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PubMed2003

Effects of the phenolic contents of Mauritian endemic plant extracts on promoter activities of antioxidant enzymes.

Oxidative stress has been associated with a variety of pathologic conditions in humans. Increasing the transcriptional activities of antioxidant enzymes might be a strategy to prevent oxidative stress-associated diseases such as atherosclerosis and cancer. In the present paper, we studied the effects of extracts from 12 Mauritian endemic plants on the promoter activities of antioxidant enzymes; Cu, Zn-superoxide dismutase (Cu,Zn-SOD), Mn-superoxide dismutase (Mn-SOD), catalase, and glutathione dismutase (GPx). The levels of total phenolic compounds, total flavonoids, and proanthocyanidins were measured. Four luciferase expression vectors (pGL3-Basic) with promoter region of each enzyme were constructed, transfected to COS7 cells followed by an exposure to each extract (25 microg/ml, 24h, non-toxic dose). Thereafter, luciferase activities were evaluated in comparison with a control luciferase vector with a herpes simplex virus thymidine kinase promoter. Mauritian endemic plants contained high amounts of total phenols, flavonoids and proanthocyanidins. Total phenols and flavonoids were proportionally associated with Cu,Zn-SOD promoter activity, whereas they were inversely correlated with catalase promoter activity. These results suggest that the chemopreventive potentials of the extracts might reside in their abilities to modulate the expression of the antioxidant enzyme genes.

Animals↗
PubMedDate not supplied

Indirect estimation of cause of death structure in Africa and contemporary theories of mortality.

This paper is a critical assessment of techniques used for the estimation of cause of death structure in Africa in the light of contemporary theories of mortality. The technique mostly used for the indirect estimation of cause of death structure is based on the mortality experience in Western countries. With the marked differences in the epidemiologic transition experienced in Western countries and those being experienced in African countries, it is not very likely that an estimation of cause of death structure based on data from the former can accurately estimate cause of death structure in the latter. This argument is supported in the paper through a comparison of observed estimates of cause of death structure for some African populations with indirect estimates. It is proposed that a better approach is to use a residual method whereby one proceeds from nearly true estimates of cause of death rates to obtain estimates for unknown causes via the known general mortality.

Africa↗
PubMed2002

Repetitive injections of dendritic cells matured with tumor necrosis factor alpha induce antigen-specific protection of mice from autoimmunity.

Mature dendritic cells (DCs) are believed to induce T cell immunity, whereas immature DCs induce T cell tolerance. Here we describe that injections of DCs matured with tumor necrosis factor (TNF)-alpha (TNF/DCs) induce antigen-specific protection from experimental autoimmune encephalomyelitis (EAE) in mice. Maturation by TNF-alpha induced high levels of major histocompatibility complex class II and costimulatory molecules on DCs, but they remained weak producers of proinflammatory cytokines. One injection of such TNF/DCs pulsed with auto-antigenic peptide ameliorated the disease score of EAE. This could not be observed with immature DCs or DCs matured with lipopolysaccharide (LPS) plus anti-CD40. Three consecutive injections of peptide-pulsed TNF/DCs derived from wild-type led to the induction of peptide-specific predominantly interleukin (IL)-10-producing CD4(+) T cells and complete protection from EAE. Blocking of IL-10 in vivo could only partially restore the susceptibility to EAE, suggesting an important but not exclusive role of IL-10 for EAE prevention. Notably, the protection was peptide specific, as TNF/DCs pulsed with unrelated peptide could not prevent EAE. In conclusion, this study describes that stimulation by TNF-alpha results in incompletely matured DCs (semi-mature DCs) which induce peptide-specific IL-10-producing T cells in vivo and prevent EAE.

Animals↗
PubMed1979

Nutritional anemia: its understanding and control with special reference to the work of the World Health Organization.

Since 1949, the World Health Organization, recognizing the public health importance of nutritional anemia, has sponsored efforts directed towards its understanding and control. During this period, often as a result of the work of the Organization, advances have been made in many areas. Basic understanding of iron, folate and vitamin B12 nutrition, and the various factors which may influence the availability and requirements of these factors, has greatly increased. Surveys in a number of countries have highlighted the widespread prevalence of nutritional anemia, particularly in developing countries. The major factor responsible is a deficiency of iron, whith folate deficiency also playing a role in some population groups, especially in preganant women. There is increasing evidence that anemia adversely affects the health of individuals and may have profound socioeconomic consequences. Control of nutritional anemia is possible by providing the deficient nutrient(s) either as therapeutic supplements or by fortification of commonly used foodstuffs. Some control programs are reviewed and suggestions for further action outlined. The Organization still has an important role to play in this field, encouraging the development of control programs and providing advice and technical assistance ot member countries.

Adolescent↗
PubMedDate not supplied

Dendritic cells matured with TNF can be further activated in vitro and after subcutaneous injection in vivo which converts their tolerogenicity into immunogenicity.

Dendritic cell (DC) maturation can occur by different types of stimuli. Previously, we described that murine DC matured with tumor necrosis factor (TNF) up-regulate surface MHC and costimulatory molecules but lack cytokine release, and therefore termed them semi-mature DC. These TNF/DC-induced tolerance after intravenous (i.v.) injection in a model of experimental autoimmune encephalomyelitis (EAE). Here, we show that TNF/DC are not terminally differentiated but can still respond to the microbial stimulus lipopolysaccharide. Subcutaneously injected TNF/DC induce an unpolarized T(H)1/T(H)2 response and are not protective in the experimental autoimmune encephalomyelitis model. Although TNF/DC home to the draining lymph node, they remain negative for intracellular cytokine stainings. However, the nonmigrating, endogenous DC started to produce interleukin (IL)-12p40, TNF and little IL-6, IL-10, and MCP-1 in a bystander fashion. Together, DC matured with the inflammatory stimulus TNF remains responsive to further signals in vitro and in vivo. These signals can be provided by pathogens or the subcutaneous injection route, which can convert them from tolerogenic to immunogenic DC. These findings are important for selecting the appropriate injection route of human DC for tumor immunotherapy.

Animals↗
PubMed2004

Using molecular markers with high mutation rates to obtain estimates of relative population size and to distinguish the effects of gene flow and mutation: a demonstration using data from endemic Mauritian skinks.

We propose a method of analysing genetic data to obtain separate estimates of the size (N(p)) and migration rate (m(p)) for the sampled populations, without precise prior knowledge of mutation rates at each locus ( micro(L)). The effects of migration and mutation can be distinguished because high migration has the effect of reducing genetic differentiation across all loci, whereas a high mutation rate will only affect the locus in question. The method also takes account of any differences between the spectra of immigrant alleles and of new mutant alleles. If the genetic data come from a range of population sizes, and the loci have a range of mutation rates, it is possible to estimate the relative sizes of the different N(p) values, and likewise the m(p) and the micro(L). Microsatellite loci may also be particularly appropriate because loci with a high mutation rate can reach mutation-drift-migration equilibrium more quickly, and because the spectra of mutants arriving in a population can be particularly distinct from the immigrants. We demonstrate this principle using a microsatellite data set from Mauritian skinks. The method identifies low gene flow between a putative new species and populations of its sister species, whereas the differentiation of two other populations is attributed to small population size. These distinct interpretations were not readily apparent from conventional measures of genetic differentiation and gene diversity. When the method is evaluated using simulated data sets, it correctly distinguishes low gene flow from small population size. Loci that are not at mutation-migration-drift equilibrium can distort the parameter estimates slightly. We discuss strategies for detecting and overcoming this effect.

Animals↗
PubMed1996

Lack of association of angiotensin I-converting enzyme gene polymorphism and premature myocardial infarction in Mauritian Indians.

Eighty-five young Mauritian Indians, male survivors of premature myocardial infarction (MI) and thus belonging to a high risk group, were compared with 108 stringently selected controls for a possible association between premature MI and an insertion/deletion (I/D) polymorphism in the gene encoding angiotensin I-converting enzyme (ACE). The frequency of the D allele was 0.42 in the MI group and 0.43 in the control group, and thus no association between I/D polymorphism of ACE with susceptibility to early-onset MI was found in this population group. Other gene components of the renin-angiotensin system and lipid metabolism need to be explored to understand the genetic factors involved in causing MI at an early age.

Adult↗
PubMed1994

Charles-Edouard Brown-Séquard: double-hyphenated neurologist and forgotten father of endocrinology.

This year is the Centenary of the death of Brown-Séquard who, although remembered today only for his eponymous syndrome, was as well known in the Victorian medical world as Robert Maxwell was to newspaper readers in the past decade. His position in the history of endocrinology is paradoxical; a good case can be made for saying that he invented the doctrine of internal secretion. Yet, the excesses of the organotherapy movement he founded at the end of his life discredited endocrinology and probably delayed the discovery of insulin.

Diabetes Mellitus↗
PubMed1975

A longitudinal psychophysiological study of three-year-old Mauritian children: preliminary report.

The rationale for using the high-risk-group research design in the search for the aetiology of schizophrenia is described. A longitudinal study is being made of three-year-old Mauritian children who underwent a variety of physiological and psychological tests. Groups of these children, selected on the basis of their responses to electrodermal stimulation, are now attending nursery schools established on the island as part of this study. A control group of children do not attend nursery school. It is intended to follow-up these children over the next two decades. Mention is made of the benefits of this research to the development of para-medical and educational services in a developing country.

Child, Preschool↗
PubMed2005

Expression of human IL-1alpha after intramarrow gene transfer into healthy non-human primate by adenoviral vector.

Interleukin-1alpha (IL-1alpha) is a multifunctional cytokine that stimulates myelopoiesis in macaque. However, daily systemic injections of IL-1alpha are associated with severe side effects. We therefore investigated the feasibility of a gene therapy strategy aimed at increasing the IL-1alpha local production in bone marrow with limited release of the vector into the blood circulation. Intra-medullar administration of adenoviral vector containing human IL-1alpha (huIL-1alpha) gene resulted in enhanced neutrophil, monocyte and platelet counts during the two first weeks after injection. The DNA vector, the transgene expression and the huIL-1alpha production was detected in treated bone marrow without significant detection of huIL-1alpha in the peripheral blood. Associated with huIL-1alpha production, we observed concomitant plasma C reactive protein and IL-1Ra peaks in the acellular fraction of treated bone marrow at days 3 and 7. No abnormal clinical side effects were observed in any of the animals following the adenoviral vector injection.

Adenoviridae↗