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A Mall

Publications and source records attributed to A Mall.

17 recordsLinked to original sources

The effect of rapamycin on the healing of the ureteric anastomosis and wound healing.

Rapamycin is a potent immunosuppressive agent that also inhibits fibroblastic activity and therefore may affect the healing of various tissues. The aim of this study was to investigate the effect of rapamycin on wound healing and the healing of the ureteric anastomosis. Large White/Landrace pigs were subjected to a laparotomy and division and immediate anastomosis of the ureter. The animals were randomly allocated to receive either rapamycin or placebo. The animals were sacrificed on postoperative day 5, and strips of the skin and fascia closure and the ureteric anastomosis excised and used to determine the tensile strength, hydroxyproline levels, and histological changes. The tensile strength and the hydroxyproline levels in the ureter and fascia were lower in the rapamycin-treated animals. There was no difference in the tensile strength in the skin, although the hydroxyproline levels were lower. This study shows that healing of the ureteric anastomosis and fascia and skin closure may be impaired by rapamycin.

Anastomosis, Surgical↗

Effect of rapamycin on the healing of the bile duct.

Besides its potent immunosuppressive properties, rapamycin also has antitumor and antifungal effects. Rapamycin also inhibits the proliferation of fibroblasts and therefore may impair the healing of various tissues. We investigated the effect of rapamycin on the healing of the bile duct anastomosis. The study was undertaken in pigs that were subjected to a laparotomy under general anesthesia. The bile duct was mobilized and divided and immediately reanastomosed. The animals were randomly allocated to receive either rapamycin or placebo. The animals were sacrificed on the postoperative day 5, then the biliary anastomosis was excised and used to determine the tensile strength, hydroxyproline levels, and the histological changes. The tensile strength and the hydroxyproline levels in the biliary anastomosis were lower in the animals treated with rapamycin. The liver function tests were normal. These studies show that rapamycin may impair the healing of the biliary anastomosis.

Anastomosis, Surgical↗

Restoration of liver mass after partial hepatectomy--implications for living donor liver transplantation.

In living donor liver transplantation, the recipient liver undergoes more rapid regeneration than the remnant liver in the donor. In this study we investigated the factors which may be responsible for the difference in the regenerative response between the donor and the recipient. Long Evans rats were subjected to either partial hepatectomy (PH) or sham operation (SH) and were treated with liver cytosol (C) and cyclosporine (Cy). The rats were sacrificed at 24, 48, 72 and 96 hours and 1 and 2 weeks postoperatively. The livers were removed to determine the liver weight/body weight (LW/BW) ratio and the mitotic index. The mitotic index, serum aspartate transferase (AST) and serum alanine transferase (ALT), although unchanged in the SH groups, were increased in the rats treated with PH + C + Cy, and were greater than after PH only. However LW/BW ratios increased after PH but had returned to preoperative levels by 2 weeks. The changes in LW/BW ratio were not modified by the cytosol or cyclosporine.

Alanine Transaminase↗

Prolonged survival of baboon renal allografts using idarubicin-conjugated anti-CD4 monoclonal antibodies.

Tolerance to organ allografts in rodents and pigs can be easily achieved. However, tolerance induction in a large primate model has been more elusive. In this study, we have used an anti-CD4, murine monoclonal antibody as a carrier for the cytotoxic drug idarubicin (IDA) to delete or inactivate alloreactive T-cells responding to a renal allograft in a baboon transplant model. Fourteen Chacma baboons weighing between 15-25 kg received heterotopic renal allografts. Recipient and donor pairs were selected on the basis of ABO compatibility. Seven animals were given no immunosuppression and served as the control group. The remaining 7 animals received anti-CD4 IDA. The first 2 animals in this group received 2 mg IVI intraoperatively and three doses at 48-h intervals thereafter. The last 5 animals received a larger dose of 1 mg/kg, starting 24 h preoperatively and again on postoperative days 2 and 5. The untreated animals promptly rejected their allografts with a mean survival of 10 days. The survival of the 2 animals treated with 2 mg anti-CD4 IDA was 7 days each. However, the animals treated with 1 mg/kg anti-CD4 IDA survived 7, 18, 20, 40 and > 40 days. Peritransplant administration of anti-CD4 IDA prolonged renal allograft survival in a large primate model. This unique immunoconjugate has the potential of tolerance induction.

Animals↗

Tumour necrosis factor levels during acute rejection and acute tubular necrosis in renal transplant recipients.

Plasma tumour necrosis factor levels were measured serially in 16 patients following renal transplantation, and in 10 patients on haemodialysis and in 12 patients on peritoneal dialysis. The patients on peritoneal dialysis had lower plasma TNF levels than the patients on haemodialysis. There was a decrease in TNF levels immediately following renal transplantation; this is probably related to the bolus doses of methylprednisolone administered intra-operatively. Patients with acute rejection had higher levels of TNF than non-rejecting patients. The increase in TNF levels in rejecting patients was observed 2 days before the clinical manifestation of acute rejection. There was a marked decrease in TNF levels in rejecting patients in response to treatment with steroids. Patients with delayed graft function had higher levels of TNF on the first post-operative day compared to patients with immediate function. These changes in plasma TNF levels following renal transplantation have important clinical and therapeutic implications.

Acute Disease↗

Annexins possess functionally distinguishable Ca2+ and phospholipid binding domains.

All annexins bind Ca2+ and phospholipids, although individual annexins differ markedly in their affinities for these ligands. Annexin I binds phosphatidylserine (PS) at lower [Ca2+] than annexin V, while annexin V exhibits a higher affinity for PS than does annexin I. To identify the structural determinants of these properties, we characterized a series of chimeric annexins. A chimera containing repeat 1 of annexin V used to repeats 2, 3, and 4 of annexin I exhibited a Ca2+ requirement for PS binding close to that of annexin I, while chimeras containing repeat 1 of annexin I fused to repeats 2, 3, and 4 of annexin V required higher [Ca2+], similar to that of annexin V. In contrast, the overall affinity for PS vesicles was determined by the source of repeat 1. The chimera that contained repeat 1 of annexin V exhibited a high affinity for PS, while a chimera that contained repeat 1 of annexin I had a low affinity for PS similar to that of annexin I. We conclude that the [Ca2+] requirement for phospholipid binding and the overall phospholipid affinity of annexins are determined by distinct domains.

Annexins↗

Administration of sucralfate prolongs survival of animals with experimental peptic ulceration.

Ligation of the pig bile duct (BDL) results in 100% incidence of pars esophageal ulceration within 48 hours of the procedure. Usually such ulceration is uniformly fatal unless a highly selective vagotomy is performed simultaneously with the BDL. The administration of sucralfate to pigs with BDL prolonged their survival for up to 7 days, with evidence of healing of the ulcer on macroscopic and histologic observations. An increase in cell proliferation in the squamous epithelium of the ulcerated area was also seen in this sucralfate group. These features were not seen in controls, pigs with BDL only, or pigs with BDL and with magaldrate (Riopone), colloidal bismuth subcitrate (DeNol), or carbenoxolone. Analysis by Sepharose 2B gel filtration showed that there was no significant difference in the amounts of polymeric mucin in any group, with a wide scatter of the data seen especially for pigs in the untreated BDL-only group. This study suggests that sucralfate may enhance healing in this experimental pig ulcer model via a mechanism independent of the stimulation of mucus secretion. We propose that coating the mucosa with sucralfate provides a temporary substitute barrier that creates a microenvironment conducive to wound repair by mucosal proliferation.

Aluminum Hydroxide↗

Sucralfate in the prevention of porcine experimental peptic ulceration.

Sucralfate is the first drug to be shown to prevent ulceration in bile duct-ligated pigs. Usually such ulceration is uniformly fatal. Seven pigs in each of four groups in this study received only saline, or sucralfate (1 g every six hours), famotidine (40 mg per day), or misoprostol (200 micrograms every six hours). A Foley catheter was placed into a gastrectomy after bile duct ligation. Similar groups of sham-operated pigs were also prepared. After 48 hours, all saline-, famotidine-, or misoprostol-treated pigs showed severe macroscopic ulceration, whereas only two of those treated with sucralfate showed minimal macroscopic ulceration. Until now, only highly selective vagotomy has reduced ulceration caused by bile duct ligation. The present results suggest that acid inhibition is not the only important factor in healing bile duct ligation-induced peptic ulceration.

Alprostadil↗

[Clinical pathology of the glomerulus--from phenomenon to entity. The mesangial lesion].

The numerous findings discussed lead to the following conclusions: 1. The mesangial lesions, which may take a wide range of different forms, can be classified into two groups according to whether an underlying immunological pathomechanism is involved. Those that result from such a pathomechanism represent various types of glomerulonephritis. 2. Amongst these immunologically-mediated glomerulonephritides mesangioproliferative glomerulonephritis (and, of this group, IgA nephritis) is the most common. Membranoproliferative glomerulonephritis is the most severe of these diseases. Either may be idiopathic or secondary, or may occur in association with systemic disease. 3. The number of macrophages in the mesangial lesions in glomerulonephritis correlates with the severity of the glomerulonephritis, the localization of the immune complex deposits and the degree of proteinuria. If the immune complex deposits extend out of the mesangium into the subendothelial space, the number of macrophages is higher, the structural changes are more marked, and proteinuria is more severe. 4. Various pathomechanisms and nosologic entities can lead to mesangial lesions of the type seen in mesangioproliferative glomerulonephritis or membranoproliferative glomerulonephritis. On the other hand, the same entity may be associated with mesangial lesions of different severity, and consequently the prognosis varies. Differential diagnosis of the mesangial lesions, which represent heterogeneous nosologic entities, requires the use of light microscopic, immunohistochemical, and electron microscopic techniques. Exact diagnosis is necessary because of the differences in prognosis. 5. The course and prognosis of mesangial lesions are determined by immunological and nonimmunological factors. Long-term studies have demonstrated that prognostically relevant information can already be gained at the time of biopsy by the assessment of certain morphological features (e.g., immunohistological findings, severity of glomerulonephritis, the presence of focal/segmental lesions) and clinical parameters (e.g., proteinuria, hematuria, hypertension, and serum creatinine concentration). The decisive predictor of an unfavorable prognosis is the presence of interstitial fibrosis.

Glomerular Mesangium↗

Catalytic activities of alkaline phosphatase and N-acetyl-beta-D-glucosaminidase in human cortical nephron segments: heterogeneous changes in acute renal failure and acute rejection following kidney allotransplantation.

The catalytic activities of alkaline phosphatase and N-acetyl-beta-D-glucosaminidase, constituents of luminal brush-border membranes and lysosomes of kidney tubular cells, were measured in human kidney allografts in the maintenance and recovery phases of acute renal failure and in acute rejection crisis. The enzyme activities were fluorometrically determined in single microdissected cortical nephron segments of biopsies from 4 kidney allografts taken intraoperatively and postoperatively at different periods, which exhibited either good function or dysfunction. For comparison, the unaffected part of a human kidney nephrectomized due to hypernephroma as well as a biopsy of a morphologically normal human kidney were examined. Both enzymes displayed highest activities in the proximal part of the human nephron. In some intraoperative and postoperative biopsies with acute renal failure, alkaline phosphatase activity was reduced in proximal tubules, predominantly in the straight portion. This reduction could not be correlated with function. In acute rejection, very low alkaline phosphatase activities were uniformly found in proximal convoluted and straight tubules. Furthermore, intraoperative biopsies and biopsies of the functioning allograft have only approximately 50% of normal N-acetyl-beta-D-glucosaminidase activity in proximal convoluted tubules, but generally normal values in the straight portion. However, in acute renal failure, this enzyme activity was several-fold enhanced along the whole nephron, when compared with intraoperative values. In acute rejection, N-acetyl-beta-D-glucosaminidase activity was slightly reduced in proximal convoluted tubules, when compared with biopsies showing good function. It is suggested that the decrease of proximal tubular enzyme activities is the consequence of increased enzymuria and inadequate enzyme regeneration. On the other hand, the overshoot of N-acetyl-beta-D-glucosaminidase activity in the maintenance phase of acute renal failure appears to indicate increased degradative capacity, associated with cellular regeneration along the whole nephron.

Acetylglucosaminidase↗

Altered distribution pattern of Na+-K+-ATPase and succinate dehydrogenase activities along the nephron in human acute post-transplant renal failure.

The catalytic activities of Na+-K+-ATPase and succinate dehydrogenase, marker enzymes for active salt reabsorptive capacity of renal basolateral plasma membranes and for respiratory capacity of mitochondrial cristae membranes, were studied in the maintenance phase of human acute post-transplant renal failure. Biopsies of 4 kidney-allografts taken at transplantation operation and additionally at different post-transplantation periods, either with good function or in various stages of dysfunction, were compared with the unaffected part of a human kidney nephrectomized due to hypernephroma. In single nephron segments, Na+-K+-ATPase activity was determined after microdissection by microfluorometry, and succinate dehydrogenase activity was determined by a microphotometric procedure in stained cryosections. In intraoperative and postoperative biopsies of a well-functioning allograft, both Na+-K+-ATPase and succinate dehydrogenase activities did not differ from those of normal renal tissue. In contrast, the catalytic activities were found to be decreased in the distal tubules of 2 anuric allografts when compared with their intraoperative controls. In addition, succinate dehydrogenase activity was reduced in distal tubules of a recovering allograft. Catalytic activities appeared to be unaffected in glomeruli, proximal tubules, and collecting ducts. It is suggested that the predominant distal tubular alterations with regard to these parameters are a consequence of increased distal tubular vulnerability due to circulatory and metabolic conditions.

Acute Kidney Injury↗

[Bacterial urinary tract infections in nephropathies caused by analgesics. Clinico-pathologic correlations].

The clinical findings and past history with regard to bacterial urinary infection were correlated with the morbid-anatomical findings in 51 cases of analgesic nephropathy, confirmed clinically and histologically. Light-microscopy and immunohistology indicated that clinical and morphological findings agreed in 64.7%. In 23.5% of cases there was evidence of destruction without any history of urinary tract infection, while in 11.8% there was no destruction even after urinary tract infections. Clinical findings and morphological results were thus complementary in that the incidence of bacterial urinary tract infection with renal involvement was definitely higher in analgesic nephropathy than on isolated assessment by clinical means or histology alone.

Adult↗

Unchanged glycolytic capacity in rat kidney under conditions of stimulated gluconeogenesis. Determination of phosphofructokinase and pyruvate kinase in microdissected nephron segments of fasted and acidotic animals.

The glycolytic capacity in rat kidney was studied under conditions of stimulated gluconeogenesis like 48 h starvation and 48 h acidosis induced by force-feeding with a NH4Cl/glucose solution. Rats fed ad libitum and force-fed with a glucose solution served as controls. The specific activities of the key enzymes phosphofructokinase and pyruvate kinase were determined in single segments of the nephron. The determinations were performed by microdissection of lyophilized tissue sections followed by enzymatic analysis, including oil well technique, enzymatic amplification, and fluorometric measurement. In the distal portion of the nephron of both fed and force-fed animals a 10-fold higher specific activity of phosphofructokinase and pyruvate kinase was found compared with the proximal portion, known as the site of renal gluconeogenesis. Starvation and acidosis altered neither the distribution pattern nor the specific activities of these enzymes. From these results it is concluded that renal glycolysis does not undergo alterations at the level of enzymatic activities in favour of renal gluconeogenesis, probably because of the separate localization of both pathways within the nephron.

Acidosis↗

Carbohydrate metabolism in rat kidney: heterogeneous distribution of glycolytic and gluconeogenic key enzymes.

The distribution pattern of the unidirectional enzymes of gluconeogenesis and glycolysis, fructose-1,6-bisphosphatase (EC 3.1.3.11) and phosphofructokinase (EC 2.7.1.11), within the nephron was studied by the microdissection and oil-well techniques according to LOWRY and PASSONNEAU [11]. Fructose-1,6-bisphosphatase activity was found to be highest in the proximal convolution, whereas phosphofructokinase revealed its highest activity in the thick ascending limb of Henle's loop. Starvation and NH4Cl acidosis led to an increase of fructose-1,6-bisphosphatase activity in the proximal convolution. These results indicate a clear separation of the glucose synthesizing and degrading pathways within the nephron, which is maintained in conditions that stimulate gluconeogenesis.

Acidosis, Renal Tubular↗