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Biomedical subjects

A Lazzarin

Publications and source records attributed to A Lazzarin.

340 records · Page 19Linked to original sources
PubMedDate not supplied

Impact of HAART on liver histology of HIV/HCV coinfected patients.

The impact of HAART on the progression of HCV related liver disease is controversial. This retrospective study compares the grading and staging of chronic viral hepatitis in HIV/HCV coinfected subjects treated or not with antiretroviral therapy (ART) including protease inibithors (PI). The liver histology of 44 HIV/HCV coinfected patients on ART for more than 12 months, 26 coinfected patients naïve for ART and 31 HCV monoinfected patients were analysed by the Ishak score. None of the multivariate models calculated to test if liver histopathology (Ishak grading or staging) between HIV/HCV coinfected patients versus HCV monoinfected or antiretroviral-treated versus untreated HIV+ subjects showed any statistical difference. No significant difference between grading and staging was evidenced either in PI treated subjects versus patients on ART without PI.

Adult↗
PubMedDate not supplied

Sequence analysis of NS3 protease gene in clinical strains of hepatitis C virus.

The amino terminal region of the non structural gene 3 (NS3) of hepatitis C virus (HCV) is a chymotripsinlike serine-protease responsible for cleavage of the non structural proteins of Hepatitis C virus (HCV). In order to investigate the genetic variation of this region, we developed a nested PCR to obtain NS3 protease sequences from 54 patients chronically infected with HCV genotypes 1a, 1b and 3, respectively. Comparison of nucleotide and amino acids sequences of NS3 protease domain with consensus sequence obtained within the same genotype, showed 3.73% nucleotide divergence and 1.64% amino acid divergence in isolates of genotype 3a, whereas isolates 1a exhibited 4.45% nucleotide and 4% amino acid change, respectively. Finally, NS3 sequence from 1b isolates revealed 6.47% nucleotide and 3.5 % aa changes. Comparison of consensus amino acid sequences derived from isolates 1a, 1b and 3, with the HCV prototypes showed a low amino acid sequence diversity. However, the consensus sequence of HCV genotype 3 isolates showed an amino acid changed from the prototype, that was located within a region important for enzyme structure and activity. These results indicated that the NS3 protease gene is highly conserved within the same HCV genotype. The domains involved in enzyme function were highly conserved in 1a and 1b strains, whereas consensus sequence of isolates 3a showed that the majority of these strains were not perfectly conserved in one of such regions. These findings altogether suggested that the NS3 protease enzyme of HCV may constitute an important target for antiviral therapy, but the NS3 protease variability of isolates 3 within a region that is a potential target for antiviral therapy could pose a problem for structure based drug development.

Adult↗
PubMedDate not supplied

[Respiratory complications in 44 patients with acquired immunodeficiency syndrome].

Observation was carried out of 44 patients affected with pulmonary pathology during the course of AIDS, each of whom presented a severe respiratory insufficiency, admitted to the Clinic of Infectious Diseases between May 1987 and March 1989. In the patients suffering from their first respiratory infection, a lower mortality rate was observed (11/28, 39.2%) compared with the patients suffering from a second or successive infection (10/16, 62.5%). In sixteen cases, the etiological agent was Pneumocystis carinii while in 14 subjects it was impossible to perform bronchoscopy due to particular conditions of the respiratory apparatus and diagnosis was made according to CDC clinical criteria. Several parameters were furthermore evaluated (age, duration of the symptoms prior to admittance, LDH, PaO2, WBC) as potential prognostic indices; at the conclusion of the study, no statistically significant differences were found, however, between the group of survivors and the deceased. For the specific anti PCP therapy, a great variety of drugs were administered; among them, first choice was given to cotrimoxazole. In particularly critical patients, methylprednisolone was added. In 21 patients, a mechanical respiratory aid (C-PAP) was applied with favourable results in 16 of them.

Acquired Immunodeficiency Syndrome↗
PubMedDate not supplied

Heterogeneity in exposed uninfected individuals.

In spite of repeated exposures to HIV, some individuals remain seronegative and apparently uninfected. A variety of mechanisms potentially able to confer resistance to HIV infection, including cell-mediated and (unconventional) humoral immune responses, as well as mutations affecting receptors for virus entry have been considered and analysed. In this article, we want to discuss recent reports on specific immune responses and genetic factors potentially involved in mechanisms of protection, and to present some of our data relative to a cohort of people sexually exposed to HIV-1, but persistently seronegative. These EU (exposed uninfected) individuals can be distinguished from "normal" unexposed controls on the basis of significantly increased frequencies of a number of immunological parameters that might be considered "unconventional" correlates of HIV infection/protection. However, EU individuals are highly heterogeneous since the various unconventional immune responses considered can be present in all possible combinations. Aim of future research will be to ascertain the role of such immune responses in the maintenance of the protection state, or their secondary nature as signals of a particular kind of infection.

Genetic Variation↗
PubMedDate not supplied

Increased plasma levels of the C-C chemokine RANTES in patients with primary HIV-1 infection.

To investigate the role played by chemokines in the natural history of human immunodeficiency virus (HIV) infection, we measured the plasma levels of RANTES. MIP-1 alpha and MIP-1 beta in a cohort of patients with primary HIV-1 infection (PHI) followed longitudinally. The cohort included 17 patients with well-documented history of acute HIV syndrome within two months of the first observation. The mean plasma concentration of RANTES, but not that of MIP-1 alpha or MIP-1 beta, was significantly higher in patients with PHI (192.3 ng/ml) than in five HIV-seronegative controls (8.0 ng/ml) studied during the same time period. Treatment of blood with a cocktail of drugs preventing platelet activation, followed by high-speed centrifugation, reduced the levels of RANTES by approximately 2 logs both in patients and in controls, indicating that the bulk of RANTES was released by platelets, which are known to store this chemokine in their alpha-granules, in the immediate aftermath of blood drawing. No correlation was seen between the levels of RANTES and the number of HIV genome equivalents in plasma. These data suggest that large amounts of pre-formed RANTES are stored in platelets and, possibly, in other blood cells during the early phases of HIV infection. The possible role of this HIV-suppressive chemokine in the control of viral replication during PHI remains to be established.

Chemokine CCL5↗
PubMedDate not supplied

Soluble CD30, tumour necrosis factor (TNF)-alpha, and TNF receptors in primary HIV-1 infection: relationship with HIV-1, RNA, clinical outcome and early antiviral therapy.

The natural course of human immunodeficiency type 1 (HIV-1) infection varies considerably. The identification of laboratory disease markers has become critically important to patient management. This study, carried out on 37 patients with primary HIV-1 infection (PHI), shows that, along with plasma HIV-1 RNA and CD4+ T cell counts, evaluation of plasma levels of some immune activation markers (sCD30, TNF-alpha, and sTNFR-I) may help to identify patients at risk of a more rapid disease progression, suggesting that immune activation is among the factors who determine the rate of disease progression. Early combination antiviral therapy significantly decreased levels of virus load and of immune activation markers, suggesting that it may reduce the extent of immune activation through the suppression of HIV-1 replication. Among others, sCD30 could be a more sensitive marker of immune activation, and it might be also useful in the monitoring of the response to antiviral therapy.

Anti-HIV Agents↗
PubMedDate not supplied

Experiences in immune reconstitution. The rationale for interleukin-2 administration to HIV-infected individuals.

Since the clinical earliest descriptions of patients with acquired immune deficiency syndrome (AIDS) it has been very clear that a profound state of immunologic dysfunction was the underlying cause of the emergence of life-threatening opportunistic infections and tumors. In addition to the progressive loss of CD4 "helper" T lymphocytes, a profound defect in interleukin-2 (IL-2) production was recognized as a major pathogenic component of the new disease. For these reasons, attempts to administer IL-2 to individuals infected with the human immunodeficiency virus (HIV), the causative agent of AIDS, have been made since the mid eighties, however with little success. On the other hand, the propensity of HIV to replicate in activated lymphocytes and macrophages, under the influence of the cytokine network, has represented, and in part still does, a major hurdle for the rationale of administering IL-2 or other cytokines to HIV-infected individuals. Major steps forward towards an understanding of the role of multiple components of the immune system, coupled with a potentially successful protocol of IL-2 administration in vivo, resulting in the stable uprising of circulating CD4+ T cells, shed an optimistic light on the possibility to achieve a substantial immune reconstitution in HIV-infected individuals, thus preventing the onset of AIDS.

Adjuvants, Immunologic↗