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Biomedical subjects

S Videla

Publications and source records attributed to S Videla.

At least 19 recordsLinked to original sources

Selective inhibition of phosphodiesterase-4 ameliorates chronic colitis and prevents intestinal fibrosis.

The phosphodiesterase-4 (PDE4) inhibitors may be an important target in the treatment of several inflammatory conditions. The anti-inflammatory effect of PDE4 inhibitors bears similarities with that of steroids, without interfering with the hypophysary-adrenal-axis. We compared the effect of rolipram, a selective PDE4 inhibitor, with steroids on the clinical course of experimental colitis induced by 2,4,6-trinitrobenzenesulfonic acid (TNBS). Three groups of rats (n = 20) received TNBS. One group received methylprednisolone from day 7, another group received rolipram from the same day, and control group received no further treatment. On days 14 and 21 after TNBS instillation, sets of 10 rats underwent colonic dialysis to measure eicosanoid release. Colonic lesions were blindly scored, and colons were homogenized for quantification of myeloperoxidase (MPO) activity and collagen content. Concentration of tumor necrosis factor alpha (TNF-alpha) and transforming growth factor beta1 (TGF-beta1) in colonic tissue was also measured. Both treatments reduced significantly the eicosanoid release and MPO activity. On day 14, both rolipram and methylprednisolone significantly reduced TNF-alpha content, but TGF-beta1 was only inhibited by rolipram. On day 21, lesion scores and collagen content were significantly reduced only in rolipram-treated group. In conclusion, PDE4 inhibition by rolipram markedly ameliorates the course of chronic colitis and it is superior to methylprednisolone in preventing late collagen deposition.

3',5'-Cyclic-AMP Phosphodiesterases↗

Chronic venous insufficiency of the lower limbs: suitability of transcutaneous blood gas monitoring as an endpoint to evaluate the outcome of pharmacological treatment with calcium dobesilate.

This pilot clinical trial was designed to further investigate the effects of calcium dobesilate in the treatment of chronic venous insufficiency (CVI) by means of a novel endpoint, transcutaneous oxygen pressure (TcPO2), and to evaluate the suitability of this endpoint for future research. Patients with mild to moderate CVI without active ulcers were randomized to receive calcium dobesilate 1000 mg/day, 2000 mg/day or placebo for 12 weeks. The primary efficacy endpoint was TcPO2 in the distal third of the internal side of the leg. Secondary endpoints included assessment of venous reflux and clinical symptoms. Patients in the dobesilate 1000 mg/day and placebo groups showed a mild increase in TcPO2 (adjusted mean change 2.67 mmHg and 1.56 mmHg, respectively), while those treated with 2000 mg/day of the active drug showed a decrease (adjusted mean change -0.53 mmHg). Conversely, clinical symptoms and venous reflux improved in all groups, especially with dobesilate, but differences with placebo were not significant. Treatment was very well tolerated. Although the absence of significant differences prevented confirmation of sensitivity, a trend favoring calcium dobesilate in clinical and hemodynamic parameters was observed. This improvement was not reflected by TcPO2.

Adolescent↗

A nested polymerase chain reaction (Ln-PCR) for diagnosing and monitoring Leishmania infantum infection in patients co-infected with human immunodeficiency virus.

We investigated a Leishmania-specific nested polymerase chain reaction (Ln-PCR) for the diagnosis and treatment monitoring of L. infantum infections in patients co-infected with human immunodeficiency virus (HIV). Peripheral blood and bone marrow samples from 89 HIV patients in Spain suspected of having leishmaniasis were examined by different diagnostic techniques (Ln-PCR, microscopy, NNN culture and indirect fluorescent antibody test). The sensitivity of Ln-PCR compared with microscopy and culture of bone marrow was 95.45% using blood and 100% when using bone marrow. 38 of these patients with confirmed leishmaniasis were entered in a chemotherapy trial (reported elsewhere), and samples from them were collected before treatment, one month after treatment ended and during follow-up (1-20 months), and examined similarly. Ln-PCR was shown to be a good method for testing efficacy of treatment and for predicting relapses after treatment (relapses were predicted on average 5 months earlier than when using classical diagnostic techniques). We suggest that Ln-PCR (especially using peripheral blood) should be the technique of choice for diagnosis, monitoring the success of treatment, and predicting relapses in patients with HIV and suspected or confirmed L. infantum infection.

AIDS-Related Opportunistic Infections↗

Role of microecology in chronic inflammatory bowel diseases.

Inflammatory bowel diseases (IBD) are chronic conditions of unknown etiology. Current therapy mitigates the severity of acute bouts of mucosal inflammation but an eradication therapy is lacking. Growing incidence of IBD is associated with social development. Epidemiology suggests a relationship between the establishment of the individual gut flora and the risk of developing IBD. Patients show an impaired tolerance towards commensal bacteria of the resident flora. Unrestrained activation of the intestinal immune system against some commensal bacteria appears to be responsible for the characteristic relapsing course of these diseases. Wide-spectrum antibiotic therapy reduces bacterial load and mitigates intestinal inflammation in human IBD and in animal models. Current research aims at the identification of probiotics for bacterial antagonism therapies. Probiotics are living microorganisms which upon ingestion in certain numbers exert health benefits beyond inherent basic nutrition. Colonization with a Lactobacillus reuteri strain can prevent the development of colitis in genetically susceptible mice. Other studies have used a bacterium genetically engineered to secrete the antiinflammatory cytokine IL-10 and demonstrated a therapeutic effect in animal models of colitis. Moreover, some probiotics may naturally exhibit antiinflammatory properties when interacting with the human gut mucosa. Prebiotics such as inulin have also been shown to prevent colonic inflammation in animal models. Preliminary clinical trials with probiotics in IBD are encouraging. Probiotics offer a valuable tool for the prevention and control of inflammatory bowel diseases.

Animals↗

Molecular weight distribution of Pinus radiata kraft mill wastewater treated by anaerobic digestion.

Kraft mill is responsible for massive discharge of highly polluted effluents. The main characteristics of this effluent are high toxicity and low biodegradability due to tannin, lignin and chlorophenol compounds. The composition may vary dramatically depending, for instance, on the utilised feedstock and process. The purpose of this work was to investigate the molecular weight distribution of Pinus radiata kraft pulping wastewater treated by anaerobic digestion by using two types of anaerobic reactors: fixed bed and sludge blanket. Anaerobic sludge blanket (UASB) and anaerobic filter (AF) were operated. In both reactors, the total alkalinity ranged between 1.0 and 1.5 g CaCO3/l, while the organic load rate (OLR) was increasing during operation from 1.2 to 3.3 gCOD/l d. COD and total phenolic compounds (UV215) removal ranged between 30-50% and 13-20%, respectively, while the BOD5 removal ranged 60-90%. However only a partial biodegradation (10-43%) of tannin and lignin was observed. Results from ultrafiltration analyses indicated that the fraction with a molecular weight (MW) < 1000, COD and colour decreased after anaerobic treatment, but the total phenolic compounds increased. In the 1000 < MW < 10,000 fraction, there was no change in COD, UV215 and colour. In the > 10,000 MW fraction, colour and COD fraction increased by 14% and 5%, respectively, after anaerobic treatment. It can be concluded from this study, that treatment with UASB or AF reactors is not enough, under the conditions tested, for a large COD removal from Pinus radiata wastewater.

Anaerobiosis↗

A multicenter, randomized, clinical trial of hormonal therapy in the prevention of rebleeding from gastrointestinal angiodysplasia.

BACKGROUND & AIMS: The efficacy of hormonal therapy for recurrent bleeding from gastrointestinal angiodysplasia remains uncertain. We investigated the efficacy of long-term estrogen-progestagen therapy in the prevention of rebleeding from gastrointestinal angiodysplasia. METHODS: Seventy-two noncirrhotic patients bleeding from gastrointestinal angiodysplasia confirmed by endoscopy or angiography were randomized to receive in double-blind conditions treatment with ethinylestradiol (0.01 mg) plus norethisterone (2 mg) (1 tablet/d), or placebo (1 tablet/d) for a minimum period of 1 year (range: 1-2 years). RESULTS: Four patients could not be assessed because they did not attend the first follow-up visit. Failure of treatment occurred in 13 of 33 (39%) patients in the treatment group and in 16 of 35 (46%) patients in the placebo group (P = NS). No significant differences between groups were found according to number of bleeding episodes (0.7 +/- 1.0 vs. 0.9 +/- 1.5) and transfusional requirements (0.9 +/- 1.9 vs. 0.7 +/- 1.5 units). Treatment received was not an independent predictor for rebleeding prevention in the multivariate regression analysis. Severe adverse events (2 vs. 1) and mortality (0 vs. 1 patient, respectively) were similar between the treatment and placebo groups. CONCLUSIONS: Continuous estrogen-progestagen treatment is not useful in the prevention of rebleeding from gastrointestinal angiodysplasia.

Adult↗

Therapeutic effect of phenantroline in two rat models of inflammatory bowel disease.

BACKGROUND: Phenantroline is a zinc-chelator that inhibits biological activities of matrix metalloproteinases (MMPs). Over-expression of MMPs can accelerate tissue destruction and disrupt subsequent tissue repair. The effects of phenantroline in two rat models of inflammatory bowel disease (IBD) are evaluated: transmural colitis induced by trinitrobenzensulphonic acid (TNBS) and distal colitis caused by dextran sulphate sodium (DSS). METHODS: Transmural colitis was induced by TNBS in two groups of 15 rats each, and distal colitis was induced by DSS in two other groups of 15 rats each. Phenantroline was administered by oral gavage at 20 mg kg(-1) day(-1) to the test groups, whereas matched control groups received oral vehicle. On the last day of dosing, rats were subjected to intracolonic dialysis under anaesthesia for assessment of luminal eicosanoid release (PGE2, TXB2 and LTB4) and euthanized. Colons were removed and lesions were blindly scored according to macroscopic and histological scales. Myeloperoxidase (MPO) activity was measured in homogenates of colonic tissue. RESULTS: In the TNBS model, phenantroline treatment significantly reduced colonic strictures; in the DSS model, phenantroline significantly decreased scores of epithelial injury. In both models, the levels of PGE2, TXB2 and LTB4 and tissue MPO were not significantly altered. CONCLUSIONS: Although phenantroline did not modify the activity of inflammatory mediators, this compound substantially reduced intestinal injury associated with tissue remodelling.

Animals↗

Dietary inulin improves distal colitis induced by dextran sodium sulfate in the rat.

OBJECTIVES: Inulin stimulates intracolonic generation of butyrate and growth of lactic acid bacteria. This study investigated whether inulin protects against colitis. METHODS: Rats with dextran sodium sulfate colitis received inulin either orally (1% in drinking water, or 400 mg/day) or by enema. Matched groups received vehicle. In addition, fecal water obtained from inulin-fed rats was administered by enema to rats with colitis and compared with fecal water from control rats. Finally, rats with colitis received daily enemas of either butyrate (at 40 or 80 mmol/L) or vehicle. Inflammation was assessed by eicosanoid asssay in rectal dialysates and MPO activity in colonic tissue. Mucosal lesions were blindly scored by microscopic examination. Luminal pH was measured from cecum to rectum by a surface microelectrode. RESULTS: Oral inulin prevented inflammation, as evidenced by lower lesion scores (p < 0.05), decreased release of mediators (p < 0.05), and lower tissue MPO (p < 0.05) as compared with controls. Inulin induced acidic environment (pH <7.0) from cecum to left colon and increased counts of lactobacilli. Fecal water from inulin-fed rats also reduced scores (p < 0.05) and inflammation (p < 0.05). However, inulin or butyrate enemas had no effect. CONCLUSIONS: Oral inulin reduces the severity of dextran sodium sulfate colitis. The effect seems to be mediated by modification of the intracolonic milieu.

Animals↗

Accuracy of helical computed tomographic angiography for the diagnosis of colonic angiodysplasia.

BACKGROUND & AIMS: The diagnosis of colonic angiodysplasia is often challenging and relies on endoscopy or catheter angiography. We investigated whether computed tomographic angiography (CTA) contributes to the diagnosis of colonic angiodysplasia. METHODS: Twenty-eight patients with suspected bleeding from colonic angiodysplasia were prospectively evaluated. Gastrointestinal bleeding was investigated by colonoscopy plus visceral angiography and by CTA. The level of agreement between CTA and the former procedures was determined. RESULTS: CTA images of diagnostic quality were obtained in 26 patients. Eighteen patients were diagnosed with colonic angiodysplasia by colonoscopy plus visceral angiography, and 14 by CTA (kappa = 0.68; P < 0.001). Sensitivity, specificity, and positive predictive values of CTA for detection of colonic angiodysplasia were 70%, 100%, and 100%, respectively. CTA signs including accumulation of vessels in the colonic wall, early filling vein, and supplying enlarged artery were present in 55%, 50%, and 22% of cases, respectively. None of these signs were present in the 8 patients with obscure gastrointestinal bleeding and negative diagnostic investigation of the digestive tract. CONCLUSIONS: CTA is a sensitive, specific, well-tolerated, and minimally invasive tool for the diagnosis of colonic angiodysplasia.

Aged↗

Somatostatin plus isosorbide 5-mononitrate versus somatostatin in the control of acute gastro-oesophageal variceal bleeding: a double blind, randomised, placebo controlled clinical trial.

BACKGROUND: Variceal bleeding is a severe complication of portal hypertension. Somatostatin reduces portal pressure by decreasing splanchnic blood flow, and nitrates by diminishing intrahepatic resistance. Experimental studies have shown that the combination of somatostatin and nitrates has an additive effect in decreasing portal pressure. AIM: To compare the therapeutic efficacy of either intravenous infusion of somatostatin plus oral isosorbide 5-mononitrate or somatostatin alone in gastro-oesophageal variceal bleeding associated with liver cirrhosis. METHODS: A unicentre, double blind, placebo controlled, clinical trial was conducted. Sixty patients bleeding from oesophageal or gastric varices were randomised to receive intravenous infusion of somatostatin (250 microg/hour) plus oral isosorbide 5-mononitrate (40 mg/12 hours) (group I) or somatostatin infusion plus placebo (group II) for 72 hours. RESULTS: The two groups of patients had similar clinical, endoscopic, and haematological characteristics. Control of bleeding was achieved in 18 out of 30 patients (60%) in group I and 26 out of 30 patients (87%) in group II (p<0.05). There was no significant difference in mean transfusion requirements between the two groups: 2.6 (2.2) v 1.8 (1.6) respectively; means (SD). Mortality and side effects were similar in the two groups, but development of ascites was higher in group I (30%) than in group II (7%) (p<0.05). CONCLUSION: In cirrhotic patients with acute gastro-oesophageal variceal bleeding, addition of isosorbide 5-mononitrate to somatostatin does not improve therapeutic efficacy, induces more adverse effects, and should not be used.

Acute Disease↗

Antiinflammatory effects of enterically coated amoxicillin-clavulanic acid in active ulcerative colitis.

The inflammatory activity of colonic mucosal lesions may be stimulated by intraluminal bacteria. Our aim was to investigate whether administration of broad-spectrum antibiotics decreases inflammatory activity in ulcerative colitis. To this end, we performed a randomized, 5-day study with either oral enterically coated amoxicillin-clavulanic acid (1 g + 250 mg, t.i.d.); i.v. methylprednisolone (40 mg/day) and oral placebo (t.i.d.); or both i.v. methylprednisolone and oral amoxicillin-clavulanic acid as above, in 30 patients with clinically active ulcerative colitis. Before and after 5 days of treatment, intestinal inflammation was assessed by the quantification of mucosal release of eicosanoids and interleukin-8 by rectal dialysis in each patient. Breath H2 excretion after oral lactulose was determined as an index of metabolic activity of colonic flora. The total release of (IL-8) interleukin-8 and eicosanoids significantly decreased in patients treated with antibiotic or steroids and antibiotic. Antibiotic treatment, but not steroids, markedly inhibited breath H2 excretion. In conclusion, short-term treatment with enteric-coated amoxicillin-clavulanic acid decreases the intraluminal release of IL-8 and other inflammatory mediators.

Adolescent↗

Antitumor necrosis factor therapy in rat chronic granulomatous colitis: critical dose-timing effects on outcome.

Inhibition of tumor necrosis fact (TNFalpha) is of potential benefit in the treatment of chronic inflammatory conditions. However, TNFalpha plays an important role in host defenses against infection, and blocking TNFalpha production may also have adverse effects. We tested the efficacy and safety of anti-TNFalpha therapy in experimental colitis induced by trinitrobenzenesulfonic acid. We cultured colonic wall specimens for bacterial growth and measured native TNFalpha protein synthesis in colonic tissue at days 0, 1, 4, 10 and 18 after induction of colitis. Anti-TNFalpha therapy (monoclonal g1 immunoglobulin, 15 mg/kg i.p., every third day) was started on either day 4 or day 10 after induction of colitis. On day 18, we measured the release of inflammatory mediators and scored colonic lesions. In acute lesions, several species of the common flora were grown, including Streptococcus, Staphylococcus, Bacteroides, clostridia and enterobacteria. In chronic lesions, only enterobacteria, clostridia and lactobacilli were isolated. TNFalpha production by inflamed colonic tissue was increased in both acute and chronic lesions. Anti-TNFalpha therapy induced a significant decrease in the release of inflammatory mediators and histopathological remission when treatment started on day 10. However, anti-TNFalpha therapy increased eicosanoid release and lesion scores when treatment started on day 4. In conclusion, acute colonic lesions showed polymicrobial infection. Anti-TNFalpha therapy induced remission of chronic intestinal inflammation, but early treatment did not prove effective.

Animals↗

[Contribution to the study of dermatomycosis in Catalonia].

We report the results of a study which aim was the mycological identification of specimens coming from patients included in a clinical trial. A total of 445 specimens from patients with clinical diagnosis of dermatomicosis were processed during 8 months (138 pityriasis versicolor, 28 cutaneous candidosis and 279 dermatophytosis). A 48% of pityriasis versicolor cultures were positive for Malassezia furfur, 50% of candidosis cultures were positive for yeasts and 67% of dermatophytosis cultures were positive for dermatophytes. According to our results Candida albicans was the principal causative agent for cutaneous candidosis and Trichophyton mentagrophytes and Trichophyton rubrum were the most frequent isolated species causing dermatophytosis.

English Abstract↗

Flutrimazole 1% dermal cream in the treatment of dermatomycoses: a multicentre, double-blind, randomized, comparative clinical trial with bifonazole 1% cream. Efficacy of flutrimazole 1% dermal cream in dermatomycoses. Catalan Flutrimazole Study Group.

BACKGROUND: Flutrimazole is a new imidazole derivate. Its antifungal activity has been demonstrated in in vivo and in vitro studies to be comparable to that of clotrimazole and higher than bifonazole. AIM: To compare the efficacy and tolerability of flutrimazole cream 1% with a reference drug, bifonazole, in the treatment of dermatomycoses, eligible for topical treatment exclusively. METHODS: A multicentre, double-blind, randomized, parallel-group clinical trial was conducted. Patients with clinically and mycologically (KHO and/or culture) diagnosed fungal infection of the skin were included in this study and were randomized into two treatment groups: 1% flutrimazole or 1% bifonazole, applied to the affected area (target lesion) once a day. The principal criterion of efficacy, 'cure', was based on clinical and mycological assessment. RESULTS: Four hundred and forty-nine patients were included in the study (228 flutrimazole, 221 bifonazole). 'Intention-to-treat' analysis of the data showed a difference between the treatments in terms of the rate of cure (clinical and mycological) after 4 weeks: 73% in the flutrimazole group and 65% in the bifonazole group (p = 0.05). From a safety point of view, flutrimazole and bifonazole were well tolerated, and the overall incidence of adverse effects (mainly mild local effects like irritation or burning sensation) was 5%. CONCLUSIONS: One percent flutrimazole applied topically once a day in the treatment of fungal infections of the skin presents a better efficacy than bifonazole and a good tolerability.

Administration, Topical↗

Role of intestinal microflora in chronic inflammation and ulceration of the rat colon.

Bacteria and their products stimulate inflammatory responses. The effects of different antimicrobial regimens (amoxicillin/clavulanic acid, tobramycin, imipenem, vancomycin, metronidazole) were investigated on the course of experimental colitis induced by trinitrobenzenesulphonic acid (TNB) in the rat. On day 7 and 21 after the induction of colitis, matched groups of control and antibiotic treated rats were subjected to colonic dialysis to measure eicosanoid release, and killed for morphological assessment of the colonic lesions (macro and microscopic scores). Stool samples were cultured. Selective antibiotic treatment against Gram positive, Gram negative or anaerobic bacteria had no effect on colonic lesion scores. By contrast, certain broad spectrum antibiotics (amoxicillin/clavulanic acid or the association of imipenem plus vancomycin) significantly reduced macro and microscopic scores. Rats receiving these antibiotics did not develop chronic colitis as shown by the virtual absence of colonic strictures, adhesions, fibrosis, and granulomas. On day 21 after TNB, the intracolonic release of prostaglandin E2, thromboxane B2, and leukotriene B4 was significantly higher in control than in antibiotic treated rats. Control stool cultures showed abundant colony forming units of both aerobic and anaerobic bacteria. Amoxicillin/clavulanic acid and imipenem plus vancomycin induced appreciable reductions in luminal bacteria. In conclusion, certain broad spectrum antibiotics prevent chronic colitis. The normal colonic flora seems to play an important pathogenetic part in the progression of inflammatory colonic lesions to chronicity.

Animals↗

[Post-cesarean uterine scar].

The American College of Obstetricians and Gynecologists recommends that women with one previous cesarean section be allowed a trial of labor. One of the exclusions to this recommendation are women with 2 or more previous cesarean section because of the risk of uterine dehiscence. We measured fibrosis in a sample obtained from the uterine scar region, finding the higher rate of fibrosis (35.7%) for the group with one previous cesarean section. We conclude that uterine scar shows no clear differences after one, two or more cesarean sections, so the risk of uterine scar dehiscence could be similar.

Adult↗