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.     

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.     

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.     

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.     

Regional non-nodal metastases of cutaneous melanoma

The authors studied the prognosis of patients with so called local recurrences, satellites and in-transit metastases from cutaneous melanoma on the basis of 291 patients. These are the 19.3% of the 1503 patients with stage I and II melanoma originally submitted to surgical treatment at the National Cancer Institute of Milano (Italy). The majority of patients were males (M/F = 0.7): 102 had local recurrence, 99 in-transit metastases, 24 satellites and 66 both local and in-transit metastases. Regional non-nodal metastases were not related with the site of origin, and inadequate treatment of primary. These metastases were more frequently observed in patients who were submitted to regional node dissection no matter whether in discontinuity or in continuity with primary tumor. The frequency of regional non-nodal metastases was found to increase with increasing thickness of primary melanoma or, in stage II patients, with the number of involved nodes. Local and in-transit metastases were related with prognostic criteria in the same way. The overall survival was very close between in-transit and local metastases. Similar survival rates were observed comparing regional non-nodes and disseminated cutaneous and subcutaneous metastases. The authors conclude that the distinction between local recurrences, satellites and in-transit metastases is artificial and that these metastatic events are not prognostically dissimilar from metastases in distant skin areas.     

Pedal consequences of rhabdomyolysis: a case report.

The authors present an unusual case that has been seldom reported in the literature. The clinical rhabdomyolysis syndrome, resulting from muscle disintegration, can be the result of numerous etiologic events and have serious sequelae. The pedal manifestations result from muscular and neurologic insult. The patient in this reported case survived rhabdomyolysis despite renal and hepatic failure requiring diuresis and hemodialysis. The only permanent long-term sequelae the patient suffered was flexible hammertoe deformities and parasthesias of all lesser digits of both feet. The follow-up is over 8 years.