PubMed Health⌕ Search

Biomedical subjects

V Richard

Publications and source records attributed to V Richard.

At least 19 recordsLinked to original sources
PubMed2005

Targeting endothelial dysfunction in hypertensive subjects.

The endothelium is a favourite early target of cardiovascular risk factors and cardiovascular diseases like hypertension. This key role of the endothelium results from its capacity to respond to numerous autocrine and paracrine stimuli and to mechanical factors like shear stress but also from the pathophysiological consequences of endothelial dysfunction on vasomotor tone, arterial stiffness, arterial remodelling, and inflammation, all of which are factors that play a critical role in atherosclerosis and target-organ damage. In hypertension, endothelial dysfunction has been shown at the level of both resistance and conduit arteries and mainly results from an increase in nitric oxide (NO) degradation by interaction between NO and superoxide anions, while in experimental models of hypertension a decrease in NO production can also be observed. The fact that forearm endothelial dysfunction is a marker of future cardiovascular events in patients with hypertension stresses the importance of the clinical evaluation of endothelial function and of the evaluation of the effects of the different antihypertensive drug classes on this parameter. In this context, many studies have demonstrated that angiotensin-converting enzyme inhibitors, the perindopril-indapamide combination, and angiotensin II type I receptor (AT1) blockers improve endothelium-dependent vasodilatation partly independently of arterial pressure. Both their antioxidant effects and the stimulation of the release of NO are involved in their beneficial effects. For calcium antagonists, only the recent drugs have been shown to improve endothelial function with a simultaneous improvement in several markers of oxidative stress. Finally, beta-blockers classically do not affect endothelial function. Only nebivolol, a beta-blocker with NO donor properties, has been shown to improve endothelial function, but this effect results from the increase in NO and not from the beta-blocking properties of the drug.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2005

Transcriptional regulation of parathyroid hormone-related protein promoter P3 by ETS-1 in adult T-cell leukemia/lymphoma.

Parathyroid hormone-related protein (PTHrP) plays a primary role in the development of humoral hypercalcemia of malignancy seen in the majority of adult T-cell leukemia/lymphoma (ATLL) patients with human T-cell lymphotropic virus type-1 (HTLV-1) infection. HTLV-1 Tax has been shown to complex with ETS-1 and SP1 to transactivate the PTHrP P3 promoter. Previously, we established a SCID/bg mouse model of human ATL with RV-ATL cells and showed that PTHrP expression was independent of Tax. In this study, we report an inverse correlation of PTHrP with tax/rex mRNA in multiple HTLV-1-positive cell lines and RV-ATL cells. Stimulation of Jurkat T cells with PMA/ionomycin upregulated the PTHrP P3 promoter by a previously characterized Ets binding site and also induced protein/DNA complex formation identical to that observed in RV-ATL cells. Further, we provide evidence that cotransfection with Ets-1 and constitutively active Mek-1 in HTLV-1-negative transformed T cells with stimulation by PMA/ionomycin not only resulted in a robust induction of PTHrP P3 but also formed a complex with ETS-1/P3 EBS similar to that in ATLL cells. Our data demonstrate that transcriptional regulation of PTHrP in ATLL cells can be controlled by T-cell receptor signaling and the ETS and MAPK ERK pathway in a Tax-independent manner.

Adult↗
PubMed2005

[Community financing for health care in Africa: mutual health insurance].

Health care in sub-Saharan Africa is increasingly financed by direct payments from the population. Mutual health insurance plans are developing to ensure better risk sharing. However mutual health insurance cannot fully resolve all equity issues. The low resources available for contribution and the limited availability of care services especially in the public sector cannot guarantee the quality of care necessary for the development of mutual health insurance. National governments must not forget their responsibility especially for defining and ensuring basic services that must be accessible to all. Will mutual health insurance plans be a stepping-stone to universal health care coverage and can these plans be successfully implemented in the context of an informal economy?

Africa South of the Sahara↗
PubMed2004

[Factors explaining quality of primary health care in Logone Occidental (Chad)].

The extent of the deficit in human and financial resources associated with alarming health indicators in the developing countries has prompted us to undertake an evaluation of the quality of the primary health care provided in our country. The study was designed to identify the determinants of the quality of primary care delivered in the health centers of Western Logone in Chad by comparing systematic data collected from public and private health structures and an adapted questionnaire. Data were collected from 24 healthcare centers providing care for 395699 people, 73.1% of the population of the district of Logone Occidental. The average costs born by patients receiving care delivered by the different centers was not statistically different between the centers financed by public funds and those with denominational support: 944 Fcfa versus 1315 Fcfa. Variable statistically correlated with quality of care were: number of qualified healthcare workers in the center, training level of the center's manager, average patient-born cost of consultation, average healthcare expenditure per capita in the recruitment area (p<0.01). Considering the importance of the medical district in the organization of healthcare systems in the countries of Sub-Saharan Africa, quality assessment must become a continuous, supervised activity enabling proper description of the processes involved and propositions for local solutions designed to improve the quality of care.

Adult↗
PubMed2004

Alternative splicing of parathyroid hormone-related protein mRNA: expression and stability.

Parathyroid hormone-related protein (PTHrP) is a multifunctional protein that is often dysregulated in cancer. The human PTHrP gene is alternatively spliced into three isoforms, each with a unique 3'-untranslated region (3'-UTR), encoding 139, 173 and 141 amino acid proteins. The regulation of PTHrP mRNA isoform expression has not been completely elucidated, but it may be affected by transforming growth factor-beta1 (TGF-beta1). In this study, we examined differences in the PTHrP mRNA isoform expression in two squamous carcinoma cell lines (SCC2/88 and HARA), an immortalized keratinocyte cell line (HaCaT), and spontaneous human lung cancer with adjacent normal tissue. In addition, the effect of TGF-beta1 on PTHrP mRNA isoform expression and stability was examined. Cell-type specific expression of PTHrP mRNA isoforms occurred between the various cell lines, normal human lung, and immortalized human keratinocytes (HaCaT). PTHrP isoform expression pattern was significantly altered between normal lung tissue and the adjacent lung cancer. In vitro studies revealed that TGF-beta1 differentially altered the mRNA steady-state levels and mRNA stability of the PTHrP isoforms. Protein-RNA binding studies identified different proteins binding to the 3'-UTR of the PTHrP isoforms (139) and (141), which may be important in the differential mRNA stability and response to cytokines between the PTHrP isoforms. The data demonstrate that there is cell-type specific expression of PTHrP mRNA isoforms, and disruption of the normal regulation during cancer progression may in part be associated with TGF-beta1-induced changes in PTHrP mRNA isoform expression and stability.

3' Untranslated Regions↗
PubMed2004

Correlation between complete response to anthracycline-based chemotherapy and topoisomerase II-alpha gene amplification and protein overexpression in locally advanced/metastatic breast cancer.

UNLABELLED: Anthracycline-based regimens are among the most active but also with greater risk of both acute and long-term side effects, namely cardiotoxicity. Predictive markers of response to anthracyclines are therefore essential. Topoisomerase-IIalpha (topo-II) is the target of anthracyclines and preliminary data suggest its promising role as a predictive marker of sensitivity to these drugs. After screening a population of about 350 patients with locally advanced or metastatic breast cancer, two subgroups were selected for the present analysis: a study group (31 patients), composed of 14 complete responders (CR-a) and 17 true non-responders (PD-a) to anthracycline-based CT, and a control group (28 patients), composed of 7 CR (CR-t) and 21 true non-responders (PD-t) to taxane-based CT. True non-responders were defined as progressive disease (PD) within the first three cycles of CT. Archival tumor samples of these patients were collected, biological markers evaluated and their status correlated with response to therapy. HER-2 and topo-II gene status were evaluated by FISH (Vysis multi-color probe-positivity cut-off: >/=2 ratio for HER-2 and >/=1.5 for topo-II), topo-II protein was evaluated by IHC (positivity cut-off >10%). All cases in which HER-2 gene was non-amplified did not show topo-II gene aberrations. No association was found between HER-2 gene amplification and response to anthracyclines (5/14 (36%) CR and 5/17 (29%) PD to anthracycline-based CT were HER-2+). The topo-II gene was amplified in 3/14 (21%) CR but only in 1/17 (6%) PD to anthracyclines. Amplification of the topo-II gene was seen in 1/7 (14%) CR and in 3/21 (14%) PD to a taxane-based CT. Topo-II protein was overexpressed in 6/11 (55%) CR and in 2/17 (12%) PD to anthracyclines, while in the control group, overexpression was seen in 5/7 (71%) CR and 8/20 (40%) PD. IN CONCLUSION: i) HER-2 gene amplification did not seem to be correlated with response to anthracyclines. ii) Both topo-II gene amplification and protein overexpression seem to correlate with response to anthracyclines, although other factors, such as p53 and cell proliferation, are most likely to be involved. iii) The role of combined evaluation of several relevant markers and of potential 'molecular signatures' are currently being evaluated in prospective randomized clinical trials.

Adult↗
PubMed2004

Coronary endothelial cells: a target of ischemia reperfusion and its treatment?

Ischemia/reperfusion injury of the heart is not limited to cardiomyocytes but also extends to coronary vascular cells, and especially coronary endothelium. Indeed, in different animal models, ischemia followed by reperfusion (but not ischemia alone) markedly decreases endothelium-dependent relaxations of coronary arteries, and especially those induced by nitric oxide (NO), while endothelium-independent responses and smooth muscle responsiveness are usually maintained. Such injury to the endothelium appears to depend on the increased production of oxygen-derived free radicals upon reperfusion, leading to an increased degradation of NO and an acute inflammatory response characterized by an increased adhesion of neutrophils to endothelial cells. Indeed, reperfusion injury to the endothelium may be prevented by free radical scavengers, by prevention of adhesion and/or activation of neutrophils, by exogenous NO supply or increased endogenous production of NO, as well as by ischemic preconditioning. Given the essential role of the endothelium and of NO in the regulation of vasomotor tone, as well as platelet and leukocyte function, it is likely that such changes in coronary endothelial function have important adverse consequences in terms of altered perfusion, and increased risk of vasospasm, but also on the long-term risk of thrombosis and atherosclerosis. Although these coronary endothelial alterations have been essentially evaluated in experimental models and are indeed difficult to assess in the human coronary circulation in the context of myocardial infarction, data obtained in healthy volunteers demonstrate that such post-ischemic alterations of endothelial function may be detected in the peripheral circulation, with underlying molecular mechanisms similar to those demonstrated experimentally. A better understanding of the mechanisms responsible for such endothelial injury may lead to the development of new treatments that protect the endothelium during ischemia and reperfusion, but also possibly in other diseases associated with endothelial dysfunction.

Animals↗
PubMed2004

[Outbreak of meningitis in the province of Logone occidental (Chad): descriptive study using health ministry data from 1998 to 2001].

UNLABELLED: Outbreaks of meningitis are a public health problem in sub-Saharan Africa where more than thousand cases are declared every year In Chad, the last outbreak happened between 1998 and 2001. The objective of this study is to describe epidemiologic profile of meningitis in the province of Logone Occidental from 1998 to 2001. METHODS: Study used epidemiologic data of surveillance's tools from years 1998 to 2001 in Chad. RESULTS: Data of the study indicated a two-yearly cycle with outbreaks in 1998 and 2000 occurring in endemic background during 1999 and 2001. The first cases began in January with an incidence rate close to 30 for 100.000/week. The epidemic peak occurred on the 11th week (1999-2001), on the 12th week (1998-2000) during dry season. Outbreak continued 9 weeks and stopped on the 16th week (April-May). The lethality average was 12% and reached 30% at the beginning of the outbreak. DISCUSSION: Despite vaccination campaigns during outbreaks, epidemiology did not change in Chad. Quality of epidemiological surveillance is not sufficient and political reaction is too slow. Moreover, human, material and financial deficiency add to these difficulties. Integrated vaccination against meningitis into the immunization preventive program was evocated but would not permit enough collective immunity. Biotope changes generated by human activity could contribute to perpetuating outbreaks. New outbreak of W135 meningitis in Burkina Faso (2002) may change the epidemiological profile of the meningitis in sub-Saharan Africa. CONCLUSION: Meningitis outbreaks control using vaccination after the first cases appears to be limited, however this strategy must be evaluated in Chad to know vaccination covering, target population and protection after vaccination.

Chad↗
PubMed2004

[Funding for healthcare in sub-Saharan Africa--cost recovery].

The Bamako Initiative was adopted in 1988 to establish a community strategy to support and fund primary health care. During the 1990s sub-Saharan countries progressively signed on to this program. Cost recovery still poses the problem of financial accessibility due to the absence of a risk-sharing policy in association with geographic accessibility due to inadequate monitoring of health coverage. Demand-related price elasticity has excluded low-income groups for whom indigent classification and accompanying management measures have usually remained in the planning stages. Implementation of funding mechanisms to ensure reduction of inequities is limited by an economy founded mainly on informal principles.

Africa South of the Sahara↗
PubMed2003

Genome-based detection methods of Macrobrachium rosenbergii nodavirus, a pathogen of the giant freshwater prawn, Macrobrachium rosenbergii dot-blot, in situ hybridization and RT-PCR.

The availability of specific and rapid detection methods is essential for monitoring the health status of farmed species, particularly in viral diseases as in this case early diagnosis is a critical factor in containing disease outbreaks. Three complementary genome-based methods were developed for the detection of Macrobrachium rosenbergii nodavirus (MrNV), i.e. dot-blot hybridization, in situ hybridization and reverse transcriptase-polymerase chain reaction (RT-PCR). Detection limits were established for dot-blot hybridization and RT-PCR and are c. 7 fg and 8 pg of viral RNA, respectively. In situ hybridization indicated that infection was confined to the striated muscle tissue. As a result of its sensitivity, RT-PCR can be used for in-depth investigations to examine the extent of the viral infection and establish the onset of infection in hatcheries. The application of RT-PCR on samples collected from prawn farms in China showed the possible use of this method in routine health monitoring.

Animals↗
PubMed2003

Transgenic models of metabolic bone disease: impact of estrogen receptor deficiency on skeletal metabolism.

Estrogen has protective effects on the skeleton via its inhibition of bone resorption. Mechanisms for these effects and the selectivity to the estrogen receptor alpha (ER alpha) or ER beta are unclear. The purpose of our study was to determine the impact of the ER alpha on skeletal metabolism using murine models with targeted disruption of the ER alpha and beta. Mice generated by homologous recombination and Cre/loxP technology yielding a deletion of the ER alpha exon 3 were evaluated and also crossed with mice with a disruption of the exon 3 of the ER beta to result in double ER alpha and ER beta knockout mice. Skeletal analysis of long bone length and width, radiographs, dual X-ray absorptiometry, bone histomorphometry, micro computerized tomography, biomechanical analysis, serum biochemistry, and osteoblast differentiation were evaluated. Male ER alpha knockout mice had the most dramatic phenotype consisting of reduced bone mineral density (BMD), and bone mineral content (BMC) of femurs at 10 and 16 weeks and 8-9 months of age. Female ER alpha knockout mice also had reduced density of long bones but to a lesser degree than male mice. The reduction of trabecular and cortical bone in male ER alpha knockout mice was statistically significant. Male double ER alpha and ER beta knockouts had similar reductions in bone density versus the single ER alpha knockout mice suggesting that the ER alpha is more protective than the ER beta in bone. In vitro analysis revealed no differences in osteoblast differentiation or mineralized nodule formation among cells from ER alpha genotypes. These data suggest that estrogens are important in skeletal metabolism in males; the ER alpha plays an important role in estrogen protective effects; osteoblast differentiation is not altered with loss of the ER alpha; and compensatory mechanisms are present in the absence of the ER alpha and/or another receptor for estrogen exists that mediates further effects of estrogen on the skeleton.

Absorptiometry, Photon↗
PubMed2002

Plasma lysine concentration and availability of 2-ketoglutarate in liver mitochondria.

Defects of lysine metabolism are rare, but hyperlysinemia is a concomitant of many inborn errors of metabolism, including urea cycle abnormalities, pyruvate carboxylase deficiency and L-2-hydroxyglutaric aciduria. We have hypothesized that mitochondrial lysine degradation is regulated by bioavailability of 2-oxoglutarate in the same compartment, and our studies in physiologic fluid derived from patients with the above described disorders supports our hypothsis. Our data further suggest that patients with isolated L-2-hydroxyglutaric aciduria may have a defect in 2-ketoglutarate metabolism. The current report summarizes our studies.

Alanine↗
PubMed2002

[Study of HIV seroprevalence in patients with pulmonary tuberculosis in 1999 in Chad].

Tuberculosis is the most common opportunistic disease occurring in the course of human immunodeficiency virus (HIV) infection. With the development of HIV infection in Chad, tuberculosis has quickly become a major public health concern. The purpose of this cross-sectional study in two tuberculosis centres (Moundou and Ndjamena) was to evaluate HIV seroprevalence, epidemiological characteristics and risk factors in patients with tuberculosis. All patients with positive sputum-smears who had never been treated for tuberculosis previously were eligible. A total of 466 patients (sex ratio M/F: 1.96) were included during the six-month period between January and June 99. Each subject was asked to fill out an anonymous standardized questionnaire with detailed information on demographic characteristics, sexual behavior and other risk factors for HIV infection. Data were compared using the Chi-square test, Student's T test and multivariate analysis (logistic regression). One third (33.2%) of patients was seropositive for HIV-1. Mean age was 31.1 years in HIV-positive group and 33.6 years in the HIV-negative group (p = 0.02). The age groups with the highest risk for HIV were 20-29 years and 30-39 years (p < 0.01). Women were more often seropositive that men (39.5% versus 30.1%; p = 0.04). Seropositive patients were more likely to have multiple sexual partners (mean: 1.76; p < 0.01) and a history of sexually transmitted disease (19.9% versus 8.1%; p = 0.01). The mean age at the time of first sexual relations was 16.3 years in the HIV group and 17.1 years in the control (p < 0.01). The percentage of seropositive patients was 39.6% at Moundou and 29.8% at N'djamena (p > 0.01). Multivariate analysis showed that early age of first sex relation (OR = 0.85; 95% IC: 0.74-0.97), higher number of sexual partners (OR = 1.8; 95% CI: 1.4-2.4) and level of education were strongly correlated with HIV infection. The prevalence of HIV in tuberculosis patients is a good indicator of HIV-infection in developing countries. Prevalence of HIV infection is high in tuberculosis patients in Chad. Surveillance for tuberculosis and AIDS must be strengthened in Chad. Mores cooperation is needed between tuberculosis and AIDS control programs. Emphasis should be placed on screening for tuberculosis, early tuberculosis treatment and diagnosis of HIV in tuberculosis patients.

Adolescent↗
PubMed2001

Induction of heme-oxygenase-1 prevents the systemic responses to hemorrhagic shock.

Oxidant-mediated reperfusion injury of the gut is a major contributor of the systemic inflammatory response in hemorrhagic shock. Recent studies have suggested that heme-oxygenase-1 (HO-1) represents an endogenous protective mechanism against oxidant stress. We assessed whether HO-1 induction modulates the synthesis of tumor necrosis factor-alpha (TNF-alpha) in hemorrhagic shock. In rats submitted to hemorrhagic shock, pretreatment with hemoglobin (Hb) increased HO-1 mRNA expression in macrophages. This increased expression was associated with a decreased expression of TNF-alpha mRNA, as well as decreased plasma concentrations of TNF-alpha. These effects of Hb were reduced by the HO-1 inhibitor tin-protoporphyrin (Sn-PP 20 micromol/kg), while Sn-PP had no effect in the absence of Hb. In parallel, Hb pretreatment reduced pulmonary edema, vascular injury, and increased mesenteric blood flow, and these effects were reduced by Sn-PP. Thus, induction of HO-1 is protective in hemorrhagic shock, possibly through its antioxidant properties. Interventions that induce HO-1 may be beneficial in the treatment of shock states, leading to a reduced systemic inflammatory response.

Animals↗
PubMed2001

Classification of hybrid crows in quail using artificial neural networks.

In galliforms, calls are strongly determined genetically and no influence of learning has ever been demonstrated. Hybridization is a useful tool for investigating patterns of heritability. The vocal repertoire of the European quail (Coturnix c. coturnix) and of the Japanese quail (C. c. japonica) are similar except for their crows. The European quail possesses two forms of crows and the Japanese quail only one form. We produced hybrids from the following crosses; F(1), F(2) and backcrosses. Visual analysis of spectrograms showed that hybrid crows presented all intermediaries between the three forms of crows produced by the two subspecies. According to the level of analysis of a crow, visual classifications of spectrograms probably include some subjectivity. Artificial Neural Networks (ANN) are now widely used as a powerful classification technique in behavioural sciences. We trained an ANN to recognize the three crows of the two subspecies. Then we analysed its classification of hybrid crows. The ANN revealed important inter-individual variability between the crows of the F(1) and the F(2) crosses. Birds issued from backcrosses produced crows similar to those of the European quail to which they were backcrossed. This study confirms that ANN is a useful tool to classify spectrograms rapidly.

Journal Article↗
PubMed2001

Functional evidence for a role of vascular chymase in the production of angiotensin II in isolated human arteries.

BACKGROUND: In human arteries, angiotensin-converting enzyme (ACE) inhibitors incompletely block the production of angiotensin (Ang) II from Ang I. This ACE-independent production of Ang II appears to be caused by serine proteases, one of which presumably is chymase. However, several serine proteases may produce Ang II, and the exact role of chymase in the vascular production of Ang II has never been directly evaluated using selective chymase inhibitors. METHODS AND RESULTS: Rings of human mammary arteries were subjected to either Ang I or the chymase-selective substrate [pro,(11) D-Ala(12)] Ang I in the absence or the presence of the ACE inhibitor captopril, the serine protease inhibitor chymostatin, or the selective chymase inhibitor C41. Captopril only partially inhibited (by 33%) the response to Ang I. In the absence of captopril, C41 markedly reduced (by 44%) the response to Ang I, and this effect was identical to that of chymostatin. C41 also significantly reduced the response to Ang I in the presence of captopril, although this inhibitory effect was slightly less than that of captopril in combination with chymostatin. [Pro,(11)D-Ala(12)] Ang I induced potent contractions that were not affected by captopril but were abolished by chymostatin and markedly reduced by C41. In addition, we found that prior treatment of the patients with an ACE inhibitor did not affect the in vitro response to Ang I (in the absence or the presence of captopril) or to [Pro,(11)D-Ala(12)] Ang I. CONCLUSIONS: Our results reinforce the hypothesis that chymase is a major serine protease implicated in the ACE-independent production of Ang II in human arteries.

Angiotensin I↗
PubMed2001

Humoral hypercalcemia of malignancy: severe combined immunodeficient/beige mouse model of adult T-cell lymphoma independent of human T-cell lymphotropic virus type-1 tax expression.

The majority of patients with adult T-cell leukemia/lymphoma (ATL) resulting from human T-cell lymphotropic virus type-1 (HTLV-1) infection develop humoral hypercalcemia of malignancy (HHM). We used an animal model using severe combined immunodeficient (SCID)/beige mice to study the pathogenesis of HHM. SCID/beige mice were inoculated intraperitoneally with a human ATL line (RV-ATL) and were euthanized 20 to 32 days after inoculation. SCID/beige mice with engrafted RV-ATL cells developed lymphoma in the mesentery, liver, thymus, lungs, and spleen. The lymphomas stained positively for human CD45RO surface receptor and normal mouse lymphocytes stained negatively confirming the human origin of the tumors. The ATL cells were immunohistochemically positive for parathyroid hormone-related protein (PTHrP). In addition, PTHrP mRNA was highly expressed in lymphomas when compared to MT-2 cells (HTLV-1-positive cell line). Mice with lymphoma developed severe hypercalcemia. Plasma PTHrP concentrations were markedly increased in mice with hypercalcemia, and correlated with the increase in plasma calcium concentrations. Bone densitometry and histomorphometry in lymphoma-bearing mice revealed significant bone loss because of a marked increase in osteoclastic bone resorption. RV-ATL cells contained 1.5 HTLV-1 proviral copies of the tax gene as determined by quantitative real-time polymerase chain reaction (PCR). However, tax expression was not detected by Western blot or reverse transcriptase (RT)-PCR in RV-ATL cells, which suggests that factors other than Tax are modulators of PTHrP gene expression. The SCID/beige mouse model mimics HHM as it occurs in ATL patients, and will be useful to investigate the regulation of PTHrP expression by ATL cells in vivo.

Animals↗