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R Faggioni

Publications and source records attributed to R Faggioni.

At least 37 records · Page 2Linked to original sources
PubMed1995

Mechanisms of interleukin-2-induced depression of hepatic cytochrome P-450 in mice.

Interleukin-2 (15 micrograms/mouse, i.p. twice daily for 4 days and once on the 5th day) significantly lowered cytochrome P-450 and heme content and increased heme oxygenase mRNA accumulation; the activities of 7-ethoxycoumarin O-deethylase, ethoxy- and pentoxyphenoxazone O-dealkylases were decreased. The activity of the type O form of hepatic xanthine oxidase increased, but there was no increase in lipid peroxide, expressed in terms of microsomal malondialdehyde. In vivo inactivation of xanthine oxidase activity by feeding mice with tungstate did not substantially change the degree of interleukin-2-induced cytochrome P-450 depression, suggesting that the two processes are not causally linked. Induction of tolerance to endotoxin by a 4-day pretreatment with lipopolysaccharide resulted in 50% protection against this depression despite inhibition of the interleukin-2 induced formation of tumor necrosis factor. This suggests that the release of tumor necrosis factor per se does not fully account for the depression of cytochrome P-450. Dexamethasone, already used in patients to reduce the toxicity of interleukin-2 therapy, provided full protection against the cytochrome P-450 depression.

Animals↗
PubMed1995

[Comparative study of administration time of mitomycin C in trabeculectomy: 2.5 or 5 minutes?].

BACKGROUND: To analyse the inocuity and the incidence of complications of a 0.2 mg/ml solution of Mitomycin C (M.M.C.), for two application time, 2.5 or 5 minutes. METHODS: 110 trabeculectomies were realised in 99 patients; they were high-risk (HR) patients in 66 cases, and low-risk (LR) patients in 44 cases. M.M.C. was used for 2.5 minutes in 44 cases (20 HR patients, 24 LR patients), and for 5 minutes in 66 cases (46 HR patients, 20 LR patients). RESULTS: In both groups HR and LR, there is no significant difference on the pressure lowering whether the 0.2 mg/ml solution of M.M.C. is used during 2.5 minutes or 5 minutes (Student t-test at 6 months: HR: p = 0.224; FR: p = 0.542). For the early and late complication in the HR group, there is no significant difference whether M.M.C. is used 2.5 or 5 minutes. In the LR group, there is a significant difference for hypothalamy (p = 0.035) and choroidal detachment (p = 0.027). In this LR group, there is no significant difference in the late complications. CONCLUSIONS: A 0.2 mg/ml solution of M.M.C., when indicated, may be used as well in the HR and LR group during 2'30". In the HR group, if there are several risk factors, we propose to adapt the application time between 2.5 and 5 minutes, and increase it by 1/2 or 1 minute for each risk factor.

Adult↗
PubMed1995

Independent down-regulation of central and peripheral tumor necrosis factor production as a result of lipopolysaccharide tolerance in mice.

Lipopolysaccharide (LPS) induces a variety of central and peripheral effects that are largely mediated by cytokines, including tumor necrosis factor (TNF). Peripheral (intravenous [i.v.]) administration of LPS (2.5 micrograms per mouse) induced TNF levels in the serum and spleen but not in the brain, while central (intracerebroventricular [i.c.v.]) administration of LPS induced TNF production both in the brain and in the periphery. Mice challenged with LPS after LPS pretreatment (35 micrograms per mouse, intraperitoneally, as a single dose on day -3 or as a 4-day treatment on days -5 to -2) were unresponsive in terms of induction of serum TNF. When peripherally LPS-tolerant mice (where LPS pretreatment was given intraperitoneally) were challenged with an i.c.v. dose of LPS, brain (but not serum) TNF was still produced, meaning that the LPS-tolerant state was confined to the periphery. However, if LPS pretreatment was given i.c.v. (35 micrograms, as a single dose), the brain, like the periphery, became LPS tolerant in terms of TNF production. We investigated how tolerance to LPS affected two of its actions, decrease in food intake and induction of serum corticosterone (CS). After an i.v. challenge in peripherally LPS-tolerant mice, no decrease in food intake was observed, but this response was still elicited by an i.c.v. challenge. LPS tolerance reduced the CS response to i.v. and i.c.v. challenge. These results suggest that LPS-induced decrease in food intake might be a fully central effect, while the increase of serum CS might be due to both central and peripheral actions.

Animals↗
PubMed1994

Defective inflammatory response in interleukin 6-deficient mice.

Systemic and localized inflammation elicit a number of host responses which include fever, cachexia, hypoglycemia, and major changes in the concentration of liver plasma proteins. Interleukin 6 (IL-6) is considered an important mediator of the inflammatory response, together with IL-1 and tumor necrosis factor alpha (TNF-alpha). The purpose of this study was to unequivocally determine the role of IL-6 in these phenomena making use of IL-6-deficient mice that we have recently generated by gene targeting. We report here that in the absence of IL-6, mice are unable to mount a normal inflammatory response to localized tissue damage generated by turpentine injection. The induction of acute phase proteins is dramatically reduced, mice do not lose body weight and only suffer from mild anorexia and hypoglycemia. In contrast, when systemic inflammation is elicited through the injection of bacterial lipopolysaccharide (LPS), these parameters are altered to the same extent both in wild-type and IL-6-deficient mice, demonstrating that under these conditions IL-6 function is dispensable. Moreover, we show that LPS-treated IL-6-deficient mice produce three times more TNF-alpha than wild-type controls, suggesting that increased TNF-alpha production might be one of the compensatory mechanisms through which a normal response to LPS is achieved in the absence of IL-6. We also show that corticosterone is normally induced in IL-6-deficient mice, demonstrating that IL-6 is not required for the activation of the hypothalamic-pituitary-adrenal axis. Our results reinforce the idea that different patterns of cytokines are involved in systemic and localized tissue damage, and identify IL-6 as an essential mediator of the inflammatory response to localized inflammation.

Acute-Phase Reaction↗
PubMed1994

[Re-evaluation of the role of argon laser trabeculoplasty in therapy of glaucoma].

BACKGROUND: The pressure lowering effect of Argon laser trabeculoplasty (ALT) has been well demonstrated in the past. Today some clinicians tend to avoid ALT perhaps because it has been used in erroneous indications. The aim of this study was to re-evaluate the usefulness of ALT and to define its indication in the treatment of glaucoma. PATIENTS AND METHODS: A collective of 81 patients treated by ALT entered in a data bank between 1989 and 1991 were analysed retrospectively, focussing on: the percentage of patients requiring trabeculectomy (TE) after ALT, the mean time from ALT to TE, the stage of disease progression at which the decision for ALT was taken and the post-ALT evolution of ocular pressure (IOP), visual field and optic disc. RESULTS: After a mean follow-up of 28 +/- 10.5 months a TE was performed in 25% of cases. It was found that in our clinical practice the decision for ALT tended to be taken at a rather late stage of disease. For the patients that did not need a TE, the mean decrease of IOP at the end of follow-up was 5.4 mm Hg and the analysis of glaucoma parameters showed that there was no significant worsening of disease. The disease progression in the group of patients that were operated was already significantly worse than the total collective before ATL was performed. CONCLUSIONS: ALT is useful in the treatment of glaucoma, as long as it is not considered as an alternative to TE and as long as the patients benefit from a strict follow-up. Advanced cases should however be operated without delay.

Aged↗
PubMed1994

Chlorpromazine specifically inhibits peripheral and brain TNF production, and up-regulates IL-10 production, in mice.

We have previously shown that chlorpromazine (CPZ) inhibits tumour necrosis factor (TNF) production and protects against endotoxic shock in mice. In this paper we investigated the effect of pretreatment with CPZ, 4 mg/kg i.p. 30 min before, compared with dexamethasone (DEX; 3 mg/kg) on the induction of other endotoxin (lipopolysaccharide; LPS)-induced cytokines in the serum of mice, i.e. interleukin-1 alpha (IL-1 alpha), IL-6 and IL-10, and TNF. We also studied the effect of CPZ on serum and spleen-associated TNF. Both DEX and CPZ inhibited TNF production, whereas induction of IL-1 and IL-6 was inhibited by DEX but not by CPZ. DEX did not affect IL-10, while CPZ potentiated its induction. CPZ also inhibited spleen-associated TNF induction in LPS-treated mice, suggesting an effect on the synthesis of TNF. CPZ inhibited TNF induction by Gram-positive bacteria (heat-killed Staphylococcus epidermidis) and by anti-CD3 monoclonal antibodies. Intraperitoneal administration of CPZ also inhibited the induction of brain-associated TNF induced by intra-cerebroventricular injection of LPS. Therefore, CPZ is a more specific inhibitor of TNF production than DEX; in particular, CPZ increased the induction of IL-10, which is a 'protective' cytokine known to inhibit LPS toxicity and TNF production. CPZ inhibited TNF production in vivo, irrespective of the TNF stimulus used to induce TNF. Finally, CPZ did not induce the 'rebound' effect of DEX that, when given 24 hr before LPS, potentiates TNF production, but it did inhibit TNF production after 24 hr.

Animals↗
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

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

Molecular mapping and detoxification of the lipid A binding site by synthetic peptides.

Endotoxin [lipopolysaccharide (LPS)], the major antigen of the outer membrane of Gram-negative bacteria, consists of a variable-size carbohydrate chain that is covalently linked to N,O-acylated beta-1,6-D-glucosamine disaccharide 1,4'-bisphosphate (lipid A). The toxic activity of LPS resides in the lipid A structure. The structural features of synthetic peptides that bind to lipid A with high affinity, detoxify LPS in vitro, and prevent LPS-induced cytokine release and lethality in vivo were defined. The binding thermodynamics were comparable to that of an antigen-antibody reaction. Such synthetic peptides may provide a strategy for prophylaxis and treatment of LPS-mediated diseases.

Amino Acid Sequence↗
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

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↗
PubMed1992

N-acetylcysteine and glutathione as inhibitors of tumor necrosis factor production.

TNF is a major mediator in the pathogenesis of endotoxic shock, and its inhibition has a protective effect in various animal models of sepsis or endotoxin (lipopolysaccharide, LPS) toxicity. LPS treatment also induces an oxidative damage mediated by increased production of reactive oxygen intermediates. N-Acetylcysteine (NAC) is an antioxidant and a precursor of the synthesis of glutathione (GSH) and was reported to protect against LPS toxicity and LPS-induced pulmonary edema. In this study we investigated the effect of NAC on TNF production and LPS lethality in mice. The results indicated that oral administration of NAC protects against LPS toxicity and inhibits the increase in serum TNF levels in LPS-treated mice. The inhibition was not confined to the released form of TNF, since NAC also inhibited LPS-induced spleen-associated TNF. On the other hand, the inhibitor of GSH synthesis, DL-buthionine-(SR)-sulfoximine (BSO), had the opposite effect of potentiating LPS-induced TNF production, and this was associated with a decrease in liver GSH levels. Repletion of liver GSH with NAC reversed this effect. NAC was also active in inhibiting TNF production and hepatotoxicity in mice treated with LPS in association with a sensitizing dose of Actinomycin D. These data indicate that GSH can be an endogenous modulator of TNF production in vivo. On the other hand, NAC pretreatment did not inhibit other effects of LPS, particularly induction of serum IL-6, spleen IL-1 alpha, and corticosterone, in the same experimental model, suggesting that the observed effect could be specific for TNF.

Acetylcysteine↗
PubMed1992

[Short and long-term advantages and disadvantages of prolene monofilament sutures in penetrating keratoplasty].

The authors have studied the short and long-term advantages and inconveniences of Prolene monofilament sutures employed in perforating keratoplastic surgery. Contrary to Nylon, Prolene has the advantage of no structural or tensional modifications, postoperative measurements of corneal astigmatism thus remaining more stable with the time. Accordingly, where very little or no astigmatism is noted, the slight or no change in corneal refraction with time is an obvious advantage ot the patient. However, the use of Prolene in the beginning can cause some problems with continuous suture tension, either excessive or insufficient, which can result in serious complications. With training, these difficulties can be overcome and excellent results obtained.

Astigmatism↗
PubMed1992

[Long-term results of congenital glaucoma microsurgery--retrospective study].

Medium and long term results of trabeculotomy and goniotomy operations for primary congenital glaucomas treated in Lausanne between 1965 and 1990 were studied retrospectively. Parameters evaluated were intraocular pressure (IOP) and final visual acuity (VA). Data on IOP were available for 38 eyes. 66% underwent trabeculotomy and/or goniotomy (first group) the others needed further surgical or medical treatment (second group). IOP was equal or inferior to 19 mmHg in 88% of the first group and 62% of the second group at the end of the study (mean follow-up 13.1 years). Data on VA were available for 32 eyes. In the first group, 65% showed a VA of more than 0.5 compared to 33% for the second group. Therefore, we can consider trabeculotomy and goniotomy as early operations as advisable in first intention treatment of primary congenital glaucoma.

Female↗
PubMed1992

[Effect of naftidrofuryl (Praxilene) in primary open angle glaucoma: prospective double-blind study].

The positive effect of Naftidrofuryl (Praxilène), a specific serotonine-S2 receptor antagonist, has already been described in the treatment of normal pressure glaucoma. Despite the fact that in POAG intraocular pressure (IOP) is the primary ethiopathogenic mechanism, vascular factors could also influence the progression of the disease, especially in old patients with cardiovascular risk factors. We have studied the effect of Naftidrofuryl versus placebo in a randomised double-blind study on 42 POAG patients. Visual acuity, IOP, Visual field (Octopus program G1), Arterial pressure, Plasma viscosity have been recorded at 0, 12 and 24 weeks. Our results showed no difference between the Naftidrofuryl and the Placebo group for each studied parameter except a decrease of CLV at 12 weeks in the Naftidrofuryl group (p = 0.012). This suggests that Naftidrofuryl is not as effective in POAG as it is in normal tension glaucoma. Other studies with a greater patient - collective and the use of other vasoactive substances will be necessary in the future.

Aged↗
PubMed1991

[Treatment of normal pressure glaucoma with a serotonin S2 receptor antagonist, naftidrofuryl (praxilen)].

35 normal tension glaucoma patients were followed during 8 to 11 month. 12 patients received 2 x 200 mg/day Naftidrofuryl, a serotonine S2 receptor antagonist. As controles, another 23 patients were followed without treatment. The treated group, compared with the 23 non treated patients showed a significant increase in visual acuity (p = 0.001), a significant increase of the MS (p = 0.03), and a non significant decrease of the MD and CLV on the Octopus visual field (p, NS). The physiology and physiopathology of serotonine and S2 receptor antagonist are discussed.

Aged↗
PubMed1990

[3 years' clinical experience with IOGEL lenses].

A total of 63 IOGEL PC-12 and 12 IOGEL 1103 intraocular lenses have been implanted at Lausanne and Basle University Eye Hospitals, and followed up for up to 3 years. In general, the functional and anatomic results are good. From a comparison of the behavior of IOGEL lenses implanted in the sulcus and capsular bag it is concluded that given a suitable surgical technique the IOGEL 1103 lens with implantation in the capsular bag may be recommended.

Acrylates↗