The behavioral activity of the thyrotropin-releasing hormone (TRH) analogue, L-6-ketopiperidine-2- carbonyl-leucyl-L-prolinamide (RGH 2202), has been studied in the rat. The number of errors in a radial maze test was reduced after acute intraperitoneal (IP) injection of RGH 2202 at the dose of 5 or 10 mg/kg. Grooming activity was increased with a lower dose, 1 mg/kg. Hypoxia-induced amnesia, as assessed with active and passive avoidance behavior tests, was reversed in rats treated with 5 or 10 mg/kg of the drug. The loss of learning and memory capacity shown by aged rats in the same behavioral tests was also reduced after injection of RGH 2202. In a test for sexual activity of male rats, the higher dose of the drug induced a facilitation of mounting and ejaculations, while smaller doses were ineffective. The rotorod test revealed a decreased number of falls in animals treated with 5 or 10 mg/kg of RGH 2202. In all behavioral tests, the same doses of natural thyrotropin-releasing hormone (TRH) were less effective, indicating that this analogue may be qualified as a potentially active drug in human pathologies.

Animals↗

PubMedDate not supplied

Effects of RGH 2202 on cognitive and motor behavior of the rat.

The behavioral activity of the thyrotropin-releasing hormone (TRH) analogue, L-6-ketopiperidine-2-carbonyl-leucyl-L-prolinamide (RGH 2202), has been studied in animal models of central neurotransmission disruption. In 24-month-old rats, repeated administration of the peptide (5 or 10 mg/kg/day, injected IP for 20 days) was followed by a facilitated acquisition of active avoidance behavior in the shuttle-box test and retention of passive avoidance reaction in a step-through passive avoidance task. Also, ambulation in an open field was increased and motor performance and co-ordination in the rotorod test was facilitated by the treatment. Scopolamine-induced amnesia was reverted by RGH 2202 in adult rats tested both in active and passive avoidance tasks. Cognitive deficits induced in rats by prenatal manipulation with methylazoxymethanol (MAM) were reduced in adulthood by repeated administration with RGH 2202. These results indicate that the TRH-analogue, RGH 2202 may improve cognitive and motor disturbances in aging or induced by central neurotransmission disruption. It is possible that the peptide is functioning, at least in part, by intervening with the central cholinergic neurotransmission.

Age Factors↗

PubMedDate not supplied

Protein immobilization in crosslinked alginate microparticles.

Oral administration of peptide and protein drugs requires their protection from the acidic and enzymatic degradation in the gastro-intestinal environment and their targeting to the absorption zone. For this purpose, an alginate microsystem, as a carrier of bovine serum albumin (BSA), as a model protein, was developed using a spray-drying technique. A hardening process with Ca2+ and chitosan (CS) provided a system with resistance to the gastro-intestinal barriers and of appropriate size for targeting to the Peyer's patches. The present work aims to evaluate the effects of the ratio of sodium alginate (Na-A) and BSA as well as the pH of the crosslinking medium on the microsystem properties. Microparticle morphological and dimensional characteristics did not change significantly with the formulation variables. BSA loading at a pH value less than the protein isoelectric point (pI) was higher than that at a pH similar to the pI owing to an electrostatic interaction between the charged protein and the polyanionic alginate. The maximum encapsulation efficiency was obtained at the highest Na-A/BSA ratio. Protein release in a simulated gastro-intestinal fluid was not affected by the preparative variables, but was controlled by the pH-dependent nature of the polymer material. Polyacrylamide gel electrophoresis (PAGE) demonstrated the stability of the protein to both the preparative conditions and the gastro-intestinal pH values.

Alginates↗

PubMedDate not supplied

Papaverine hydrochloride release from ethyl cellulose-walled microcapsules.

The mechanism of papaverine hydrochloride release from ethyl cellulose-walled microcapsules in both simulated gastric and intestinal fluid is discussed. The microcapsules were prepared by coacervation using different core: wall ratios. The rupture of the thin-walled microcapsules after release in simulated gastric fluid was shown and attributed to the internal osmotic pressure, supporting a mechanism for drug dissolution. The internal osmotic pressure produced only a few small holes in the thin-walled microcapsules after release in simulated intestinal fluid. No rupture of the thick-walled microcapsules after release in either medium was shown. Therefore these release data fitted diffusion-type kinetics. It is suggested that the internal osmotic pressure developed after penetration of the medium is affected by the ratio between the core dissolution rate and the drug diffusion rate through the wall.

Capsules↗

PubMedDate not supplied

[Thyroid metastasis of a renal carcinoma. 3 clinical cases].

The clinical finding of metastasis to the thyroid is a very rare event. When a metastasis from a renal carcinoma is diagnosed, it is usually the distant evidence of a tumour discovered and removed surgically months or years before, or it may be the first clinical sign of an as yet undiagnosed asymptomatic renal tumour. A case of massive retrosternal goiter in a 65-year-old patient, operated on for a right renal carcinoma (nephrectomy 6 years before), is reported. The goiter, causing compression symptoms and dyspnoea, was treated by total thyroidectomy. The pathological diagnosis was metastasis from renal carcinoma. The authors present a second case of nodular goiter, in a 79-year-old woman, 9 years after a right nephrectomy for a renal carcinoma. The expanding nodule, diagnosed intraoperatively as carcinoma, was treated by total thyroidectomy. The postoperative pathological diagnosis was metastasis from renal carcinoma. The authors report a third case of an expanding nodule of the thyroid, in a 65-year-old patient, diagnosed intraoperatively as a metastasis from renal carcinoma, treated by right lobectomy and isthmusectomy. An abdominal CT scan revealed a renal asymptomatic tumor, treated by right nephrectomy. The diagnosis can be established by means of fine needle aspiration biopsy preoperatively or intra- or postoperative histology. Surgical therapy may resolve the compression symptoms and improve the prognosis.

Adenocarcinoma, Clear Cell↗