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Biomedical subjects

S Gatti

Publications and source records attributed to S Gatti.

At least 109 records · Page 6Linked to original sources
PubMed1994

Mechanisms of interleukin-2-induced hydrothoraxy in mice: protective effect of endotoxin tolerance and dexamethasone and possible role of reactive oxygen intermediates.

Interleukin (IL)-2 is known to induce vascular leak syndrome (VLS), which was suggested to be mediated by immune system-derived cytokines, including tumor necrosis factor (TNF). To characterize the role of TNF in IL-2 toxicity in C3H/HeN mice, we used two approaches to downregulate TNF production in vivo: treatment with dexamethasone (DEX) and induction of endotoxin (lipopolysaccharide) (LPS) tolerance by a 4-day pretreatment with LPS (35 micrograms/mouse/day). Mice were then treated with IL-2 for 5 days (1.8 x 10(5) IU/mouse, twice daily). Both DEX and LPS tolerance blocked development of hydrothorax in IL-2-treated mice and inhibited TNF induction. DEX and LPS tolerance also ameliorated IL-2 toxicity in terms of decrease in food intake and inhibited the increase of the acute-phase protein, serum amyloid A (SAA). The IL-2 activation of splenic natural killer (NK) cell activity was also diminished by DEX and, to a lesser extent, by LPS-tolerance. Treatment with IL-2 also caused induction of the superoxide-generating enzyme xanthine oxidase (XO) in tissues and serum and induced bacterial translocation in the mesenteric lymph nodes (MLN). These data suggest that multiple mechanisms, including NK cell activity, cytokines, and reactive oxygen intermediates, might be important in the vascular toxicity of IL-2.

Animals↗
PubMed1994

Evaluation of serine alpha 1-antitrypsin and polymorphonuclear leukocyte elastase contents and their immunogenetic correlation in psoriasis.

The purpose of our study was to quantify the serum content of alpha 1-antitrypsin (alpha 1-AT) and polymorphonuclear leukocyte elastase (PMN-E) in of 21 patients affected by active and stationary psoriasis, and 12 normal controls. HLA typing was also performed to identify a correlation among HLA antigens, age at onset of psoriasis and biochemical results. alpha 1-AT levels were within the normal range in all patients, even in those with active, extensive, inherited and juvenile psoriasis, and in the controls. These data allow us to exclude, in our patients, the presence of rare or defective phenotypes, frequently associated with reduced serine levels of alpha 1-AT. The PMN-E serine content was greatly increased in 3 patients, increased in 2, and slightly modified in 6 cases. All patients with the highest PMN-E levels reported a positive family history and absence of pulmonary, hepatic and atopic diseases. An increased psoriatic inheritance has been observed in the CW6-positive subjects (7/20), comparing B13 and DR6 antigen frequency. No correlation among HLA antigens, age at onset, clinical phase, or biochemical results could be established.

Adolescent↗
PubMed1994

Role of xanthine oxidase and reactive oxygen intermediates in LPS- and TNF-induced pulmonary edema.

We studied the role of reactive oxygen intermediates (ROI) in lipopolysaccharide (LPS)-induced pulmonary edema. LPS treatment (600 micrograms/mouse, IP) was associated with a marked induction of the superoxide-generating enzyme xanthine oxidase (XO) in serum and lung. Pretreatment with the antioxidant N-acetylcysteine (NAC)--1 gm/kg orally, 45 minutes before LPS--or with the XO inhibitor allopurinol (AP)--50 mg/kg orally at -1 hour and +3 hours--was protective. On the other hand nonsteroidal antiinflammatory drugs (ibuprofen, indomethacin, and nordihydroguaiaretic acid) were ineffective. These data suggested that XO might be involved in the induction of pulmonary damage by LPS. However, treatment with the interferon inducer polyriboinosylic-polyribocytidylic acid, although inducing XO to the same extent as LPS, did not cause any pulmonary edema, indicating that XO is not sufficient for this toxicity of LPS. To define the possible role of cytokines, we studied the effect of direct administration of LPS (600 micrograms/mouse, IP), tumor necrosis factor (TNF, 2.5 or 50 micrograms/mouse, IV), interleukin-1 (IL-1 beta, 2.5 micrograms/mouse, IV), interferon-gamma (IFN-gamma, 2.5 micrograms/mouse, IV), or their combination at 2.5 micrograms each. In addition to LPS, only TNF at the highest dose induced pulmonary edema 24 hours later. LPS-induced pulmonary edema was partially inhibited by anti-IFN-gamma antibodies but not by anti-TNF antibodies, anti-IL-1 beta antibodies, or IL-1 receptor antagonist (IL-1Ra).

Acetylcysteine↗
PubMed1993

Induction of tumor necrosis factor-alpha mRNA in the brain after peripheral endotoxin treatment: comparison with interleukin-1 family and interleukin-6.

The constitutive expression of tumor necrosis factor-alpha (TNF alpha) mRNA and its induction (60 min later) by peripheral injection of Escherichia coli lipopolysaccharide (2 mg/kg i.p.) was demonstrated by polymerase chain reaction (PCR), in the pituitary and hypothalamus but not in the striatum or hippocampus of the rat. The pattern of TNF alpha mRNA induction is different from that observed for mRNAs of IL-1 alpha and IL-1 beta, IL-1ra and IL-6 respectively. This demonstration of the induction of TNF alpha in the brain may contribute to our understanding of the central effects of TNF alpha in fever and anorexia.

Animals↗
PubMed1993

Hepatitis C virus infection in liver allograft recipients.

The impact of HCV infection after liver transplantation remains a topic of discussion. The aims of this study were to define the prevalence of anti-HCV antibodies in liver donors; the risk of acquired HCV infection and HCV re-infection according to the pre-transplant anti-HCV status; the prevalence of HCV infection in post-transplant chronic hepatitis. Sera from 42 recipients with follow up longer than 6 months and their donors were tested for anti-HCV. By results at pre-transplant time patients were classified as follows: donor (D) negative and recipient (R) negative (D-/R-) 31; D-/R+ 9; D+/R- 1; D+/R+ 1. Twenty-one patients with sustained hepatic dysfunction underwent liver biopsy. In group D-/R-, 5 patients showed anti-HCV positivity and 3 (9.7%) of them had acquired HCV hepatitis. In group D-/R+, 6 patients showed persistent anti-HCV positivity and 4 (44.4%) of them had recurrent HCV hepatitis; of these 2 died due to liver failure. The 2 patients of groups D+/R- and D+/R+ had normal liver function. Anti-HCV negative hepatitis was found in 2 patients. The prevalence of anti-HCV positivity in liver donors appeared low (3.2%). Acquired HCV infection rate was 9.7%. Pre-transplant HCV infection led to a high incidence of recurrence (44.4%). HCV was the major etiological agent in post-transplant chronic hepatitis (77.8%).

Adolescent↗
PubMed1993

Mast cells do not contribute to the rapid appearance of TNF in the serum of LPS-treated mice: a study with mast cell-deficient mice.

Mast cells have been proposed to be an important source of tumor necrosis factor (TNF). The purpose of this work was to investigate their relevance in the rapid appearance of TNF in the serum of mice after injection of an endotoxin (lipopolysaccharide, LPS). We have therefore measured TNF levels in serum and spleen homogenates of mast cell-deficient mice (WBB6F1-W/Wv) or their normal littermate controls. The results indicated that mast cell-deficient mice are not defective in their LPS-induced TNF production. They also tend to produce more interleukin 6 (IL-6) than normal mice. To test other conditions where mast cells might be stimulated to produce TNF, we measured TNF in mice injected with the mast cell degranulator, compound 48/80 or during anaphylactic shock. Anaphylactic shock induced very low levels of TNF in the serum, while compound 48/80 (4.2 mg/kg) was ineffective. These data suggest that mast cells do not contribute significantly to systemic TNF production in these experimental models.

Anaphylaxis↗
PubMed1993

Autoradiographic localization of putative melatonin receptors in the brains of two Old World primates: Cercopithecus aethiops and Papio ursinus.

The distribution of putative melatonin receptors in the brains of two Old World primates of the superfamily Catarrhina, Cercopithecus aethiops and Papio ursinus, was characterized using 2-[125I]iodomelatonin autoradiography. The specific binding demonstrated a discrete distribution pattern. The median eminence was intensely labelled, and examination at the light microscopic level demonstrated that the binding was confined to the small layer of cells comprising the pars tuberalis of the pituitary gland. The collar of pars distalis, present in the baboon (Papio ursinus), was diffusely labelled. No binding was detected in the pars distalis proper or the neural lobe of the pituitary gland. The binding in the suprachiasmatic nuclei was weaker, but well discernible. Diffuse faint specific binding was found in the frontal cortex and the dentate gyrus of the hippocampus. Two non-neural sites expressed strong, well-delineated binding: the walls of some brain blood vessels (the vertebral and spinal arteries, the inferior cerebellar and acoustic arteries, the basilar, pericallosal, internal carotid arteries, the arteries forming the circle of Willis) and the choroid plexuses. Binding in the arteries of the circle of Willis, the pars tuberalis and the suprachiasmatic nuclei was readily displaceable. Addition of 1 microM unlabelled 2-iodomelatonin following 45 min of preincubation with the radioactive ligand completely abrogated the binding. Co-incubation with guanosine 5'-O-(3-thiotriphosphate) led to a significant decrease in the apparent binding density in the pars tuberalis and abolished binding in the suprachiasmatic nuclei, but was without effect on the binding in the walls of the adjacent arteries, forming the circle of Willis, in the cortex and in the hippocampus. This qualitative distribution pattern demonstrates that in the two primate species studied, melatonin high-affinity, G-protein-linked binding sites are present in the pars tuberalis and the hypothalamic suprachiasmatic nuclei, and that melatonin may be acting as a synchronizer of the endogenous pacemakers' circadian activity, apart from its possible reproductive effects at the level of pars tuberalis, where the highest receptor density was observed. The strongly labelled arterial walls, and the flimsy labelled cortex and hippocampus, expressed different characteristics: though the binding was readily reversible, it was apparently not regulated by a guanine nucleotide-binding protein.

Animals↗
PubMed1993

HIV-1 and parasitic infections in rural Tanzania.

A sample of 300 sexually-active adults was selected at random from patients, from the rural area of Malenga Makali, Tanzania, who were attending a dispensary because they had diarrhoea of at least 2 weeks' duration. The potential associations between the patient's health (in terms of the World Health Organization's clinical definition of AIDS), HIV-1 seroprevalence and malaria and other parasitic infections were then investigated. Although, HIV-1 seroprevalence was 20.6% overall, the level of seroprevalence was directly correlated with the distance between the patients' home villages and the nearest main road. Strict application of the clinical definition of AIDS gave 98.7% specificity, 46% sensitivity and a predictive value of 90.6% when validated by HIV-1 seropositivity. Although malaria infection was more common in HIV-1 seropositives than in the seronegatives, the intensity of the Plasmodium falciparum infections, intestinal amoebiasis and giardiasis did not appear to be correlated with HIV-1 infection. In contrast, intestinal infections with Cryptosporidium parvum and Isospora belli were virtually restricted to HIV-1 seropositive individuals who had had diarrhoea for a relatively long time.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Protein synthesis and gene expression in transplanted and postischemic livers.

The expression of some genes has been comparatively studied in transplanted rat liver and in liver reperfused after ischemia in situ. Experiments on protein synthesis by tissue slices from cold-stored or transplanted livers show that rat livers that retain a good capacity for protein synthesis during storage undergo a profound impairment in the capacity for protein synthesis during the first hours after transplantation. This recovers in the following hours. There is never any indication of synthesis of stress proteins, and of hsp 70 in particular. The steady-state level of mRNAs for albumin, transferrin, and beta-actin, which are well expressed in reperfused postischemic livers in vivo, are reduced early after transplantation and recover only many hours later. Run-on analysis shows that an early defect in transcription and a partial recovery of this process later on are responsible for these changes. The steady-state levels of the same mRNAs are well maintained in donor livers preserved in University of Wisconsin solution for at least 12 hr, and less satisfactorily in Euro-Collins solution. Results of run-on analysis parallel the data on mRNA levels. The behavior of these mRNAs is, therefore, clearly different in reperfused and transplanted liver. The early stages of liver transplantation seem to be characterized by a depressed capacity of gene expression, without the reactive phenomenon of activation of stress protein genes that occurs in reperfused postischemic livers.

Animals↗
PubMed1993

Pachyonychia congenita with late onset of nail dystrophy--a new clinical entity?

Pachyonychia congenita syndrome (PCS) is a genetic disease with an autosomal dominant mode of transmission in which the main sign, pachyonychia, usually arises at birth or in childhood together with other disorders of keratinization. A 28-year-old woman developed subungual hyperkeratosis of all toe-nails and thumb-nails associated with pain on pressure and walking. She had a scrotal tongue with leucokeratotic areas, blister formation, plantar hyperkeratosis, palmoplantar hyperhidrosis and dental cavities since childhood. The present case, interpreted as PCS of late onset, could be a clinical variant of the Jadassohn-Lewandowsky syndrome with the late onset of pachyonychia or else an additional form of PCS due to the expression of a new and different allele.

Adult↗
PubMed1993

Role of tumour necrosis factor and reactive oxygen intermediates in lipopolysaccharide-induced pulmonary oedema and lethality.

The purpose of this study was to characterize the role of tumour necrosis factor (TNF) and neutrophils (PMN) in the pathogenesis of pulmonary oedema induced by endotoxin (lipopolysaccharide (LPS)). Intraperitoneal administration to BALB/c mice of 0.6-1 mg of LPS caused pulmonary oedema and lethality. This was associated with production of TNF in serum and bronchoalveolar lavage fluid and with accumulation of PMN in the lung. In this experimental model, we could block TNF production by different means: pretreatment 30 min before LPS with 4 mg/kg of i.p. chlorpromazine (CPZ), 3 mg/kg of i.p. dexamethasone (DEX), 1 g/kg p.o. of N-acetylcysteine (NAC, an antioxidant precursor of glutathione), or an anti-TNF MoAb. CPZ, DEX and anti-TNF completely prevented LPS lethality but not pulmonary oedema or pulmonary PMN infiltration, indicating that: (i) lung oedema is not the main cause of death after LPS; and (ii) lung oedema induced by LPS is not mediated by TNF. Pretreatment with NAC not only inhibited TNF production but also protected against LPS-induced pulmonary oedema, indicating that reactive oxygen intermediates are implicated. NAC also blocked TNF production in blood and in bronchoalveolar lavage. We also tested the effect of PMN depletion induced with cyclophosphamide (CP) or 5-fluorouracil (5-FU). While no pulmonary PMN infiltrate was observed in PMN-depleted mice, neutropenia did not prevent LPS lethality or oedema, indicating PMN do not play an important role in the toxic effects of LPS in this experimental model.

Acetylcysteine↗
PubMed1993

Is age an important risk factor for the outcome of elective abdominal aneurysm surgery?

This retrospective study involves 590 patients who underwent elective abdominal aortic surgery in the years 1966-1990. These patients are subdivided into three groups by time of intervention: 1st = 1966-1978; 2nd = 1979-1988; 3rd = 1988-1990, and each group is subdivided into two subgroups according to whether age is over or under 70. A progressive decrease in mortality is statistically significant through these years. No difference in the age-subgroups were observed except for a greater rate of minor postoperative complications. Elective surgical repair of aneurysmatic disease of the abdominal aorta is a safe procedure also in patients over 70 years in the presence of correct hemodynamic intraoperative monitoring and of a skilled surgical equipe.

Age Factors↗