Effects of exogenous insulin, glucagon, and somatostatin on islet hormone secretion in the perfused chicken pancreas

The effects of exogenous insulin were examined in the isolated perfused chicken pancreas with the duodenum excluded. At low background glucose (50 mg/dl), exogenous insulin infused at a concentration of 20,000 microU/ml elicited clear stimulation of somatostatin secretion while simultaneously inhibiting glucagon release. When the background glucose concentration was elevated to 750 mg/dl, exogenous insulin, had no effect on either somatostatin or glucagon release. When graded doses of exogenous insulin were infused into the chicken pancreas at low background glucose, low concentrations (200 microU/ml) had little effect on somatostatin or glucagon release, but higher concentrations (2000 and 20,000 microU/ml) had clear effects on both somatostatin and glucagon secretion. Glucagon infused at 100 ng/ml stimulated both insulin and somatostatin release. When somatostatin was infused at 25 ng/ml, clear inhibition of glucagon was seen with insulin inhibited to a lesser extent. This study supports the notion of a negative feedback relation between B and D-cells of the pancreatic islets and suggests a paracrine mediation.     

A genetic association study of D-dimer levels with 50 K SNPs from a candidate gene chip in four ethnic groups

Introduction

D-dimer, a fibrin degradation product, is related to risk of cardiovascular disease and venous thromboembolism. Genetic determinants of D-dimer are not well characterized; notably, few data have been reported for African American (AA), Asian, and Hispanic populations.

Materials and Methods

We conducted a large-scale candidate gene association study to identify variants in genes associated with D-dimer levels in multi-ethnic populations. Four cohorts, comprising 6,848 European Americans (EAs), 2,192 AAs, 670 Asians, and 1,286 Hispanics in the National Heart, Lung, and Blood Institute Candidate Gene Association Resource consortium, were assembled. Approximately 50,000 genotyped single nucleotide polymorphisms (SNPs) in 2,000 cardiovascular disease gene loci were analyzed by linear regression, adjusting for age, sex, study site, and principal components in each cohort and ethnic group. Results across studies were combined within each ethnic group by meta-analysis.

Results

Twelve SNPs in coagulation factor V (F5) and 3 SNPs in the fibrinogen alpha chain (FGA) were significantly associated with D-dimer level in EAs with p < 2.0 × 10^− 6. The signal for the most associated SNP in F5 (rs6025, factor V Leiden) was replicated in Hispanics (p = 0.023), while that for the top functional SNP in FGA (rs6050) was replicated in AAs (p = 0.006). No additional SNPs were significantly associated with D-dimer.

Conclusions

Our study replicated previously reported associations of D-dimer with SNPs in F5 and FGA in EAs; we demonstrated replication of the association of D-dimer with FGA rs6050 in AAs and the factor V Leiden variant in Hispanics.     

Metabolic changes in the rat anterior pituitary and prolactin production following estradiol treatment

The effects of estradiol treatment on the synthesis and release of prolactin and GH in castrated male rats were studied in connection with the anterior pituitary enzymes that represent the hexosemonophosphate shunt, glycolytic, oxidative, and lysosomal activity. LDH and G6P-DH activities increased by 15%–30% at 12 hr and by 70% at 72 hr after estrogen administration. PK activity showed a statistically significant elevation of 20%–40% only after 48–72 hr. ICDH, MDH, acid phosphatase activities, and water-soluble protein concentrations were unchanged. Serum prolactin concentration increased about 400% 24 hr after estradiol injection, and the pituitary synthesized 1000%–1500% more radioactive prolactin in vitro than did control glands. However, no significant increase in prolactin synthesis was observed 12 hr after estradiol treatment.It is suggested that the primary effect of estradiol is on the synthesis of prolactin and that the increased rate of secretion is secondary. Radioimmunoassayable prolactin in the incubated gland tissue and its medium was greatly increased after estradiol treatment. A slight but statistically significant accumulation and decreased release of radioactive GH were also observed. The results suggest a correlation of pituitary prolactin production with the tissue's metabolic activity.     

Pacemaker pseudodysfunction with a coronary sinus pacemaker

A permanent transvenous coronary sinus pacemaker functioned effectively for 22 months both as an atrial and ventricular pacemaker. Slow atrial flutter resulted in failure of the pacemaker to capture the myocardium and thus incorrectly suggested pacemaker dysfunction. Transtelephonic evaluation of this phenomenon was particularly difficult and could have resulted in unnecessary replacement of the pacing unit     

Apparent coexistent valvular and subvalvular left ventricular outflow tract obstruction.

A patient is presented in whom coexisting bicuspid valvular aortic stenosis and asymmetrical septal hypertrophy were suggested by echocardiography. A focal area of hypertrophy noted at operation was excised. Subsequent histological examination did not reveal evidence to support the echographic and surgical observations. The necessity for careful intraoperative assessment of the degree and nature of subvalvular muscular hypertrophy is stressed. The absence of classic echographic findings in these patients is noted.     

Field potential and single unit analyses of the avian dorsal motor nucleus of the vagus and criteria for identifying vagal cardiac cells of origin

The compound action potential components and their associated fiber contingents were investigated in the pigeon vagus nerve with a view toward identifying the vagal cardioinhibitory fibers. In the cervical vagus, the compound action potential evoked by electrical stimulation included four major components that conducted at 17.0-30.0 (A-wave), 8.0-14.5 (B2-wave) and 0.8-2.0 (C-wave) m/sec. Cardiac slowing was not elicited until activation of the Bl-wave, and the bradycardic response was maximal when this component was maximized. Electron microscopic analysis of the cervical vagus revealed myelinated fibers 1.1-6.8 micron in diameter and unmyelinated fibers 0.3-1.4 micron in diameter. A contingent of myelinated fibers approximately 2-4 micron in diameter apparently generated the Bl-wave, while the prominent unmyelinated fiber contingent (37%) accounted for the C-wave. Analysis of various vagal branches indicated that approximatley 20% of the cervical vagal fibers exit the main trunk between cervical and mid-thoracic levels, but few of these are the larger myelinated fibers greater than 2 micron in diameter. The upper abdominal vagus consists largely of unmyelinated and small myelinated fibers, and consequently the vast majority of larger myelinated fibers found in the cervical vagus exit between mid-thoracic and upper abdominal levels, presumably in the cardiac branches. Direct examination of the cardiac branches confirmed this. Thus, it is concluded that the Bl-wave of the compound action potential is uniquely associated with cardiac slowing, that this component is generated by myelinated fibers ranging from 2 to 4 micron in diameter, and that almost all such fibers are destined for the cardiac branches of the vagus.     

Mount St. Helens' volcanic ash: hemolytic activity

Volcanic ash samples from four Mount St. Helens' volcanic eruptions were subjected to mineralogical, analytical, and hemolytic studies in order to evaluate their potential for cytotoxicity and fibrogenicity. Plagioclase minerals constituted the major component of the ash with free crystalline silica concentrations ranging from 1.5 to 7.2%. The in vitro hemolytic activity of the volcanic ash was compared to similar concentrations of cytotoxic and inert minerals. The ash was markedly hemolytic, exhibiting an activity similar to chrysotile asbestos, a known fibrogenic agent. The hemolysis of the different ash samples varied with particle size but not with crystalline silica concentration. The results of these studies taken in conjunction with the results of our animal studies indicate a fibrogenic potential of volcanic ash in heavily exposed humans.     

Early asymptomatic lead exposure and development at school age.

Sixty-seven 7-year-old children, who had asymptomatic lead exposure between 1 and 3 years of age, were compared in their performance on a series of psychologic tests to 70 children of the same age and socioeconomic background who presumably did not have significant exposure to lead. Exposed children had deficits in global IQ and associative abilities, in visual and fine motor coordination, and in behavior. School failure due to learning and behavior problems was more frequent in the lead exposed than in the control group.