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Biomedical subjects

M Saffran

Publications and source records attributed to M Saffran.

At least 19 recordsLinked to original sources
PubMed2000

Evidence for biosynthesis of preproinsulin in gut of rat.

Glucagon and other pancreatic peptides are made in the gut, but there is little evidence for the formation of insulin. The demonstration of insulin receptors on the mucosa of gut epithelium suggests that there may be an autocrine or paracrine role for insulin made in the gut. Such insulin may control cell division, the secretion of other peptides from the same or neighboring cells, or motility and absorption. To search for the ability of the gut to make insulin, sections of freshly excised segments of rat gut were treated with an antiserum against porcine insulin. Intracellular immunoreactivity appeared in glandular cells in the stomach and colon but not in the small intestine. Preproinsulin mRNA was detected in similar cells in the stomach and colon by in situ hybridization, using specific oligonucleotide probes. Rat preproinsulin 1 and 2 mRNAs were transcribed by reverse transcriptase to the corresponding cDNAs, which were then amplified by polymerase chain reaction, utilizing specific oligonucleotide primers. Restriction analysis confirmed the identity of rat preproinsulin 1 and 2 mRNA in the colon and rat preproinsulin 1 mRNA in the stomach. Neither was found in the small intestine. Base sequences of the cDNAs were identical to the coding regions of pancreatic rat preproinsulin 1 and 2 messages. These observations are strong evidence for the synthesis of preproinsulin in the gut of the rat.

Animals↗
PubMed1991

Where the hormones, there moan I.

This autobiography traces the effects of "marriages" of different fields on the development of new directions of research. Such events occurred several times in my career and generated much of my research.

Endocrinology↗
PubMed1991

Oral insulin in diabetic dogs.

Bovine crystalline insulin, mixed with an absorption enhancer, was loaded by hand into gelatin capsules, which were then coated with an azopolymer designed to deliver the insulin in the upper colon. In 34 experiments with 14 pancreatectomized mongrel dogs of both sexes, the coated capsules were administered orally after a pre-dose period of 1 h. The dogs had cannulae in the portal vein, hepatic vein and femoral artery and Doppler flow probes on the portal vein and hepatic artery. Insulin and food were withdrawn the day before an experiment. Responses measured were plasma glucose, plasma insulin, hepatic glucose production rate, hepatic plasma flow rate and plasma glucagon-like immunoactivity (GLI). Control experiments, with capsules without insulin, produced small changes from 'pre-dose' values. Insulin-containing capsules, without the azopolymer coating, resulted in some early changes consistent with upper gastrointestinal absorption. Single oral doses (66 to 400 nmol/kg) of insulin in completely coated capsules produced peaks of portal plasma insulin and transient decreases in plasma glucose, hepatic glucose production, hepatic plasma flow and plasma GLI. The changes usually began 1.5-2 h after administration of a single dose, and lasted for up to 3 h, but were not significantly related to the dose of insulin. Multiple oral doses of insulin, given at 1.5-h intervals, resulted in multiple peaks of plasma insulin, a continuing dose-dependent fall in plasma glucose to near-euglycaemia with the highest dose, and profound decreases in hepatic glucose production and plasma GLI. These data demonstrate that insulin absorbed from the gastrointestinal tract causes changes in glucose metabolism in the diabetic dog that are consistent with the action of insulin primarily on the liver and that repeated oral doses are necessary to correct the hyperglycaemia.

Administration, Oral↗
PubMed1988

Vasopressin: a model for the study of effects of additives on the oral and rectal administration of peptide drugs.

We previously observed, using a relatively primitive assay, that small oral doses (on the order of 1 microgram = 1 nmol = 1000 pmol per rat) of vasopressin can produce antidiuresis in hydrated rats, and that the oral activity was enhanced by simultaneous administration of an inhibitor of intestinal proteolysis. A more sensitive semi-automated computer-linked apparatus was used to conveniently and quickly compare the antidiuretic activities of the two natural and one synthetic vasopressin peptides by several routes of administration. (The approximate dose in pmol that resulted in a 50% decrease in urine flow is indicated in square brackets.) Intravenous lysine vasopressin was used as the benchmark dose [5]. Arginine and lysine vasopressin [3500], and the synthetic analogue, 1-deamino-8-D-arginine vasopressin (DDAVP) [20], were active by oral administration. The oral activities of arginine and lysine vasopressin were always enhanced by the simultaneous administration of aprotinin [1000], a natural inhibitor of trypsin; the effect of aprotinin on the oral activity of DDAVP was inconsistent. The vasopressins were more active when administered by the rectum: arginine vasopressin [20] and DDAVP [10]. The rectal activities of the peptides were increased by the absorption adjuvant, 5-methoxysalicylate (arginine vasopressin [10]; DDAVP [0.5]). The vasopressin peptides were also delivered by mouth in an impermeable coating of an azoaromatic cross-linked polymer, which is degraded by bacteria in the colon, to release the peptides in the upper colon for absorption (lysine vasopressin [525]).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1986

A new approach to the oral administration of insulin and other peptide drugs.

The oral administration of peptide drugs is well known to be precluded by their digestion in the stomach and small intestine. As a new approach to oral delivery, peptide drugs were coated with polymers cross-linked with azoaromatic groups to form an impervious film to protect orally administered drugs from digestion in the stomach and small intestine. When the azopolymer-coated drug reached the large intestine, the indigenous microflora reduced the azo bonds, broke the cross-links, and degraded the polymer film, thereby releasing the drug into the lumen of the colon for local action or for absorption. The ability of the azopolymer coating to protect and deliver orally administered peptide drugs was demonstrated in rats with the peptide hormones vasopressin and insulin.

Administration, Oral↗
PubMed1985

A first-year, student-managed course to correlate basic sciences with clinical medicine.

A course for first-year medical students was designed to illustrate the correlation of the biochemistry and physiology content of the curriculum with clinical applications. The course included early exposure of the students to clinical problems; the use of patients in the classroom; joint teaching by clinical and basic science faculties; independent learning, reading, and evaluation of the literature; and the use of reading, writing, and communication skills. The course was begun in 1981 as a faculty-directed course, but responsibility for the course was gradually transferred to the students until the entire presentation, from introduction and interview of the patient to the correlation of the clinical application with the basic sciences, was carried out by the students.

Biochemistry↗
PubMed1985

Effects of a summer preview program of study skills and basic science topics on the academic performance of minority students.

A summer preview program was designed to enhance the academic performance of minority students in medical school. In the five-week program the students met from 8:00 AM to noon, five days a week. The two components of the program were study skills and selected basic science topics deemed critical for success in the first year.This paper is an analysis of three years (1980 to 1982 inclusive) of the program. Only three of the 14 participating minority students failed to complete the requirements of the first year of the curriculum. In contrast, nine of the 11 nonparticipating minority students did not complete the requirements for the first year. The conclusion is that the program can enhance the academic performance of minority students in the first year of the medical school curriculum.

Achievement↗
PubMed1982

Properties of CRF from normal and Brattleboro rat median eminence.

Most of the corticotrophin-releasing factor (CRF) activity of normal rat median eminence (ME) extract binds to a neurophysin affinity column. The bound material contains the large and small factors, which we have previously demonstrated to be required together for full activity. Most of the CRF activity of Brattleboro rat ME extract, which contains as much CRF activity as the ME extract of a normal rat, does not bind to a neurophysin affinity column. The CRF activity of Brattleboro rat ME extract resides entirely in a large molecule as determined by Sephadex G-25 chromatography. The different properties of Brattleboro and normal rat CRF suggest that the CRF activity in the Brattleboro rat may result from a substance which is different from that in a normal rat.

Animals↗