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Biomedical subjects

M Aprahamian

Publications and source records attributed to M Aprahamian.

At least 37 records · Page 2Linked to original sources
PubMed1993

Trophic and enzymatic adaptation of the intestine to biliopancreatic bypass in the rat.

Biliopancreatic bypass (BPB), the exclusion of a duodenojejunal loop from the digestive continuity, has been proposed as a bariatric procedure for treatment of morbid obesity. The present study in rats investigated the effect of this surgical procedure on the mucosae of the ileum directly anastomosed to the stomach, and of the jejunum irrigated only by biliopancreatic secretions. The proximal part of the ileum adapted by two-fold increases in its mucosal mass, total protein and RNA content; DNA content was four-fold higher than in sham-operated animals. There was a correlated increase of mucosal enzyme content, except for lactase. In the distal ileal mucosae, a slight, transient augmentation of mucosal mass, protein, DNA and RNA content was observed which tended to compensate for the shortening of the functional gut. No morphological changes were found in the excluded loop, probably because of an endoluminal stimulation by biliopancreatic secretions. Thus, in BPB, biliopancreatic secretions seem to exert trophic effects on the intestinal mucosa, but they are less potent than the endoluminal nutrition that restores the oral-aboral mucosal gradient.

Adaptation, Physiological↗
PubMed1993

Distribution of pheophorbide A in normal tissues and in an experimental pancreatic cancer in rats.

The in vivo administration and distribution of a potent new photosensitizer, pheophorbide A (PH-A), was investigated in rats. The spectral characteristics were determined. This hydrophobic compound was solubilized by an ethanol/phosphate-buffered saline (PBS) mixture (v/v) and sonicated immediately before i.v. administration. Tissue distribution and the affinity of PH-A for an acinar pancreatic tumor were determined in Lewis rats for up to 48 h after a single i.v. administration of 3 mg kg-1 body wt. Methanol-extracted PH-A was quantitatively determined by fluorescence spectrophotometry at 665.6 nm. The PH-A uptake pattern showed that the reticulo-endothelial system is the major target of PH-A, followed by the gut and then the lung and pancreas. PH-A concentrations in skin were very low. The presence of an enterohepatic cycle was suggested by the PH-A biliary output, intestinal uptake and blood concentrations. Tumor PH-A retention was longer than pancreatic retention. The ratio of tumoral to peri-tumoral pancreas PH-A was 6.7:1, 24 h after i.v. administration. With its similar tissue pattern, better absorption spectrum and lower skin toxicity, PH-A could be a more potent photosensitizer than hematoporphyrin derivatives.

Animals↗
PubMed1992

Diffusion properties of an artificial membrane used for Langerhans islets encapsulation: an in vitro test.

Glucose and insulin permeability of an artificial membrane (AN69, HOSPAL, Sweden) used for Langerhans islets encapsulation were investigated. In vivo, a 1 and 7 d intraperitoneal implantation of the AN69 membrane in rats induced a loss of permeability towards glucose and insulin probably due to a protein-coating performed after implantation. In vitro, a protein-coating of the AN69 membrane with fetal calf serum solution reproduced similar results. Thus this in vitro test which mimicks in vivo conditions should be proposed to evaluate rapidly the physicochemical properties of a membrane suitable for pancreatic islets encapsulation.

Acrylic Resins↗
PubMed1992

In vitro resistance of artificial connective tissues to human bile and pancreatic juice.

The resistance of connective tissue generated from elastin, placenta extracts and human collagen was tested by in vitro incubation with bile and pancreatic juice to investigate the potential use in human digestive surgery. The resistance, determined by macroscopical and microscopical examinations, has been directly compared to those of bovine collagen matrices (Spongel, Pangen, Helistat, Translagen). Only the compact and cross-linked human collagen patch resisted both bile and pancreatic juice. All other biomaterials tested dissolved either in bile or in pancreatic juice. The in vivo behaviour of this new human collagen matrix and its involvement in gastrointestinal wound healing must now be investigated.

Animals↗
PubMed1991

[Photodynamic therapy in oncological digestive tract surgery].

Photodynamic therapy is a useful new antitumoral treatment, since it is relatively selective and noniatrogenic. The photosensitizers become preferentially localized in the tumoral tissue, where their excitation by light causes the production of free cytotoxic radicals. If haematoporphyrin derivatives are the most widely used photosensitizers, numerous molecules are being tested. Now used as a palliative photodynamic therapy could logically be used as adjuvant treatment in curative surgical excision. The practical utility of peroperative photodynamic therapy in gastroenterological surgery is being evaluated experimentally and clinically.

Chlorophyll↗
PubMed1991

Effect of prolonged administration of long-acting somatostatin on caerulein, CCK-8 and GRP induced pancreatic growth in the rat.

This work investigates the effects of the long-acting somatostatin analogue, octreotide also named SMS 201-995 or Sandostatin, on pancreatic growth in function of the dose and duration of treatment. Octreotide was administered s.c. twice daily, while pancreatico-trophic peptides, caerulein and CCK-8 (1.8 nmol/kg b.wt.) or GRP (3.6 nmol/kg b.wt.) were administered s.c. three times daily. Octreotide (1,10,20 micrograms/kg b.wt.) administered for 4 days reduced pancreatic growth induced by caerulein in a dose-dependent manner. This effect, significant from 10 micrograms/kg, was more obvious with 20 micrograms/kg. At this latter dose, octreotide inhibited significantly the increase in pancreatic weight and protein, RNA, DNA and enzyme content induced by a 4- or 10-day treatment with GRP. A similar effect was observed after a 4-day treatment with CCK-8, but after a 10-day treatment only protein and enzyme contents were reduced. Octreotide by itself did not affect pancreatic size and composition after a 10-day treatment, but decreased enzyme content after a 4-day treatment. It is concluded that octreotide exerts an antitrophic effect on the rat exocrine pancreas which depends on the dose and duration of treatment and can be modulated by the trophic factor applied for a long-term.

Amylases↗
PubMed1991

Prevention of anastomosis leakage: an artificial connective tissue.

Anastomosis leakage still causes considerable morbidity and mortality after digestive tract surgery. We report here our experience of the use of reconstituted connective tissue created from elastin, fibronectin and collagen in preventing anastomosis leakage and closing intestinal fistulas. In animal studies (56 rats), this connective tissue was used as a patch applied with fibrin sealant to the edges of a 1 cm diameter colonic defect. In a clinical evaluation, eight patients had an intestinal fistula closed by a simple sewn suture reinforced by a sealed patch and seven patients had a high risk anastomosis reinforced by a sealed patch, in most cases as an alternative to staged surgery. In animal studies, complete reconstitution of the three colonic layers was obtained without retraction and without inflammatory reaction within 40 days, while the patch was slowly resorbed. In clinical trials all 15 defects and anastomoses healed without complication. Three patients died from other causes and, at autopsy, the patch was found to have remained in place covering the suture line. If these results are confirmed by a prospective clinical trial, such biomaterial offers the possibility of reducing the occurrence of anastomosis leakage, especially in high risk circumstances.

Adult↗
PubMed1991

Inhibition of the growth of transplanted rat pancreatic acinar carcinoma with octreotide.

The effects of octreotide on transplanted azaserine-induced pancreatic acinar tumours were investigated in the rat. When tumours became palpable, rats were treated either with octreotide (40 micrograms/kg per day, by infusion) or NaCl 0.9% (controls) for 14 days. Tumours were then analysed for their size, composition and somatostatin receptors. Octreotide induced a 80% reduction in tumour growth rate during the first 2 days of treatment. This rate was less marked from day 4 to day 15. The tumour weight, protein, DNA, RNA and enzyme content were reduced in parallel by 50 to 60%. A homogeneous distribution density and a high affinity of somatostatin receptors were found by receptor autoradiography and in vitro binding assays in tumours of both groups. These findings indicate that octreotide reduces the growth rate of the transplanted pancreatic acinar tumour and may exert its inhibitory effect directly via specific somatostatin receptors on tumour cells.

Animals↗
PubMed1991

In vitro and in vivo studies of the properties of an artificial membrane for pancreatic islet encapsulation.

Encapsulation of pancreatic islets with an artificial membrane has been proposed as a means of immunoprotection after transplantation. Such a membrane should be biocompatible, nondegradable, and should allow the passage of insulin and glucose while preventing that of antibodies and lymphocytes. Thus, we have studied in vitro and in vivo, the characteristics of an acrylonitrile membrane (AN69, HOSPAL, Sweden) for islet encapsulation. The AN69 membrane composed of a fiber network with a porous structure, allowed a satisfactory passage of glucose (75% of the initial amount within one hour) but not of insulin (only 7%). The morphological state of rat islets cultured on membranes under both conditions for 2 weeks was similar to that of islets cultured on dishes; in addition rat fibroblasts retracted after a 3-day culture. Finally, the membrane was unaltered after a 12 month implantation in the peritoneal cavity of rats. When the surface properties of the AN69 membrane were changed by adsorption of a hydrophilic copolymer or by protein coating, the permeability of the membrane was modified. Glucose and insulin diffusion were significantly decreased after protein-coating, whereas glucose diffusion was preserved and that of insulin doubled after adsorption of a copolymer onto the membrane. In addition, after a 12-month implantation in the rat, the membrane surface treated by the copolymer was altered leading to the adhesion of macrophages. In conclusion, the AN69 acrylonitrile membrane may be useful for pancreatic islet encapsulation; its insulin permeability should be increased by a surface treatment aimed at increasing its hydrophilic properties. However the stability of this treatment seems to be an important factor in preserving the biocompatibility of the membrane.

Acrylonitrile↗
PubMed1991

The effect of site of administration in the gastrointestinal tract on the absorption of insulin from nanocapsules in diabetic rats.

Isobutylcyanoacrylate nanocapsules have been used as drug carriers for the enteral absorption of insulin. Their absorption has been studied by measuring fasted glycaemia in streptozotocin-induced diabetic rats after a single administration of encapsulated insulin (100 units kg-1) at various sites along the gastrointestinal tract. Glycaemia decreased from the second day, the intensity and duration depending on the site of administration (65% ileum, 59% stomach, 52% duodenum and jejunum, 34% colon). This hypoglycaemic effect lasted up to the 18th day after administration for ileum and jejunum, the 15th day for stomach and duodenum, and the 13th day for colon. In-vitro, nanocapsules protect insulin against proteolysis from pepsin, chymotrypsin and trypsin. These results suggest (i) that insulin is protected by nanocapsules in the gastrointestinal tract, (ii) that it is absorbed in an active form, and (iii) that ileum is the most potent site of absorption.

Animals↗
PubMed1991

Malnutrition and body weight loss after biliopancreatic bypass in the rat.

In this study designed to investigate the nutritional state induced by biliopancreatic bypass in the rat, the pancreatico-biliary secretions were diverted via the duodenum and jejunum into the distal ileum, the remaining intestine being directly anastomosed to the stomach after antrectomy. Bypassed animals lost weight: it was only 56 percent of that of controls after 36 days and death by cachexia resulted within two months of the procedure. The reduced food intake (16 percent less than control) at the 36th postoperative day cannot by itself explain the weight loss, since pair-fed rat weights did not differ statistically from controls at 36 days. Protein-energy malabsorption occurred: drops in serum protein concentration (25 percent less than control), triglycerides (40 percent less) and total cholesterol (28 percent less) were recorded from the 12th postoperative day on. Biliopancreatic bypass may be an adequate procedure of treatment for morbid obesity simultaneously aggravated by metabolic disorders.

Analysis of Variance↗
PubMed1990

[Improvement in the healing of colonic anastomoses by vitamin B5 and C supplements. Experimental study in the rabbit].

To study the effects of vitamins B5 and C on the healing process of colonic anastomoses, 3 groups of 20 rabbits were given daily either placebo (group A), or vitamin B5 (100 mg/kg: group B) or vitamin C (100 mg/kg: group C). After 8 days of supplementation, via a midline incision and under general anaesthesia, 2 colonic segments were removed, and the continuity was restored. On the 3rd post-operative day, the rabbits were killed and the anastomoses were removed. Mechanical properties of both normal colon and anastomoses were determined by using bursting pressure tests, number of burst anastomoses, fibroblast count, hydroxyproline concentration and determination by microanalysis of trace element content: Mg, P, S, Ca, Fe, Cu, Zn and Mn. Vitamin B5 (p = 0.03) and vitamin C (p less than 0.01) both decreased the number of burst anastomoses. Furthermore the required bursting pressure values were higher with vitamin C (p = 0.01) than in controls. Both vitamins restored normal Zn levels at the anastomotic site, whereas these levels decreased on the 3rd post-operative day during the normal healing process of colonic anastomosis. Moreover, vitamins B5 and C increased Fe, Cu and Mn levels, which are intimately all involved in collagen synthesis. Vitamins B5 and C enhance the colonic wound healing process in the rabbit, acting together in synergy in vivo as well as in vitro, as previously demonstrated.

Anastomosis, Surgical↗
PubMed1989

Repair of experimental arteriotomy in rabbit aorta using a new resorbable elastin-fibrin biomaterial.

A new artificial connective matrix which results from two reactions of fibrinogen and fibronectin on elastin was used to obturate a slit made in the abdominal aorta of rabbit. The so-called Elastin-Fibrin biomaterial behaved as a scaffold through which all the different structures were restored to their former condition. At 3 months, the material had disappeared and no thrombus, no inflammation or reject had been detected.

Animals↗
PubMed1989

Some factors affecting properties of elastin-fibrin biomaterial.

The elasticity, mechanical strength and permeability of a new biomaterial made of elastin and fibrin were investigated. It was shown that gamma-irradiation to sterilize the product, and sulphur derivatives (Merceptyl, thiourea, cystein) working as reticulating agents modified these properties. Depending on whether or not the biomaterial needs to be stiff, strong or elastic both physical processes could intervene separately or together. The good permeability of this material allows it to be used in several surgical fields as a true artificial connective matrix.

Biocompatible Materials↗
PubMed1989

Evidence for a direct trophic effect of bombesin on the mouse pancreas: in vivo and cell culture studies.

The present work studied the effect of chronic bombesin on the mouse pancreas and analyzed whether or not this effect was direct. Bombesin administered s.c. 3 times daily for 4 days at various concentrations (0.1, 1, 10, 20 micrograms/kg b. wt.) induced pancreatic growth in a dose-dependent manner. This growth was characterized by an increase in pancreatic weight, its protein and RNA contents suggesting cellular hypertrophy. Pancreatic enzyme content was also increased, especially for amylase (14-fold) and at a lesser degree for chymotrypsin and lipase (2.5-fold). The DNA content of the gland increased significantly after a 1 microgram/kg bombesin treatment suggesting hyperplasia. [3H]thymidine incorporation into DNA increased slightly from 24 h after the first bombesin injection and more obviously at 72 and 96 h indicating DNA synthesis. To determine the direct effect of bombesin on pancreatic acinar cell growth cells were cultured as monolayers on collagen gels in media lacking added hormones and containing 2.5% FBS with or without bombesin (1 microM-1 nM) or caerulein (10 nM). [3H]thymidine incorporation into DNA was increased by caerulein (10 nM) and bombesin (100 nM and 1 microM). Therefore, it is concluded that bombesin is a pancreaticotrophic peptide in mice. Moreover, it is suggested that this effect occurs directly on pancreatic cells.

Amylases↗
PubMed1989

Effect of a new CCK-receptor antagonist, CR 1409, on pancreatic growth induced by caerulein, CCK-8, bombesin and gastrin-releasing peptide in the rat.

The effect of a peripheral cholecystokinin (CCK)-receptor antagonist, CR 1409, on pancreatic growth has been studied in the rat. 1.8 nmol/kg CCK-8 or caerulein and 3.6 nmol/kg bombesin or gastrin-releasing peptide (GRP) administered subcutaneously 3 times daily for 4 successive days increased pancreatic weight and its content in protein, enzymes and RNA but not in DNA, suggesting cellular hypertrophy. CR 1409 (10 mg/kg) administered intragastrically 30 min prior to peptides prevented pancreatic growth due to CCK-8 or caerulein but not that induced by bombesin and GRP. It is concluded that bombesin and GRP act on the exocrine pancreas directly rather than through the release of CCK.

Animals↗