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Biomedical subjects

F Castelli

Publications and source records attributed to F Castelli.

At least 19 recordsLinked to original sources
PubMed2006

Key questions in antiretroviral therapy: Italian Consensus Workshop (2005).

A panel of leading Italian specialists in infectious diseases, virologists and immunologists met in Rome in 2005 to review critical data and discuss recommendations for each of the key questions in antiretroviral therapy today: When to start treatment? How to start? When to switch? What to switch to? Whether to stop or not to stop treatment, and how? The method of a nominal group meeting was used and recommendations were graded for their strength and quality using a system based on the one adopted by the Infectious Diseases Society of America. Main conclusions are summarized and critically discussed in this consensus statement, as well as some of the most recent data supporting these recommendations are provided.

Anti-HIV Agents↗
PubMed2006

Reduction of mother-to-child transmission of HIV at Saint Camille Medical Centre in Burkina Faso.

One thousand three hundred and twenty-eight pregnant women with less than 32 weeks of amenorrhea received voluntary counseling and testing at Saint Camille Medical Center from May 1, 2002 to December 30, 2004. Following informed consent and pre-test counseling, HIV screening was performed in 1,202 women. According to the prevention protocol, HIV-positive women received a single dose of Nevirapine (200 mg) during their labor, while their newborn received a single dose of Nevirapine (2 mg/kg) within 72 hr from birth. HIV seroprevalence (11.2%) was higher than in the overall population. One hundred and ninety-three children were born at the end of December 2004; 53 children (27.5%) followed a short breastfeeding protocol for 4 months, while 140 (72.5%) were fed artificially. All the children underwent RT-PCR test for HIV 5-6 months after their birth: 173 (89.6%) were HIV negative whilst 20 children (10.4%) were HIV positive. Out of the 20 positive children 5/53 (9.4%) had received breast milk for 4 months, while the remaining 15/140 (10.7%) had been fed artificially (P = 0.814). Artificially fed babies (3/140 (2.1%)) and 1/53 (1.9%) of those breast fed for 4 months deceased according to mortality rate of HIV-positive children. This shows that there is no statistically significant difference (P = 0.648) between the mortality of artificially fed (3/140 or 2.1%) and breast-fed (1/53 or 1.9%) children. Artificially fed children (20/140 (14.3%)) and 5/53 (9.4%) of breast-fed children died within 6-10 months. This figure indicates that there is no significant difference between the mortality rate of artificially and that of breast-fed children (P = 0.427). Although the HIV prevention program reduced significantly the vertical transmission of HIV at Saint Camille Medical Center, the mortality of artificially fed children was still high due to gastrointestinal diseases. The HIV diagnosis by RT-PCR technique was of great help in the early identification of HIV-infected children.

Adolescent↗
PubMed2003

HIV/HTLV co-infection: frequency and epidemiological characteristics among patients admitted to an Italian hospital.

BACKGROUND: Human T-cell leukemia/lymphoma viruses (HTLV) and HIV share identical modes of transmission and co-infections may be detected in populations that are highly exposed to common risk factors. MATERIALS AND METHODS: A total of 599 serum samples from HIV-positive patients attending our outpatient clinic during the last semester of 2000 were tested to assess the prevalence of HTLV co-infection in both Italian (n = 472) and non-European HIV-infected patients (n = 127). RESULTS: 72 samples were positive for HTLV-II. Most of the HTLV-II-positive patients were Italian (71/72, 98.6%) and 98.5% of them had acquired the HIV infection through use of intravenous recreational drugs. CONCLUSION: These data demonstrate a high HTLV-II exposure among HIV-positive intravenous drug users in our area which was not previously considered to be an area of endemicity for HTLV-II.

Adult↗
PubMed2003

Characterization of viro-immunological responses in a closely followed cohort of heavily pretreated patients: evidence from the GenPheRex Study.

OBJECTIVES: To assess prevalence and predictive factors of viro-immunological discordant trends in a cohort of heavily pretreated patients. METHODS: Factors associated with viro-immunological discordant trends either as categorical or continuous measures have been studied in 159 heavily pretreated HIV-positive patients from a multicentre prospective study of real- vs. virtual-phenotype. Univariate and multivariate logistic regressions were used to assess risk factors for categorical discordant responses, ceasing follow-up at week 32 since enough patients had been on the original drug combination for a sufficient amount of time to evaluate their immune response. Complementary linear regression analysis was performed over the entire 48 weeks' follow-up considering CD4 and plasma viral load (pVL) as continuous measures. RESULTS: Among 58 virological responder patients (> or =1 log10 HIV-1 RNA copies/mL decrease) and 101 virologically non-responders, immunological discordances (increase in CD4 count of< or > or =100 cells/microL) were observed in 58.6% and 38.6%, respectively. Baseline CD4 count was associated with discordant responses in both groups. Multivariable linear regression over the entire 48 weeks' follow-up demonstrated significant correlation between absolute decrease in pVL and increase in CD4 count (HR 28.06, 95%CI 35.32-20.79; P<0.001), also the use of protease inhibitors (PIs) in the salvage regimen (HR 36.57, 95%CI 15.45-57.68; P<0.001) and >8 months on treatment (HR 41.64, 95%CI 19.27-64.01; P<0.001) correlated with highly significant immune recovery. CONCLUSIONS: These data confirm that therapy, possibly including PIs, should be continued in heavily pretreated patients and that hard-to-reach pVL undetectability is not essential to obtain immunologic recovery; however, this is strongly increased by the degree of pVL reduction that should be achieved.

Anti-HIV Agents↗
PubMed2003

Editorial introduction to the paper by A. Castellani "Researches on the Etiology of Sleeping Sickness" reprinted from the Journal of Tropical Medicine, June 1, 1903.

The paper by Professor Aldo Castellani represents the first report suggesting the causative role of Trypanosoma spp. in the pathogenesis of sleeping sickness and confirms his pivotal role in solving the etiologic dilemma of the disease. Professor Castellani also contributed to a large extent to many other important microbiological discoveries, mainly in the field of mycology, protozoology and bacteriology.

Angola↗
PubMed2002

Novel promiscuous HLA-DQ HIV Nef peptide that induces IFN-gamma-producing memory CD4+ T cells.

We describe the highly conserved sequence 56-68 of the HIV Nef protein as the first promiscuous HLA-DQ HIV-derived peptide. The Nef peptide exhibits an albeit rare capacity to bind 6 different HLA-DQ molecules whereas no binding is observed with the 10 HLA-DR molecules tested. In agreement with these data, after immunization with the Nef peptide, HLA-DQ transgenic Abeta degrees mice display a vigorous cellular and humoral response while the specific immune response of HLA-DR expressing mice is minimal. The promiscuous potentiality of the Nef 56-68 peptide in humans has been confirmed by ex vivo immunization experiments with CD4+ T cells from 14 healthy donors expressing different HLA genotypes. Nef 56-68 specific CD4+ T cells rapidly acquire a memory cell phenotype and are characterized by the preferential usage of the TCR Vbeta 6.1 gene segment and predominant production of IFN-gamma. Taken together, these data indicate that the Nef 56-68 peptide constitutes an attractive component of vaccines aiming at inducing or enhancing HIV-specific T cell immunity.

Alleles↗
PubMed2002

Study on the mechanisms of the antibacterial action of some plant alpha,beta-unsaturated aldehydes.

AIMS: In this paper the mechanisms involved in the antibacterial effect of six 2E-alkenals [(E)-2-hexenal, (E)-2-eptenal, (E)-2-octenal, (E)-2-nonenal, (E)-2-decenal and (E,E)-2,4-decadienal] were investigated. METHODS AND RESULTS: We measured the release of carboxyfluorescein (CF) trapped in liposomes of phosphatidylcholine (PC) following exposure to the aldehydes mentioned above, in comparison with that elicited by hexanal and nonanal; the modifications of the thermotropic behaviour of liposomes of dimyristoylphosphatidylcholine (DMPC) induced by (E,E)-2,4-decadienal (the aldehyde endowed with the highest microbicidal activity) were evaluated by means of differential scanning calorimetry. With the exception of hexanal, all aldehydes tested caused rapid CF leakage from PC liposomes. The effectiveness order correlates well with the chain length and the presence of the alpha,beta-double bond. Furthermore (E,E)-2,4-decadienal is able to interact with and cross DMPC bilayers. CONCLUSIONS: The present findings suggest that the 2E-alkenals tested elicit, very likely, a gross perturbation of the lipidic fraction of plasmatic membranes and are able to penetrate into bacterial cells. SIGNIFICANCE AND IMPACT OF THE STUDY: These data represent an interesting background for a rational employment of the plant 2E-alkenals tested as antimicrobial agents.

Aldehydes↗
PubMed2002

STI epidemics in the Indian Ocean region: can the phase be assessed?

The Indian Ocean provides a unique opportunity to curb the HIV epidemic in its nascent phase through strengthening STI control programmes. Making effective and appropriate health services available should be regarded as the first priority for STI control in the region and, whenever possible, core groups should be identified and targeted to interrupt transmission within such networks.

Developing Countries↗
PubMed2002

Long-term response in patients receiving HAART including nelfinavir: experience from two Italian centers.

Many studies have demonstrated that the long-term, virological, immunological and clinical effectiveness of highly active antiretroviral therapy (HAART) is mainly related to durable suppression of viral replication. Among the specific antiretroviral agents available today, nelfinavir has been widely used in the last 3 years. This open label, non comparative, retrospective study on 307 patients living with HIV aimed to evaluate the effectiveness of an antiretroviral (ART) regimen including nelfinavir as first-line HAART in terms of rate and durability of viro-immunological response. Most patients, 258/307 (84%), were pre-treated whereas only 49/307 (16%) were treatment naive. The median baseline CD4 cell count was 223 cells/mm3 for naive patients and 317 cells/mm3 for experienced patients whereas median HIV RNA values were 2,500 and 82,000 copies/ml for experienced and naive patients respectively. Median times spent on nelfinavir were 839 and 897 days for experienced and naive patients respectively, with 171/258 pre-treated patients (66%) remaining on nelfinavir-based therapy up to 24 months. Overall, the mean CD4 increase was 196 cells/mm3 with a relevant increment of 165 in experienced patients and 367 cells/mm3 in naive patients (p<0.01). The mean viral load variation in naive patients was -2.22 log10 and in experienced patients -0.53 log10 (p<0.01). In conclusion, nelfinavir, as part of HAART, demonstrated long-term benefit (almost two-thirds of patients stayed on nelfinavir up to 24 months). The response rate in patients naive to antiretroviral therapy was better than for experienced patients. Although there were some differences related to the baseline CD4 level, the overall response rate was good, supporting the role of nelfinavir in HAART.

Adolescent↗
PubMed2001

When to start highly active antiretroviral therapy in chronically HIV-infected patients: evidence from the ICONA study.

OBJECTIVES: To compare the response to highly active antiretroviral therapy (HAART) in individuals starting HAART at different CD4 cell counts. DESIGN: The mean increase in CD4 cell count and rate of virological failure after commencing HAART were measured in antiretroviral-naive patients (1421) in a large, non-randomized multicentre, observational study in Italy (ICONA). Clinical endpoints were also evaluated in a subset of patients who started HAART with a very low CD4 cell count. RESULTS: After 96 weeks of therapy, the mean rise in CD4 cell count was 280, 281 and 186 x 10(6) cells/l in patients starting HAART with a CD4 cell count < 200, 201--350 and > 350 x 10(6) cells/l, respectively. Patients starting HAART with a CD4 cell count < 200 x 10(6) cells/l tended to have a higher risk of subsequent virological failure [relative hazard (RH), 1.15; 95% confidence interval (CI), 0.93--1.42] compared with patients starting with > 350 x 10(6) cells/l. There was no difference in risk between the 201--350 and the > 350 x 10(6) cells/l groups (RH, 1.0; 95% CI, 0.79--1.29). The incidence of new AIDS-defining diseases/death in patients who started HAART with a CD4 count < 50 was 0.03/person-year (95% CI, 0.10--0.33) during the time in which the patient's CD4 cell count had been raised to > 200 x 10(6) cells/l. CONCLUSIONS: There was no clear immunological or virological advantage in starting HAART at a CD4 cell count > 350 rather than at 200--350 x 10(6) cells/l. The increase in CD4 cells restored by HAART is meaningful in that they are associated with reduced risk of disease/death.

Adolescent↗
PubMed2001

In vitro evaluation of the antioxidant activity and biomembrane interaction of the lazaroid U-74389G.

The aim of this paper was to clarify whether the interaction of the lazaroid U-74389G with phospholipid membranes might be relevant as to its antioxidant activity. Thus we evaluated the "in vitro" antioxidant activity of U-74389G in two experimental models: 1) bleaching of the stable 1,1-diphenyl-2-picrylhydrazyl radical; 2) peroxidation, induced by the water-soluble radical initiator 2,2'-azobis(2-amidino-propane) hydrochloride, on mixed dipalmitoyl-phosphatidylcholine/linoleic acid unilamellar vesicles. Moreover, given that biophysical techniques may help in explaining the role of a drug in its interaction with the microenvironment of the model lipid membranes, we used a classical approach to investigate the U-74389G/model membrane interaction: the differential scanning calorimetry technique on dimyristoylphosphatidylcholine multilamellar and unilamellar vesicles and the Langmuir-Blodgett technique on dimyristoylphosphatidylcholine monolayers. The results evidenced the strong antioxidant activity of U-74389G (especially in a membranous system) and its capability to interact with and be transported across model membranes. Thus one can speculate that U-74389G can act as scavenger of chain-propagating lipid peroxyl radicals within the membranes and may be able to protect not only cell membranes, but also intracellular components against peroxidative attack. Furthermore, also if there is no certain proof that the effect on the lipid packing order may play a key role in its antioxidant activity, the fluidifying effect on phospholipid bilayers of U-74389G favourably complements its free radical scavenging characteristics.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed2001

CD11b expression identifies CD8+CD28+ T lymphocytes with phenotype and function of both naive/memory and effector cells.

A previously unreported CD8(+)CD28(+)CD11b(+) T cell subset occurs in healthy individuals and expands in patients suffering from primary viral infections. In functional terms, these cells share the features of naive/memory CD8(+)CD28(+)CD11b(-) and terminally differentiated effector CD8(+)CD28(-)CD11b(+) subpopulations. Like CD28(-) cells, CD28(+)CD11b(+) lymphocytes have the ability to produce IFN-gamma, to express perforin granules in vivo, and to exert a potent cytolytic activity. Moreover, these cells can respond to chemotactic stimuli and can efficiently cross the endothelial barrier. In contrast, like their CD11b(-) counterpart, they still produce IL-2 and retain the ability to proliferate following mitogenic stimuli. The same CD28(+)CD11b(+) subpopulation detected in vivo could be generated by culturing naive CD28(+)CD11b(-) cells in the presence of mitogenic stimuli following the acquisition of a CD45RO(+) memory phenotype. Considering both phenotypic and functional properties, we argue that this subset may therefore constitute an intermediate phenotype in the process of CD8(+) T cell differentiation and that the CD11b marker expression can distinguish between memory- and effector-type T cells in the human CD8(+)CD28(+) T cell subset.

CD28 Antigens↗
PubMed2001

Analysis of HIV-1 mutation patterns in patients failing antiretroviral therapy.

The emergence of mutations encoding drug resistance is supposed to be a significant limitation to the clinical efficacy of inhibitor compounds directed against specific HIV-1 enzymatic targets. We have used a commercial test (Visible Genetics Inc., Paris, France) to study the prevalence of mutations occurred in HIV-1 protease and reverse transcriptase (RT) genes in 93 HIV-1 infected patients treated with at least one regimen containing a protease inhibitor (PI) and failing to the current therapeutic regimen. Protease mutations conferring resistance to at least one PI were detected in 46/93 (49.4%) of strains, 25 (26.8%) of which showed resistance to all PIs. Reverse transcriptase mutations conferring resistance to at least one RT inhibitor were detected in 57/93 (61.2%) of strains, 18 (19.3%) of which showed resistance to all RT inhibitors. The most frequent RT mutations were T215Y/F, M41L, and M184V (41.9, 40.8, and 40.8%, respectively), while L63P, L10R/V, and A71V/T (58, 41.9, and 34.4%, respectively) were the most represented protease substitutions. We have found no mutations encoding for multiple dideoxynucleoside resistance (Q151M or T69SS). Twelve of our patients (12.9%) had no mutation encoding drug resistance and were completely sensitive to all RT and protease inhibitors. Therefore, not all virological failures are caused by HIV-1 genomic resistance.

Acquired Immunodeficiency Syndrome↗
PubMed2001

Long-term benefit of genotypic-guided therapy and prevalence of multinucleoside resistance in an Italian group of antiretroviral multiexperienced patients.

Multiple nucleoside resistance involves specific genetic changes in the HIV-1 reverse transcriptase gene, such as Q151M mutation and an insertion of two serine aminoacids at RT codon 69. Among 432 patients failing antiretroviral therapy, five (1.15%) harboured viruses with Q151M mutation into the RT gene and no viruses were identified harbouring insertion at codon 69. Also we have studied the long-term benefit of HIV genotypic testing with the failure to reach a viral load below 50 copies/ml within 1 year of antiretroviral therapy using as the primary end-point. A group of 64 HIV-positive antiretroviral multiexperienced patients were examined, all of them failing the current ART. HIV-RNA changed -0.8 log at month 4 and +0.1 log and -0.5 log at months 8 and 12, respectively. The proportion of patients with viral load below 50 copies/ml was 19.3, 32.8, and 28.1% at months 4, 8, and 12, respectively. In multidrug-experienced patients, genotype-guided therapy is not in fact able to achieve complete viral suppression in more than 30% of patients after 1 year of ART. The development of more precise resistance tests and interpretations are needed for better control of HIV replication. Other metabolic/pharmacokinetics factors of poor drug adherence should also be assessed.

Acquired Immunodeficiency Syndrome↗
PubMed2001

Depressive disorders and personality variables in HIV positive and negative intravenous drug-users.

BACKGROUND: Only a few reports investigated the prevalence of depression in intravenous drug-users with HIV infection, including both asymptomatic and symptomatic subjects. In the same group, the association of depression and personality diagnoses was also poorly researched. METHODS: A consecutive sample of intravenous drug-users was collected from patients admitted to an infectious disease clinic, another random sample was taken from out-patients attending a methadone maintenance treatment program. Subjects were first screened with the Hospital Anxiety and Depression Scale, and then all positive subjects were evaluated with the Composite International Diagnostic Interview. Depression was diagnosed according to DSM-IIIR. In-patients were also given a structured personality inventory (Karolinska Psychodynamic Profile). RESULTS: HIV-positive patients had a high rate of depression (major depression 36.2%, dysthymic disorder 7.1%) when compared to HIV-negatives (15.7 and 3.9%, respectively). In-patients had the highest rate of depression, irrespective of HIV clinical staging. A personality disorder was diagnosed in 36% of the sample, but these subjects were no more significantly depressed. LIMITATIONS: Poor detection of depression by the admitting physician may have led to selective hospitalization of patients with both HIV and mood disorder. The composition of the sample may also be biased by the help-seeking behavior of HIV patients who are also depressed. CONCLUSION: Physicians treating AIDS patients should be alerted to the high rate of depression in clinical HIV illness, in order to identify and properly treat depression.

Adult↗
PubMed2001

Biomimetic transport of simple olive biophenol and analogues through model biological membranes by differential scanning calorimetry.

The different interactions of p-hydroxybenzoic acid (1), a simple biophenol (BP) found in olives and their food products, and its substitute analogues, benzoic (2), anisic (3), and toluic (4) acids, with a model membrane represented by dimyristoylphosphatidylcholine (DMPC) multilamellar vesicles (MLV) was studied by differential scanning calorimetry (DSC). The influence of their different lipophilic character on transfer and absorption processes through an aqueous medium into a lipid bilayer was also investigated. DSC experiments allowed monitoring of the interaction of BP with biomembranes by considering the effects exerted on the thermotropic behavior of DMPC multilamellar and unilamellar vesicles at different pHs (4 and 7.4). The examined compounds affect the transition temperature (T(m)) of phospholipid vesicles, causing a shift toward lower values, which is modulated by the molecular fraction entering into the lipid bilayer, as well as by their molecular interaction with the lipids. Kinetic calorimetric measurements were performed on suspensions of blank liposomes immediately after being added to fixed weighed amounts of powdered compounds and after increasing incubation periods at 37 degrees C. T(m) shifts, due to molecular dissolution and transfer of the compounds into the membrane surface occurring during the incubation time, were compared with those determined by a fixed molar fraction of free compounds directly dispersed in the membrane. The results show that the kinetic process, involved in molecular release, transfer through aqueous medium, and uptake by the model membrane surface, is influenced by lipophilicity as well as by pH, acting on the acid solubility and membrane disorder, allowing us to gather useful information on the BP intake process of olive derived foodstuffs.

Calorimetry, Differential Scanning↗