Impact of single and multiple sets of resistance exercise in type 1 diabetes.

To examine glycemic and glucoregulatory responses to resistance exercise (RE) sessions of different volume in type 1 diabetes (T1DM). Eight T1DM (seven males: one female; age: 38 ± 6 years, HbA1C : 8.7 ± 1.0%/71 ± 11 mmol/mol) attended the research facility fasted and on four separate occasions, having taken their usual basal insulin, but omitted morning rapid-acting insulin. Participants completed a 1SET (14 min), 2SET (28 min), 3SET (42 min) RE session (eight exercises × 10 repetitions) at 67 ± 3% one-repetition-maximum followed by 60-min recovery, or a resting trial (CON). Venous blood samples were taken before and after exercise. Data (mean ± SEM) were analyzed using repeated-measures analysis of variance (P ≤ 0.05). RE did not induce hypoglycemia (BG < 4 mmol/L). During recovery, blood glucose (BG) concentrations remained above pre-exercise after 1SET (15-60 min, P < 0.05) and 2SET (0-60 min, P < 0.05) but comparable (P > 0.05) with pre-exercise after 3SET. BGIAUC(area-under-curve) (mmol/L/60 min) was greater after 1SET and 2SET vs CON (1SET 103.6 ± 36.9 and 2SET 128.7 ± 26.1 vs CON -24.3 ± 15.2, P < 0.05), but similar between 3SET and CON (3SET 40.7 ± 59.3, P > 0.05). Under all trials, plasma creatine kinase levels at 24 h post-exercise were similar (P > 0.05) to pre-exercise. RE does not induce acute hypoglycemia or damage muscle. BG progressively rose after one and two sets of RE. However, inclusion of a third set attenuated exercise-induced hyperglycemia and returned BG to that of a non-exercise trial.

The helical content of zein, a water insoluble protein, in non-aqueous solvents.

The conformation of zein, a seed protein from corn, was determined by optical rotary dispersion measurements in a wide variety of nonaqueous solvents. Over a wide range of dielectric constants, in pure and mixed solvent systems, the helical content was independent of dielectric constant. Determination of the helical content of insulin and ribonuclease in several of these solvents indicated a variation in secondary structure comparable of that of zein. Though virtually insoluble in water, zein not only is a globular protein in nonaqueous solutions, but has conformational properites characteristic of more conventionally behaving globular proteins.

Hyperprolactinemia--a review of recent clinical advances.

Since the radioimmunoassay for serum prolactin became available eight years ago, prolactin has become a hormone of considerable clinical interest. An elevated serum prolactin concentration is the most frequent hormone marker for pituitary tumors. Secreted in excess, prolactin causes dysfunction of the hypothalamic-pituitary axis, the gonads, and the adrenal cortex. In women, menstrual disturbances, galactorrhea, infertility, and hirsutism result. Impotence, oligospermia, and decreased libido are common in men. These metabolic abnormalities attributed to prolactin excess are corrected when prolactin concentrations are lowered by either medical or surgical therapy. The availability of effective therapy mandates early recognition and proper management of the patient with hyperprolactinemia.

Oat-bran intake selectively lowers serum low-density lipoprotein cholesterol concentrations of hypercholesterolemic men.

To evaluate selected metabolic effects of plant fibers, we fed control and oat-bran diets in an alternating sequence to eight men with previously documented hypercholesterolemia. The two solid diets differed only in the inclusion of 100 g of oat bran in the test diet. We randomized diet sequences and the measured intakes of carbohydrate, protein, fat, and cholesterol were virtually identical on the two diets. Serum total cholesterol concentrations were stable on control diets whereas a progressive reduction was observed in seven men on oat-bran diets. On oat-bran diets, average reductions in serum total cholesterol concentrations were 13% (p less than 0.01, N = 8); plasma low-density lipoprotein cholesterol concentrations were 14% lower (p less than 0.05) while high-density lipoprotein cholesterol concentrations were not changed. Fasting and postprandial serum glucose, insulin, and triglyceride concentrations were similar on the two diets. Fecal excretion of total bile acids was 54% higher (p less than 0.001) on oat-bran diets than on control diets but neutral steroid excretion was slightly lower while on oat bran. Palatable and inexpensive high-fiber foods such as oat bran may have a role in the treatment of certain patients with hypercholesterolemia.

Halofenate in the treatment of type II hyperlipoproteinemia. Double blind comparison with clofibrate.

A double-blind study comparing halofenate, a new lipid-lowering investigation drug, with an established drug, clofibrate, was conducted on 33 clinic patients with Type II hyperlipoproteinemia for a period of 48-96 weeks. All but 10 patients had some type of symptomatic major vascular disease. With respect to serum cholesterol levels, a comparable proportion (56-59%) of patients in each group responded to the respective treatment but the magnitude of lowering was substantially less for the halofenate responders (12% mean decrease versus 25%). Type IIa patients in both groups were more likely than Type IIb patients to have a favorable cholesterol-lowering response. Weight gain of 5% or greater was prejudicial to cholesterol lowering. In the case of serum triglycerides, the proportion of patients responding to clofibrate treatment was somewhat greater (87% versus 57% for halofenate) but the mean magnitude of lowering (27-34%) was comparable for responders in the two groups. Weight gain did not influence appreciably the triglyceride-lowering effect. Elevated concentrations of triglyceride (Type IIb) in the control period favored a triglyceride lowering response by clofibrate but was only a moderate influence on the response to halofenate.

Estradiol and progesterone binding in uterine leiomyomata and in normal uterine tissues.

To explain the sensitivity of uterine leiomyomata to endogenous and exogenous estrogens, specific cytosol receptor proteins for estradiol-17 beta and progesterone were found in tissue from uterine leiomyomata and compared with the concentrations of receptors in normal myometrium and endometrium from the same patient. The concentration of cytoplasmic estrogen receptors in leiomyomata (40.5 +/- 7.6 cytoplasmic estrogen receptors in leiomyomata (40.5 +/- 7.6 fmole/mg cytosol proteins, mean +/- SEM) was significantly greater than that found in myometrium (16.5 +/- 1.5) and significantly less than that found in endometrium (131 +/- 15.1). The concentration in leiomyomata of cytoplasmic progesterone receptors (104.4 +/- 41.2 fmole/mg cytosol protein, mean +/- SEM) was also greater than that found in myometrium (80.8 +/- 29.9) and less than that of endometrium (194.7 +/- 5.5); however, individual variation precluded statistical significance. The presence of cytoplasmic receptor proteins in myomatous tissues explains the sensitivity of the leiomyoma to endogenous or exogenous steroids and may provide information useful in the clinical management of this neoplastic disorder.

Smoking and disease: effect on serum antitrypsin in hospitalized patients.

The mean serum antitrypsin (AT) activity for 1,829 patients hospitalized with medical problems exceeded the mean for a group of blood bank donors by 51%. Analysis of data from individual patients in terms of the general category (there were 16) of their disease and smoking status (smoker, nonsmoker, former smoker) indicated significant differences due to disease status and smoking status. The highest mean AT levels were associated with infectious, respiratory, and neoplastic diseases. Smokers had significantly higher mean levels than nonsmokers, and lung cancer patients had significantly higher mean levels than those with other malignant neoplasms. Among smokers (as a group) mean AT levels. through elevated relative to nonsmokers were not significantly related to duration or intensity of smoking; but former smokers showed a decline (with time following cessation of smoking) in their mean AT level to the mean level for nonsmokers. These findings provide further evidence of the sensitivity of serum antitrypsin activity to environmental influences.

Molecular weight of an extremely hydrophobic protein, zein, in dimethylformamide and in formamide.

Both alpha zein purified from a commericial preparation and beta zein prepared fresh from corn are soluble in the nonaqueous solvents formamide and dimethylformamide; in this regard zein resembles water soluble proteins such as insulin, ribonuclease, and lysozyme. On the basis of osmotic pressure measurements made in both formamide and dimethylformamide, alpha zein has a number average moleular weight of 21000-24000 daltons and shows no tendency to aggregate or dissociate. Beta zein exists in an aggregated state (dimer and higher forms) in dimethylformamide. Formamide dissociates the beta zein dimer into monomer units but aggregation to higher species occurs with increasing protein concentration.

Changes in chromosomes of bone marrow after intravenous injections of 7,12-dimethylbenz(a)anthracene and related compounds.

Multiple intravenous injections of an emulsion containing 7,12-dimethylbenz(a)anthracene (DMBA) or 7,8,12-trimethylbenz(a)anthracene (TMBA) induce a high incidence of leukemia in rats. Twenty-four hours after a single injection, about half of the metaphase cells in the marrow have chromosomes with breaks. Although breaks were inflicted on chromosomes of various sizes and morphology, these aberrations were nonrandom in that members of the nos. 1 and 2 chromosome pairs were involved to an extent greater than expected on the basis of their size and number. Distinctive karyotypic abnormalities involving the no. 2 chromosome were observed in half of the leukemic rats, whereas these abnormalities were not observed in nonleukemic, DMBA-treated rats. Benzo(a)pyrene and benzo(e)pyrene, polycyclic aromatic hydrocarbons which did not induce leukemia, produced fewer breaks of the no. 2 (and other) chromosomes than did DMBA or TMBA.

Lipid composition of rat mammary carcinomas, mammary glands, and related tissues: endocrine influences.

The lipids of mammary glands and mammary carcinomas from rats in various hormonal states were studied and compared with each other, with adipose tissue, and with a new transplantable sarcoma derived from cultured mammary carcinoma cells. When large doses of estradiol-17 Beta were administered to the host, cells of a few carcinomas became engorged with triglyceride containing an increased proportion of C(10)-C(14) fatty acids-a characteristic of milk fat. Cancers capable of fatty transformation must retain in latent form the enzyme system for fatty acid synthesis possessed by mammary epithelium; estradiol-17 Beta apparently activates this system. The lipid composition of retroperitoneal adipose tissue resembled that of the mammary tissue of virgin rats; this indicates similarity between retroperitoneal fat and the adipose component of mammary gland. Relative to the dry nonfat material present, the phospholipid content of adipose tissue was greater than that of the other tissues. Generally, differences in lipid composition between tissues were in amounts of triglyceride present and proportions of fatty acids in the triglyceride fraction. The ratios of cholesterol and cholesterol ester to phospholipid were similar in normal and neoplastic tissues. The amounts of free fatty acid, monoglyceride, and diglyceride were roughly proportional to the amount of triglyceride present.

Insulin resistance in uremia: amino acid metabolism.

After infusion of 250 ml of essential L-amino acids, plasma levels of alpha-amino nitrogen (alpha-AN2) in six chronic renal failure (CRF) patients were not different from those in six carefully matched control (CON) subjects. Plasma insulin increments increased significantly within both groups but were higher in the CRF group (p less than 0.05 at 40 min, p less than 0.005 at 55 min). Growth hormone levels were also higher in the CRF group. Previous studies have shown delayed clearance of plasma alpha-AN2 after casein hydrolysate infusion, despite similarly increased insulin and growth hormone levels in CRF patients. We conclude that essential amino acids are probably more easily metabolized than casein hydrolysate in uremic subjects, but that normal metabolism occurs at the expense of higher plasma levels of insulin and growth hormone.

An experiment eliminating the rotating carrier mechanism for the active transport of Ca ion in sarcoplasmic reticulum membranes.

An experiment has been carried out to test the rotating carrier mechanism of the translocation event in membrane transport. To the Ca-ATPase in intact sarcoplasmic reticulum membranes, 2,4-[3H]dinitrophenyl-cadaverine has been covalently attached by the action of the enzyme, transglutaminase. The binding of anti-2,4-dinitrophenyl antibodies to the 2,4-dinitrophenyl-modified membranes was found to have no effect on either the Ca-ATPase activity or the Ca ion transport rate of the membranes. These results rule out the rotating carrier mechanism in this system. A different scheme for the translocation process, the aggregate rearrangement mechanism, is discussed.

Comparison of the clastogenic and carcinogenic effects of intravenous beta-propiolactone and benzo(a)pyrene in rats.

Scored at 24 hours, the LD-50 of a solution of beta-propiolactone administered intravenously to young rats was 225 +/- 55 mg/kg. Twenty-four hours after a single intravenous injection (100 mg/kg = 1.4 m mole/kg) of beta-propiolactone into male and female rats of both the Long-Evans and Sprague-Dawley strains, the incidence of breaks found in the chromosomes of metaphase marrow cells was low (8.8 percent vs. 5.0 percent in controls). The s5 chromosomes were preferentially damaged. A 200 mg/kg dose increased the incidence modestly to 11.3 percent. In comparison, a single intravenous dose of benzo(a)pyrene (40 mg/kg = 0.16 m mole/kg) produced a break incidence of 19 percent. In long-term experiments multiple (five) intravenous injections (100 mg/kg each) of beta-propiolactone given in a 6 week period elicited only two neoplasms (a chloro-leukemia and a mammary fibroadenoma) among 37 animals during the following 12-13 months. In contrast, four injections of benzo(a)pyrene (40 mg/kg) produced a 14-times greater mammary tumor incidence in the Sprague-Dawley female rat than did beta-propiolactone. Marrow cell chromosome examination indicated no significant chromosomal changes due to the earlier beta-propiolactone treatment except for one animal with a consistent 43-chromosome karyotype resulting from S1 trisomy; no neoplasm was evident in that animal. Earlier treatment with benzo(a)pyrene produced a persistent and significant elevation in break incidence. Both the carcinogenic and clastogenic effects of intravenous beta-propiolactone are low in rats and are not comparable in magnitude to those produced by benzo(a)pyrene.

Normal serum-lipids in renal-transplant patients.

In contrast to previous reports, most patients (78%) with a successful renal transplant being followed up at the University of Kentucky Medical Center had a normal serum-lipid profile. The patients with hyperlipidaema (22%) had normal fasting insulin levels; they received similar immunosuppressive therapy but were significantly older and more obese than those with normal lipids. This lower prevalence of hyperlipidaemia and the absence of fasting hyperinsulinaemia are tentatively attributed to the use of alternate-day corticosteroid therapy in stable renal-transplant patients. If confirmed, the relative infrequency of hyperlipidaemia in patients of alternate-day corticosteroid therapy would be an additional advantage of that therapy over a daily regimen.