAIN OUTCOME MEASURES: Clinical efficacy was measured weekly using psoriasis severity scoring. Therapeutic outcomes after 4 weeks were compared in paired biopsy samples from treated lesions using objective histopathological measures (quantitative reduction in epidermal acanthosis and keratin 16 expression). RESULTS: Clinical resolution of psoriasis was achieved on 86% of paired sites treated with NB UV-B vs 73% treated with BB UV-B. Histopathological resolution of epidermal hyperplasia (marked by keratin 16 expression) was achieved in 88% of lesions treated with NB UV-B vs 59% treated with BB UV-B. Epidermal acanthosis was reduced more completely by NB UV-B treatment. Clinical resolution of psoriatic lesions occurred more rapidly following NB UV-B treatment, with some patients achieving complete resolution after 2 to 3 weeks of treatment. CONCLUSIONS: Narrowband UV-B offers a significant therapeutic advantage over BB UV-B in the treatment of psoriasis, with faster clearing and more complete disease resolution. The erythema response to NB UV-B treatment was significantly more intense and persistent compared with BB UV-B. Considerably more necrotic keratinocytes were observed in histopathological sections of skin treated with NB UV-B after a single 2.0-minimum erythema dose exposure. Treatment should be coupled with obligate minimum erythema dose testing to NB UV-B and close clinical observation during dose increases.     

Imidazoline receptor proteins are regulated in platelet-precursor MEG-01 cells by agonists and antagonists

A morphological analysis was done of 15 cases of malignant cerebral lymphomas selected from the material of 160 brains of patients, who died in the course of full-blown acquired immune deficiency syndrome (AIDS) during the period of 1987-1997. Cases with cerebral lymphomas comprised 9.4% of the whole collection. There were 13 males and 2 females in the studied group. The patients age ranged from 25 to 61 years. In 10 cases lymphomas were localized solely in the central nervous system, and in further 4 they were accompanying systemic neoplastic process. In one case lack of clinical and autopsy data did not permit classification of neoplasm to the primary or to the secondary group. In 13 cases immunophenotype of the lymphomas was characterized by immunohistochemical methods. In 11 cases neoplastic cells originated from B cells line and in 2--from T cells line. In 10 cases lymphomas were found in macroscopic examination, in the remaining 5 cases they were disclosed at the brain histopathology. The dynamics and extensiveness of the neoplastic process were different in particular cases. In most of them the process was multifocal and manifested in the form of diffuse proliferation, formed tumors with changing nature of their delineation and as multilayer perivascular cuffs. The characteristic feature of diffuse neoplasmatic growth was the appearance of large coagulative necroses in the central parts of tumors. Neoplastic foci were localized most often in the cerebral hemispheres (white matter, basal ganglia, periventricular regions), less frequently in the brain stem and cerebellum. In one case diffuse lymphoid growth involved selectively leptomeninges. In most of the cases leptomeningeal infiltrations accompanied large parenchymal neoplastic foci. The most striking feature of our collection consisted in concomitance of cerebral lymphomas with HIV-specific brain pathology and/or opportunistic infections mostly of viral etiology. Their frequency was much higher than in cases of AIDS without cerebral lymphomas. Another finding which seems to be worth mentioning was the appearance of morphological exponents of various pathological processes such as for instance multinuclear giant cells, CMV inclusions within neoplastic tissue. The relatively frequent presence of numerous HIV-specific giant cells on the periphery of lymphomatous tumors suggests pathogenetic participation of immune deficiency virus in the blastomatous transformation of lymphoid cells within the central nervous system.     

A comparison of the effect of ski sidecut on three-dimensional knee joint kinematics during a ski run

BACKGROUND: Knowledge of Helicobacter pylori infection has grown rapidly during the last decade and management of its associated pathology has changed concordantly. METHODS: We surveyed the management of H. pylori infection among members of the Dutch Society of Gastroenterology in 1995 via a postal questionnaire. RESULTS: Almost all 226 respondents (response rate 54%) treated patients for H. pylori infection and the responses suggested that at least 0.1% of Dutch citizens were treated for H. pylori infection in 1995 by this group of specialists. 98% of the respondents treated the H. pylori infection in patients with duodenal ulcer, 91% in cases of gastric ulcer, 56% in cases of gastric lymphoma, 33% in cases of premalignant changes in gastric mucosal histology, 32% in cases of non-ulcer dyspepsia, and 30% in cases of chronic use of proton pump inhibitors. The main diagnostic methods used were histology (93%), urease test (60%), and culture (46%). Triple therapy was most commonly used (54%), followed by quadruple therapy (26%) and double therapy (13%). Follow-up detection of H. pylori was routinely done by 42% of the respondents, while 48% did so only when confirmation of eradication was considered clinically relevant. Most specialists did follow-up detection after 8-12 weeks. CONCLUSIONS: In 1995 most Dutch specialists treated H. pylori in patients with associated ulcer disease. There was no consensus on its role in other diseases. Diagnostic methods and treatment regimens for eradication differed widely.     

Regulatory phosphorylation of AMPA-type glutamate receptors by CaM-KII during long-term potentiation

Long-term potentiation (LTP), a cellular model of learning and memory, requires calcium-dependent protein kinases. Induction of LTP increased the phosphorus-32 labeling of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptors (AMPA-Rs), which mediate rapid excitatory synaptic transmission. This AMPA-R phosphorylation appeared to be catalyzed by Ca2+- and calmodulin-dependent protein kinase II (CaM-KII): (i) it correlated with the activation and autophosphorylation of CaM-KII, (ii) it was blocked by the CaM-KII inhibitor KN-62, and (iii) its phosphorus-32 peptide map was the same as that of GluR1 coexpressed with activated CaM-KII in HEK-293 cells. This covalent modulation of AMPA-Rs in LTP provides a postsynaptic molecular mechanism for synaptic plasticity.