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Biomedical subjects

F Castelli

Publications and source records attributed to F Castelli.

At least 55 records · Page 3Linked to original sources
PubMed1997

Comparison of pharmacokinetics and dynamics of two dosage regimens of foscarnet in AIDS patients with Cytomegalovirus retinitis.

OBJECTIVE: To compare the pharmacokinetics of foscarnet administered as an infusion twice daily (BID) or thrice daily (TID), and to compare the effects on the electrolyte balance, cardiac and renal functions over a 3-week induction treatment of Cytomegalovirus (CMV) retinitis. METHODS: Pharmacokinetics/dynamics of foscarnet were investigated on treatment days 1, 14 and 21. Twelve AIDS patients with CMV retinitis completed the investigation period. Concentrations of foscarnet and electrolytes were assayed by high-performance liquid chromatography (HPLC) and by an ion-selective analyser, respectively. RESULTS: The pharmacokinetics of the two regimens were essentially similar. Foscarnet plasma and creatinine clearances were 2.0 and 1.6 ml.min-1.kg-1, respectively, in the BID group at steady state (day 21). In the TID group the corresponding values were 1.8 and 1.7 ml.min-1.kg-1, respectively. In both regimens the elimination half-life of foscarnet was 2-3 h. Ionized calcium concentrations were transiently decreased and strongly inversely correlated to foscarnet plasma concentrations in both regimens with no significant differences between groups. A trend towards prolongation of the QTc interval was seen when data from both treatments were analysed together. CONCLUSION: Our data suggest comparable pharmacokinetics of foscarnet after intermittent administration BID or TID during a 3-week induction period.

AIDS-Related Opportunistic Infections↗
PubMed1997

Plasmodium falciparum: an electronmicroscopy study of caveolae and trafficking between the parasite and the extracellular medium.

Caveolae containing grape-like tubulovesicular structures were observed in the cytoplasm and in the parasitophorous vacuole of ring- and trophozoite-stage Plasmodium falciparum parasites. In appliqué-forms intact caveolae and free vesicles were also seen to bud off the surface of infected erythrocytes directly from the parasitophorous vacuole where the parasite was in close vicinity to the host cell membrane. The mean vesicle diameter was 0.08-0.1 micron. No such structure was observed in schizonts, segmenters or in the cytoplasm of infected or uninfected erythrocytes. These structures may represent morphological evidence in P. falciparum of a "window" through which the parasite would have direct access to the extracellular milieu. They may constitute carrier vesicles containing parasite membrane transport molecules possibly involved in malaria pathogenesis and/or immunity.

Animals↗
PubMed1997

Dipalmitoylphosphatidylcholine/linoleic acid mixed unilamellar vesicles as model membranes for studies on novel free-radical scavengers.

Large unilamellar vesicles (LUVs) are generally accepted to be a suitable model for peroxidation studies. In the present report, dipalmitoylphosphatidylcholine (DPPC)/linoleic acid-mixed LUVs were employed as model membranes to verify the inhibitory effect of tocopherol (an efficient representative antioxidant) against 2,2'-azobis(2-amidinopropane)hydrochloride-induced peroxidation (evaluated by monitoring conjugated diene accumulation). In this model, the appropriate experimental conditions (particularly, liposome composition and peroxidation temperature) were selected following characterization of bilayer physical state, and not only by evaluation of peroxidation rate. Thus, the experiments described provide a routine screening procedure that would be appropriate for assessing the activity profile of novel free-radical scavengers.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1997

The placenta and malaria.

Placental malaria is recognized as a common complication of malaria in pregnancy in areas of stable transmission, and is particularly frequent and severe in primigravidae. Many hypotheses, based on a systemic or local failure of the immunological response to malaria, have been proposed to explain the 'preference' of the parasites for replication in the placenta. Some of the hypotheses are briefly reviewed here, with a particular focus on the discovery of an uncommon subpopulation of Plasmodium falciparum which can adhere and massively sequester in the placenta. Histologically, placental malaria is characterized by the presence of parasites and leucocytes within the intervillous spaces, pigment within macrophages, fibrin deposits and trophoblasts, proliferation of cytotrophoblastic cells and thickening of the trophoblastic basement membrane. The exact mechanisms leading to placental changes and determining the observed impairment of materno-foetal exchange are incompletely understood. Parasites are unlikely to be directly responsible for the placental pathology, but leucocytes, through the production of non-chemotactic cytokines, might be associated with the thickening of the trophoblastic basement membrane, and might cause a mechanical blockage of oxygen and nutrient transport across the placenta. There is sound epidemiological evidence that placental malaria determines low birthweight, mainly mediated by intrauterine growth retardation, and increases the risk of death and disease during the first year of life. Antimalarial chemoprophylaxis significantly reduces placental malaria and prevents the development of low birthweight. It is likely that, in areas of high endemicity, the placenta is where the drama of maternal malaria is mostly played. A deeper understanding of the mechanisms involved in this process is of key importance in the design of protective interventions which are effective and acceptable during the gestation period.

Disease Susceptibility↗
PubMed1997

Detection of clonal T cell populations with closely related T cell receptor junctional sequences in persons at high risk for human immunodeficiency virus (HIV) infection and in patients acutely infected with HIV.

The T cell repertoires were characterized for CD4+ and CD4 lymphocytes derived from 2 patients with acute human immunodeficiency virus (HIV) infection and from 25 HIV-seronegative persons at high risk for acquiring HIV. Oligoclonal expansions of CD4 cells were detected in the HIV-infected patients and in 2 of 3 uninfected high-risk subjects with a reduced number of CD4+ lymphocytes. Furthermore, nucleotide sequencing revealed that some of the T cell receptor (TCR) beta variable segments (TCRBV), which were highly selected in the high-risk subjects, shared closely related junctional sequences, with the TCRBV predominantly expanded in the HIV-infected patients. Since the likelihood that these similarities occurred by chance is extremely low, these data provide direct molecular evidence in support of several cellular and serologic studies suggesting that some persons remain uninfected despite exposure to HIV.

CD4 Lymphocyte Count↗
PubMed1996

Age-Specific Anti-Hepatitis A Virus Seroepidemiology in Italian Travelers: Indications for Anti-Hepatitis A Vaccination.

Background: Hepatitis A virus (HAV) circulation in the environment is decreasing in most industrialized Western countries. This decrease has lead to low seroprevalence rates in adults. As a consequence, many nonimmune unprotected travelers from areas of low prevalence are considered at risk of acquiring HAV infection when traveling to high HAV endemic areas in developing countries. The recent HAV inactivated vaccine has proved safe and effective, and its use in different geographic areas should be guided by local age-specific HAV seroprevalence rates. The aim of this paper is to describe the age-specific sero-epidemiology of HAV infection in travelers from a highly industrialized region in Northern Italy (Lombardy). Methods: Seven hundred and forty-four consecutive travelers aged from 20 to 59 years, subdivided in 10-year age groups, gave blood samples in the collaborative Health Centers in the Lombardy region and sera were tested for HAV IgG antibodies. A questionnaire was given to travelers that investigated alimentary habits and a history of previous travel. Results: Anti-HAV seroprevalence was 18.0%, 58.0%, 75.8%, and 89.5% in the 20-29, 30-39, 40-49, and 50-59 age groups, respectively. Age was the single most important determinant of anti-HAV seroprevalence. The influence of previous travels, eating shellfish, or ingestion of self-cultivated vegetables was ruled out by multivariate analysis. Conclusions: In the Lombardy region (Northern Italy), age specific anti-HAV seroprevalence rates are much higher than those reported in other Western European countries. The cost-benefit analysis suggested that travelers born after 1960 do not need serologic screening before vaccination. Whenever possible, however, HAV serologic screening is advisable for travelers born before 1960. However, the severity of the disease in older subjects, and the proved safety of HAV vaccination in immune subjects, may advise d'emblée HAV vaccination without prior screening, when serologic investigation is unfeasible because of lack of time or the unavailability of testing facilities.

Journal Article↗
PubMed1996

Herpes zoster and progression to AIDS in a cohort of individuals who seroconverted to human immunodeficiency virus. Italian HIV Seroconversion Study.

A prospective study of 1,198 individuals who seroconverted to human immunodeficiency virus (HIV) was conducted to estimate the incidence and determinants of herpes zoster and to determine whether herpes zoster can accelerate the progression to AIDS. Herpes zoster was diagnosed for 48 individuals (4%). After adjusting for the CD4 cell count, individuals acquiring HIV infection through sexual contact were more likely to have herpes zoster than were injection drug users (relative hazard, 1.50). The crude relative hazard of AIDS for individuals who had herpes zoster compared with those without herpes zoster was 2.44; the adjusted relative hazard was 1.08. After adjusting for the CD4 cell count, fever was the only specific characteristic of herpes zoster that was significantly associated with a more rapid progression to AIDS (relative hazard, 6.52). Data suggest that herpes zoster occurs more frequently in individuals acquiring HIV infection through sexual transmission. There was no evidence that herpes zoster per se is an independent cofactor of progression of HIV disease, although febrile episodes of herpes zoster may predict a faster progression to AIDS.

AIDS-Related Opportunistic Infections↗
PubMed1996

Filgrastim to treat neutropenia and support myelosuppressive medication dosing in HIV infection. G-CSF 92105 Study Group.

BACKGROUND: Patients with HIV infection frequently experience disease or treatment-related myelosuppression leading to neutropenia. Neutropenia often leads to dose-reduction or discontinuation of important myelosuppressive therapy. OBJECTIVE: To examine the efficacy and safety of filgrastim for reversing neutropenia and determine the effect of this on use of myelosuppressive medications. DESIGN: Open-label, non-comparative, multicentre study in 200 HIV-positive patients with neutropenia [absolute neutrophil count (ANC) < 1.0 x 10(9)/l]. Filgrastim was started at 1 microgram/kg/day subcutaneously for 28 days. This initial treatment phase was followed by a maintenance phase, using 300 micrograms on 1-7 days/week. In both phases the dose of filgrastim was adjusted to achieve an ANC of 2-5 x 10(9)/l. RESULTS: Filgrastim reversed neutropenia in 98% of patients (ANC > or = 2 x 10(9)/l), with a median time to reversal of 2 days (range 1-16) and a median dose of 1 microgram/kg/day (range 0.5-10). Most patients (96%) achieved reversal of neutropenia with a filgrastim dose of < or = 300 micrograms/day (< or = 1 vial/day). Normal ANCs were then maintained with a median of 1 microgram/kg/day (range 0.22-10.6) during the treatment phase and 3 x 300 micrograms vials/week (range 1-7) during the maintenance phase. Ganciclovir, zidovudine, co-trimoxazole and pyrimethamine were the drugs most frequently considered to be causing neutropenia, and 83% of patients received one or more of these in the study. Filgrastim allowed > 80% of patients to increase or maintain dose-levels of these four medications or add them to their therapy. The number of these four medications received per patient increased by > 20% during filgrastim therapy. Filgrastim was well tolerated. CD4, CD8 and total lymphocyte counts all increased slightly, and there was no difference in HIV-1 p24 antigen levels. CONCLUSION: Filgrastim rapidly reverses neutropenia and maintains normal ANC in patients with HIV infection. This allows greater use of myelosuppressive medications without the potentially life-threatening complications of neutropenia.

Adolescent↗
PubMed1996

Structure-activity studies on monoamine oxidase inhibitors by calorimetric and quantum mechanical calculations.

Structure-activity relationship studies were carried out on a new series of hydrazino-thiosemicarbazide derivatives, which inhibit monoamino oxidase (MAO). Fifty-five compounds were synthesized and tested "in vitro" for their inhibitory effects on rat liver mitochondrial MAO. The most efficient MAO inhibitors were the benzylidene derivatives (sequence: see text] where R is the piperonyl radical and ethyl or isopropyl substituents are in R1 position. Correlation of MAO activity with hydrophobic, electronic and steric properties of tested compounds, evaluated by means of Quantum Mechanical calculations and calorimetric analysis (DSC) suggest that electronic and steric parameters give a better fit than hydrophobicity with the biological activity.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1996

Short report: primaquine-tolerant Plasmodium vivax in an Italian traveler from Guatemala.

Plasmodium vivax infections caused by strains with low sensitivity to primaquine are widespread in the Western Pacific and Southeast Asia, and have been recently reported from Central America as well. We report a case of primaquine failure in a P. vivax infection acquired in Guatemala. A 28-year-old Italian woman developed two months after returning from Guatemala a vivax malaria attack that was treated with a standard chloroquine course (1,500 mg over three days) combined with primaquine (15 mg/day for 14 days). Two months later, she had a relapse that was again treated with chloroquine and primaquine at the same doses. After two more months, a second relapse occurred: this time primaquine (30 mg/day for 14 days was administered; the patient remained well during a follow-up period of six months and all parasitologic examination results were negative. Doses of primaquine as high as 6 mg/kg total dose may be indicated in the treatment of vivax malaria cases from Central America.

Adult↗
PubMed1996

[The application of a new diagnostic protocol for stroke in the young].

Cerebral infarction before the age of 45 years accounts for 4-6% of all strokes. The etiology remains unexplained in a significant proportion of patients even after extensive investigations. The reported risk factors of this age group are cardiopathies, hypertension, smoking, hypercholesterolemia, reduction of anticoagulant proteins, hypercoagulable states, antiphospholipid antibodies primary syndrome, antiphospholipid antibodies secondary syndrome, some hemoglobinopathies, hyperviscosity syndromes, vasculitis, collagen vascular diseases, fibromuscular dysplasia, arterial dissections, migraine, myopathy encephalopathy lactic acidosis stroke like episodes, homocystinuria, familial amyloid angiopathy, microangiopathy with retinopathy encephalopathy and deafness, systemic lupus erythematosus, use of cocaine, traumas or manipulations of neck, AIDS. From 1/1/94 to 04/30/95 we observed 19 patients with cerebral infarctions and 9 patients with transitory ischemic attacks in young people. The aim of our study was to apply a diagnostic protocol by sequential tests of first level and second level. According to this protocol we found that the more common risk factors were ischemic cardiopathy, hypertension, smoking and hypercholesterolemia. Moreover we observed other independent risk factors, although less frequent, like the antiphospholipid antibodies, neurolupus, AIDS, deficit of protein S.

Adult↗
PubMed1995

The ability of CD4+ cells from HIV+ individuals to express CD40 ligand after in vitro stimulation is not impaired.

Interaction between the B cell glycoprotein CD40 and its ligand (CD40L), expressed by activated T cells, is of crucial importance in the generation of specific antibody response, which is impaired in HIV+ individuals. We studied the expression of CD40L by lymphocytes activated with PMA plus ionomycin in 17 HIV+ individuals and 12 healthy donors. In HIV+ individuals, the percentage of cells expressing CD40L was lower than that in the controls (22.6 +/- 14.7 vs 40.1 +/- 12.0; P < 0.002) and clearly correlated with that of CD4+ peripheral blood lymphocytes (r = 0.83; P < 0.001); therefore, the reduced CD40L expression might be explained by the decrease of the CD4+ cells. In fact, the expression of CD40L by purified CD4+ cells was comparable in individuals with and without HIV infection. These data indicate that the ability of CD4+ cells from HIV individuals to express CD40L is not impaired, at least after optimal stimulation in vitro.

Adult↗
PubMed1995

Flavonoids as antioxidant agents: importance of their interaction with biomembranes.

Flavonoids, a group of phenolic compounds widely occurring in the plant kingdom, have been reported to possess strong antioxidant activity. In the present study, four flavonoids (quercetin, hesperetin, naringenin, rutin), chosen according to their structural characteristics, were tested in two different in vitro experimental models: (1) Fe(2+)-induced linoleate peroxidation (Fe(2+)-ILP), by detection of conjugated dienes; and (2) autooxidation of rat cerebral membranes (ARCM), by using thiobarbituric acid for assay of free malondialdehyde production. The results obtained were also interpreted in the light of flavonoid interactions, studied by differential scanning calorimetry, with dipalmitoylphosphatidylcholine (DPPC) vesicles as a biological membrane model. The antilipoperoxidant activity of the flavonoids tested can be classified as follows: rutin > hesperetin > quercetin > naringenin in the Fe(2+)-ILP test: quercetin > rutin > hesperetin > naringenin in the ARCM test. Quercetin, hesperetin, and naringenin interacted with DPPC liposomes causing different shifts, toward lower values, of the main transition peak temperature (Tm) typical for DPPC liposomes; however, no change in Tm of DPPC dispersion was observed in the presence of rutin. The hypothesis will be discussed that flavonoid capacity to modify membrane-dependent processes, such as free-radical-induced membrane lipoperoxidation, is related not only to their structural characteristics but also to their ability to interact with and penetrate the lipid bilayers.

Animals↗
PubMed1995

Epidemiology of traveler's diarrhea.

Annually, over 75 million international passengers travel to tropical areas, more than 20 million of whom come from industrialized countries. They experience a high rate of traveler's diarrhea (TD), varying from 20 to 56%, which may result in serious limitations to their activities. The cause of TD is considered to be infectious in the overwhelming majority of cases and, apart from differences in relative importance, the list of responsible microbial agents is fairly constant regardless of geographic origin. The ingestion of contaminated food or water is considered to be the principal mode of transmission of the enteric pathogens of TD. Several factors have been proposed as playing a role in the etiogenesis of diarrhea in travelers, including personal (age, socioeconomic status, body weight, preexisting gastrointestinal illnesses), behavioral (mode of travel, standard of accommodation, eating in public places, dietary errors) and travel-related (destination, duration of stay, country of origin, season) factors, which are reviewed in detail.

Animals↗
PubMed1994

Correlation between monoamino oxidase inhibitor activity of some thiazol-2-ylhydrazines and their interaction with dipalmitoylphosphatidylcholine liposomes.

A calorimetric investigation has been carried out on the influence exerted by some 1-(alkoxybenzoyl)-2-(4-substituted thiazolyl-2-yl)hydrazines, possessing monoamine oxidase inhibitory (MAOI) activity, on the thermotropic behavior of model membranes constituted by dipalmitoylphosphatidylcholine (DPPC) vesicles. Attention was paid to evaluate how structural variations of drugs may influence drug-lipid interaction. The examined drugs were found to modify the gel to liquid-crystal phase transition of DPPC liposomes, by causing a shift of the transition temperature (Tm) toward lower values and a negligible variation in the enthalpy changes (delta H). The different effects on DPPC thermotropic behavior of these MAOI drugs could be considered in terms of different substituents on the molecule's backbone. The calorimetric results were related to drug's MAO inhibitory activity measured by fluorescence techniques and the apparent distribution coefficient of the compounds in water/n-octanol. A hypothesis on a correlation between a drug's structure, inhibitory activity, and membrane interaction has been suggested.

1,2-Dipalmitoylphosphatidylcholine↗