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Biomedical subjects

Salvatore Musumeci

Publications and source records attributed to Salvatore Musumeci.

33 records · Page 2Linked to original sources
PubMed2004

Interleukin-2 plus ribavirin versus interferon-alpha-2b plus ribavirin in patients with chronic hepatitis C who did not respond to previous interferon-alpha-2b treatment.

BACKGROUND: Interferon (IFN)-alpha-2b therapy has been shown to improve clinical conditions of patients with chronic hepatitis C. Several studies showed that the addition of ribavirin to IFNalpha-2b greatly improved the biochemical as well as the virologic and histological response rate in patients with chronic hepatitis C. The aim of this study was to evaluate biochemical, virologic, and histological responses as well as adherence to a treatment employing ribavirin plus low doses of recombinant interleukin (IL-2) or IFNalpha-2b in subjects with chronic active hepatitis C, which relapsed or did not respond to previous treatment with interferon alone. PATIENTS AND METHODS: We evaluated all 75 consecutive adult patients with chronic hepatitis C admitted to our department, who were previously treated with one course of recombinant or lymphoblastoid IFNalpha-2b (3 million to 6 million IU three times a week for at least 4 months), and either relapsed or did not respond to this treatment. Sixty patients met the inclusion criteria for enrollment in our study. Randomization was performed on the basis of a computer-generated list. The treatment schedule was based on subcutaneous administration of recombinant IFNalpha-2b (Intron A) at a dosage of 3 million IU every day, or IL-2 (aldesleukin) at a dose of 1 million IU every day, with oral ribavirin administered 400 mg twice daily (morning and night) [for patients weighing <75 kg] or 500 mg twice daily (for those weighing > or = 75 kg). The planned treatment period was 6 months. RESULTS: Both IFN and IL-2 treatment groups achieved a significant biochemical response with respect to baseline values at the end of the treatment (p < 0.0001 for both) and at the end of the follow up (p < 0.001 for both). The differences between the two groups at the end of treatment and at the end of the follow up were significant (p < 0.04 and p < 0.003 respectively) in favor of IL-2-treatment. The virologic response rate for IL-2-treated patients was significantly higher than for IFN-treated patients at months 3 (p < 0.05) and 6 (p < 0.05) of the treatment. Both groups showed significant improvement in histological activity index with respect to baseline values, but the difference between the groups was not significant. No withdrawals have been registered. CONCLUSION: The combination of IL-2 and ribavirin seems to increase the probability of a sustained biochemical and virologic response in patients with chronic hepatitis C that is unresponsive to IFN. Our study showed that IL-2 plus ribavirin may provide a clinically important option that appears to be well tolerated and effective in patients with chronic hepatitis C virus infection.

Adult↗
PubMed2003

Plasma chitotriosidase activity in acute Plasmodium falciparum malaria.

BACKGROUND: Chitotriosidase is a functional chitinase secreted by activated macrophages. It is encoded by a gene located on chromosome 1q31-32, whose mutations may be responsible for chitotriosidase deficiency, encountered in almost 6% of Caucasian population. OBJECTIVE: This study reports firstly plasma chitotriosidase activity in African children with acute Plasmodium falciparum malaria. The chitotriosidase activity was correlated to objective parameters reflecting the status of the disease and compared with those found in healthy African children. RESULTS: We found that plasma chitotriosidase levels are significantly increased in African children with acute malaria (185.0+/-141.0 nmol/h/ml; median 150; range 11-521) with respect to reference values obtained in age matched African children (84.4.5+/-72.8 nmol/ml/h; median 63; range 4-350) (P<0.001). Moreover the levels of chitotriosidase were higher in African children than in Caucasian children matched for age (28.86+/-18.7 nmol/h/ml; median 24; range 1-98) (P<0.0001). A remarkable significant correlation was found between plasma chitotriosidase and reticulo-endothelial activation, as judged by thrombocytopenia degree and serum ferritin level in children with acute malaria. CONCLUSION: Based on this study, it appears that genetic and environmental features might be responsible for diversity of plasma chitotriosidase activity in black children living in Burkina Faso.

Acute Disease↗
PubMed2003

Plasma lipid composition and LDL oxidation.

Low-density lipoprotein (LDL) oxidation in vivo depends on lipid composition and on plasma antioxidant status. The aim of our study was to investigate the relationship between plasma lipid composition and LDL oxidation and, in particular, to explore whether LDL-cholesterol/triglycerides ratio (LDL-C/TG) and LDL-cholesterol/high-density lipoprotein (HDL)-cholesterol ratio (LDL-C/HDL-C) can be used as predictive parameters of LDL oxidation in vivo. In 87 volunteers over a wide range of age plasma lipids and LDL oxidation were studied. Blood was collected after 12 h overnight fast. LDL oxidation was estimated by the level of conjugated diene (BDC) in the lipid fraction isolated from plasma after gradient ultra-centrifugation. The results were expressed as micromol/l (BDC/l) to evaluate the level of oxidized LDL, and as nmol of BDC for mg of LDL-cholesterol (BDC/LDL-C) for the evaluation of LDL oxidation degree. BDC/l correlated significantly with age, total and LDL-C, apolipoprotein B and TG, while BDC/LDL-C negatively correlated with total cholesterol, apolipoprotein B, LDL/TG and LDL/HDL ratios. Age of subjects significantly correlated with total and LDL-C and apolipoprotein B. TG have a significant inverse correlation with HDL-C. Our results support the hypothesis that among the several factors involved in LDL oxidation the most important determinants are LDL/TG. Plasma triglycerides appear to be very important even when circulating cholesterol levels are within normal limits. Moreover, we found that the LDL/HDL ratio is also very important with regard to the putative protective role of HDL against LDL oxidation in vivo. In conclusion, plasma lipid parameters must be evaluated not only for their absolute values but also for their mutual ratios as expression of plasma lipid homeostasis. Both LDL/TG and LDL/HDL ratios can be used as predictive parameters of in vivo LDL oxidation.

Adolescent↗
PubMed2003

Atorvastatin treatment does not affect gonadal and adrenal hormones in type 2 diabetes patients with mild to moderate hypercholesterolemia.

Atorvastatin, a second generation synthetic 3-hydroxy 3-methylglutaryl-coenzyme-A (HMG-CoA) reductase inhibitor used in the treatment of hypercholesterolemia, reduces both intracellular cholesterol synthesis and serum cholesterol levels, and this could have a potential negative impact on gonadal and adrenal steroidogenesis. Hypercholesterolemia in type 2 diabetes, even when mild, must be treated in an aggressive way, due to the more strict therapeutic goals than in the non diabetic population. Since the wide use of 3-hydroxy 3-methylglutaryl-coenzyme-A (HMG-CoA) reductase inhibitor (statins) in type 2 diabetes, the main aim of our study was to evaluate the effects of "therapeutic" doses of atorvastatin on gonadal and adrenal hormones in 24 type 2 diabetic patients (16 males and 8 postmenopausal females), with mild to moderate hypercholesterolemia (LDL-cholesterol = 150.1 +/- 32.0 and 189.9 +/- 32.9 mg/dl, respectively) studied before and after a 3 months treatment with atorvastatin (20 mg/day). In all patients, lipids and serum cortisol, dehydroepiandrosterone sulphate (DHEA-S), androstendione and sex hormone binding globulin (SHBG) were measured, with the addition, only in males, of testosterone and free testosterone index. After atorvastatin treatment a significant decrease in total and LDL cholesterol was observed (p < 0.05), while HDL-cholesterol did not significantly change ( p = N.S.), as no significant difference was found between steroid hormones measured before and after atorvastatin either in male and females. In conclusion, our data suggest that, in type 2 diabetic patients, the use of atorvastatin has no clinically important effects on either gonadal or adrenal steroid hormones.

Adrenal Cortex Hormones↗
PubMed2002

Epidemiology of bacterial resistance in gastro-intestinal pathogens in a tropical area.

During 1999-2000 a total of 4131 faecal specimens were collected and analysed at the medical centre St. Camille at Ouagadougou. Eight hundred and twenty-six (8.0%) grew significant bacteria. Escherichia coli (35%), Salmonella spp. (15%) and Shigella spp. (10%) were most frequently isolated. A large number of E. coli strains were resistant to aminopenicillins (>90%) and cotrimoxazole (80%); for Yersinia spp the resistance was 80 and 25%, respectively. Norfloxacin was the most active antibiotic but was rarely used. The study showed that it is necessary to create antibiotic-resistance surveillance centres in developing countries so that therapy may be appropriate and the spread of antibiotic resistance to other developed countries via increased emigration may be reduced.

Anti-Bacterial Agents↗
PubMed2002

The immune response to Plasmodium falciparum malaria.

Malaria is still a major cause of severe disease which is responsible for millions of deaths, mostly in children under 5 years old, in tropical countries, especially sub-Saharan Africa. Complications of severe anaemia and cerebral malaria are thought to be the major cause of morbidity and mortality but recent evidence suggests that the host's immunological response could also contribute to the pathophysiology of the disease in human beings. Intensive studies of the immune response to malaria parasites in human beings have provided a wealth of information about the cells and cytokines implicated in the pathophysiology of survival and fatal outcome in severe infections. This review focuses on the pivotal role of macrophages and other important cellular effectors, molecules, and cytokines involved in the activation of the immune response at the different stages of human falciparum malaria. Our understanding of the putative mechanisms by which cytokines may mediate beneficial and harmful effects, through activation of phagocytic cells, could help to develop new treatment strategies, regardless of the emergence of parasite multidrug resistance.

Cytokines↗
PubMed2002

Increased levels of interleukin-12 in Plasmodium falciparum malaria: correlation with the severity of disease.

Interleukin (IL)-12, produced by mononuclear phagocytes, activates the T-helper 1 (Th1) cells and helps, as a mediator, the innate immune response to intracellular microbes. In Plasmodium falciparum infection, this proinflammatory cytokine has immunoregulatory functions with effects on the immune response to the blood stage of disease, but also induces protection and reduces malarial anaemia. In this study, the levels of IL-12 were determined in 73 African children, aged 2-144 months (median 19.5 months), who had severe or mild P. falciparum malaria. IL-12 was determined using the enzyme-linked immunosorbent assay. The levels of IL-12 were found to be significantly elevated (21.6 +/- 18.3 pg/ml) in patients who suffered less severely from the disease. In contrast, the levels of IL-12 were found to be lower (13.1 +/- 7.11 pg/ml) in patients who suffered more severely from the disease.

Animals↗
PubMed2002

Modification in the frequency of Hb C and Hb S in Burkina Faso: an influence of migratory fluxes and improvement of patient health care.

The incidence of hemoglobinopathies (Hb C and Hb S) is relatively high in West Africa. In order to calculate the gene frequency of these hemoglobinopathies, 6619 students from 23 local schools in Ouagadougou, Burkina Faso, West Africa, and 2582 individuals living in five villages near Ouagadougou, all situated in Savanna, were studied. As expected, the gene frequency in the city schools was 0.111 for the betaC gene and 0.051 for the betaS gene; in the five villages it was 0.122 for the betaC gene and 0.047 for the betaS gene. This data is somewhat different from that published in a previous study by Labie et al. [2] in the humid Savanna region, that showed a higher prevalence of betaC (0.14) than betaS (0.03), and is in contrast to data from the arid Sahel region that showed a higher prevalence of betaS (0.1) compared to betaC (0.05). The higher rate of betaS and lower rate of betaC in students in Ouagadougou, and in the individuals living in the five villages near Ouagadougou, suggest the possible influence of migratory fluxes of the betaS gene from the country region of Sahel. The dramatic increase in the prevalence of Hb SS patients, not reported in the study of Labie et al., [2] may be the result of reduced mortality due to environmental change. In addition, the improved health conditions of Hb SC and the increased life expectancy of Hb SS, may also have facilitated the increase of the betaS gene and the focus on secondary prevention for the control of correlated diseases.

Adolescent↗
PubMed2002

Biological and clinical presentation of patients with hemoglobinopathies attending an urban hospital in Ouagadougou: confirmation of the modification of the balance between Hb S and Hb C in Burkina Faso.

The incidence of hemoglobinopathies (Hb C and Hb S) is relatively high in West Africa. In order to characterize the clinical phenotypes of these hemoglobinopathies 10,166 subjects were studied for suspected hemoglobinopathies at the Laboratory of the Centre Medical Saint Camille (CMSC), Ouagadougou, Burkina Faso. A high rate of Hb SC (6.49%) and Hb SS (1.93%) individuals were detected at the CMSC as a consequence of a selective process, whereby patients with anemia or symptoms of vascular occlusive crisis underwent blood tests. The higher frequency of Hb SC may be explained by the fact that this condition is less severe than the SS status, and it requires frequent clinical and laboratory review. On the other hand, the frequency of Hb CC is very low because it does not interfere with their health status. Moreover, the high percentage of Hb S (12.29%) and Hb C (19.28%) trait individuals may be explained by the fact that, in general, all Hb SS and Hb SC patients followed at the CMSC have parents, siblings and other relatives who could have been referred by the center to receive blood tests. The dramatic increase over the past few years in the prevalence of Hb SS [who were absent in the 1984 study of Labie et al. [5]] and of Hb SC, may be attributed to its reduced lethality due to social and health changes. In conclusion, secondary prevention for the control of concurrent and associated diseases is essential in Hb SS and Hb SC patients for improving health and life expectancy.

Adolescent↗
PubMed2002

Oxidized LDL antibodies (OLAB) in patients with beta-thalassemia major.

Thalassemic (TM) patients are subjected to peroxidative tissue injury because of continuous blood transfusions. It has been documented that circulating LDL from TM patients show marked oxidative modification, that could represent an event leading to atherogenesis. We investigated in 75 beta-TM patients the levels of oxidized LDL antibody (OLAB) to asses their correlation with total cholesterol, LDL and HDL cholesterol, triglycerides Apo A-1 and Apo B. OLAB/mg chol-LDL is greater in TM patients than healthy controls (p<0.001). No correlation was found between OLAB and age, sex of patients, mean blood consumption, mean serum ferritin, mean transaminases, PT, PTT, and fibrinogen. A significant positive correlation was found between OLAB and triglycerides in TM patients (p<0.001). Also a significant correlation was found between OLAB/mg chol-LDL and level of triglycerides in TM patients, but not with total cholesterol, LDL and HDL chols, Apo A-1 and Apo B. On the contrary in the healthy controls this correlation between OLAB and OLAB/mg chol-LDL versus triglycerides was negative and not significant. High levels of OLAB/mg chol-LDL in patients with beta-thalassemia, in absence of evident signs of atherosclerosis, suggest some regulatory mechanisms on the lipid peroxidation which modulate the deposition of ox-LDL in the macrophages and support the hypothesis that both serum iron and triglycerides are involved in the pathogenesis of LDL oxidation.

Adolescent↗
PubMedDate not supplied

Plasma levels of interleukin-18 and interleukin-12 in Plasmodium falciparum malaria.

Interleukin (IL)-18 produced primarily by mononuclear phagocytes synergizes with IL-12 for interferon-gamma production from T, B and natural killer cells. It has been also demonstrated that, in Plasmodium falciparum malaria, IL-18 could have an immunoregulatory function. The aim of this study was to detect the plasma levels of IL-12 and IL-18, using an enzyme-linked immunosorbent assay, in 105 African children affected by mild and severe Plasmodium falciparum malaria to correlate the production of these cytokines with the severity of the disease. The levels of IL-18 and IL-12 were higher (25.7 +/- 7.6 pg/ml and 17.1 +/- 7.8 pg/ml, respectively) in children with mild malaria than in children with a severe form of the disease (21.5 +/- 10 pg/ml and 13.2 +/- 5.5 pg/ml, respectively). A positive correlation was observed between IL-18 and IL-12. This finding suggests that the production of these two cytokines (IL-18 and IL 12) may be coregulated and both have an immunoregulatory effect on the immune response in Plasmodium falciparum infection.

Animals↗
PubMedDate not supplied

Plasma levels of interleukin-12 (IL-12), interleukin-18 (IL-18) and transforming growth factor beta (TGF-beta) in Plasmodium falciparum malaria.

The interaction between pro- and anti-inflammatory cytokines such as interleukin 12 (IL-12), interleukin 18 (IL-18) and transforming growth factor beta (TGF-beta) may play an important role in malaria pathogenesis and outcome. IL-18 cooperates with IL-12 in the IFN-gamma production by T, B, and NK cells, and synergizes with IL-12 for IFN-gamma production by Th1 cells. Recently it has been demonstrated that these cytokines modulate the immunoresponse in Plasmodium falciparum malaria. The aim of this study was to measure the plasma levels of IL-12, IL-18 and TGF-beta in 105 African children with various degrees of malaria, and correlate the production of these cytokines with the severity of the disease. IL-12, IL-18 and TGF-beta levels were determined using enzyme-linked immunosorbent assay. The severity of malaria was established by parasitemia, clinical symptoms and haematological parameters. The levels of IL-12, IL-18 and TGF-beta were found to be significantly elevated (15.6 + / - 12.3, 22.7 + / - 13.8 pg/ml and 25.14 + / - 13.22 pg/ml respectively) in all of the children. IL-12 and IL-18 levels were significantly lower (13.2 + / - 5.53 and 21.5 + / - 10 pg/ml pg/ml) in children with severe disease, whereas the level of TGF-beta was higher (28.09 + / - 12.39 pg/ml). In contrast, IL-12 and IL-18 levels were found to be higher (17.32 + / - 7.8 pg/ml and 25.7 + / - 7.6 pg/ml) in patients with mild disease, whereas the level of TGF-beta was lower (20.92 + / - 12.76 pg/ml) compared to the severe malaria group. The correlation between IL-12 and IL-18 demonstrated a progressive relationship up to a value of IL-12 < 25 pg/ml, while IL-18 remained stable at higher levels of IL-12. An inverse correlation was found between IL-12 and TGF-beta up to a value of IL-12 < 30, after which the level of TGF-beta remained stable. This finding suggests that fine mechanisms regulate the interaction between IL-12, IL-18 and TGF-beta in the immune response to Plasmodium falciparum.

Animals↗