Effects of taxol on TNF-alpha and IL-6 production by human peripheral blood cells.
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Biomedical subjects
Publications and source records attributed to G Mancuso.
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In order to elucidate the effects upon the human immune system of aflatoxin B1 produced by the food-contaminating mould Aspergillus flavus, phagocytosis, microbicidal activity, superoxide production and intrinsic antiviral activity were studied in monocytes exposed to aflatoxin B1 for different times at concentrations ranging from 0.1 to 1 pg/ml. Phagocytosis and microbicidal activity were significantly impaired (p < 0.05) by aflatoxin B1 at doses as low as 0.1 pg/ml. However, pretreatment of monocytes with aflatoxin B1 did not modify intrinsic antiviral activity or superoxide production. These results confirmed data obtained from animals fed with mycotoxin-contaminated foods. The potential danger to human health of exposure to mycotoxins demonstrates the necessity for careful microbiological control of food.
In an epidemiological study of occupational dermatitis in 5 different shoe factories, 246 workers were interviewed, examined and patch tested using standard and occupational patch test series. The prevalence of occupational contact dermatitis was 14.6% (36/246): 8.1% (20/246) irritant contact dermatitis (OICD) and 6.5% (16/246) allergic contact dermatitis (OACD). Among the latter, the most common occupational allergens were p-tert-butylphenol-formaldehyde resin and mercaptobenzothiazole. 6% (15/246) presented with hyperkeratosis of the fingertips, while 3.2% (8/246) reported pruritus sine materia (PSM) present only during working hours. 2 workers presented with vitiligo-like leukodermic patches on the backs of their hands and on their forearms. Some jobs were more frequently associated with skin complaints. In the assembly department, OACD was most frequent (11.4%), attributed to contact with adhesives and, to a lesser degree, with rubber and leather. OICD caused by contact with the solvents contained in adhesives and varnishes was most frequent in the assembly and trimming departments (17.1% and 15.6%, respectively). PSM, probably caused by the dust present in the working environment was reported by 33.3% of the workers in the sole-cutting and scraping departments. Hyperkeratosis of the fingertips, as a reaction to the continuous trauma of leather on the skin, was observed most frequently (41.6%) in the sole-cutting department.
Unlike the antibiotics erythromycin and penicillin G, sodium fusidate (fusidin) pretreatment (80 mg/kg of body weight) increased the survival rate of neonatal BALB/c mice challenged with Salmonella enteritidis lipopolysaccharide. Fusidin also significantly reduced the plasma tumor necrosis factor alpha levels. Hence, fusidin may prove useful in the management of bacterial sepsis in humans.
Cryptococcus neoformans-induced tumor necrosis factor alpha (TNF-alpha) production may lead to increased human immunodeficiency virus replication in patients with AIDS. In order to identify cryptococcal components that are predominantly responsible for stimulating TNF production, various concentrations of glucuronoxylomannan (GXM), galactoxylomannan (GalXM), mannoproteins (MP), and alpha(1-3) [corrected] glucan were added to whole-blood cultures. All of the cryptococcal components tested, as well as whole heat-killed cryptococci, were capable of inducing TNF-alpha release in a dose-dependent manner. MP were significantly more potent than any of the other cryptococcal components tested or heat-killed cryptococci in stimulating TNF-alpha production (P < 0.05). GXM, in contrast, was significantly less potent in this activity than either GalXM or MP (P < 0.05). As little as 0.5 microg of MP per ml was sufficient to produce moderate but significant elevations of TNF-alpha release. Maximal MP-induced TNF-alpha levels were similar to those induced by Salmonella enteritidis lipopolysaccharide, our positive control. Further experiments using isolated leukocytes suggested that monocytes were the cell population mainly responsible for TNF-alpha production, although the participation of other cell types could not be excluded. The presence of complement-sufficient plasma was a necessary requirement for TNF-alpha induction by GXM, GalXM, and low doses of MP. High MP concentrations (100 microg/ml) were also capable of stimulating TNF-alpha production in the absence of plasma. These data indicate that soluble products released by C. neoformans are capable of inducing TNF-alpha secretion in human leukocytes. This may be clinically relevant, since high concentrations of such products are frequently found in the body fluids of AIDS patients infected with C. neoformans.
We investigated the role of interleukin-10 (IL-10) in a neonatal mouse model of lethal group B streptococci (GBS) sepsis. Plasma IL-10 levels significantly increased at 24 and 48 h after GBS inoculation. Neutralization of IL-10 with specific antibodies had no effect on lethality. Administration of recombinant IL-10 at 20 or 4 h before challenge, but not at later times, resulted in decreased tumor necrosis factor alpha levels and improved survival. IL-10 could be potentially useful for the treatment of GBS sepsis.
The aim of this study was to assess the role of gamma interferon (IFN-gamma) in a neonatal mouse model of group B streptococcal (GBS) sepsis. IFN-gamma was produced by spleen cells at 24, 48, and 72 h after GBS challenge. Treatment with anti-IFN-gamma at 6 h before challenge totally abrogated the IFN-gamma response but did not affect survival. Subcutaneous administration of recombinant IFN-gamma (2,500 IU per pup) at 18 h after challenge resulted in increased survival time and reduced blood colony counts at 48 and 72 h. In vitro preincubation of neonatal whole blood with IFN-gamma before the addition of GBS resulted in significant restriction of bacterial growth. These data indicate that administration of recombinant IFN-gamma can partially restore impaired host defenses against GBS in neonatal mice. This cytokine may be useful for the treatment of neonatal infections.
BACKGROUND: Multiple tendinous and tuberous xanthomas are characteristically associated with hyperlipidemic states. However, normolipidemic tendinous and tuberous xanthomas have been reported in the literature, with normal levels of cholesterol, cholestanol and plant sterols. OBJECTIVE AND METHOD: To delineate the disorder and to suggest its likely origin, a case of apparently normolipidemic severe tuberous and tendinous xanthomatosis was studied. Several lipoprotein and lipid analyses, clinical tests and histological studies were performed over a period of 5 years in the propositus and his family. RESULTS: At the first lipid analysis, no quantitative or qualitative alterations of the lipoprotein fractions or of the apoproteins AI, B, CII, CIII, E were detected in the propositus and xanthomatosis was classified as normolipidemic. During the follow-up, the patient showed a nonconstant hypertriglyceridemia and/or hypercholesterolemia associated with the presence of small and dense VLDL and LDL. An increase in apo-B was observed. There was an unusual quantity of conjugated dienes of arachidonic acid in the plasma and in the LDLs of the patient, present only in small traces in the control population. The family study and the long follow-up of the lipid analysis of the propositus were compatible with the diagnosis of familial combined hyperlipidemia. CONCLUSION: Our data highlight the importance of a critical review of studies regarding normolipidemic xanthomatosis, since only after an extensive follow-up and sequential analyses of lipoprotein fractions is it possible to exclude the presence of time variables and complex lipoprotein abnormalities.
Rendu-Osler-Weber disease is an hereditary disorder characterized by cutaneo-mucous telangiectasis and vascular abnormalities in several organs. Bleeding, especially epistaxis, represents the most important clinical feature. Pulmonary arteriovenous fistulae can cause hypoxaemia, haemoptysis, polycythaemia and clubbing. Diagnosis is based on family and personal history, teleangiectasis, laboratory (haemochrome, fibrinogen, PT, PTT) and instrumental findings (endoscopy and/or roentgen). Therapy depends on symptoms. Embolization of pulmonary arteriovenous fistulae and laser treatment of intestinal vascular abnormalities have been successful. Danazol treatment yielded controversial results. We report the case of a patient admitted for arterial hypertension and recurrent epistaxis. Rendu-Osler-Weber disease diagnosis was made based on positivity at family and personal history, clinical examination, laboratory and instrumental findings. In conclusion we underline the pivotal role of anamnesis and clinical examination in the differential diagnosis of hereditary bleeding disorders and emphasize the importance of early diagnosis for the correct therapeutic approach.
We present a clinical case in which a patient with a brain metastasis had a clinical onset simulating a stroke. Computerized tomography showed a lesion which was diagnosed as ischaemic, whereas magnetic resonance imaging showed an expansive lesion surrounded by an aedematous region of probable neoplastic nature. Indeed histology confirmed the neoplastic origin of the lesion. This kind of presentation is very uncommon but when an hypodense area is detected on CT scan one should always think to this occurrence. Neuroradiology is often necessary for a correct diagnosis. CT scan might usefully be integrated by MRI to distinguish between stroke and brain neoplasty.
The sensitivity of a newly devised nephelometric method for determining antistreptolysin O antibodies was compared with the hemolytic inhibition assay. Three hundred-thirty single serum samples from children with and without evidence of group A streptococcal infection were analyzed by the two techniques. The nephelometric method results correlated well with those of the reference test (concordance: r = 0.88). Furthermore, 134 pairs of acute and convalescent phase sera from patients with culture-proven GAS infection and 50 pairs from children who served as control subjects were examined. The nephelometric assay was more sensitive in detecting significant ASO antibody rises than the hemolytic assay. The automated nephelometric method appears to be a much simpler and sensitive procedure for testing ASO antibodies.
OBJECTIVES: To estimate survival trends for persons with haemophilia and HIV/AIDS. DESIGN AND METHODS: Survival analysis conducted among the cohort of HIV-positive haemophiliacs with AIDS at the Italian Haemophilia Registry. Kaplan-Meier method was used to estimate survival times, stratifying for demographic and clinical covariates. Cox proportional hazards model was applied in order to identify factors independently associated with survival. RESULTS: Median survival from the first AIDS diagnosis to death was estimated to be 17.0 months for 176 individuals with AIDS. Median survival after AIDS diagnosis increased from 12.0 months in December 1983-December 1988 to 17.0 months in January 1989-May 1990 and to 25.0 months in June 1990-December 1991. Median survival times were significantly (P < 0.001) lower for individuals diagnosed with non-infective AIDS indicator diseases (lymphoma, AIDS-associated neurological disease, Kaposi's sarcoma, wasting syndrome: 4.0 months), in comparison with haemophiliacs diagnosed with Pneumocystis carinii pneumonia (PCP; 18.0 months) or other infections (35.0 months). Antiretroviral treatment after AIDS diagnosis was associated with a longer survival than that estimated for individuals with no treatment after AIDS; the same was true for PCP prophylaxis. Younger age at HIV seroconversion and at AIDS diagnosis were associated with a longer survival. Multivariate analysis showed that factors independently associated with survival were type of AIDS indicator disease and antiretroviral administration after AIDS diagnosis. CONCLUSIONS: This study indicates an increasing survival from AIDS diagnosis to death over time, also as a result of the introduction of antiretroviral therapy. Survival trends are similar to those reported among homosexual men and intravenous drug users with AIDS, suggesting a similar access to the health-care system for individuals with AIDS. Survival studies may improve our understanding of the natural history of HIV infection and may indicate the impact of preventive measures.
Contamination of food with mycotoxins is a major health problem. Impairment of several immune functions has been repeatedly reported in animals fed with contaminated fodder. Since the liver is a major target of toxicity by aflatoxins, the effects of aflatoxins B1, and its hepatic metabolites Q1 and M1 on Kupffer cell function was investigated in vitro. Aflatoxin B1 induced significant (P < 0.05) inhibition of phagocytosis, intracellular killing of Candida albicans, and intrinsic anti-Herpes virus activity at concentrations as low as 0.01 pg ml-1. Aflatoxin Q1 and M1 had similar effects on phagocytosis and microbicidal activity, but were two- to ten-fold less potent than aflatoxin B1.
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Previous studies have indicated that tumor necrosis factor-alpha (TNF-alpha) may play a pathophysiologic role in experimental sepsis by group B streptococci (GBS). We tested the efficacy of some TNF-alpha and eicosanoid inhibitors in a neonatal rat model of GBS disease. The drugs tested included cloricromene, SKF86002, pentoxifylline, CGS8515, ibuprofen and LY203647. None of these compounds were protective against GBS infection, with the exception of pentoxifylline, that produced a moderate enhancement of survival time. Further studies are needed to ascertain if specific inhibitors of TNF-alpha, alone or in conjunction with antibiotics, may be effective as therapeutic agents in neonatal GBS sepsis.
Malnutrition clinical conditions in Sicily, Italy, are examined. Malnutrition today is a result of excess of eating, while immediately after the Second World War, it was a result of deficiency of eating. The main interest in this study is to examine the relationship between social and nutritional conditions in children who are a vulnerable part of the whole population. This is also confirmed by other data reported on this subject, in Sicily.
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The potential role of tumor necrosis factor alpha (TNF alpha) and eicosanoids in the pathogenesis of experimental neonatal sepsis models was investigated. Lethality was induced in neonatal rats by administration of heat killed group B streptococci (GBS, 7 mg kg-1 intracardially) or Salmonella enteritidis endotoxin (0.35 mg kg-1 intracardially). The relative efficacy of six compounds with putative TNF alpha and eicosanoid inhibitory actions were tested. These were: ibuprofen (3 and 20 mg kg-1), a cyclo-oxygenase inhibitor; CGS85515 (30 mg kg-1), a lipoxygenase inhibitor; LY203647 (30 mg kg-1), a leukotriene D4 receptor antagonist; pentoxifylline (10, 50 and 100 mg kg-1), a TNF inhibitor; cloricromene (2 and 10 mg kg-1), a thromboxane A2 synthetase inhibitor with TNF alpha inhibitory actions; and SKF86002 (2.5, 5, 10 and 20 mg kg-1), a dual cyclo-oxygenase/lipoxygenase inhibitor with TNF alpha inhibitory activity. Pentoxifylline, cloricromene and SKF86002, when given intraperitoneally 2 h before challenge, produced 45, 52 and 61% reductions, respectively, in plasma levels of TNF alpha at 2.5 h post-injection with killed GBS (P < 0.05). On the contrary, pretreatment with ibuprofen, CGS85515 or LY203647 did not significantly affect TNF alpha levels. All compounds significantly attenuated the lethality by killed GBS and S. enteritidis endotoxin. These data suggest that TNF alpha and eicosanoids contribute to the pathogenesis of shock induced by killed GBS and endotoxemia.