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Biomedical subjects

P Machado

Publications and source records attributed to P Machado.

17 recordsLinked to original sources
PubMed2006

Mucosal leishmaniasis patients display an activated inflammatory T-cell phenotype associated with a nonbalanced monocyte population.

Leishmania braziliensis is a parasite that can induce at least two clinical forms of leishmaniasis in humans: cutaneous leishmaniasis (CL) and mucosal leishmaniasis (ML). In humans, the specific mechanisms that determine which form will develop following infection are not well established. In this study, peripheral blood mononuclear cells from 17 CL and 9 ml patients were compared both ex vivo and after culture with soluble leishmania antigen (SLA). Patients with ML presented a higher frequency of activated T cells as measured by ex vivo frequencies of (CD4+)(CD69+), (CD4+)(CD28-), (CD4+)(CD62L-) and (CD8+)(CD69+) than those with CL. Moreover, after stimulation with SLA, patients with ML presented a higher frequency of TNF-alpha-producing CD4+ and CD14+ cells than CL individuals. While CL patients displayed a positive correlation between the frequency of IL-10 and TNF-alpha-producing monocytes, the ML patients did not. This lack of a positive correlation between IL-10-producing and TNF-alpha-producing monocytes in ML patients could lead to a less controlled inflammatory response in vivo. These results corroborate with a model of an exacerbated, unregulated, immune response in ML patients and point to key immunomodulatory leucocyte populations and cytokine networks that may be involved in the development of immunopathology in ML patients.

Antigens, CD↗
PubMed2002

Effect of prenatal stress on the hormonal response to acute and chronic stress and on immune parameters in the offspring.

The effect of prenatal stress on the time course of the corticosterone response to acute and chronic stress and on hematological and immunological parameters in the offspring were analized in the present study. Pregnant Sprague-Dawley rats were stressed daily for 2 hours during the last week of gestation, and female and male off-spring were studied during adulthood. Corticosterone response to acute immobilization stress was not significantly different in either control or prenatally stressed rats. However, after 10 days of immobilization stress the corticosterone response completely disappeared in the control animals but not in the prenatally stressed group: high levels of corticosterone were found during the first hour of stress, although they were lower than those found in acutely stressed rats. Adrenal hypertrophy in response to prenatal stress was observed in females but not in male offspring, and chronic stress only increased adrenal weights in the male control group. Prenatal stress decreased the total peripheral leukocyte count, altered its diferential count decreasing lymphocytes and increasing neutrophil and eosinhophil counts, and significantly reduced the percentage of peripheral lymphocyte T CD8+ subset in male offspring. Chronic stress also reduced the percentage of the peripheral T CD8+ lymphocyte subset in the control group but not in the prenatally stressed group. These results suggest that the exposure to stress during pregnancy alters the adaptative response of the hypothalamus-pituitary-adrenocortical axis to chronic stress and presumably the immune competence in the offspring.

Acute Disease↗
PubMed2001

Successful treatment of refractory mucosal leishmaniasis with pentoxifylline plus antimony.

Mucosal leishmaniasis is characterized by an intense inflammatory reaction and tissue damage with few parasites in the lesion. On the basis of previous observations that suggest a possible role of tumor necrosis factor alpha (TNF-alpha) in the pathology of this disease, an open-label study was performed to evaluate the efficacy of the treatment with an inhibitor of TNF-alpha (pentoxifylline) associated to antimony therapy in 10 patients with refractory mucosal leishmaniasis. Patients were treated with pentavalent antimony (20 mg per kilogram of body weight per day) plus orally administered pentoxifylline 400 mg 3 times daily for 30 days. Nine of 10 patients fulfilled the criteria for cure: they experienced complete reepithelization of the mucosal tissue 90 days after therapy and displayed no evidence of relapse at 1 year of follow-up. The TNF-alpha levels before therapy (776 +/- 342 pg/mL) fell to 94 +/- 57 pg/mL (P < 0.05) within 60 days after therapy. Our results indicate that pentoxifylline plus antimony therapy should be considered in all patients with mucosal leishmaniasis that is refractory to treatment.

Administration, Oral↗
PubMed1999

Randomized, double-blind study of stibogluconate plus human granulocyte macrophage colony-stimulating factor versus stibogluconate alone in the treatment of cutaneous Leishmaniasis.

The response to recombinant human granulocyte macrophage colony-stimulating factor (GM-CSF) in the treatment of cutaneous leishmaniasis was evaluated. Twenty patients with cutaneous leishmaniasis who had lesions for 60 days were enrolled in a double-blind placebo trial of GM-CSF with standard parenteral sodium stibogluconate (20 mg/kg-1/day-1) for 20 days. Ten patients were randomized to receive intralesionally injected GM-CSF (200 microgram) at enrollment and 1 week after, and 10 patients received saline as placebo. GM-CSF- and antimony-treated patients healed faster than patients who received antimony alone (49+/-32.8 vs. 110+/-61.6 days, P<.05). Seven of 10 patients were healed of their lesions before 40 days after therapy in the GM-CSF group, compared with only 1 of 10 patients in the placebo group (relative risk, 7; 95% confidence interval, 1.04-47.00). Thus, GM-CSF plus antimony significantly increased the chance of lesion healing in 40 days.

Adolescent↗
PubMed1998

Production of host-protective (IFN-gamma), host-impairing (IL-10, IL-13) and inflammatory (TNF-alpha) cytokines by PBMC from leprosy patients stimulated with mycobacterial antigens.

The production of IFNgamma, IL-10, IL-13 and TNFalpha was determined using PBMC from 7 tuberculoid (TT) and 7 lepromatous leprosy (LL) patients, after stimulation with several mycobacterial antigens, in an attempt to characterize the cytokine responses to these antigens. The results showed that TT patients displayed higher IFNgamma levels than LL patients with the mycobacterial antigens tested, but no differences in IL-10 production were observed between the two groups. MLSC antigen was associated with the lowest IFNgamma production in TT and LL groups. Only BCG could be identified with stimulation of IFNgamma production in some LL patients. The mycobacterial antigens SP+, SP- and BCG were associated with higher TNFalpha production in patients and controls, suggesting that these antigens could be involved in immunopathological effects. Our findings showed that the antigens tested were associated with a heterogeneous cytokine production in leprosy patients. Further studies are required to establish if an individual antigen can be identified as inducing a protective immune response in leprosy.

Antigens, Bacterial↗
PubMed1992

Epidermolysis bullosa acquisita in a 3 1/2-year-old girl.

A 3 1/2-year-old girl had a subepidermal bullous eruption with immunopathologic features that were consistent with epidermolysis bullosa acquisita or bullous systemic lupus erythematosus. This report highlights the difficulty encountered in distinguishing between epidermolysis bullosa acquisita and other bullous disorders that involve the dermoepidermal junction and the need for modern immunologic investigations in the diagnosis of bullous diseases in children.

Child, Preschool↗
PubMed1992

Expression of the alpha 6 beta 4 integrin in lesional skin differentiates bullous pemphigoid (BP) from epidermolysis bullosa acquisita (EBA).

The integrin alpha 6 beta 4 complex is a protein of the membrane of basal keratinocytes, localized at the surface of cells in contact with the basement membrane zone in normal skin. The expression of alpha 6 beta 4 was investigated in several autoimmune blistering skin diseases including bullous pemphigoid (BP), epidermolysis bullosa acquisita (EBA), bullous systemic lupus erythematosus (BSLE), and pemphigus vulgaris (PV) by an indirect immunofluorescence technique. In lesional bullous skin of BP, alpha 6 beta 4 expression was either absent, or in some cases represented an unusual irregular patchy staining. In contrast, in lesional bullous skin from EBA, BSLE, and PV, alpha 6 beta 4 expression was comparable to that observed in normal skin, i.e., a linear staining of the BMZ. Thus, analysis of the alpha 6 beta 4 integrin reactivity on lesional skin, in conjunction with the typical localization of collagen IV, allows a rapid and accurate distinction between BP and EBA.

Diagnosis, Differential↗
PubMed1992

Serological diagnosis of bullous pemphigoid (BP): comparison of the sensitivity of indirect immunofluorescence on salt-split skin to immunoblotting.

Specialized immunological assays are required for the accurate diagnosis of bullous dermatoses such as bullous pemphigoid (BP), epidermolysis bullosa acquisita and bullous lupus erythematosus. The aim of this study was to analyse and compare the sensitivity of indirect immunofluorescence (IF) on salt-split skin and immunoblotting for the detection of circulating autoantibodies in BP. Of the BP patients selected for the study, 74/79 (94%) had circulating autoantibodies detected by at least one of the two methods. Both methods had comparable sensitivity and detected BP-specific autoantibodies in 82-85% of the patients. Because 20% of the patients were found to be positive by only one of the methods, both methods should be used in the diagnosis of BP. Indirect IF on salt-split skin is easier to perform and is preferable in routine analysis, but Western blotting may be used as a complementary assay with sera showing no reactivity on salt-split skin.

Autoantibodies↗
PubMedDate not supplied

T cells in bullous pemphigoid. Presence of activated CD4+ T cells at the basement membrane zone in pre- and peri-bullous skin.

Bullous pemphigoid (BP) is an auto-immune blistering skin disease associated with the presence of autoantibodies directed to BP antigens located at the basement membrane zone of the dermal-epidermal junction. The present study was designed to test for the involvement of cellular immune mechanisms in the pathogenesis of blister formation. An immunohistochemical analysis of the lesional, peri-lesional, and pre-lesional mononuclear cell infiltrates, performed in 7 BP patients, revealed the following observations: 1) all the skin biopsies contained a high percentage of mononuclear cells within the inflammatory cellular infiltrate; 2) T cells (CD3+, CD45RO+), with a phenotype of activated helper T cell (CD4+, CD25+) were consistently found; 3) T cells were found beneath the bullae but, more importantly, also at the dermal-epidermal junction in close contact with the basement membrane zone in pre- and peri-bullous lesions. These results show that activated T cells are found at the early phase of the onset of BP lesions and suggest that they could play a role, in association with autoantibodies, in the pathogenesis of bulla formation.

Antigens, CD↗
PubMedDate not supplied

[Megavisceral syndrome. Report of 2 cases].

Two patients with splanchnomegaly are presented, and it is proved through experimental, clinical, anatomicopathological, and epidemiological investigations that Trypanosoma cruzi--the etiological agent of Chagas' disease--causes splanchnomegaly in those countries where this disease is endemic. It is neither assured nor denied that Trypanosome cruzi has been the causal agent of splanchnomegaly in the studied patients. It is suggested that in further investigations this problem may be cleared up.

Adult↗