Interactions of acetylcholine and epinephrine on the dynamics of insulin release in vitro

An in vitro system for perifusion of rat pancreatic islets has been utilized to define the effects of epinephrine on acetylcholine-induced insulin release over varying concentrations of the two agents. Perifusion of islets with epinephrine before challenge with acetycholine produced marked enhancement of both phases of cholinergically induced insulin release; enhancement of the first phase being more marked with increase in acetylcholine concentration and the converse being observed with the second phase. Perifusion of islets with epinephrine during stimulation with acetylcholine produced inhibition of insulin release, an effect dependent upon the concentration of epinephrine and of acetylcholine. There was an order of difference in the acetycholine concentration needed to overcome significant epinephrine-mediated inhibition of the first phase of insulin release (5 X 10(-4) mug/ml) and that needed to overcome inhibition of the second phase (5 X 10(-3) mug/ml). Comparison of the effects of various concentrations of epinephrine on glucose- and acetyl-choline-induced insulin release revealed that epinephrine was a less potent inhibitor of the first phase of acetylcholine-induced insulin release than of the first phase of glucose-induced insulin release. These data provide some insight into the potential interactions between cholinergic and adrenergic autonomic systems in modifying insulin release.     

Pelvic lymphadenectomy can be omitted in selected patients with carcinoma of the prostate: development of a system of patient selection

OBJECTIVES: The prevalence of pelvic lymph node metastases in men with clinically localized prostate cancer has decreased dramatically over the past decade, possibly due to efforts at early detection. With a significantly lower incidence of pelvic node involvement, it may be possible to identify a segment of patients for whom pelvic lymph node dissection (PLND) may be omitted. This study was conducted to develop a method to select patients for whom PLND could be omitted. METHODS: We analyzed serum prostate-specific antigen (PSA), clinical stage, biopsy Gleason score, and final pathologic stage in 481 men with clinically localized prostate cancer. These variables were compared to the risk of positive pelvic lymph nodes. RESULTS: Logistic regression analysis determined that combining all three variables provided the best determination of final pathologic stage. A series of probability curves have been created to estimate the risk of positive lymph nodes in a given patient. Based on the distribution of patients in this study and using these probability functions, PLND could be avoided in up to 50% of patients with localized prostate cancer diagnosed by contemporary methods. CONCLUSIONS: In properly selected patients, pelvic lymphadenectomy can be omitted in the staging and treatment of localized prostate cancer.     

Mechanics of caloric stimulation in a case with a plug in the horizontal semicircular canal

Cytochrome P-450cam hydroxylates d-camphor, using molecular oxygen and reducing equivalents transferred via putidaredoxin. We constructed mutant genes in which Phe-350 of P-450cam was replaced by Leu, Tyr, or His by site-directed mutagenesis, expressed them in Escherichia coli, purified the mutant proteins, and compared their enzymic properties with those of the wild type P-450cam. NADH oxidation rate of the Tyr mutant in the reconstituted system with putidaredoxin and putidaredoxin reductase was similar to that of the wild type enzyme, while the Leu mutant and the His mutant showed 67% and 17% activity of that of the wild type, respectively. The affinities of these mutant proteins for camphor and the oxidized form of putidaredoxin were much the same as those of the wild type protein. Rate constants for the reduction reaction of P-450cam by reduced putidaredoxin, a physiological electron donor for P-450cam, of Tyr and His mutants were much the same as that of the wild type enzyme, whereas the Leu mutant showed approx. half that of the wild type. Thus, the aromatic ring of Phe-350 of P-450cam probably contributes to enhancing efficiency of the electron transfer yet does not seem to be essential for the reaction.     

HLA associations of seropositive rheumatoid arthritis in a Cree and Ojibway population

Eucalyptus globulus (eucalyptus) is used as a traditional treatment for diabetes. In this study, incorporation of eucalyptus in the diet (62.5 g/kg) and drinking water (2.5 g/L) reduced the hyperglycemia and associated weight loss of streptozotocin-treated mice. An aqueous extract of eucalyptus (AEE) (0.5 g/L) enhanced 2-deoxy-glucose transport by 50%, glucose oxidation by 60% and incorporation of glucose into glycogen by 90% in mouse abdominal muscle. In acute, 20 min incubations, 0.25-0.5 g AEE/L evoked a stepwise 70-160% enhancement of insulin secretion from the clonal pancreatic beta-cell line (BRIN-BD11). The stimulatory effect of 0.5 g/L AEE was unaltered by the presence of 400 micromol diazoxide/L and prior exposure to AEE did not alter subsequent insulin secretory response to L-alanine, thereby negating adetrimental effect on cell viability. The effect of AEE was not potentiated by glucose or demonstrable in cells exposed to a depolarizing concentration of KCl. Further study of the insulin-releasing effects of AEE revealed the activity to be heat stable, acetone insoluble, stable to acid, but abolished by exposure to alkali. Sequential extraction with solvents revealed activity in both methanol and water fractions, indicating the presence of more than one biologically active extract constituent. These data indicate that Eucalyptus globulus represents an effective antihyperglycemic dietary adjunct for the treatment of diabetes and a potential source for discovery of new orally active agent(s) for future therapy.     

Did Cook's sailors have Tapanui 'flu? --chronic fatigue syndrome on the Resolution

The 1982 publication of the Resolution journal of Johann George Reinhold Forster provided justification for his recognition as a scientist, and gave a remarkable insight into his character. It also included an account of an illness suffered by many of the sloop's crew, including Forster, after a period ashore at Queen Charlotte Sound. The symptoms of the illness were remarkably similar to those now clustered as the chronic fatigue syndrome.     

Evaluation of once-weekly therapy for tuberculosis using isoniazid plus rifamycins in the mouse aerosol infection model

Once-weekly therapy with combinations of isoniazid plus a rifamycin was tested in the mouse low-dose aerosol infection model against two strains of Mycobacterium tuberculosis. Combinations of isoniazid and rifalizil and isoniazid and rifapentine were both highly effective. These animal model data thus support the evaluation of these regimens under clinical conditions.     

Changes of plasma volume and plasma composition in water-deprived rats

Plasma volume, hematocrit, protein and electrolyte concentrations in plasma were measured in control and water-deprived rats every three days after starting the experiment until the 15th day. Plasma volume variations, as related to body weight, suggest that water loss from plasma was proportional to total body water at three days and after 9 days of water deprivation. Greater plasma water than body water loss was found during the period between 3 and 9 days. Plasma protein and electrolyte variations suggest that during water deprivation there is a loss of protein, sodium and potassium from plasma, which is proportionally less than that of plasma water. Potassium, calcium and inorganic phosphorus were lost proportionally to plasma water. The variations in plasma volume changes were partially explained as due to variations in plasma protein and electrolyte concentrations.