Biomedical subjects

M Doroana

Publications and source records attributed to M Doroana.

8 recordsLinked to original sources

PubMed2006

Changes in blood cell membrane properties in HIV type-1-infected patients.

To evaluate the possible HIV-1 infection-induced changes in cell membrane properties and in calcium signaling, membrane fluidity, acetylcholinesterase (AChE, a glycosylphosphatidylinositol-anchored protein) activity, and intracellular calcium concentration ([Ca2(+)](int)) were evaluated in lymphocytes and erythrocytes of infected individuals, previous to their engagement in antiretroviral therapy. Membrane fluidity was assessed by fluorescence spectroscopy measurements, using the fluorescence probes 1,6-diphenyl-1,3,5-hexatriene (DPH) and 1-[4-(trimethylamino)-phenyl]-6-phenyl-1,3,5-hexatriene (TMA-DPH). AChE activity was determined by the colorimetric Ellman's method and [Ca2(+)](int) using the fluorescent fura-2 acetoxymethyl ester. When compared with the control group, lymphocytes of infected patients presented significantly decreased membrane fluidity, decreased AChE activity, and increased [Ca2(+)](int). Erythrocytes from HIV-infected patients presented decreased [Ca2(+)](int) when compared with the control group and decreased membrane fluidity near the lipid/water interface. Our data show that HIV-1 infection leads to biochemical and biophysical changes in the membrane itself and in membrane protein activity in lymphocytes (average of infected and noninfected subpopulations) and even in erythrocytes. The present observations are in agreement with a process of facilitated propagation of the infection to new cells, stimulation of virion production, and maintenance of a reservoir of erythrocyte-bound infectious virus.

Acetylcholinesterase↗

PubMed2000

Bulk cytokine production versus frequency of cytokine-producing cells in HIV1 infection before and during HAART.

Cytokine imbalances play a major role in HIV immunopathogenesis. This study analyzes simultaneously the frequency of cytokine-producing cells at the single cell level by flow cytometry and the disturbances in cytokine secretion assessed by ELISA in a cohort of asymptomatic HIV1 patients in different stages of CD4 depletion and during antiretroviral therapy (HAART). Early in the disease, there is an increased frequency of IFN-gamma(+) lymphocytes and bulk IFN-gamma production, in parallel with a reduced proportion of IL4(+) cells and IL4 secreted. The two IL4 measurements are significantly correlated. No such correlation was found for IFN-gamma, which is consistent with a large variation in the amount of IFN-gamma released per individual cell. Moreover, HAART was associated with a reduction to normal levels in the bulk IFN-gamma secretion concomitant with a persistency of the overexpanded IFN-gamma(+) cell subset in the peripheral blood. This study emphasizes the importance of using a conjoint approach to assess the cytokine network in trials of antiretroviral and/or immune-based therapies to avoid missing significant effects which are possibly relevant in the clinical setting.

Adult↗

PubMed1999

Kinetics of the changes of lymphocyte subsets defined by cytokine production at single cell level during highly active antiretroviral therapy for HIV-1 infection.

The effects of highly active antiretroviral therapy on cytokine imbalances associated with HIV-1 infection have not been characterized. Using single cell analysis by flow cytometry, we show that a significant recovery in the frequency of IL-2-producing cells was only observed in patients with a sustained control of viral replication and that the overexpanded CD8 T cell population of CD28- IFN-gamma + cells was not significantly reduced after 1 yr of effective therapy. Moreover, a detrimental role of IL-4 is suggested by the association between an enhanced proportion of IL-4-producing cells within the CD4 and particularly the CD8 subset and viral load rebound. Finally, the kinetics of changes of cell subsets assessed for simultaneous production of different cytokines supports the view that cell reconstitution during highly active antiretroviral therapy is initially due to redistribution of terminally differentiated cells, followed by peripheral expansion of less differentiated ones and a late progressive increase of the proportion of functionally defined naive/memory precursor lymphocytes. These data bring new support for the role of cytokine imbalances in AIDS pathogenesis and may be relevant for the definition of immunointervention targets.

Adult↗

PubMed1999

Early reduction of the over-expression of CD40L, OX40 and Fas on T cells in HIV-1 infection during triple anti-retroviral therapy: possible implications for lymphocyte traffic and functional recovery.

Fas, CD40L and OX40 are members of the tumour necrosis factor (TNF) receptor superfamily with critical roles in T cell activation and death, B cell function, dendritic cell maturation and leucocyte traffic regulation. The aim of this study was to evaluate the effects of anti-retroviral therapy (HAART) on CD40L, OX40 and Fas expression on freshly isolated peripheral blood T cells by three-colour flow cytometry and compare them with lymphoproliferative responses, peripheral blood cell counts and viral load. Fourteen asymptomatic HIV-1+ patients treated with Lamivudine, Stavudine and Nelfinavir were prospectively investigated sequentially for 48 weeks. At baseline, patients exhibited significantly enhanced proportions and counts of CD40L+ and OX40+ cells within the CD4 subset which were corrected by weeks 8-16 of HAART. Interestingly, in the five patients showing viral load rebound during therapy in spite of increasing CD4 counts, the reduction of the levels of these costimulatory molecules was similarly maintained. Therapy induced a decrease in the over-expression of Fas, particularly in the CD4 subset where normal levels were reached at week 8. This reduction occurred in parallel with the major recovery of lymphoproliferative responses. Higher basal levels and lower reduction of Fas were associated with suboptimal suppression of viraemia. In conclusion, this previously undescribed increased expression of CD40L and OX40 may play a role in the HIV-associated pan-immune activation and represent a possible target for immunointervention, as suggested for several immunologically mediated diseases. Moreover, HAART induced an early correction of the over-expression of Fas, CD40L and OX40 in CD4 T cells which could be involved in the recovery of the cell traffic disturbances and in the T cell renewal capacity.

Acquired Immunodeficiency Syndrome↗

PubMed1996

Switching from zidovudine to didanosine in patients with symptomatic HIV infection and disease progression. ddI Iberian Study Group.

This study evaluated the efficacy of switching to didanosine in patients who were clinically or immunologically progressing despite zidovudine therapy. This multicenter, open-label study involved 400 patients with the acquired immunodeficiency syndrome (AIDS) or AIDS-related complex (ARC), who had tolerated zidovudine for at least 12 weeks and had signs of clinical or immunological disease progression. They were randomly assigned to receive 600 mg/d of zidovudine (n=133), 500 mg/d of didanosine (n=131), or 200 mg/d of didanosine (n=136). The primary end point was a new AIDS-defining event or death. The study was prematurely terminated, after the first interim analysis, mainly owing to results of two controlled studies demonstrating that a change to didanosine was associated with an improved outcome in patients with advanced HIV-1 disease. The median duration of follow-up was 53 weeks. The primary end point rates were 41, 58, and 59 (per 100 person-years) in the didanosine 500 mg, didanosine 200 mg, and zidovudine groups (zidovudine vs. didanosine 500 mg, relative risk 1.28, 95% confidence interval, 0.88-1.86, p = 0.19; didanosine 200 vs. 500 mg, relative risk 1.24, 95% confidence interval, 0.85-1.79, p = 0.26). In subjects with a baseline CD4 count of 100/mm3 or more, the primary end point rates were 8, 29, and 25 (per 100 person-years) in the didanosine 500 mg, didanosine 200 mg, and zidovudine groups, respectively (zidovudine vs. didanosine 500 mg, relative risk 2.96, 95% confidence interval 0.91-9.62, p = 0.07). No difference was seen in survival. In the didanosine 500 mg group, more patients had a 50% increase in CD4 cells (10% vs. 1% in zidovudine group, p = 0.01) and an increase of > or = 2.5 kg in body weight (2% versus 3%). Fatal pancreatitis developed in one patient assigned to didanosine 500 mg and in one to zidovudine. Our data suggest that switching from zidovudine to currently recommended doses of didanosine in subjects with ARC or AIDS who show evidence of clinical and laboratory disease progression can be associated with improvements in clinical outcome as well as in surrogate markers of HIV disease progression. This effect tended to be greater among individuals with higher CD4 counts (>100/mm3).

AIDS-Related Complex↗

PubMed1996

[Cerebral toxoplasmosis in AIDS patients, CT and MRI images and differential diagnostic problems].

Cranial computed-tomographies (CT) and magnetic resonance imaging (MRI) of 14 patients with AIDS and central nervous system toxoplasmosis (CNST) were reviewed. In spite of the low specificity of CT and MRI findings in CNS mass lesions of AIDS patients, there are some features which have been observed as more typical of CNST, namely: 94.9% of the lesions were round shaped and 94.5% had ring or nodular enhancement; 81.3% of the cases presented multiple lesions; 60.2% of the lesions were localized at the cerebral cortical or corticomedullary junction (100% of the cases showed at least 1 lesion in this localization); 34.6% of the lesions had less than 1cm in diameter.; on nonenhanced CT, 91.3% of the lesions were hypodense.; On T2-weighted MR images, 53.4% of the lesions had at least one hypointense zone on T2-weighted images. The existence of target-shaped lesions with hypointense centre on T2-weighted MR images (29.3% the observed lesions) is also suggestive of CNST, which, to our belief, had not been previously reported and will need confirmation with larger series. The visualization of iso/hyperdense lesions on nonenhanced CT or irregular shape lesions is uncommon in CNST. The finding of a solitary lesion, on CT or MR, it is not, by itself, a good criterion of differential diagnosis.

AIDS-Related Opportunistic Infections↗

PubMed1992

[Emphysematous cholecystitis].

Emphysematous cholecystitis (EC) is a rare and dramatic disease that requires prompt therapeutic procedures. The authors report a case of a 70-year-old-woman, admitted to the Intensive Care Unit for Infectious Diseases of the Santa Maria Hospital, with the diagnosis of EC. The literature on EC is also reviewed.

Aged↗

PubMed1992

[Febrile coma and disseminated intravascular coagulation following heat stroke].

A clinical case that occurred in a 42 years old female and which fulfils the diagnostic criteria for the entity described as Heat Stroke is presented. In this case, besides the usual manifestations of hyperpyrexia without sweating along with consciousness disorders, features of consumptive coagulopathy, rhabdomyolysis and well marked laboratory liver dysfunction have also been found. The severity of this situation and its less common occurrence in temperate climates, together with the uncertainty in establishing the diagnosis, namely when infection is suspected--in the present case the initial diagnosis was Sepsis, which led to patient's admission in an infectious diseases intensive care unit--motivate the authors to make this report. Furthermore, they consider this case to be a good example of the varied clinical and laboratory manifestations and possible severe complications that Heat Stroke may display.

Adult↗