Biomedical subjects

R Fabia

Publications and source records attributed to R Fabia.

13 recordsLinked to original sources

PubMed1998

De novo hepatitis B infection after liver transplantation: source of disease, incidence, and impact.

New-onset hepatitis B (de novo B) after liver transplantation (OLTX) is an emerging concern. The goals of our study were to determine the incidence and pattern of this infection, to attempt determination of risk factors and the role of immunosuppression, and to review its morbidity/mortality. Over a 10-year period, 1078 OLTX were performed in 956 patients at our institution. Eight hundred twenty-six patients had proven negative hepatitis B surface antigen (HBsAg) before transplantation. Among these, 14 patients (1.7%), 8 women and 6 men, ages 21-59 years (median, 42 years), developed positive HBsAg after transplantation and were defined as de novo B. In 10 of 14 patients (71%), positive HBsAg was revealed during routine annual visits, whereas 4 patients had titer verification prompted by illness. Blood product use (cryoprecipitate, fresh-frozen plasma, platelets, and packed red blood cells) during the transplant hospitalization was similar between groups. Pretransplant hepatitis C infection was more prevalent among the 14 patients with de-novo B (7 of 14, 50% v 129 of 812, 16%; P < or = 05). Hepatitis B vaccine had been given to 12 patients (86%) (but not given to 2) who developed de novo B. Incidence and severity of rejection were similar in both populations, although de novo B patients had more late rejections. Our use of immunosuppressive protocols was the same in both groups. Mean follow-up of the infected patients is 24 (5-51) months. Twelve of these 14 de novo B patients were not clinically ill, with normal or near-normal transaminase levels. One of 14 has died from complications related to hepatic artery revascularization, and another is well after repeat OLTX for biliary strictures. Half of these de novo B patients remain free from viral antigens in their transplanted liver tissue. The high percentage of positive hepatitis C patients who acquire de novo B may indicate a link between these two viral infections and potential risk factor for de novo B. The origins of this infection are most likely multifactorial, needing further study. De novo B after liver transplantation is preliminarily associated with little clinical morbidity and mortality.

Adult↗

PubMed1998

Protection by cyclosporine A against normothermic liver ischemia-reperfusion in pigs.

BACKGROUND: Cyclosporine A (CYA) is primarily utilized as an immunosuppressant, but its mechanisms of action (including decreased neutrophilic free radical production and stabilization of mitochondrial and lysosomal membranes) may have beneficial effects in ischemia and reperfusion (IR) injury. This study was undertaken to examine the effect of CYA pretreatment on porcine liver histopathologic changes and enzymatic release caused by ischemia and reperfusion. MATERIALS AND METHODS: CYA was administered orally for 4 days prior to surgery in two doses (10 or 20 mg/kg) while controls received only the control vehicle. Pigs were then exposed to 4 h of hepatic ischemia followed by 2 h of reperfusion. RESULTS: Significant decreases in AST levels compared to controls were seen in high dose CYA pigs at the end of ischemia and at 30-min intervals during the reperfusion period. Controls exhibited necrotic hepatocytes and severe inflammatory cell infiltration, while high dose CYA animals demonstrated mild inflammatory cell infiltrates. Controls had decreased survival--20% did not survive reperfusion. CONCLUSIONS: This study indicates that CYA may be useful in decreasing initial damage resulting from warm hepatic IR injury.

Alanine Transaminase↗

PubMed1998

Colon carcinoma in patients undergoing liver transplantation.

BACKGROUND: Organ recipients are at risk for certain neoplasms. Ulcerative colitis (UC) is itself a strong risk factor for the development of colon carcinoma (CCa). Transplant patients with UC might be at higher risk for CCa. We analyzed these patients to compare the incidence and pattern of CCa development in these and non-UC patients following liver transplantation (OLTX). PATIENTS AND METHODS: Retrospective study of 1,085 OLTX patients. RESULTS: In 1,022 patients without UC, 1 patient (< 0.1%) developed adenocarcinoma in a colonic polyp 46 months after OLTX. Sixty-three of 108 (60%) patients undergoing OLTX simultaneously had UC. Five OLTX patients (8%) with UC developed colon adenocarcinoma 22 to 66 (mean 48) months after OLTX. Two have died. CONCLUSIONS: Coexistent UC in patients requiring OLTX constitutes a potentially high risk for the development of colonic cancer, a late-appearing event. These patients require close observation and frequent colonoscopic/histologic screening of the colon.

Adenocarcinoma↗

PubMed1997

Meal patterns prior to and following liver transplantation in rats.

Afferent nerves of the liver have been suggested to have a major influence on feeding behavior. Nevertheless, total liver denervations (TLD) in rats, that were verified by histofluorescence technique, did not change short or long term meal patterns. However, these studies have been criticized that the TLD procedures may have missed some liver innervation. In the present study meal patterns were conducted prior to and following liver transplantation in rats using a transplant procedure with arterialization. The transplanted rats recovered their pre-operative body weight in 7.5 +/- 0.6 days and meal pattern analysis was conducted two days later. In comparison with pre-surgery there was no differences in 24 h food intake (gms); dark phase: intake (gms), meal size (gms), meal duration (min), inter-meal interval (min), and frequency; and light phase: intake (gms), meal size (gms), meal duration (min), inter-meal interval (min), and frequency. These data, like earlier work in TLD rats showing that the animals consumed normal meals (when offered a variety of diets), starting with the first meal post-surgery, question the importance of liver afferents in the control of feeding behavior.

Animals↗

PubMed1997

Effect of pentoxifylline on hepatic ischemia and reperfusion injury.

BACKGROUND: Although pentoxifylline has been shown to improve tissue oxygenation and restore hepatocellular function after hemorrhagic shock, its effect on hepatic ischemia and reperfusion injury has not been fully clarified. The purpose of this study was to determine whether pentoxifylline exerted beneficial effects on liver histopathologic changes and enzymatic release caused by ischemia and reperfusion. METHODS: Warm, reversible hepatic ischemia/reperfusion injury was induced in four groups of pigs. Preoperative oral (24 mg/kg or 50 mg/kg) or intraoperative intravenous (50 mg/kg) pentoxifylline was administered. Control animals received intravenous normal saline solution. RESULTS: Untreated control animals exhibited significant liver damage expressed by hepatic histopathologic changes and high plasma levels of aminotransferases. Decreased animal survival was seen in the untreated group. All treated animals survived. Pentoxifylline given orally did not improve histopathologic changes or enzyme release. Intravenous administration caused significant amelioration of liver tissue damage, marked reduction of aspartate aminotransferase levels, and mild attenuation of alanine aminotransferase levels, as compared with control. CONCLUSIONS: This study indicates that intraoperative, intravenous pentoxifylline reduces hepatic injury after warm ischemia and reperfusion.

Administration, Oral↗

PubMed1996

The role of transient mucosal ischemia in acetic acid-induced colitis in the rat.

The importance of early microcirculatory changes in the rat colon after exposure to acetic acid was investigated. Administration of 4% acetic acid for 15 sec into an exteriorized colonic segment induced a marked, transient (starting 2 min after the challenge with acetic acid and persisting for 15 min) decrease in the colonic blood flow as estimated by a laser-Doppler flowmeter. Four days after acetic acid administration, a uniform colitis had developed in the exteriorized colonic segment with a total morphological score (TMS) of 15.1 +/- 0.8, myeloperoxidase activity (MPO) increased more than threefold, and plasma exudation into the colonic lumen increased sevenfold. Administration of hydrochloric acid (HCl) with the same pH as the acetic acid or sodium acetate (pH 7.0) did not affect colonic blood flow or produce colitis. Mechanical colonic ischemia, induced by a controlled increase in the intraluminal pressure, resulted in several pathological features of colitis with a TMS of 7.3 +/- 0.2, combined with a significant increase in MPO activity. The TMS and MPO were further increased when mechanical colonic ischemia was combined with HCl or sodium acetate. Pretreatment with SOD and catalase 5 or 15 min before acetic acid administration did not affect the transient ischemia immediately following acetic acid administration. However, it partially prevented the development of colitis. It is concluded that immediate transient ischemia accompanied by the generation of oxygen free radicals might be of importance in the pathogenesis of acetic acid-induced colitis in the rat.

Acetic Acid↗

PubMed1996

Reperfusion injury.

Reperfusion injury, precipitated by lack of oxygen, is likely to play a major role in many clinical conditions, including shock, coronary artery occlusion disease, and solid organ transplantation. Certain tissues, such as the intestinal mucosa, may be especially susceptible because of the specific microvascular anatomy. Structural changes include not only swelling of the organelles but also the entire cell due to the entry of water and electrolytes. Lysosomal ruptures precede cell death. Other key substances which either participate in or are part of oxygen free radical formation in tissue injury are calcium ions, leukocytes, and bacteria. Leukocyte adhesion has been implicated as a critical step in vascular endothelium injury, leading to increased microvascular permeability and thrombosis. Induction of neutropenia or the administration of antileukocyte adhesion monoclonal antibodies, preventing typical injuries, implies a central role of the white blood cells in reperfusion injury. Specifically, oxygen free radical formation in the intestines may trigger or cause injury in other distant organs, e.g., the heart and lungs, and affect overall vascular function. So-called "bacterial translocation" from the intestines to the lymphatic vessels and the bloodstream is a more recently discovered phenomenon whose role is largely unknown. Ischemic preconditioning is still another concept, mainly tested in the canine heart, that has potential clinical applications. Reperfusion of ischemic tissue occurs with solid organ transplantation, often after considerable cold ischemia time. Protective mechanisms include oxygen free radical scavengers, i.e., allopurinol and superoxide dismutase. Other measures proven to be effective during the implantation are blood volume expansion with colloid solutions and/or electrolyte solutions, and the administration of a calcium antagonist. The mechanisms of these measures are likely related to improved renal microcirculation and relief of vasospasm.

Animals↗

PubMed1994

Topical anticolitic efficacy and selectivity of the glucocorticoid budesonide in a new model of acetic acid-induced acute colitis in the rat.

AIMS: To study the effect of local or parenteral administration of the glucocorticoid budesonide in the acetic acid-induced colitis model in the rat. METHODS: Colitis was induced in an exteriorized colonic segment by administration of 4% acetic acid for 15 s. Four days later, this colonic segment with colitis was examined using a morphological scoring system, and measurements of myeloperoxidase activity and of plasma exudation into the colonic segment. The experimental colitis showed morphological similarities to human ulcerative colitis, with 3-fold increase in myeloperoxidase activity and 6-fold increase in the plasma exudation. Budesonide in different doses administered for 3 days, starting one day after acetic acid instillation, prevented the development of colitis in a dose-dependent manner. The best effect of budesonide on the morphological score was achieved after local treatment at a dose of 10(-5) M twice daily (76% reduction compared with a control colitis group) and parenteral treatment with 0.75 mg/kg (80% reduction). These doses also normalized myeloperoxidase activity and significantly reduced the plasma exudation. The systemic effects of the drug were most pronounced in the group treated with parenteral budesonide. This group showed the greatest reduction in body weight and a significant reduction of the weight of adrenal glands and spleen (as compared to controls). Thymus weight in animals treated systemically was significantly lower than in locally treated animals. In the group treated with local budesonide the weight of adrenals was reduced. However, the weights of spleen and thymus were not reduced and the reduction of the body weight was even less than in the control group. CONCLUSION: Local treatment with budesonide at a dose of 10(-5) M (0.17 mg/kg if completely absorbed, but only 0.03 mg/kg with 15% bioavailability on colonic application) was as effective as parenteral treatment at a dose of 0.75 mg/kg in the attenuation of acetic acid-induced colitis in the rat, but resulted in minor systemic side-effects.

Acetates↗

PubMed1993

Effect of putative phospholipase A2 inhibitors on acetic acid-induced acute colitis in the rat.

Phospholipase activation may play an important role in ulcerative colitis. This hypothesis was tested by evaluating the effect of two non-selective phospholipase (PL) A2 inhibitors, quinacrine and p-bromophenacyl-bromide (pBPB), on acetic acid-induced colitis in the rat. The calcium antagonist verapamil, which may also act as a PLA2 inhibitor, was also tested. Acute colitis was induced in an isolated colonic segment by instillation of 4 per cent acetic acid for 15 s; this induces a uniform colitis after 4 days. The severity of colitis was evaluated histologically, by measuring myeloperoxidase (MPO) activity and by determining plasma exudation into the lumen of the colon (permeability) with 125I-labelled albumin given intravenously. All three putative PLA2 inhibitors tested were found to prevent the development of colitis. Intravenous administration of quinacrine 10 mg kg-1 at 30 min before instillation of acetic acid resulted in a normal mucosal appearance, normal MPO activity and a significantly reduced increase in plasma exudation into the colon. A similar effect was achieved using verapamil. Intracolonic administration of either quinacrine or pBPB also prevented acetic acid-induced colitis. However, three doses, starting immediately after acetic acid administration and repeated on the first and second days, were needed to achieve this, whereas one dose produced only a partial effect. PLA2 may play an important role in acetic acid-induced colitis and inhibition of its activity may offer an alternative mode of treatment in ulcerative colitis.

Acetates↗

PubMed1993

Impairment of bacterial flora in human ulcerative colitis and experimental colitis in the rat.

Changes in the colonic mucosa-associated microflora were determined both in patients with active and inactive ulcerative colitis and in rats with acetic acid-induced colitis. In patients with active ulcerative colitis, significant decreases in the number of anaerobic bacteria (Brain Heart Infusion medium), anaerobic gram-negatives and Lactobacillus were found, whereas no changes were seen in the number of aerobic bacteria and Enterobacteriaceae. In patients with inactive ulcerative colitis, no significant differences in colonic mucosa-associated microflora could be demonstrated. Similar changes were seen in rats with acetic acid-induced colitis. Thus, 4 days after acetic acid administration, at which time the colitis was well developed as evaluated by morphological appearance and myeloperoxidase activity, reduction in the number of anaerobic bacteria and Lactobacillus was seen. The first day after acetic acid administration, when the colitis had not developed, or after 14 days, when the colitis had been overcome, no alterations were seen in the mucosa-associated microflora as compared with control rats. We conclude that a reduction in the number of anaerobic bacteria and Lactobacillus is a common feature in active colitis regardless of the origin of colitis.

Acetates↗

PubMed1993

The effect of exogenous administration of Lactobacillus reuteri R2LC and oat fiber on acetic acid-induced colitis in the rat.

The potential beneficial effect of exogenous administration of Lactobacillus on acetic acid-induced colitis was evaluated in the rat. Colitis was induced by instillation of 4% acetic acid for 15 sec in an exteriorized colonic segment. This produced uniform colitis with a threefold increase in myeloperoxidase (MPO) activity of the colonic tissue (an index of neutrophil infiltration) and a sixfold increase in plasma exudation into the lumen of the colon (mucosal permeability) as evaluated 4 days after acetic acid administration. Intracolonic administration of L. reuteri R2LC immediately after acetic acid administration, at a dose of 5 ml of 7 x 10(7) colony-forming units (CFU)/ml in two forms: either as pure bacterial suspension or as fermented oatmeal soup, prevented the development of colitis. Thus, the morphologic score, MPO activity, and mucosal permeability were almost normalized by Lactobacillus treatment. Initiating the treatment 24 h after acetic acid administration or using lower doses of 1 ml for 3 consecutive days resulted in a smaller protective effect. We conclude that exogenous administration of L. reuteri R2LC prevents the development of acetic acid-induced colitis in the rat.

Acetates↗

PubMed1992

Acetic acid-induced colitis in the rat: a reproducible experimental model for acute ulcerative colitis.

There exists no ideal model for experimental ulcerative colitis in common laboratory animals. Therefore, we tried in the present study to establish a reproducible model for inducing colitis in rats by using acetic acid. A blind loop of the colon including the cecum, ascending colon and part of the transverse colon, was brought out through two colostomies. After mechanical washing with warm normal saline, acetic acid was instilled at different doses (4, 6 and 8%) for different exposure times (10, 15, 20, 25 and 30 s). The excluded colon was examined by light microscopy on the 1st, 2nd, 3rd, 4th, 7th and 14th days after operation and acetic acid instillation. We found that 4% acetic acid for 15 s produced a moderate, superficial colitis on the 1st day after operation, whereafter a uniform colitis evolved in all rats on the 4th day after operation. The developed colitis showed morphological similarities with human ulcerative colitis. Signs of healing and regeneration of the mucosa were seen on the 7th day, and the mucosa became almost normal at the 14th day after operation. 6 or 8% acetic acid solution or exposure times exceeding 15 s resulted in severe, deep colitis with a concomitant high mortality rate. In contrast, at exposure times less than 15 s, acetic acid induced only mild superficial colitis. We conclude that by using 4% acetic acid for 15 s in the excluded colon a uniform and reproducible colitis pathologically resembling human ulcerative colitis could be achieved. Furthermore, no mortality was encountered and the general health of the rats was similar to that of the controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetates↗

PubMed1992

Effects of phosphatidylcholine and phosphatidylinositol on acetic-acid-induced colitis in the rat.

The therapeutic effects of exogenous phosphatidylcholine and phosphatidylinositol on acetic acid-induced colitis in rats were evaluated. A uniform colitis developed 4 days after instillation of 4% acetic acid for 15 s in an excluded colonic segment, also resulting in a 6-fold increase in mucosal permeability. Instillation of 12.5 mg phosphatidylcholine once daily from the day after acetic acid instillation and for the following 2 days prevented partially the development of colitis causing partial mucosal restoration. By increasing the phosphatidylcholine dose to 25 and 50 mg, a better preventive effect was achieved. By starting the phosphatidylcholine instillation immediately after the acetic acid exposure, almost complete prevention of the colitis could be obtained. Similarly, 50 mg phosphatidylinositol in each instillation with the first administration immediately after acetic acid administration resulted in complete prevention of the colitis and a significant decrease in mucosal permeability expressed as a plasma exudation into the colonic lumen. Similar results were obtained when phosphatidylcholine was administered immediately after acetic acid, but the drug then had to be applied twice daily. In contrast, a single application of the same total dose (150 mg) of the two different phospholipids, either 30 min before or immediately after acetic acid administration, could not prevent the development of colitis. It is concluded that both phosphatidylcholine and phosphatidylinositol have a therapeutic effect on the development of acetic acid-induced colitis in the rat.

Acetates↗