Budesonide ameliorates early portal hypertension in the rat: possible antiexudative splanchnic action

Major portal pressure increase occurs on the second day post-stenosing–ligation of the portal vein in the rat and it is associated with pancreatic edema, intraperitoneal free exudate, hypoalbuminemia and hypoproteinemia. All this suggests the development of a regional exudative inflammatory response. In order to verify this hypothesis the steroid budesonide, whose antiinflammatory activity could prevent these alterations, was administered to rats with prehepatic portal hypertension. Wistar male rats were divided into the following groups: Control rats that were administered saline solution (CS; n = 10), Control rats that were administered budesonide (36 mg/kg per day; CB; n = 10), triple stenosing ligation of portal vein (TSLP) with saline solution (n = 10) and triple stenosing ligation of portal vein with budesonide (36 mg/kg per day; n = 10). In rats with prehepatic portal hypertension at 48 h of postoperative evolution, budesonide decreases the incidence of pancreatic edema, of peritoneal free exudate, of mesenteric adenopathies and prevents hypoproteinemia, hypoalbuminemia and hyper--globulinemia. Some of the macroscopic intra-abdominal alterations and some of the changes in the electrophoretic pattern found in portal hypertensive rats could have an inflammatory etiopathogeny because budesonide shows an effective prophylaxis.     

Clinical benefits of neoral C2 monitoring in the long-term management of renal transplant recipients

BACKGROUND: Cyclosporine monitoring using the 2-hr postdose sample, C2, has been shown to have advantages in monitoring de novo renal transplant recipients. The purpose of this study was to assess cyclosporine exposure, using C2, in stable renal transplant patients previously monitored by C0 to determine the effect of dose reduction on patients with C2 more than 10% above target and the course of those with C2 at and more than 10% below target, whose dose was not modified. METHODS: One hundred and seventy-five patients, three or more months after transplantation, had C2 assessed. The relationship of C2 to C0 and of both to renal function was analyzed by linear regression. Blood pressure, serum creatinine level, and lipids were followed for a mean of 15+/-2.6 months. RESULTS: Eighty-five patients had values more than 10% above target, 42 were within 10% of target, and 48 were more than 10% below target. Cyclosporine dose was reduced in all patients above target. In this group, serum creatinine level was stable overall, but fell significantly in 46 (54%) of 85 from 153+/-55 to 132+/-49 microM. Blood pressure also fell in that group from 135/82 to 131/77. Serum creatinine level was stable in the remaining two groups of patients. CONCLUSIONS: These data suggest that dose reduction in many overexposed patients leads to improvements in renal function and blood pressure. Further study is required to confirm the long-term benefits of this strategy.     

Diabetic rats transplanted with adult porcine islets and immunosuppressed with cyclosporine A, mycophenolate mofetil, and leflunomide remain normoglycemic for up to 100 days

BACKGROUND: Transplantation of adult porcine islets (APIs) offers a possible means of treating diabetes. However, isolating APIs has been notoriously difficult. Furthermore, islet xenograft rejection must be prevented. MATERIALS AND METHODS: APIs were isolated by a modified automated method. API quality was assessed by static glucose stimulation (SGS), by transplantation to diabetic nude mice and by intraperitoneal glucose tolerance tests (IPGTTs). The morphologic characteristics of API xenograft rejection in rats were studied immunohistochemically. Furthermore, APIs were transplanted to diabetic rats that were either left untreated or immunosuppressed with cyclosporine A (CsA), mycophenolate mofetil (MMF) and leflunomide (LEF). B-glucose and porcine C-peptide levels were monitored and grafts were studied morphologically. RESULTS: Large numbers of APIs were isolated. At SGS, insulin release increased significantly. All nude mice transplanted with APIs were normoglycemic within 24 hr and remained so for up to 1 year. During IPGTTs, B-glucose levels were rapidly regulated to porcine levels. In untreated rats, API xenografts were destroyed within 6 days by a cellular infiltrate consisting mainly of macrophages. In untreated diabetic rats normoglycemia was sustained for 5.5+/-0.3 days. Rats immunosuppressed with CsA+MMF+LEF remained normoglycemic for 59.6+/-11.3 days. In 3 of 11 rats, normoglycemia was sustained for up to 101 days. Porcine C-peptide was detected in serum. At recurrence of hyperglycemia, many mononuclear cells were found close to the xenografts. However, only occasional cells infiltrated the grafts and many APIs were intact. CONCLUSIONS: Well-functioning APIs can be isolated in large numbers. API xenografts can be protected from rejection and can maintain an adequate function for up to 100 days, in rats immunosuppressed with CsA+MMF+LEF.     

Cardiovascular diseases and the nitric oxide pathway

Fifteen years after its discovery, NO has fully reached an established position in physiology, medicine and therapeutics. It is difficult to find a biological function or a pathological condition where NO does not play a relevant role. Discoveries in the NO field have historically evolved from cardiovascular research, although its influences have already covered nearly all the medical specialties. This review analyzes, step by step, the pathway through which NO is synthesized in the cells of the cardiovascular system and the main physiological and pathological routes it undergoes once it is released. We focus on various diseases affecting the cardiovascular system (atherosclerosis, hypertension, diabetes mellitus and septic shock). We describe in detail those steps of the NO pathway in which anomalies have been detected and may account for the pathophysiology of these diseases. In atherosclerosis, hypertension and diabetes mellitus, the endothelial form of NOS is upregulated, but is very sensitive to environmental conditions, such as substrate or cofactor deficiencies or increases in LDL or glucose. In this situation NOS synthesizes superoxide anion instead of NO leading to oxidative and nitrosative stress. In diabetes mellitus and, very importantly, in septic shock, the inducible form of NOS is highly upregulated. Overproduction of NO appears to underlie the hypotension and tissue damage of septicemia and the destruction of beta-cells in diabetes mellitus. New knowledge of the role of NO in these diseases has started to influence therapeutic design. We also review the current status of research on NO-based therapies.     

Validity and reliability of the Mexican resilience measurement scale in families of children with chronic conditions

Background

The resilience to face disease is a process of positive adaptation despite the loss of health. It involves developing vitality and skills to overcome the negative effects of adversity, risks, and vulnerability caused by disease. In Mexico, the Mexican Resilience Measurement Scale (RESI-M) has been validated with a general population and has a five-factor structure. However, this scale does not allow evaluation of resilience in specific subpopulations, such as caregivers.

Method

This study investigated the psychometric properties of RESI-M in 446 family caregivers of children with chronic diseases. A confirmatory factor analysis (CFA) was performed, internal consistency values were calculated using Cronbach’s alpha coefficient, and mean comparisons were determined using t-tests.

Results

The expected five-factor model showed an adequate fit with the data based on a maximum likelihood test. The internal consistency for each factor ranged from .76 to .93, and the global internal consistency was .95. No average difference in RESI-M and its factors was found between women and men.

Conclusion

The RESI-M showed internal consistency and its model of five correlated factors was valid among family caregivers of children with chronic diseases.

     

Changes in nitric oxide release in vivo in response to vasoactive substances.

1. Changes in the release of nitric oxide (NO) in vivo were studied in rats following the administration of endothelium-dependent and -independent vasodilators as well as the NO synthesis inhibitor, NG-nitro-L-arginine methyl ester (L-NAME). NO production was assessed by measuring variations of nitrate in plasma by capillary ion analysis. 2. Intravenous administration of the endothelium-dependent vasodilators, bradykinin (2 and 10 micrograms kg-1 min-1) or substance P (0.3-3 micrograms kg-1 min-1) caused a transient dose-dependent hypotension followed by an increase in plasma nitrate concentration (maximal increments: 33 +/- 5% and 38 +/- 6%, for bradykinin and substance P, respectively). Prior administration of L-NAME (10 mg kg-1 min-1) inhibited the hypotension and increase in plasma nitrate caused by these substances. Intravenous administration of sodium nitrate (200 micrograms kg-1) also produced a transitory elevation in plasma nitrate which was similar in magnitude as that caused by the vasodilators. A rapid and transitory increment in plasma nitrate was observed after i.v. administration of authentic NO (400 micrograms kg-1). 3. Rats receiving the endothelium-dependent vasodilators, prostacyclin (0.6 micrograms kg-1 min-1) or adenosine (3 mg kg-1 min-1) intravenously showed a drop in blood pressure paralleled by a decrease in plasma nitrate (maximal decreases: 34 +/- 5% and 24 +/- 4%, for prostacyclin and adenosine, respectively). A similar effect on the plasmatic concentration of nitrate was observed when L-NAME (10 mg kg-1 min-1, i.v.) was administered to the animals. 4. This study demonstrates that (i) changes in plasma nitrate can be detected in vivo after stimulation or inhibition of NO synthase, (ii) an increased production of NO, measured as plasma nitrate, is related to the hypotension caused by bradykinin and substance P and (iii) a diminished concentration of plasmatic nitrate is associated to the hypotension induced by adenosine or prostacyclin (endothelium-independent vasodilators), suggesting that the L-arginine: NO pathway is capable of rapid down-regulation in response to a fall in blood pressure.     

Laser palliation for colorectal carcinoma.

A review was conducted of 27 patients with colorectal carcinoma treated palliatively with endoscopic neodymium:yttrium-aluminium-garnet (Nd:YAG) laser. There were 25 rectal carcinomas and 2 primary invasive sigmoid colon carcinomas. Of the 25 rectal carcinomas, there was 1 carcinoma in situ, 16 primary cancers, and 8 recurrent rectal carcinomas. The level of the lesions from the anal verge ranged from 0 to 25 cm, with a mean of 7.2 cm. The length of the lesions ranged from 1.5 to 8.5 cm, with a mean of 5 cm. The mean number of Nd:YAG laser treatments was three, with a range from one to nine. The duration of the treatments ranged from 30 to 90 minutes, with a mean of 40 minutes. Four of 27 patients (15%) developed complications. The success rate in terms of the relief of symptoms was established in 23 of the 27 patients.     

Rhythm and conduction disturbances in isolated, congenitally corrected transposition of the great arteries

The incidence and types of rhythm and conduction disturbances in 11 male and 6 female patients with congenitally corrected transposition of the great arteries and no other intrinsic complicating anomalies were studied. Patient age ranged from 5 to 54 years; follow-up ranged from 5 to 37 years. Surface electrocardiograms were recorded in each patient; 15 also underwent 24-hour Holter monitoring and 10 underwent electrophysiologic study. The conduction system of a 54-year-old woman who died suddenly, with complete atrioventricular (AV) block since age 30 years, was studied by serial histologic sections. Fifteen patients were asymptomatic and 2 reported repeated episodes of palpitation since childhood. Ten patients presented with a normal PR interval and 2 with first-degree AV block (12%). Five patients had complete AV block (29%), but none had had it at birth; first- and second-degree AV block preceded complete AV block in 2 patients. The morphologic pattern and duration of QRS suggested a junctional rhythm in 4 patients and an idioventricular pacemaker in 1 patient. Electrophysiologic studies confirmed that the complete AV block site was supra-Hisian in 2 patients and proximal to the His bundle bifurcation in 1 patient. However, histologic investigation disclosed fibrosis and disruption of the proximal nonbifurcating His bundle in the patient who died suddenly. In 2 patients with recurrent supraventricular tachycardia, electrophysiologic studies suggested reentry through James fibers (or dual AV nodal pathway) in 1 and the presence of a left lateral accessory AV pathway in the other. Holter monitoring showed a high incidence of ventricular arrhythmias.     

Galactoside-binding lectin in human tissues

Lactose-inhibitable lectin activity has been analyzed by hemagglutination assay in a variety of human tissues and cells obtained at surgery and autopsy. The lectin activity was detected in surgically removed melanoma, sarcoma, colon carcinoma, breast carcinoma, adjacent non-malignant tissues, non-malignant tissues obtained at autopsy and in cells isolated from malignant effusions. Although, on average, malignant tissue had a higher hemagglutinating titer than non-malignant tissue, similar tissues from different individuals varied widely in their apparent lectin content. The lectin was isolated from lung by affinity chromatography and was found to have a native molecular mass of 31,000 daltons and a subunit molecular mass of 14,000 daltons. Utilizing rabbit anti-lung lectin serum in an immunohistochemical assay, the lectin was found to be distributed throughout the cytoplasm of lung epithelial cells. Ouchterlony immunodiffusion analysis confirmed the presence of this lectin in a variety of tissues and in some body fluids. In vitro metabolic radiolabelling experiments showed that the presence of lectin in tissues was most likely due to endogenous synthesis rather than absorption from body fluids. Lectin isolated from several tissues was found to bind to human buffy coat cell receptors.