Nitric oxide as mediator of bradykinin-induced pancreatic circulatory and metabolic responses

Bradykinin (BK) is an endogenous nonapeptide with potent vasodilator properties of the visceral circulation. BK alters vascular tone via two BK receptor subtypes, B1 and B2. Current experimental evidence suggests that the dilator action of BK in some vessels is mediated primarily by B2 receptor activation. In addition, there are reports that BK increases endothelial generation of vasodilator factors, such as nitric oxide (NO). The present study had two aims. First, to explore the role of BK-receptors in the pancreatic vasodilatatory and metabolic responses to BK. Second aim was to examine whether endogenous NO play a role in the mediation of BK-receptors induced pancreatic circulatory and metabolic activity. In anesthetized dogs, the superior pancreatico-duodenal artery blood flow (SPBF) was measured by ultrasonic blood flowmeter (Transonic System T-206), pancreatic microcirculatory blood flow (PBF) was determined by laser Doppler flowmetry (Periflux 4001 Master). Pancreatic oxygen consumption (PVO2) was calculated as the product of the arteriovenous oxygen difference (AVO2) across the pancreatic circulation and SPBF. Drugs were infused into the superior pancreatico-duodenal artery. BK (0.01-1.0 mg/kg/min) increased maximally SPBF by 180 +/- 15%, PBF by 208 +/- 22% and PVO2 by 145 +/- 11%, respectively. Pretreatment with B2-subtype receptor antagonist, D-Arg, [Hyp3, Thi5,8, D-Phe7] BK inhibited significantly BK-induced increase in SPBF, PBF and PVO2 by 86 +/- 8%, 73 +/- 7% and 85 +/- 6%, respectively. A nitric oxide synthesis inhibitor (L-NNA) administered i.v. at dose of 25 mg/kg 20 min before BK, inhibited significantly the pancreatic hyperemic and metabolic responses. The results presented emphasize an important role of B2 receptors in the mediation of pancreatic circulatory and metabolic responses to bradykinin. Endogenous NO plays a mediatory role in the pancreatic vascular and metabolic responses due to stimulation of B2-receptors.     

Electromyographic activity of the cervical musculature during dynamic lateral bending

STUDY DESIGN: Electromyographic profiles from the neck muscles of five young, healthy men were obtained to study the muscular, activation patterns during dynamic external loading. OBJECTIVES: To examine the myoelectric activity of selected cervical muscles during dynamic loading, and to explore the reaction of the cervical muscles to different loading conditions. SUMMARY OF BACKGROUND DATA: The response of cervical muscles throughout dynamic external loading is not well understood. Electromyography provides information, within certain limitations, about the neural drive to various components of the musculature. Such information on activation, combined with geometric parameters of the musculoskeletal tissues, constitutes a tool for helping to understand the mechanism of head and neck impact-related injury. METHODS: Subjects were tested with the head and neck in the neutral and prebent positions. Dynamic loads were applied laterally to each subject by free-falling masses to create peak dynamic loads ranging from about 40 to 100 N. Force and electromyographic data were recorded, and cross-correlations from linear envelope electromyography were calculated. RESULTS: The peak electromyogram showed large differences between the two applied loads and between subjects. There were time delays (75-165 msec) between the peak applied force and the peak electromyogram. The muscles on the contralateral side demonstrated different electromyographic profiles between subjects. Within subjects, the electromyographic profiles from each muscle were consistent for the same trial conditions. CONCLUSIONS: Electromyographic profiles and the cross-correlator coefficients for cervical muscles have shown reproducible intrasubject muscle synergies, which were not sensitive to the magnitude of applied load and the posture of the head. Intersubject muscle activity patterns varied.     

The application of radionuclide infarct scintigraphy to diagnose perioperative myocardial infarction following revascularization

To evaluate the application of radionuclide infarct scintigraphy to diagnose myocardial infarction after revascularization, we obtained postoperative technetium 99m pyrophosphate myocardial scintigrams, serial electrocardiograms and CPK-MB isoenzymes in ten control and 51 revascularized patients. All control patients had negative electrocardiograms and scintigrams, but eight had positive isoenzymes. Eight revascularized patients had positive electrocardiograms, images and enzymes and two had positive scintigrams and enzymes with negative electrocardiograms. Thirty-four patients with negative electorcardiograms and scintigrams had positive isoenzymes; in only seven patients were all tests negative. Our data suggest radionuclide infarct scintigraphy is a useful adjunct to the electrocardiogram in diagnosing perioperative infarction. The frequent presence of CPK-MB in postoperative patients without other evidence of infarction suggests that further studies are required to identify all factors responsible for its release.     

A placebo-controlled trial of recombinant human ciliary neurotrophic (rhCNTF) factor in amyotrophic lateral sclerosis. rhCNTF ALS Study Group

Preclinical investigations indicated that recombinant human ciliary neurotrophic factor (rhCNTF) may have potential as therapy for amyotrophic lateral sclerosis (ALS). We evaluated the safety and efficacy of rhCNTF in a prospective, double-blind, placebo-controlled trial in 570 patients with ALS. Patients were randomized to receive 0.5, 2, or 5 micrograms/kg/day rhCNTF, or placebo, for 6 months. The primary efficacy end point was the change from baseline to the last on-treatment value of a combination megascore for limb strength (maximum voluntary isometric contraction) and pulmonary function. Secondary end points included individual arm and leg megascores, pulmonary function tests, an activities-of-daily-living outcome measure, and survival. The four treatment groups were similar at baseline with respect to age, sex, disease duration, and muscle strength values. At all doses tested, rhCNTF had no beneficial effect on the primary or secondary end points. Certain adverse events, as follows, appeared to be dose related: injection site reactions, cough, asthenia, nausea, anorexia, weight loss, and increased salivation. There was an increased number of deaths at the highest dose level. rhCNTF had no beneficial effect on any measure of ALS progression. There were increased adverse events in the 5 micrograms/kg group and increased deaths.     

Isolated tear of the anterior cruciate ligament: 5-year follow-up study

During the period 1967 to 1971, 64 cadets at the United States Military Academy, West Point, New York, had surgical repair for isolated tear of the anterior cruciate ligament. In a 5-year follow-up study to determine the functional impairment, present disability, and reinjury to the knee, 32 of the 64 patients were located and evaluated by radiographic examination and either by interview or by questionnaire. Twenty-two were commissioned to full duty. 23 had attended ranger or airborne school, and 16 had been in combat. Impairment of ordinary activities was noted by 12 and impairment of athletic endeavors by 24; pain by 71%; swelling by 66%; stiffness by 71%; and instability by 94%. Seventeen of the 32 had had a significant reinjury after the repair of the anterior cruciate ligament. Clinically, we can diagnose the isolated tear of the anterior cruciate ligament by four essential ingredients--a pop at time of injury, inability to continue participation, gross swelling of knee, and maximal swelling within 12 hr. The mechanism of injury is usually deceleration and change of direction, not contact with another player. The follow-up study on this small series indicates that the patients have progressive deterioration of the knee.     

Combination of ametopterine (MTX) and cyclophosphamide (CPM) based on the principle of partial synchronization of cell proliferation in lung cancer. Phase II study

Rat liver ribosome treatment with ethanol and 1 M NH4Cl releases some 31-33 ribosomal proteins. This split protein fraction binds Phe-tRNA, Ac-Phe-tRNA, Met-tRNAM and f-Met-tRNAF in the absence of K+ and Mg++ ions. When the split protein fraction is passed through Sephadex G-100 only six proteins are retained in the column: S10, S14, S15, S19, L35, and L36. The aminoacyl-tRNA binding activity of this protein fraction retained in the Sephadex G-100 column is similar to that of the total split protein fraction, suggesting that the above six proteins, or only some of them, are involved in the binding reaction.