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PubMed1990

[Histochemical and biochemical changes in skeletal muscles of rhabdomyolysis-sensitive racehorses following exertion. III: Elevated activity of various antioxidant enzymes].

In this communication, the results of a histochemical and biochemical enzyme study on gluteus medius muscle of horses, sensitive to exertional myopathy, during attacks of rhabdomyolysis are presented. For the biochemical study the biopsy specimens investigated were selected by means of histological and enzyme histochemical staining methods. Dissected specimens were used which contained groups of muscle fibres with a high or low activity of glucose-6-phosphate dehydrogenase. The activity of glucose-6-phosphate dehydrogenase, phosphogluconate dehydrogenase, glutathione reductase, glutathione peroxidase, superoxide dismutase, and catalase was measured microbiochemically in these dissected specimens. A rise in activity of glucose-6-phosphate dehydrogenase in pathologically changed muscle fibres was always found to be coupled with a significant rise in activity of phosphogluconate dehydrogenase, glutathione reductase, and glutathione peroxidase. In these muscle fibres, the activity of superoxide dismutase and catalase was not significantly increased. On the basis of the combined histochemical and biochemical findings it is concluded that the application of the histochemical method for the demonstration of glucose-6-phosphate dehydrogenase activity can be highly recommended for the study of antioxidant enzymes in skeletal muscles with neuromuscular defects.

Animals↗
PubMed1990

Glucagon-(19-29) exerts a biphasic action on the liver plasma membrane Ca2+ pump which is mediated by G proteins.

We have recently shown that nanomolar concentrations of glucagon-(19-29), which can derive from native glucagon by proteolytic cleavage of the dibasic doublet Arg17-Arg18, inhibit the Ca2+ pump in liver plasma membrane vesicles independently of adenylyl cyclase activation (Mallat, A., Pavoine, C., Dufour, M., Lotersztajn, S., Bataille, D., and Pecker, F. (1987) Nature 325, 620-622). We report here that the regulation of the Ca2+ pump by glucagon-(19-29) is dependent on guanine nucleotides. In the presence of 10 microM guanosine 5'-3-O-(thio) triphosphate (GTP gamma S) or 75 microM GTP, glucagon-(19-29) caused a biphasic regulation of the Ca2+ pump. ATP-dependent Ca2+ transport was inhibited in the presence of 10 pM to 1 nM glucagon-(19-29), while higher concentrations of the peptide (1-100 nM) reversed the inhibition caused by lower ones. GTP gamma S alone, at high concentrations (100 microM), reproduced the inhibitory effect of glucagon-(19-29) and induced a 40% inhibition of the basal activity of the Ca2+ pump which was reversed by low concentrations of glucagon-(19-29) (10 pM to 1 nM). Treatment of rats with cholera toxin resulted in a 70% increase in the basal activity of the Ca2+ pump, a loss of sensitivity to GTP gamma S and to the biphasic regulation by glucagon-(19-29). Treatment with pertussis toxin did not affect the response of the Ca2+ pump to GTP gamma S and glucagon-(19-29). We conclude that glucagon-(19-29) can exert a biphasic effect on the Ca2+ pump which is mediated by G protein(s) sensitive to cholera toxin.

Adenylate Cyclase Toxin↗
PubMed1990

Experimental measurement of the force exerted during spinal manipulation using the Thompson technique.

The purpose for conducting this study was to quantify the forces exerted by a chiropractor on a patient during spinal manipulative therapy. Six patients received three treatments each from two chiropractors for a sacroiliac joint fixation. The Thompson technique was used to treat the patients. The force characteristics of the spinal manipulation were analyzed with respect to the following five points: preloading force, peak force, duration of manipulation, impulse of manipulation and point of application of the peak force. The results obtained indicated that all treatments have certain common characteristics; for example, a preload force is always followed by a large thrusting force. The values for the preload force, peak force, duration and impulse were found to have large standard deviations for a given adjuster and between patients. The location of the point of application of the peak force relative to a low back reference system appeared to be very consistent. However, it was not on the posterior superior iliac spines (PSIS) as expected, but always slightly medial to this point. This is the first study to report force results which were measured directly during spinal manipulative therapy in a clinical situation. In further studies, the results of this investigation will be compared to results obtained from a large population of patients and chiropractic adjusters. Differences in the force characteristics between chiropractors will be compared to clinical and objective measures of the rehabilitation process of the patients in order to find an "optimal" way of performing spinal manipulative therapies.

Adult↗
PubMed1990

[Analysis of the shear force exerted on the tibia during standing on bilateral legs with knee flexion].

Biomechanical analysis of the two-dimensional models composed of roentgenographic pictures and electromyographic analysis about the shear force (Fs) exerted on tibia during standing on bilateral legs was conducted in 21 young adult males. The simultaneous contraction of the quadriceps and hamstrings was observed in all electromyograms (EMGs). Amplitude observed on EMGs of the hamstrings increased as the trunk flexion angle increased. The calculated average values of Fs were negative at every knee flexion angle; Negative value means posteriorly directed force. As the trunk flexion angle increased, posterior drawer force increased at knee flexion angles of 30 degrees and 60 degrees. The simultaneous contraction of the quadriceps and the hamstrings was considered to represent the main factor that influenced these results. The standing on bilateral legs with knee and trunk flexion was considered to be applicable in the early stages after anterior cruciate ligament reconstruction.

Adult↗
PubMed1990

Time course of recovery and heat acclimation ability of prior exertional heatstroke patients.

Our understanding of the time course of recovery from exertional heatstroke (EH) and the heat acclimation ability of prior EH patients is limited. This manuscript reviews previous findings regarding recovery from EH and presents original research involving the heat acclimation ability of 10 prior EH patients (PH) and 5 control subjects. Heat acclimation, by definition, distinguishes heat-intolerant from heat-tolerant prior heatstroke patients. Nine PH exhibited normal heat acclimation adaptations (40.1 degrees C, 7 d, 90 min.d-1), thermoregulation, sweat gland function, whole-body sodium and potassium balance, and blood values at 61 +/- 7 d after EH. One PH (subject A) did not adapt to exercise in the heat, was defined heat intolerant, but subsequently was declared heat tolerant (11.5 months post-EH). Three PH exhibited large, unexpected increases in serum CPK levels, which resolved upon subsequent testing, and were probably related to their detrained state and the exercise which they performed. It was concluded that: 1) sleep loss and generalized fatigue were the most common predisposing factors for PH; 2) recovery from EH was idiosyncratic and may require up to 1 year in severe cases; 3) PH were not hereditarily heat intolerant, prior to EH; 4) no measured variable predicted recovery from EH, or heat acclimation responses; 5) heat intolerance occurs in a small percentage of prior heatstroke patients, and may be transient or persistent.

Acclimatization↗
PubMed1988

Monoclonal antibodies reactive with distinct domains of the neu oncogene-encoded p185 molecule exert synergistic anti-tumor effects in vivo.

The neu oncogene encodes a 185,000 dalton transmembrane glycoprotein, p185. The current study examined the effects of p185-specific monoclonal antibody administration on the tumorigenic growth of neu-transformed NIH3T3 cells implanted into nude mice. Treatment with anti-p185 monoclonal antibodies of the IgG1, IgG2a, IgG2b subclasses was able to profoundly inhibit the growth of neu-transformed cells. Furthermore, while none of these antibodies individually was able to cause complete eradication of tumors, the administration of mixtures of antibodies reactive with two distinct regions on the p185 molecule resulted in synergistic anti-tumor effects and complete eradication of tumors in a substantial fraction of the treated animals. The effect was oncogene specific, since the growth of ras transformed cells was not influenced by anti p185 antibodies. These results demonstrate that antibodies reactive with multiple domains of a tumor antigen can exert synergistic anti-tumor effects, and suggest that therapy with monoclonal antibodies specific for the neu oncogene product may play a role in cancer treatment.

Animals↗
PubMed1989

Sequences outside a minimal immunodominant site exert negative effects on recognition by staphylococcal nuclease-specific T cell clones.

In recent years, synthetic peptides have been utilized extensively to characterize the minimal essential immunodominant sites on model protein Ag. However, little work has focused on the effect that sequences flanking these minimal recognition sites may exert on T cell recognition. Previous work with staphylococcal nuclease (Nase) demonstrated that I-Ek-restricted clones recognize the peptide 81-100, whereas I-Ab-restricted clones recognize the over-lapping but non-cross-reacting peptide 91-110. Further analysis with 15 or 10 residue peptides within the region 81-110 reveals that the minimal sequence capable of stimulating I-Ek-restricted clones is contained within the decapeptide 91-100. Addition of residues 86-90, to give the peptide 86-100, enhanced the recognition substantially, whereas addition of residues 101-105 produced a 91-105 peptide with no stimulatory ability. These results suggest that interactions between the antigenic peptide 91-100 and residues within the flanking 101-105 sequence have negative consequences for presentation of the immunodominant epitope to T cell clones. Introduction of single amino acid substitutions within 91-105 produced peptides that induce responses comparable to those seen with 91-100. These results are consistent with the suggestion of negative interactions between the minimal immunodominant site and flanking sequences in that single residue substitutions may remove these negative interactions and lead to restoration of stimulatory ability. The negative effect of flanking sequences on T cell recognition of immunodominant sites presents new considerations for development of synthetic vaccines as well as for understanding the biology of Ag processing and presentation.

Amino Acid Sequence↗
PubMed1989

Exertional rhabdomyolysis and acute renal failure following the Army Physical Fitness Test.

Rhabdomyolysis and myoglobinuric acute renal failure may occur following strenuous exercise and may be more common in less physically conditioned persons. A case of moderately severe acute renal failure after the exercise involved in a routine Army Physical Fitness Test (APFT) is described. This level of exertion, which is universally applied to Army personnel, should be recognized as a potential etiology of rhabdomyolysis. Prospective studies may help define the exact risk to renal function provided by the APFT.

Acute Kidney Injury↗
PubMed1989

[Exertional dyspnea, chest pain, dizziness].

A 66 year old patient with chest pain and exertional dyspnea is described. Auscultation and physical examination showed signs of aortic stenosis combined with aortic insufficiency. Electrocardiography revealed left ventricular hypertrophy with associated ST-segment and T-wave abnormalities. Color blood flow imaging confirmed severe combined aortic stenosis and regurgitation, the hemodynamic evaluation demonstrated the indication for aortic valve replacement.

Aged↗
PubMedDate not supplied

[The search for antibiotics not exerting activating action in the persistence of the tick-borne encephalitis virus].

Chronic tick-borne encephalitis (TBE) frequently develops in the presence of concomitant diseases requiring antibiotic therapy. Because some antibiotics, e.g. streptomycin, strongly activate persisting TBE virus, a study was carried out in search of antibiotics without the activating effect. The experiments were carried out in Syrian hamsters inoculated subcutaneously with the Vasil'chenko strain of TBE virus which at 60-348 days of the persistent infection were given florimycin, levomycetin and kanamycin. The antibiotics were administered for 3 weeks. Levomycetin showed no activating properties, while kanamycin and florimycin exerted weak activating effect on the persisting TBE virus (isolated from 5% of the specimens) without marked immunosuppressive effect or manifestation of the infection. The TBE virus strains isolated on the 205th day from the brain and 348th day from the spleen of the hamsters given kanamycin and florimycin had higher virulence than the original strain.

Animals↗
PubMed1989

1 alpha,25(OH)2D3 exerts cytostatic effects on murine osteosarcoma cells and enhances the cytocidal effects of anticancer drugs.

The effects of 1 alpha,25-dihydroxyvitamin D3 (1 alpha,25-(OH)2D3), 1 alpha-hydroxyvitamin D3 (1 alpha(OH)D3), and dexamethasone on colony formation of Dunn osteosarcoma cells (TA 102 cells) were investigated. Concentrations of 1 alpha,25(OH)2D3, 1 alpha(OH)D3, and dexamethasone at which they exerted 50% reduction of the total area of TA 102 colony formation were 9 X 10(-9) M, 9 X 10(-8) M, and 5 X 10(-6) M, respectively. Effects of anticancer drugs on TA 102 cells were also investigated and concentrations needed for 50% growth inhibition (50% inhibitory concentration values) of cis-platinum, mitomycin C (MMC), methotrexate (MTX), and Adriamycin (ADR) against TA 102 cells were calculated to be 0.07 microgram/ml, 0.0008 microgram/ml, 0.0008 microgram/ml, and 0.0005 microgram/ml, respectively. The simultaneous treatment of TA 102 cells with 10(-8) M of 1 alpha,25(OH)2D3 and anticancer drugs significantly enhanced the respective inhibitory effects on colony formation. In this treatment, the IC50 value of MMC was calculated to be 6.4 X 10(-6) micrograms/ml, which was 1/160 of the expected IC50 value of MMC (8 X 10(-4) micrograms/ml). Similar synergistic effects were observed when the cells were treated with 1 alpha,25(OH)2D3 and low concentrations of cis-platinum, MTX, or ADR.

Animals↗
PubMed1989

[Fatigue, exertional dyspnea, unsteady gait].

Exertional dyspnea and fatigue dominated the clinical picture of pernicious anemia in a 78 year old man. A disturbed gait indicated concomitant neurologic disorders. A reduced Vitamin B12 level, an abnormal Schillingtest, atrophy of gastric mucosa as well as maturation disturbance of erythrocytes and neutrophils were present as typical signs of the disease. Administration of Cyanocobalamine led to correction of blood values within three weeks.

Aged↗
PubMed1987

Gastric antisecretory and antiulcer effects of WHR1582A, a compound exerting alpha-2 adrenoceptor agonist activity.

The gastric antisecretory and antiulcer effects of a novel compound, [1-(2,-dimethylphenyl)-3-isobutoxyamidinourea]hydrochloride (WHR1582A), are described. WHR1582A was active in preclinical ulcer models induced by 18-hr pylorus ligation, aspirin, indomethacin, reserpine, stress or cysteamine. WHR1582A inhibited acid secretion in the pylorus-ligated rat and in the anesthetized, lumen-perfused rat. The antisecretory effects of WHR1582A were antagonized by yohimbine, RX781094A and phentolamine. Propranolol, prazosin, corynanthine, methysergide, sulpiride and pimozide were unable to block its activity. WHR1582A blocked acid secretion stimulated by 2-deoxy-D-glucose but was inactive against the direct parietal cell stimulants carbachol and dimaprit. WHR1582A also inhibited electrically stimulated contractions that were mediated via the vagus in the isolated rat stomach preparation. The antisecretory activity of WHR1582A was not due to a reduction in gastric mucosal blood flow. These results demonstrate that WHR1582A is an effective antiulcer-antisecretory agent that exerts its gastric effects through the activation of alpha-2 adrenoceptors located presynapitcally on the vagus.

Adrenergic alpha-Agonists↗
PubMed1989

Gallamine exerts biphasic allosteric effects at muscarinic receptors.

Although gallamine and a number of other compounds have been reported to slow the rate of dissociation of labeled ligands, especially [3H]N-methylscopolamine (NMS), from muscarinic receptors of heart and brain, there has been some dispute as to whether the dissociation of [3H]quinuclidinyl benzilate (QNB) is subject to such allosteric regulation. The present studies were intended to determine whether past discrepancies might be due to differences between tissues. We have found that gallamine modulates the dissociation of [3H]QNB from muscarinic receptors of the heart in a biphasic manner. Low concentrations (micromolar) accelerate the rate of dissociation, whereas higher concentrations (millimolar) slow it; at about 0.1 mM, the two effects cancel each other. Similar results were obtained with muscarinic receptors from the brainstem, but gallamine had only marginal effects on the dissociation of [3H]QNB in the forebrain. On the other hand, verapamil exerts only monophasic effects (slowing) on the dissociation of both [3H]NMS and [3H]QNB from heart receptors and gallamine slows the dissociation of [3H]NMS to a similar extent in all three tissues. Thus, it appears that past discrepancies in the literature can be attributed to the tissues and concentrations of gallamine that were used. Furthermore, the biphasic effects of gallamine suggest that there are multiple allosteric regulatory sites associated with muscarinic receptors.

Allosteric Regulation↗
PubMed1989

[Exertional dyspnea, fatigue, palpitations].

This 52-year old female patient suffered from exertional dyspnea, fatigue and palpitations progressive for some months. She had rheumatic fever in childhood. Physical examination and echocardiography revealed severe pure mitral regurgitation, invasive studies showed dilatation of the left atrium and ventricle, a regurgitant volume of 70% of the stroke volume and mitral valve replacement was performed.

Dyspnea↗
PubMedDate not supplied

Magnesium salts exert direct vasodilator effects on rat cremaster muscle microcirculation.

In vivo microscopic observations were made on arterioles and venules (10-20 microns i.d.) of the rat cremaster muscle circulation, using an image-splitting eyepiece and high-resolution TV image-intensification, in order to determine the microvascular effects of inorganic and organic magnesium (Mg) salts. MgSO4, MgCl2, Mg aspartate HCl, and Mg acetate were administered perivascularly and intravenously. Topical application (10(-2) to 10(1) mumol) and intravenous (i.v.) administration (5-400 mumol/kg/min) of all Mg salts, [which resulted in elevated plasma Mg levels (1.1-4.7 mg/dl over controls)], brought about rapid, almost instantaneous vasodilation of both arterioles and venules in low doses. Intravenous administration of Mg salts resulted in elevation of plasma calcium (0.5-1.5 mg/dl over controls) and decreases in plasma phosphate (0.5-1.2 mg/dl below controls); plasma Na and K were not affected. High doses (i.e. 400 mumol/kg/min) of some Mg salts, administered i.v., tended to constrict these microvessels. Diastolic and systolic arterial blood pressure as well as heart rate decreased in a dose-dependent manner upon systemic administration of all 4 Mg salts. Intravenous administration of high doses of the Mg salts (i.e., greater than 200 mumol/kg/min) often resulted in marked falls in mean arterial blood pressure (e.g. 110 to 40 mmHg) and heart rate (e.g. 460 to 130 bpm), followed by death. Administration of a variety of pharmacological antagonists and a cyclo-oxygenase inhibitor did not interfere with vasodilatation of arterioles or venules induced by Mg salts. Use of hyperosmolar sucrose partially mimicked some of the vasodilator, but not the cardiac or blood pressure lowering actions of Mg salts. These data indicate that magnesium ions: 1) bring about vasodilatation without releasing adrenergic amines, histamine, serotonin, acetylcholine, prostaglandins, or endogenous opioids; 2) are direct, potent vasodilators of intact rat cremaster muscle microvessels; 3) may have a depressive action on heart; 4) exert these microvascular and cardiac actions in low doses and 5) can produce severe hypotension and bradycardia only after i.v. administration of high doses. In addition, acute administration of various Mg salts can rapidly alter certain plasma electrolytes (e.g., Ca, PO4), at least in rats, which may be related to the microvascular actions of Mg2+.

Animals↗
PubMed1986

Metabolic regulation in skeletal muscle: influence of endurance training as exerted by mitochondrial protein concentration.

During prolonged submaximal exercise, skeletal muscle must overcome the problem of continually renewing the local supply of ATP at the ATPase site of myosin. This problem is compounded by the fact that there is little free water in the cell to enable a rapid diffusion of the compound (ATP and ADP) involved. This appears to occur via the Cr-CrP shuttle whereby the ADP produced as a result of contraction is converted to ATP via the adenylate kinase reaction with the production of AMP. The ADP used to regenerate ATP by the adenylate kinase reaction is ultimately replenished from ATP generated by the metabolic pathways and transported through the cytosol via the CK located sequentially on the myofibrils, in the cytosol, and bound to the outer surface of the inner mitochondrial membrane. The increase in the mitochondrial protein concentration of skeletal muscle that occurs with endurance training has a direct effect on improving work capacity by providing a greater potential for the CrP shuttle, produced by a greater surface area, increasing the number of transport sites for the exchange of substrates and products between the cytosol and the mitochondrial matrix, exerting a tighter control over the adenine nucleotides as they turnover during contractile and metabolic activity, and providing for a tighter control over the Embden-Meyerhof pathway to prevent excessive lactate production. The effect of these changes is to produce a more effective use of fat and carbohydrate reserves.

Animals↗