Lactobacillus strains reduce the toxic effects of a subchronic exposure to arsenite through drinking water.

The aim of the present study was to determine the efficacy of LAB strains in reducing the intestinal toxicity of arsenite [As(III)] and its tissue accumulation. For this purpose, Balb/c mice were randomly separated in four groups. One group received no treatment (control), one group received only As(III) (30 mg/L) via drinking water and the remaining two groups received As(III) via water and a daily dose of two LAB strains (Lactobacillus intestinalis LE1 and Lacticaseibacillus paracasei BL23) by gavage during 2 months. The results show that both strains reduce the pro-inflammatory and pro-oxidant response observed at the colonic level, partially restore the expression of the intercellular junction proteins (CLDN3 and OCLN) responsible for the maintenance of epithelial integrity, and increase the synthesis of the major mucin of the colonic mucus layer (MUC2), compared to animals treated with As(III) alone. Microbial metabolism of short-chain fatty acids also undergoes a recovery and the levels of fatty acids in the lumen reach values similar to those of untreated animals. All these positive effects imply the restoration of mucosal permeability, and a reduction of the marker of endotoxemia LPS binding protein (LBP). Treatment with the bacteria also has a direct impact on intestinal absorption, reducing the accumulation of As in the internal organs. The data suggest that the protective effect may be due to a reduced internalization of As(III) in intestinal tissues and to a possible antioxidant and anti-inflammatory activity of the bacteria through activation of pathways such as Nrf2 and IL-10. In vitro tests show that the protection may be the result of the combined action of structural and metabolic components of the LAB strains.

Intestinal homeostasis disruption in mice chronically exposed to arsenite-contaminated drinking water.

Chronic exposure to inorganic arsenic [As(III) and As(V)] affects about 200 million people, and is linked to a greater incidence of certain types of cancer. Drinking water is the main route of exposure, so, in endemic areas, the intestinal mucosa is constantly exposed to the metalloid. However, studies on the intestinal toxicity of inorganic As are scarce. The objective of this study was to evaluate the toxicity of a chronic exposure to As(III) on the intestinal mucosa and its associated microbiota. For this purpose, BALB/c mice were exposed during 6 months through drinking water to As(III) (15 and 30 mg/L). Treatment with As(III) increased reactive oxygen species (43-64%) and lipid peroxidation (8-51%). A pro-inflammatory response was also observed, evidenced by an increase in fecal lactoferrin (23-29%) and mucosal neutrophil infiltration. As(III) also induced an increase in the colonic levels of pro-inflammatory cytokines (24-201%) and the activation of some pro-inflammatory signaling pathways. Reductions in the number of goblet cells and mucus production were also observed. Moreover, As(III) exposure resulted in changes in gut microbial alpha diversity but no differences in beta diversity. This suggested that the abundance of some taxa was significantly affected by As(III), although the composition of the population did not show significant alterations. Analysis of differential taxa agreed with this, 21 ASVs were affected in abundance or variability, especially ASVs from the family Muribaculaceae. Intestinal microbiota metabolism was also affected, as reductions in fecal concentration of short-chain fatty acids were observed. The effects observed on different components of the intestinal barrier may be responsible of the increased permeability in As(III) treated mice, evidenced by an increase in fecal albumin (48-66%). Moreover, serum levels of Lipopolysaccharide binding proteins and TNF-α were increased in animals treated with 30 mg/L of As(III), suggesting a low-level systemic inflammation.

Mitochondria inheritance is a key factor for tolerance to dehydration in wine yeast production.

UNLABELLED: Mitochondria are the cell's powerhouse when organisms are grown in the presence of oxygen. They are also the source of reactive oxygen species that cause damage to the biochemical components of the cell and lead to cellular ageing and death. Under winemaking conditions, Saccharomyces yeasts exclusively have a fermentative metabolism due to the high sugar content of grape must. However, their production as an active dry yeast (ADY) form required aerobic propagation and a dehydration process. In these industrial steps, oxidative stress is particularly harmful for the cell. In this work, we analysed the impact of the mitochondrial genome on oxidative stress response, longevity and dehydration tolerance using the synthetic interspecific hybrids obtained between two S. cerevisiae and S. uvarum strains. The isogenic nature of nuclear DNA of such hybrids allowed us to analyse the impact of mitochondrial DNA for fermentative and oxidative stress conditions. Under grape must conditions, the inheritance of mitochondrial DNA poorly impacted the fermentative performance of interspecific hybrids, unlike the hybrids with S. cerevisiae mitochondrial inheritance, which displayed increased tolerance to oxidative stress and dehydration, and showed an extended chronological longevity when cells were grown with aeration. SIGNIFICANCE AND IMPACT OF THE STUDY: In modern oenology, yeast starters are employed to inoculate grape juice, usually in the form of active dry yeast (ADY). The dehydration process implies stressful conditions that lead to oxidative damage. Other yeast species and interspecific hybrids other than Saccharomyces cerevisiae may be used to confer novel properties to the final product. However, these yeasts are usually more sensitive to drying. Understanding the causes of oxidative stress tolerance is therefore necessary for developing the use of these organisms in industry. This study indicates the impact of mitochondrial DNA inheritance for oxidative stress resistance in an interspecific context using isogenic Saccharomyces cerevisiae × Saccharomyces uvarum hybrids.

[Perioperative tumour dissemination. 2. Effects of anaesthesia and analgesia]. / Diseminación tumoral perioperatoria. 2. Efectos de la anestesia y analgesia.

There has been growing concern over the last few years on the effect that the anaesthetic drugs used during oncological surgery could have on long-term tumour progression. In laboratory studies, it has been observed how some substances used during the anaesthetic procedure influence tumour immunosurveillance, cell proliferation or tumour angiogenesis processes. The possible clinical relevance of the anaesthetic technique used as regards long-term tumour progression and survival is still to be determined. However, based on retrospective studies, it appears that those anaesthetic techniques combined with the use of regional anaesthesia and analgesia may be beneficial compared to those that are maintained on the use of opioids. Further research should help to clarify the long-term clinical relevance of the anaesthetic process during oncological surgery.

[Perioperative tumour dissemination. 1. Influence of perioperative factors]. / Diseminación tumoral perioperatoria. 1. Influencia de los factores perioperatorios.

There has been growing concern in the last few years on the effect of anaesthetic drugs used during oncological surgery could have on tumour progression in the long-term, as well as the influence of other perioperative factors. Although much of the available data has weak evidence, the role of the surgery itself, pain, transfusion of blood derivatives, etc., have been assessed in several studies. How some substances used during the anaesthetic process can influence tumour immune surveillance, cell proliferation or tumour angiogenesis processes have been observed in laboratory studies. The possible relevance of the anaesthetic technique used as regards the long-term tumour progression and survival is still to be determined. However, based on retrospective studies, it seems that those anaesthetic techniques combined with the use of regional anaesthesia and analgesia could be beneficial compared to those that are maintained on opioid use. Further research should help to elucidate the long-term clinical relevance of the perioperative procedures, including the anaesthetic, during oncological surgery.

Condom use among female sex workers and their non-commercial partners: effects of a sexual risk intervention in two Mexican cities.

The purpose of this study was to examine whether a brief behavioural intervention promoting condom use among female sex workers (FSWs) and their clients had the added benefit of increasing condom use among FSWs and their steady, non-commercial partners (e.g. husbands, boyfriends). Participants were 362 FSWs, aged ≥18 years, living in Tijuana or Ciudad Juarez, Mexico, who received a behavioural intervention to promote condom use with clients. Repeated-measures negative binomial regression was used to assess FSWs' condom use with steady partners versus clients across time. Results showed that FSWs engaged in unprotected sex with steady partners more than with their clients, and that the intervention changed FSWs' condom use with clients but not their steady partners. HIV-prevention interventions for FSWs should promote consistent condom use across partner type. Targeting couples rather than individuals may also be necessary.

Risk factors associated with chlamydia and gonorrhoea infection among female sex workers in two Mexico-USA border cities.

Female sex workers (FSWs) aged ≥18 years without known HIV infection living in Tijuana and Ciudad Juarez, Mexico who had recent unprotected sex with clients underwent interviews and testing for chlamydia and gonorrhoea using nucleic acid amplification. Correlates of each infection were identified with logistic regression. Among 798 FSWs, prevalence of chlamydia and gonorrhoea was 13.0% and 6.4%, respectively. Factors independently associated with chlamydia were younger age, working in Tijuana versus Ciudad Juarez and recent methamphetamine injection. Factors independently associated with gonorrhoea were working in Tijuana versus Ciudad Juarez, using illegal drugs before or during sex, and having a recent male partner who injects drugs. Chlamydia and gonorrhoea infection were more closely associated with FSWs' drug use behaviours and that of their sexual partners than with sexual behaviours. Prevention should focus on subgroups of FSWs and their partners who use methamphetamine and who inject drugs.

T-cell responses and in vivo cytotoxicity in the target organ and the regional lymphoid tissue during airborne infection with the virulent Mycobacterium tuberculosis MT103 and its lipid mutant fadD26.

To ascertain the in vivo role of mycobacterial lipids phthiocerol dimycocerosates (PDIM) in experimental murine tuberculosis (Tb), airways infection was used to compare the parental virulent clinical isolate MT103 with its mutant fadD26, lacking PDIM. Lungs were assessed as the Tb-target organ and mediastinal lymph nodes as the corresponding lymphoid tissue, in order to quantify: the major T-cell subsets (CD4+/CD8+/gammadelta+) and their activation kinetics, bacillary burden, and in vivo cytotoxicity against inoculated target cells loaded with mycobacterial Ags. After 4 weeks, infection augmented total and activated CD4+ and CD8+ T cells in lungs and nodes mainly with MT103, while gammadelta+ T cells increased earlier in nodes. MT103 bacillary burden was bigger and appeared earlier than the mutant fadD26, especially in the lung than in mediastinal nodes. At day 14 of MT103 infection, there was no cytotoxicity in lungs and nodes; while with fadD26 there was some in the nodes. At day 21 of MT103 infection, important cytotoxicity was detected only in lungs; while with fadD26 both tissues showed important activity. Interestingly, unlike the infection with fadD26, cytotoxicity under MT103 fell considerably in the target organ (lung) from days 21 to 60, the advanced phase. Although upon airways infection both mycobacteria behaved similarly regarding T cell (CD4/CD8/gammadelta) stimulation kinetics; they differed in the magnitude of these responses, in the bacterial load within tissues, and to trigger in vivo cytotoxicity in lungs and regional lymph nodes. This highlights the relevance of certain mycobacterial lipids to modify crucial effector branches of immunity.

Synthesis and evaluation of rifabutin analogs against Mycobacterium avium and H(37)Rv, MDR and NRP Mycobacterium tuberculosis.

Clinical utility of rifabutin 1 (RBT), a potent antibiotic used in multidrug regimens for tuberculosis (TB) as well as for infections caused by Mycobacterium avium complex (MAC), has been hampered due to dose-limiting toxicity. RBT analogs 2-11 were synthesized and evaluated against M. avium 1581 and Mycobacterium tuberculosis susceptible and resistant strains in vitro. A selection of candidates were also assayed against non-replicating persistent (NRP) M. tuberculosis. Subsequent in vivo studies with the best preclinical candidate drugs 5 and 8, in a model of progressive pulmonary tuberculosis of Balb/C mice infected either with H(37)Rv drug-sensible strain or with multidrug resistant (MDR) clinical isolates, resistant to all primary antibiotics including rifampicin, were performed. The results disclosed here suggest that 5 and 8 have potential for clinical application.

The effects of vetrabutin chlorhydrate and oxytocin on stillbirth rate and asphyxia in swine.

Oxytocin and vetrabutin chlorhydrate (VC) are used to reduce the duration of farrowing in swine. The objective of the present study was to evaluate the use of these products on intra-partum stillbirth (IPS) rate and asphyxia. At the onset of parturition, sows (n=180) were allocated to receive 2 mL of saline (control group), oxytocin (40 IU i.m.) or 100mg of VC per 60 kg of body weight, with all treatments given i.m. Oytocin-treated sows had a higher number of IPS than the VC and Control groups (means, 1.2, 0.8 and 0.6, respectively; P<0.001), and the highest percentage of ruptured umbilical cords (76.0, 9.4 and 37.5%; P<0.003). There were differences among groups for duration of farrowing (means, 163.0, 211.2 and 306.9 min in the oxytocin, VC and control groups; P<0.001), interval between piglets (13.9, 19.2 and 28.1 min; P<0.001), and in IPS, the incidence of ruptured umbilical cords was 76.0, 9.4 and 37.5% (P<0.003) and absence of a fetal heartbeat was 53.3, 16.9 and 12.5% (P<0.05). Although oxytocin decreased both duration of farrowing and interval between piglets by approximately 50% relative to control sows, it resulted in a significantly higher rate of IPS, in association with a much higher incidence of ruptured umbilical cord and absence of a fetal heartbeat. Treatment with VC reduced farrowing duration by approximately 1.5h, with an IPS rate that was not significantly different from controls but significantly lower than that of oxytocin-treated sows.

Acute bile duct injury. The need for a high repair.

BACKGROUND: An immediate repair is considered optimal in acute biliary duct injuries; however, it may prove to be a challenge, because such repairs are usually performed on small ducts whose viability cannot always be determined. METHODS: We performed a retrospective review of the charts of patients with acute bile duct injury who underwent repair at a tertiary care academic university hospital. A total of 204 patients with acute bile duct injury were seen between 1989 and 2002. Of these, 30 were repaired within minutes to hours after the injury. These patients were divided into two groups. Group I patients had a Roux-en-Y hepatojejunostomy below the hepatic junction; Group II patients had a Roux-en-Y hepatojejunostomy at the junction level. We then performed a long-term evaluation of anastomosis function in these patients, using clinical, radiological, and laboratory. RESULTS: Twenty-eight injuries were secondary to a laparoscopy; the other two resulted from open cholecystectomies. All of the patients suffered complex injuries with complete section of the duct and substance loss (Strasberg E). There were 12 patients in group I and 18 in group II. Three cases in group I (25%) and one in group II (5%) developed anastomosis dysfunction. Mean follow-up was 56 months (range, 12-80) in group I and 52 months (range, 10-76) in group II. Two cases in group I (16%) and none in group II (0) required reoperation (p < 0.05). CONCLUSIONS: In the acute setting, complex lesions should be treated with a high bilioenteric anastomosis (at the junction level) in the first attempt at repair. Lower-level anastomoses are associated with a higher dysfunction rate and the need for radiological manipulation and reoperation. Also, stenosis of the anastomosis secondary to undetected duct ischemia in the acute repair is more frequent in low bilioenteric anastomoses.

A marked difference in pathogenesis and immune response induced by different Mycobacterium tuberculosis genotypes.

In the last decade, an unprecedented genetic diversity has been disclosed among Mycobacterium tuberculosis strains found worldwide. However, well-conserved genotypes seem to prevail in areas with high incidence of tuberculosis. As this may be related to selective advantages, such as advanced mechanisms to circumvent [M. bovis Bacille Calmette-Guerin (BCG)-induced] host defence mechanisms, we investigated the influence of strain diversity on the course of experimental disease. Twelve M. tuberculosis strains, representing four major genotype families found worldwide today, and the laboratory strain H37Rv were each used to infect BALB/c mice by direct intratracheal injection. Compared with H37Rv, infections with Beijng strains were characterized by extensive pneumonia, early but ephemeral tumour necrosis factor-alpha (TNF-alpha) and inducible isoform of nitric oxide synthetase (iNOS) expression, and significantly higher earlier mortality. Conversely, Canetti strains induced limited pneumonia, sustained TNF-alpha and iNOS expression in lungs, and almost 100% survival. Strains of the Somali and the Haarlem genotype families displayed less homogeneous, intermediate rates of survival. Previous BCG vaccination protected less effectively against infection with Beijing strains than against the H37Rv strain. In conclusion, genetically different M. tuberculosis strains evoked markedly different immunopathological events. Bacteria with the Beijing genotype, highly prevalent in Asia and the former USSR, elicited a non-protective immune response in mice and were the most virulent. Future immunological research, particularly on candidate vaccines, should include a broad spectrum of M. tuberculosis genotypes rather than a few laboratory strains.

Ontogeny and subcellular localization of rat liver mitochondrial branched chain amino-acid aminotransferase.

Branched chain amino-acid aminotransferase (BCAT) activity is present in fetal liver but the developmental pattern of mitochondrial BCAT (BCATm) expression in rat liver has not been studied. The aim of this study was to determine the activity, protein and mRNA concentration of BCATm in fetal and postnatal rat liver, and to localize this enzyme at the cellular and subcellular levels at both developmental stages. Maximal BCAT activity and BCATm mRNA expression occurred at 17 days' gestation in fetal rat liver and then declined significantly immediately after birth. This pattern was observed only in liver; rat heart showed a different developmental pattern. Fetal liver showed intense immunostaining to BCATm in the nuclei and mitochondria of hepatic cells and blood cell precursors; in contrast, adult liver showed mild immunoreactivity located only in the mitochondria of hepatocytes. BCAT activity in isolated fetal liver nuclei was 0.64 mU x mg(-1) protein whereas it was undetectable in adult liver nuclei. By Western blot analysis the BCATm antibody recognized a 41-kDa protein in fetal liver nuclei, and proteins of 41 and 43 kDa in fetal liver supernatant. In adult rat liver supernatant, the BCATm antibody recognized only a 43-kDa protein; however, neither protein was detected in adult rat liver nuclei. The appearance of the 41-kDa protein was associated with the presence of the highly active form of BCATm. These results suggest the existence of active and inactive forms of BCAT in rat liver.

[Evaluation of 20 years of experience and quality of life in patients surgically treated for liver cystic disease]. / Evaluación de 20 años de experiencia y calidad de vida en pacientes con tratamiento quirúrgico para la enfermedad quística del hígado.

UNLABELLED: Surgical treatment of liver cystic disease is reserved for symptomatic patients. The surgical approach is chosen according to the size and distribution of the cysts. In patients with massive hepatomegaly secondary to polycystic liver disease, liver transplantation is indicated with excellent results and quality of life. OBJECTIVE: To evaluate over 20-year period, the results in terms of clinical outcome of three groups of patients with cystic liver disease (EQ) who received surgical treatment and to determine postoperative quality of life. MATERIALS AND METHODS: In a 20-year period, 44 patients were operated on; 24 had simple liver cyst, 13 had polycystic liver disease, and seven cystadenomas. Using the SF36 questionnaire, self-perception of quality of life was evaluated using eight scales in two major categories: Physical component summary (PCS) and mental component summary (MCS). RESULTS: Upper abdominal pain was the main clinical symptom. Fenestration was the most frequent procedure performed. No differences in quality of life were observed in all, while good quality of life was recorded in all groups at a median follow-up of 39 months. CONCLUSIONS: Surgical treatment of cystic liver disease is reserved for symptomatic patients or complications such as rupture, infection, and hemorrhage. Therapeutic alternatives should been chosen on an individual basis. Good quality of life is obtained after surgery in these patients.

Diminished morbidity and mortality in portal hypertension surgery: relocation in the therapeutic armamentarium.

Although several effective therapeutic options are available for bleeding from portal hypertension, surgery has a well-defined role in the management of patients with good liver function who are electively operated. The aim of this investigation was to evaluate the operative mortality and morbidity of portal blood flow-preserving procedures in a highly select patient population. The records of 148 patients operated on between 1996 and 2000 using one of two techniques (selective shunts or a Sugiura-Futagawa operation [complete portoazygos disconnection]) were analyzed with particular attention to operative mortality, postoperative rebleeding, and encephalopathy. Survival was calculated according to the Kaplan-Meier method. Sixty-one patients had distal splenorenal shunts placed, and 87 patients had a devascularization procedure. Operative mortality for the group as a whole was 1.2%. In the group with selective shunts, the rebleeding rate was 4.9%, the encephalopathy rate was 9.8%, and the shunt obstruction rate was 1.6%. Survival at 24 months was 94% and at 48 months was 92%. In those undergoing devascularization, the encephalopathy rate was 5% and the rebleeding rate was 14%. Survival at 24 months was 90% and at 48 months was 86%. Portal blood flow-preserving procedures have very low morbidity and mortality rates at specialized centers. In addition, a low rebleeding rate is associated with a good quality of life. Low-risk patients with bleeding portal hypertension should be considered for surgical treatment.

Liver cirrhosis is reverted by urokinase-type plasminogen activator gene therapy.

Liver cirrhosis represents a worldwide health problem and is a major cause of mortality. Cirrhosis is the result of extensive hepatocyte death and fibrosis induced by chronic alcohol abuse and hepatitis B and C viruses. Successful gene therapy approaches to this disease may require both reversal of fibrosis and stimulation of hepatocyte growth. Urokinase-type plasminogen activator (uPA) may serve this function, as it is an initiator of the matrix proteolysis cascade and induces hepatocyte growth factor expression. In a rat cirrhosis model, a single iv administration of a replication-deficient adenoviral vector encoding a nonsecreted form of human uPA resulted in high production of functional uPA protein in the liver. This led to induction of collagenase expression and reversal of fibrosis with concomitant hepatocyte and improved liver function. Thus, uPA gene therapy may be an effective strategy for treating cirrhosis in humans.

The evolution of portal hypertension surgery: lessons from 1000 operations and 50 Years' experience.

HYPOTHESIS: Surgery for portal hypertension has evolved widely in the past decades. Selection criteria and the type of operations have evolved because of the appearance of other therapeutic alternatives, such as pharmacotherapy, endoscopic therapy, transjugular intrahepatic portosystemic shunt, and liver transplantation. We believe the surgical approach has a therapeutic role in a select patient population. DESIGN: Retrospective review of the medical records of patients operated on for bleeding portal hypertension in the past 50 years. SETTING: An academic tertiary care university hospital. PATIENTS AND METHODS: In a 50-year period, 1000 operations for the treatment of bleeding portal hypertension have been done, including shunts and devascularization procedures. In the past years, in low-risk (Child-Pugh classification A) selected patients, only portal blood flow-preserving operations have been done. RESULTS: Non-portal blood flow-preserving procedures had a wide spectrum of results, with a high encephalopathy rate and short long-term survival. The results with portal blood flow-preserving procedures in the past 10 years are as follows: operative mortality, 2.7%; postoperative encephalopathy, 6%; rebleeding, 6%; and shunt obstruction, 4%. CONCLUSIONS: Portal hypertension surgery has a role in elective operations and in low-risk selected patients, when portal blood flow-preserving procedures are done. The type of operation is selected according to the individual characteristics of each patient.

Small-diameter mesocaval shunts: a 10-year evaluation.

The use of small-diameter portosystemic shunts for the treatment of bleeding esophageal varices caused by portal hypertension has emerged as an outgrowth of the development of polytetrafluoroethylene vascular grafts, which allow the use of a narrow lumen. We report our experience with this type of graft over a 10-year period. Thirty-three patients with good liver function (Child-Pugh class A) were electively operated. The average age of these patients was 45 years (range 17 to 71 years). Twenty-nine patients had liver cirrhosis, one had portal fibrosis, and three had idiopathic portal hypertension. Operative mortality was 3%, and the rebleeding rate was 15%. Postoperative encephalopathy was observed in 14 patients (11%), three of whom had grade III to IV encephalopathy. The remaining 11 patients, had mild encephalopathy that was easily controlled. Postoperative angiography showed shunt patency in 81% of the patients, reduction in portal vein diameter in 33% of the patients, and portal vein thrombosis in 6%. Good postoperative quality of life was observed in 63% of the patients. Survival according to the Kaplan-Meier actuarial method was 81% at 12 months, 56% at 60 months, and 36% at 10 years. These shunts are a good alternative for patients being considered for surgery in whom other portal blood flow preserving procedures (i.e., elective shunts, devascularization with esophageal transection) are not feasible.

Treatment with BB-94, a broad spectrum inhibitor of zinc-dependent metalloproteinases, causes deviation of the cytokine profile towards type-2 in experimental pulmonary tuberculosis in Balb/c mice.

BB-94 (batimastat) is a broad- spectrum hydroxamic acid-based zinc metalloproteinase inhibitor that inhibits both the matrix metalloproteinases (MMP) and members of the ADAM family of enzymes such as Tumour Necrosis Factor-alpha Cleaving Enzyme (TACE). These enzymes are involved in the regulation of inflammatory processes in tuberculosis. Balb/c mice infected with M. tuberculosis via the intratracheal route were treated with BB-94 for 1 month, starting on the day of infection. Immunohistochemistry, semiquantitative RT-PCR and ELISA assays for cytokines revealed a deficit in IL-1 and IL-2 expression and a premature bias towards IL-4 expression, accompanied by a delay in granuloma formation and more rapid progression of disease in BB-94-treated animals. This situation corrected itself after the drug was withdrawn at 28 days. In contrast, when BB-94 was administered only after 1 month there were no significant changes apart from the presence of amyloid, and a paradoxically increased expression of IL-1alpha. These results cast light on mechanisms of immunity in tuberculosis and also indicate that in patients treated with similar broad-spectrum MMP inhibitors there may be a risk of inappropriate deviation of some immune responses towards a Type-2 cytokine profile.

A comparative study of the elective treatment of variceal hemorrhage with beta-blockers, transendoscopic sclerotherapy, and surgery: a prospective, controlled, and randomized trial during 10 years.

OBJECTIVE: To compare three options for the elective treatment of portal hypertension during a 10-year period. METHODS: Patients included in the trial were 18 to 76 years old, had a history of bleeding portal hypertension, and had undergone no prior treatment. Treatment options were beta-blockers (propranolol), sclerotherapy, and portal blood flow-preserving procedures (selective shunts and the Sugiura-Futagawa operation). RESULTS: A total of 119 patients were included: 40 in the pharmacology group, 46 in the sclerotherapy group,and 33 in the surgical group. The three groups showed no differences in terms of age, Child-Pugh classification, and cause of liver disease. The rebleeding rate was significantly lower in the surgical group than in the other two groups. The rebleeding rate was only 5% in the Child A surgical group, compared with 71% and 68% for the sclerotherapy and pharmacotherapy groups, respectively. Survival was better for the low-risk patients (Child A) in the three groups, but when the three options were compared, no significant difference was found. CONCLUSIONS: Portal blood flow-preserving procedures offer the lowest rebleeding rate in low-risk patients undergoing elective surgery.