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Biomedical subjects

M Rachid

Publications and source records attributed to M Rachid.

9 recordsLinked to original sources

Human immunodeficiency virus type 1 (HIV-1) genotyping in Rio de Janeiro, Brazil: assessing subtype and drug-resistance associated mutations in HIV-1 infected individuals failing highly active antiretroviral therapy.

In order to assess the human immunodeficiency virus type 1 (HIV-1) drug resistance mutation profiles and evaluate the distribution of the genetic subtypes in the state of Rio de Janeiro, Brazil, blood samples from 547 HIV-1 infected patients failing antiretroviral (ARV) therapy, were collected during the years 2002 and 2003 to perform the viral resistance genotyping at the Renageno Laboratory from Rio de Janeiro (Oswaldo Cruz Foundation). Viral resistance genotyping was performed using ViroSeq Genotyping System (Celera Diagnostic-Abbott, US). The HIV-1 subtyping based on polymerase (pol) gene sequences (protease and reverse transcriptase-RT regions) was as follows: subtype B (91.2%), subtype F (4.9%), and B/F viral recombinant forms (3.3%). The subtype C was identified in two patients (0.4%) and the recombinant CRF_02/AG virus was found infecting one patient (0.2%). The HIV-1 genotyping profile associated to the reverse transcriptase inhibitors has shown a high frequency of the M184V mutation followed by the timidine-associated mutations. The K103N mutation was the most prevalent to the non-nucleoside RT inhibitor and the resistance associated to protease inhibitor showed the minor mutations L63P, L10F/R, and A71V as the more prevalent. A large proportion of subtype B was observed in HIV-1 treated patients from Rio de Janeiro. In addition, we have identified the circulation of drug-resistant HIV-1 subtype C and are presenting the first report of the occurrence of an African recombinant CRF_02/AG virus in Rio de Janeiro, Brazil. A clear association between HIV-1 subtypes and protease resistance mutations was observed in this study. The maintenance of resistance genotyping programs for HIV-1 failing patients is important to the management of ARV therapies and to attempt and monitor the HIV-1 subtype prevalence in Brazil.

Anti-HIV Agents↗

Interference of Lactobacillus plantarum with Pseudomonas aeruginosa in vitro and in infected burns: the potential use of probiotics in wound treatment.

This study evaluated the ability of the probiotic organism Lactobacillus plantarum to inhibit the pathogenic activity of Pseudomonas aeruginosa, both in vitro and in vivo, and investigated the mechanisms involved in such protection. L. plantarum whole cultures, culture filtrates (acid filtrate and neutralised acid filtrate) and isolated, washed cells were tested in vitro for their effects on the production of the P. aeruginosa quorum-sensing signal molecules, acyl-homoserine-lactones (AHLs), and two virulence factors controlled by these signal molecules, elastase and biofilm. All were inhibited by L. plantarum cultures and filtrates, but not by isolated, washed cells. The acid L. plantarum growth medium itself had some inhibitory activity, but the greatest activity was exerted by the whole culture. To test the in-vivo activity of L. plantarum, a burned-mouse model was used in which burns infected with P. aeruginosa were treated with L. plantarum at 3, 4, 5, 7 and 9 days post-infection. Samples from skin, liver and spleen taken after 5, 10 and 15 days demonstrated inhibition of P. aeruginosa colonisation by L. plantarum. There was also an improvement in tissue repair, enhanced phagocytosis of P. aeruginosa by tissue phagocytes, and a decrease in apoptosis at 10 days. These results indicate that L. plantarum and/or its by-products are potential therapeutic agents for the local treatment of P. aeruginosa burn infections.

Animals↗

[Gaucher's disease. Substitutive enzymatic treatment in one case and a review of the literature].

Gaucher's disease, rare, hereditary and potentially mortal affection is characterized by the reduced concentration of the glucocerebroside lipid within the macrophage lysosomes. We report the case of a young 2 years old patient treated by transfusion since he was 9 months because of chronic anemia. According the clinical examination, the general state of the patients was bad ith important delayed stanturoponderal growth, a cutaneomucous paller and enormous splenomegaly. The blood count formula showed anemia with major thrombopenia. The myelogram was poor and the osteomedullar biopsy showed the presence of Gaucher's cells. The diagnosis has been confirmed by enzymatic dosage (Leucocytar b-glucosidase). The treatment of the patient has been substitutive enzymatic (inifucerase) with very favorable response. During Gaucher's disease, the enzymatic deficiency results in the pathologic accumulation of the substrate (glucocerebroside) in the lyososomes, this metabolic overloading may cause polyvisceral disease with spontaneous evolution ofter mortal. The recent discovery of a recombining glucocerebrosidase (imiglucerase) transformed the prognosis of this disease.

Anemia↗

Role of yoghurt in the prevention of colon cancer.

The beneficial effect of yoghurt consumption on health and on the improvement of the mucosal immune system is well established, as is the diet-associated risk of colon cancer. In an experimental model in BALB/c mice we demonstrated that yoghurt added to the diet for 10 consecutive days, with the procedure repeated each 10 days for 6 months, inhibited the development of a colorectal carcinoma induced by 1,2 dimethylhydrazine (DMH). The immunoregulatory mechanisms involved in the inhibition of tumour growth by yoghurt were also examined in these studies. We determined B lymphocytes IgA(+) and IgG(+), as well as CD4(+) and CD8(+) T cells in the large intestine. We measured cellular apoptosis and the cytokines TNF-alpha, IFN-gamma and IL-10. An increase in the number of IgA(+) (P<0.01) was observed, but not in IgG(+) (P<0.01), or in the CD4(+) population (P<0.01) in the mice treated with DMH and yoghurt. While in the group with the carcinogen there was an enhancement in the IgG(+) B cells (P<0.01) and CD8(+) T cells (P<0.01). Yoghurt increased the number of apoptotic cells and induced IFN-gamma and TNF-alpha cytokine release, their production being regulated by an increase in IL-10 (P<0.001). We demonstrated that yoghurt may exert antitumour activity by a decrease in the inflammatory immune response mediated by IgA(+) increase, apoptosis induction and IL-10 release.

Animals↗

Typical essential thrombocythaemia does not express bcr-abelson fusion transcript.

Essential thrombocythaemia (ET) is a chronic myeloproliferative disorder (MPD) characterized by an elevated platelet count and no identifiable underlying primary cause. According to the diagnostic criteria of the Polycythemia Vera Study Group (PVSG), ET lacks features diagnostic for other MPDs, including the Philadelphia chromosome (Ph) or bcr-abl rearrangement. Recently, some authors have reported bcr-abl transcript positivity in ET patients, but these findings remain controversial. The aim of this study was to investigate whether the bcr-abl transcript could be found in ET patients and to verify the hypothesis of a new ET variant. ET patients (n = 121) with a median age at diagnosis of 55 years were enrolled. The bcr-abl transcript status was examined by multiplex reverse transcription-polymerase chain reaction. Only two cases were positive for bcr-abl, one of which had the Ph at diagnosis. The positive bcr-abl transcript was associated, in both cases, with mild basophilia at diagnosis. After a median follow-up of 43 months (0-309 months), two patients in the bcr-abl-negative group developed Ph and bcr-abl-negative acute myeloid leukaemia (AML). In contrast, one of the two patients in the bcr-abl-positive group died from AML 13 years after diagnosis. In conclusion, our data on a large group of patients shows the rarity of the bcr-abl transcript in well-established ET. However, a subset of patients with apparent ET and basophilia may express the transcript and may constitute a novel entity intermediate between chronic myeloid leukaemia (CML) and typical ET. A prospective study is warranted in order to define better the clinical and biological characteristics of bcr-abl-expressing ET.

Adolescent↗

Immunomodulating effects of milks fermented by Lactobacillus helveticus and its non-proteolytic variant.

The effect of milks fermented by Lactobacillus helveticus and its non-proteolytic variant on mucosal and tumoral immunity was studied. Milks fermented by Lb. helveticus wild type or its non-proteolytic variant were administered orally to mice for different periods (3, 5 and 7 d). The immune response was assessed by analysing the activity of the peritoneal macrophages, the number of cells secreting IgA associated with the gut-associated lymphoid tissue and with the bronchial-associated lymphoid tissue. The number of cells was determined by direct immunofluorescence. The antitumour activity was monitored by studying the regression of the subcutaneously implanted fibrosarcomas. After 3 d feeding of milk fermented by Lb. helveticus wild type, the number of sIgA increased significantly at both the intestinal and bronchial levels, indicating that a cellular migration had occurred. This effect was not noticeable when milk fermented by Lb. helveticus Protease (-) was orally administered. Both fermented milks (wild type or its variant) exhibited an effect on the activity of the peritoneal macrophages, which might be indirectly correlated to the regression of the fibrosarcoma. Although the mechanism by which the lactic acid bacteria enhance the immune system is not clear, this study clearly suggests that the bioactive compounds released during milk fermentation might contribute to the immunoenhancing properties of these products. By releasing biopeptide, lactic acid bacteria have important implications in modulation of the host's immune response, more specifically its cellular immune response.

Adjuvants, Immunologic↗

Antitumour activity of yogurt: study of possible immune mechanisms.

The effect of yogurt on the inhibition of colon tumours induced by 1,2-dimethylhydrazine in BALB/c mice has been studied, and the hypothesis examined that yogurt induces a great reduction in the inflammatory immune response and inhibits tumour growth. Mice were assigned to five experimental groups: a control group fed with a conventional balanced diet, and four other test groups that received yogurt supplements for 2, 5, 7 or 10 consecutive days. At the end of each feeding period, mice were given subcutaneous injections of 1,2-dimethylhydrazine (20 mg/kg) once a week for 8 weeks. After tumour induction, yogurt was given again for 2, 5, 7 or 10 consecutive days each 10 d for 20 weeks. By week 20, 70% of the animals in the control group had developed colorectal tumours. From week 8, there was a considerable infiltration of mononuclear cells into the lamina propria of the large intestine. There was an increase in the number of IgG-producing cells and a slight increase in the IgA-secreting cells, and of CD8+ but not CD4+ T lymphocytes, a high level of beta-glucuronidase activity in the intestinal fluid and leucocytosis with neutrophilia in the blood. However, in the test groups given yogurt tumour growth was inhibited, the effect being more evident with 7 or 10 d treatment. The inflammatory immune response as measured by the characteristics we assessed was also reduced, with an increase in the IgA-secreting cells and in CD4+ T lymphocytes. The blood count was similar to that of normal animals and no colorectal tumours were observed in week 20. We suggest that one of the mechanisms by which yogurt exerts antitumour activity is through its immunomodulator activity, by reducing the inflammatory immune response, which was markedly increased when the carcinogen was administered.

1,2-Dimethylhydrazine↗

Immune system stimulation by probiotics.

The immune system consists of organs and several cell types. Antigen interaction with these cells induces a cellular immune response mediated by activated cells and a humoral immune response mediated by antibodies. The cellular interactions are enhanced by adhesion molecules, and the activated cells release different cytokines. These complex cellular interactions induce a systemic immune response. If the antigen penetrates by the oral route, a secretory immune response is obtained, which is mediated by secretory IgA. The determination of the number of T or B cells, the quantitative or qualitative measure of the cytokines, antibody levels, or the study of cellular function such as phagocytic activity is used to evaluate the state of the immune system. The effects of lactic acid bacteria on the systemic immune response and on the secretory immune system are described. Potential health benefits of lactic acid bacteria include protection against enteric infections, use as an oral adjuvant, the immunopotentiator in malnutrition, and the prevention of chemically induced tumors. The results showed that Lactobacillus casei could prevent enteric infections and stimulate secretory IgA in malnourished animals, but could produce bacteria translocation. Yogurt could inhibit the growth of intestinal carcinoma through increased activity of IgA, T cells, and macrophages.

Animals↗

Effect of yogurt feeding on the small and large intestine associated lymphoid cells in mice.

The effect of giving yogurt supplements to BALB/c mice on the various gut-associated lymphoid cells was studied. Animals were fed for 2, 5, 7 and 10 consecutive days. The different lymphoid cell types were identified and counted by haematoxylin-eosin staining of histological slices. The numbers of cells secreting IgA, IgG and IgM and the numbers of T lymphocytes were determined by direct immunofluorescence. The degree of activation of the intestinal macrophages in the small intestine was assessed by measuring the beta-glucuronidase (EC 3.2.1.31) released into the intestinal fluid, and also by a histochemical method. Throughout the feeding period, there were no histological alterations in the gut, but there was marked cell infiltration, mainly of plasma cells and lymphocytes. The number of macrophages on the small intestine increased significantly after feeding for 2 d, while the beta-glucuronidase activity was only slightly higher that of the controls. After a 7 d feeding period, the number of IgA secreting cells increased, while the values for cells secreting IgM and IgG and for T lymphocytes remained similar to those of the controls. The effect of giving yogurt on lymphoid cells associated with the large intestine was mainly on the numbers of IgA secreting B cells and T lymphocytes, with a marked increase during the whole feeding period in the latter type of cell. Since giving yogurt mainly enhanced the IgA secreting B cells in both small and large intestines, this increase would strengthen the host's defence mechanisms in the intestinal mucosa. Although the number of macrophages was increased, there was no enhancement in their activity, which might have harmed the host by producing an inflammatory response.

Animals↗