Biomedical subjects

G Martin

Publications and source records attributed to G Martin.

At least 19 recordsLinked to original sources

PubMed2007

Implications of inadequate parental bonding and peer victimization for adolescent mental health.

Previous studies have indicated significant associations between relatively poor mental health of children and both perceived negative parenting and exposure to peer victimization at school. This paper examines their relative contribution to the mental status of adolescent school children. Questionnaires were administered to Australian school children (n=1432) aged 12-16 years. These contained reliable self-report measures of mental health (the GHQ) parental bonding (the PBI) and degree of peer victimization. As predicted, multiple regression analyses indicated that low levels of perceived parental care, high parental control and frequent peer victimization were each significantly and independently associated with relatively poor mental health. Together, they accounted for some 17% and 27% of variance in the mental health status of adolescent boys and girls, respectively. Theoretical and practical implications of these findings are considered. Limitations of the study are also discussed (deleted).

Adolescent↗

PubMed2006

Kinetics of occurrence of some features of apoptosis during the cryopreservation process of bovine spermatozoa.

BACKGROUND: Cryopreservation/thawing of bovine spermatozoa induces a reduction in cell viability and is possibly associated with a form of programmed cell death that we previously named 'apoptosis-like phenomenon'. METHODS: In this study, we specified, by flow cytometry, the moment of appearance of some characteristics of apoptosis during the cryopreservation process. We also studied the presence and/or activation in bovine sperm cells of specific proteins involved in somatic cell apoptosis by western blot and fluorimetry. RESULTS: A decrease of the mitochondrial membrane potential (DeltaPsim) was detectable 5 min after sperm dilution in the cryopreservation medium, caspase activation after 3 h of equilibration and an increase in plasma membrane permeability after the complete process of cryopreservation/thawing. The presence of the pro-apoptotic factor Bax, a protein that facilitates the formation of mitochondrial pores, was observed in bovine spermatozoa, but the anti-apoptotic factor Bcl-2 was not detectable. Moreover, it was observed that bovine spermatozoa contain cytochrome c and apoptosis-inducing factor (AIF), two proteins usually released from the mitochondria during the apoptotic process. Activated caspase-9, involved in the mitochondrial pathway, was detected in bovine spermatozoa but not caspase-3 and -8. CONCLUSIONS: The early features of apoptosis appear as ordered events during the cryopreservation/thawing process of bovine sperm cells. Bovine spermatozoa contain the machinery necessary to proceed to apoptosis involving especially the mitochondrial pathway.

Acrosome Reaction↗

PubMed2006

Gastrokine 1 expression in patients with and without Helicobacter pylori infection.

BACKGROUND: To understand the molecular changes underlying Helicobacter pylori-related gastric diseases is mandatory to prevent gastric cancer. Proteomic technology is providing a rapid expansion of the basic knowledge, particularly in the discovery of new biomarkers involved in the tumourigenesis. AIM: To characterise changes in protein expression level of the gastric mucosa in H. pylori-infected patients. METHODS: The population enrolled comprised 41 dyspeptic patients. Proteins extracted from gastric mucosal specimens were analysed by 2-dimensional electrophoresis, sequenced by MALDI-TOF and identified by Edman's degradation. RESULTS: Twenty-one out of 41 patients had H. pylori infection of whom 17 had anti-CagA IgG antibodies. Several proteins were identified, of which Rho guanosine diphosphatase dissociation inhibitor alpha and heat shock protein 27 increased and glutathione transferase and antrum mucosa protein-18 decreased in H. pylori-positive in respect to H. pylori-negative patients. Interestingly, antrum mucosa protein-18, currently referred as gastrokine-1, showed two isoforms differing in the first N-terminal amino acid residue. Both gastrokine-1 isoforms were observed in the H. pylori-negative group whereas a lower expression or even absence of the gastrokine-1 basic isoform was found in a subgroup (7/21) of H. pylori-positive patients with moderate-severe gastritis. CONCLUSION: Our study demonstrated the presence of gastrokine-1 isoforms of which the basic isoform was reduced in a subset of patients with H. pylori infection.

Adult↗

PubMed2006

Comparative macrorestriction and RFLP analysis of Mycobacterium avium subsp. avium and Mycobacterium avium subsp. hominissuis isolates from man, pig, and cattle.

In Germany, tuberculous lesions in slaughtered pigs due to infection with members of the Mycobacterium avium complex are increasingly reported. Contaminated food originating from pig or other livestock is discussed as potential source of human infection. M. avium isolates from man (n=45), pig (n=29), and cattle (n=13) were characterised by restriction fragment length polymorphism (RFLP) with respect to insertion sequences IS1245 and IS901 as well as by XbaI-based pulsed-field gel electrophoresis (PFGE) and the results were compared by computer cluster correlation analysis, to determine potential sources of infection in man. By PCR, 55% of animal isolates was identified as M. avium subsp. avium, and 45% as M. a. hominissuis. All human isolates belonged to M. a. hominissuis. IS1245-RFLP and PFGE resulted in two distinct main groupings reflecting the two subspecies, and dividing the isolates into several subgroups. Animal isolates of M. a. hominissuis were widely distributed within the subgroups of human isolates. M. a. avium isolates, further discriminated by IS901-RFLP, formed host-associated subgroups for animals. Comparison of RFLP patterns with those of PFGE resulted in different subgroups as well as different pairs of isolates with high similarities. Only two isolates exhibited identical patterns by both methods. In general, results of both methods support the possibility that M. a. hominissuis isolates from livestock represent a source of infection for man, probably by common environmental reservoirs. There was no evidence of human infections caused by M. a. avium in Germany.

Animals↗

PubMed2006

Effect of the dissolved oxygen on the bioproduction of glycerol and ethanol by Hansenula anomala growing under salt stress conditions.

The effect of the dissolved oxygen on glycerol and ethanol productions by an osmotolerant yeast Hansenula anomala was examined during growth in media at low water activity resulting from the addition of 2M NaCl in the culture medium. High stirring rate, high culture medium aeration, as well as high mass transfer surface inhibited both glycerol and ethanol biosynthesis. In absence of oxygen, yeast used acetaldehyde as a hydrogen acceptor, leading to the stimulation of ethanol biosynthesis and accounting for the low biomass and glycerol production; the experimental ratio ethanol on glycerol produced was 5.1 when the available oxygen was lowered (low stirring rate, 500rpm) and increased to 10.2 in absence of aeration. Extracellular glycerol production was therefore optimal for a moderate stirring (1000rpm) and aeration (1.4vvm) rates. These optimal conditions resulted in an experimental ratio ethanol on glycerol produced of 4.1, namely close to the theoretical value of 4, illustrating the osmodependent channelling of carbon towards polyols production.

Biomass↗

PubMed2006

Extramedullary relapse in acute promyelocytic leukemia treated with all-trans retinoic acid and chemotherapy.

We analyzed the incidence, presenting features, risk factors of extramedullary (EM) relapse occurring in acute promyelocytic leukemia (APL) treated with all-trans retinoic acid (ATRA) and chemotherapy by using a competing-risk method. In total, 740/ 806 (92%) patients included in three multicenter trials (APL91, APL93 trials and PETHEMA 96) achieved CR, of whom 169 (23%) relapsed, including 10 EM relapses. Nine relapses involved the central nervous system (CNS) and one the skin, of which two were isolated EM relapse. In patients with EM disease, median WBC count was 26950/mm3 (7700-162000). The 3-year cumulative incidence of EM disease at first relapse was 5.0%. Univariate analysis identified age <45 years (P=0.05), bcr3 PML-RARalpha isoform (P= 0.0003) and high WBC counts (> or = 10,000/ mm3) (P<0.0001) as risk factors for EM relapse. In multivariate analysis, only high WBC count remained significant (P= 0.001). Patients with EM relapse had a poorer outcome since median survival from EM relapse was 6.7 months as compared to 26.3 months for isolated BM relapse (P=0.04). In conclusion, EM relapse in APL occurs more frequently in patients with increased WBC counts (> or = 10,000/mm3) and carries a poor prognosis. Whether CNS prophylaxis should be systematically performed in patients with WBC > or = 10,000/mm3 at diagnosis remains to be established.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2006

The outcomes of an intervention study to reduce the barriers experienced by people with intellectual disabilities accessing primary health care services.

BACKGROUND: People with intellectual disabilities (IDs) experience significant health inequalities compared with the general population. The barriers people with IDs experience in accessing services contribute to these health inequalities. Professionals' significant unmet training needs are an important barrier to people with IDs accessing appropriate services to meet their health needs. METHOD: A three group, pre- and post-intervention design was used to test the hypothesis that a training intervention for primary health care professionals would increase the knowledge and self-efficacy of participants. The intervention had two components - a written training pack and a 3-hour face-to-face training event. One group received the training pack and attended the training event, a second group received the training pack only, and a third group did not participate in the training intervention. Research measures were taken prior to the intervention and 3 months after the intervention. Statistical comparisons were made between the three groups. RESULTS: The participants in the training intervention reported that it had a positive impact upon their knowledge, skills and clinical practice. As a result of the intervention, 35 (81.4%) respondents agreed that they were more able to meet the needs of their clients with IDs, and 33 (66.6%) reported that they had made changes to their clinical practice. The research demonstrated that the intervention produced a statistically significant increase in the knowledge of participants (F = 5.6, P = 0.005), compared with the group that did not participate in the intervention. The self-efficacy of the participants that received both components of the intervention was significantly greater than the group that did not participate in the training (t = 2.079, P = 0.04). Participation in the two components of the training intervention was associated with significantly greater change in knowledge and self-efficacy than those receiving the training pack alone. CONCLUSION: This intervention was effective in addressing the measured training needs of primary health care professionals. Future research should directly evaluate the positive benefits of interventions on the lives of people with IDs.

Attitude of Health Personnel↗

PubMed2006

Improving the health of people with intellectual disabilities: outcomes of a health screening programme after 1 year.

BACKGROUND: People with intellectual disabilities (IDs) have a higher level of health needs, a higher level of which is unmet, compared with the general population. Health screening can detect unmet health needs, but it is unknown whether it effects beneficial health outcomes in the longer term. People with IDs are reliant on health management by proxy and there are many potential access barriers that may prevent health needs identified at screening from subsequently being met. This study aims to determine whether health gains can be detected 1 year after a health screening programme specific to the needs of adults with IDs. METHODS: A total of 50 participants offered the health screen intervention were individually matched for gender, age and level of IDs with 50 control participants who received standard treatment only. Outcome measures after 1 year were semi-structured review of medical case notes, and semi-structured assessment with the people with IDs and their carer. RESULTS: During the 1-year period, the incidence of health need detection was more than twice as great for intervention, compared with control participants (mean number of new needs was 4.80 compared with 2.26; P < 0.001), and the level of met new health needs was greater (mean of 3.56 compared with 2.26; P = 0.001). The level of met health promotion needs was also greater (P < 0.001), and more health monitoring needs were met for intervention compared with control participants (P = 0.039). CONCLUSIONS: This is the first study to demonstrate sustained benefits in health outcomes from a clinical intervention for adults with IDs compared with standard treatment alone. Its routine implementation is feasible, and would reduce health inequalities.

Adult↗

PubMed2005

Effect of medium osmolarity on the bioproduction of glycerol and ethanol by Hansenula anomala growing on glucose and ammonium.

The osmotolerant yeast Hansenula anomala survives in media at low water activity resulting from increasing NaCl concentrations in the culture medium by producing compatible solutes. High salinity resulted in the use of a large part of the assimilated carbon substrate (glucose) for cell maintenance (28%), required for intracellular synthesis compounds and for osmotic cell regulation. The maintenance coefficient for non-growth-associated glucose consumption was found to be 0.38 mmol glucose g biomass(-1) h(-1). For decreasing water activity, there is a competition between the pathways leading to glycerol and ethanol production, until an experimental ethanol/total glycerol ratio reached a value 3.4 for 2 mol l(-1) NaCl (close to the theoretical value of 4)-illustrating the osmo-dependent channelling of carbon towards polyols production. This competition leads to a cessation of ethanol production during the stationary state before that of glycerol. Since osmotic adjustment occurred mainly during growth, glycerol production during stationary state can be clearly related to another mechanism other than osmotic: it was excreted by a fermentative mechanism to ensure energy for cell maintenance.

Ethanol↗

PubMed2005

Comparative effects of IL-1beta and hydrogen peroxide (H2O2) on catabolic and anabolic gene expression in juvenile bovine chondrocytes.

OBJECTIVE: To compare the effects of hydrogen peroxide (H(2)O(2)) to those of interleukin-1beta (IL-1beta) on gene expression in juvenile bovine articular chondrocytes (BAC). The study analyses the activation of nuclear factor-kappa B (NF-kappaB) and activator protein-1 (AP-1) transcription factors, and the mRNA steady-state levels of the type II collagen, aggrecan core protein matrix, metalloproteinases (MMP-1, -3), and transforming growth factor-beta1 (TGF-beta1) genes. METHODS: Confluent BAC cultures were treated for 3 and 24h with IL-1beta and/or different concentrations of H(2)O(2) (Protocol 1). Following initial treatment, a part of the cells was further subjected to another 24h with medium, in the presence of IL-1beta, to determine the effect of the cytokine on H(2)O(2) pre-treated cells (Protocol 2). Total RNA and nuclear protein extractions were performed to study mRNA steady-state levels (real-time polymerase chain reaction) and AP-1/NF-kappaB DNA binding (Electrophoretic Mobility Shift Assays), respectively. RESULTS: IL-1beta enhanced both AP-1 and NF-kappaB binding, whereas H(2)O(2) only activated AP-1. H(2)O(2) pre-treatment decreased the IL-1beta activation of NF-kappaB. Both H(2)O(2) and IL-1beta down-regulated type II collagen and aggrecan expression and increased that of MMP-1 and -3. When cells were pre-treated with H(2)O(2), followed by IL-1beta, the effects were the same as those observed with H(2)O(2) alone. However, although H(2)O(2) and IL-1beta were capable of increasing TGF-beta1 expression separately, subsequent incubation with both factors led to a partial or total abolition of TGF-beta1 up-regulation. CONCLUSION: The different regulation of NF-kappaB and AP-1 by H(2)O(2) and IL-1beta underlines the distinct roles played by the two transcription factors in the regulation of gene expression. H(2)O(2) and IL-1beta exert similar effects on matrix, MMPs and TGF-beta1 gene expression. However, the association of H(2)O(2) and IL-1beta does not cause synergic effect, and rather leads, in some cases, to an opposite effect. These data provide further insights into the respective roles of reactive oxygen species and cytokine in the pathophysiology of joint diseases.

Aggrecans↗

PubMed2005

Vaccination and early protection against non-host-specific Salmonella serotypes in poultry: exploitation of innate immunity and microbial activity.

A recent European Union Directive required member states to put monitoring and control programmes in place, of which vaccination is a central component. Live Salmonella vaccines generally confer better protection than killed vaccines, because the former stimulate both cell-mediated and humoral immunity. Administering Salmonella bacteria orally to newly hatched chickens results in extensive gut colonization and a strong adaptive immune stimulus but broiler chickens are immunologically immature. However, colonization exerts a variety of rapid (within 24 h) protective effects. These include specific colonization-inhibition (competitive exclusion) in which the protective bacteria exert a profound resistance to establishment and colonization by other related bacteria. This is thought to be primarily a metabolic attribute of the vaccinating bacteria but may also involve competition for attachment sites. The presence of large numbers of bacteria originating from a live Salmonella vaccine in the intestine can also induce infiltration of polymorphonuclear cells into the intestinal wall, which confers resistance to invasion and systemic spread by virulent Salmonella strains. This opens new perspectives for vaccine usage in broilers, layers and breeding poultry but also in other animals which show increased susceptibility to infection because of their young age or for other reasons, such as oral chemoprophylaxis or chemotherapy, where the lack of established normal gut flora is an issue. We recommend that all live vaccines considered for oral administration should be tested for their ability to induce the two protective effects described above. Further developments in live Salmonella vaccines are, however, currently hindered by fears associated with the use and release of live vaccines which may be genetically modified.

Animals↗

PubMed2005

Enhancing primary health care services for adults with intellectual disabilities.

BACKGROUND: Primary health care teams have an important part to play in addressing the health inequalities and high levels of unmet health needs experienced by people with intellectual disabilities (ID). Practice nurses have an expanding role within primary health care teams. However, no previous studies have measured their attitudes, knowledge, training needs, and self-efficacy in their work with people with ID. METHODS: All practice nurses working in a defined area were identified. A purpose-designed questionnaire to measure nurse attitudes, knowledge, training needs and self-efficacy was developed and piloted. All practice nurses were then invited to participate. Data from completed questionnaires were entered onto PC and analysed. RESULTS: Of a total of 292 practice nurses 201 (69%) participated. Whilst 89% (n=179) of participants reported having infrequent contact, 25% (n=50) reported a growing workload with people with ID. Only 8% (n=16) had ever received any training in communicating with people with ID. A knowledge gap regarding the health needs of people with ID was identified. Eighty-six per cent reported having experienced specific difficulties during previous appointments, and only 23% thought they had sufficient case note information at appointments, but 68% did not modify the duration of their appointments with people with ID. Conversely, responses demonstrated that practice nurses have a high level of experience and qualification in general nursing, have positive attitudes to working with people with ID, and high self-efficacy scores were identified for work with people with ID. The practice nurses viewed ID to be a high priority area for future training. CONCLUSIONS: Primary health care teams have a key role in tackling the unmet health needs of people with ID. Whilst this project has identified factors that may impact on the accessibility of services, it has also identified practice nurses as having positive attitudes and high self-efficacy scores in their work with people with ID. This indicates that they should be targeted for specific training in this area, which may make an important contribution in enhancing future accessibility of primary health care services for people with ID.

Adult↗

PubMed2005

An exploratory study of assertive community treatment for people with intellectual disability and psychiatric disorders: conceptual, clinical, and service issues.

BACKGROUND: Assertive community treatment (ACT) has been applied to a number of disorders in the adult population, such as schizophrenia, with some degree of success; its use in the treatment of people with intellectual disability (ID) and mental illness has received little attention. Despite the high costs of ID in health and social care, there has been very little evidence-based practice for people with ID and mental illness, and it remains a neglected area of research. Aims The aims of this study were an exploratory comparison of the effectiveness of an ACT model for the treatment of mental illness in people with ID (ACT-ID) with a standard community treatment (SCT-ID) approach. METHOD: A Randomized controlled trial design was adopted and allocation was made by stratified randomization by an independent statistician. The prognostic factors used in the randomization were gender and psychiatric diagnosis (psychosis vs. affective). Service users were randomly allocated to either ACT-ID or SCT-ID. RESULTS: There were no statistically significant differences between ACT-ID and SCT-ID in terms of the level of unmet needs, carer burden, functioning and quality of life, but borderline evidence of a difference between treatment groups in quality of life in favour of SCT-ID. Both SCT-ID and ACT-ID groups decreased level of unmet needs and carer burden, and increased functioning. SCT-ID also led to a small increase in quality of life.

Adolescent↗

PubMed2004

Analysis and significance of mRNA in human ejaculated sperm from normozoospermic donors: relationship to sperm motility and capacitation.

The existence of a complex population of mRNA in human sperm is well documented but their role is not yet elucidated. Using discontinuous density gradients, we have isolated high and low motile sperm from the same semen sample. The levels of different transcripts coding for molecules either involved in nuclear condensation (protamines 1 and 2) or in capacitation [endothelial nitric oxide synthase (eNOS), neuronal nitric oxide synthase (nNOS) and c-myc] were then assessed in the two populations using semi-quantitative RT-PCR. Sperm viability was estimated by eosin-nigrosin staining and by hypo-osmotic swelling test; apoptosis percentage was measured by the TdT (terminal deoxynucleotidyl transferase)-mediated dUDP nick-end labelling technique. The contamination by somatic and germ cells was assessed by looking for specific molecular markers of these cells, respectively CD-45 and E-cadherin for somatic cells and c-kit for germ cells. The viability of sperm was unchanged in high and low motile fractions, as well as DNA fragmentation percentage. The amount of Prm-1 mRNA was significantly higher in low density motile than in the high motile fraction. In most of high motile sperm samples eNOS and nNOS transcripts were undetectable whereas they were present in the low motile sperm. In contrast, no significant variation was found in the c-myc/Prm-2 mRNA ratio between the two populations. Moreover, a partial or complete disappearance of c-myc transcripts was observed after capacitation. Thus analysing mRNA profiles could be helpful as a diagnostic tool and prognosis value for fertilization.

Adult↗

PubMed2004

Measurement of the flux of ultrahigh energy cosmic rays from monocular observations by the High Resolution Fly's Eye experiment.

We have measured the cosmic ray spectrum above 10(17.2) eV using the two air-fluorescence detectors of the High Resolution Fly's Eye observatory operating in monocular mode. We describe the detector, phototube, and atmospheric calibrations, as well as the analysis techniques for the two detectors. We fit the spectrum to a model consisting of galactic and extragalactic sources.

Journal Article↗

PubMed2004

Effect of hypoxia and reoxygenation on gene expression and response to interleukin-1 in cultured articular chondrocytes.

OBJECTIVE: To determine the effects of hypoxia and reoxygenation on the metabolism of chondrocytes and their response to interleukin-1beta (IL-1beta). The study included activation of hypoxia-inducible factor 1 (HIF-1), NF-kappaB, and activator protein 1 (AP-1) transcription factors, expression of matrix components and metalloproteases and transforming growth factor beta (TGFbeta) and TGFbeta receptors, and production of nitric oxide (NO) and prostaglandin E(2) (PGE(2)). METHODS: Bovine articular chondrocytes (BACs) were cultured to confluency in either 5% O(2) (hypoxia) or 21% O(2) (normoxia) in media supplemented with 10% fetal calf serum (FCS). BACs were preincubated for 18 hours in media with 1% FCS only and then incubated for 24 hours in the presence of IL-1beta. For reoxygenation experiments, cells were treated in the same way in 5% O(2), except that cultures were transferred to normal atmospheric conditions and used after 4 hours for RNA extraction or after 30 minutes for cytoplasmic or nuclear protein extraction. RESULTS: In hypoxic and reoxygenated chondrocytes, we observed strong DNA binding of HIF-1. IL-1beta-induced DNA binding of NF-kappaB and AP-1 was significantly higher in hypoxic and reoxygenated cultures than in normoxia. Greater activation of the MAPKs was also observed with IL-1beta treatment in hypoxia compared with normoxia. Steady-state levels of type II collagen and aggrecan core protein messenger RNA (mRNA) were decreased by IL-1beta in all instances. Matrix metalloprotease 1 (MMP-1) and MMP-3 mRNA were increased by IL-1beta in normoxia and hypoxia, whereas only MMP-3 mRNA was enhanced in reoxygenated cultures. The MMP-2 mRNA level was not significantly affected by IL-1beta in normoxia or hypoxia, whereas it was enhanced in reoxygenated cultures. MMP-9 mRNA was dramatically decreased by IL-1beta only in low oxygen tension. Tissue inhibitor of metalloproteinases 1 (TIMP-1) message was significantly enhanced by the cytokine in most instances, whereas TIMP-2 message was markedly decreased by IL-1beta in reoxygenated cultures. Stimulation of TGFbeta1 expression by IL-1beta was observed only in normal atmospheric conditions. One of the more striking findings of the study was the greater stimulating effect of IL-1beta on NO production observed in hypoxia, which was much higher than in normoxia, whereas the reverse was observed for IL-1beta-induced PGE(2) production. CONCLUSION: Oxygen level and reoxygenation stress significantly modulate gene expression and the response of articular chondrocytes to cytokines such as IL-1beta. In hypoxic conditions, which mimic the in vivo condition of cartilage, the effects of IL-1beta on both synthesis and degradative processes are significantly different from those in normoxia, conditions that are unlikely encountered by chondrocytes in a normal state. In low oxygen tension, high IL-1beta-induced NO production is associated with a significant decrease in PGE(2) synthesis. These data should influence our concept of the role of oxygen in the pathophysiology of joint disease and may help define the best conditions in which to develop bioartificial cartilage.

Aggrecans↗

PubMed2004

Schizophrenia-spectrum psychoses in people with and without intellectual disability.

BACKGROUND: Although there is an increased risk of schizophrenia-spectrum psychoses (SSP) in people with intellectual disability (ID), there is a paucity of research evidence into clinical presentation of the disorder in comparison with research into SSP in people without ID. AIMS: The aims of the study were to compare clinical, functional, and social factors in patients with mild ID (ICD-10: F70) and SSP (ICD-10: F20-9) attending a specialist mental health service for people with ID, with a control group of patients without ID but with SSP attending a generic adult mental health (GAMH) outpatient clinic. METHOD: A total of 106 patients with SSP (53 with ID and 53 from GAMH) were assessed on psychopathological symptoms, functioning scales and quality of life. They were compared using chi-squared and regression analysis where appropriate. RESULTS: People with ID and SSP appear to be more debilitated by the co-occurring disorder than those with the same disorder but without ID. Increases in observable psychopathology and "negative" schizophrenic symptoms, and decreased functional abilities were observed in the group with ID when compared to the GAMH group. The clinical implications of these findings are discussed.

Adult↗

PubMed2004

Articular chondrocytes cultured in hypoxia: their response to interleukin-1beta and rhein, the active metabolite of diacerhein.

In the present report, we show that bovine articular chondrocytes cultured in low oxygen tension, i.e. in conditions mimicking their hypoxic in vivo environment, respond to IL-1beta (10 ng/ml) by an increased DNA binding activity of NF-kappaB and AP-1 transcription factors. Incubation of the cells with 10(-5) M rhein for 24 h was found to reduce this activity, particularly in the case of AP-1. Mitogen activated kinases (ERK-1 and ERK-2) were activated by exposure of the chondrocytes to 1-h treatment with IL-1beta. This effect was greater in hypoxia (3% O(2)) than in normoxia (21% O(2)). Rhein was capable of reducing the IL-1beta-stimulated ERK1/ERK2 pathway whatever the tension of oxygen present in the environment. The mRNA steady-state levels of collagen type II (COL2A1) and aggrecan core protein were found to be significantly increased by a 24-h treatment with 10(-5) M rhein. This stimulating effect was also observed in the presence of IL-1beta, suggesting that the drug could prevent or reduce the IL-1beta-induced inhibition of extracellular matrix synthesis. IL-1-induced collagenase (MMP1) expression was significantly decreased by rhein in the same conditions. In conclusion, rhein can effectively inhibit the IL-1-activated MAPK pathway and the binding of NF-kappaB and AP-1 transcription factors, two key factors involved in the expression of several pro-inflammatory genes by chondrocytes. In addition, the drug can reduce the procatabolic effect of the cytokine, by reducing the MMP1 synthesis, and enhance the synthesis of matrix components, such as type II collagen and aggrecan. These results may explain the anti-osteoarthritic properties of rhein and its disease-modifying effects on OA cartilage, in spite of absence of inhibition at prostaglandin level.

Animals↗