Antinuclear Matrix Protein 2 Autoantibodies and Edema, Muscle Disease, and Malignancy Risk in Dermatomyositis Patients.

OBJECTIVE: Dermatomyositis (DM) patients typically present with proximal weakness and autoantibodies that are associated with distinct clinical phenotypes. We observed that DM patients with autoantibodies recognizing the nuclear matrix protein NXP-2 often presented with especially severe weakness. The aim of this study was to characterize the clinical features associated with anti-NXP-2 autoantibodies. METHODS: There were 235 DM patients who underwent testing for anti-NXP-2 autoantibodies. Patient characteristics, including muscle strength, were compared between those with and without these autoantibodies. The number of cancer cases observed in anti-NXP-2-positive subjects was compared with the number expected in the general population. RESULTS: Of the DM patients, 56 (23.8%) were anti-NXP-2-positive. There was no significant difference in the prevalence of proximal extremity weakness in patients with and without anti-NXP-2. In contrast, anti-NXP-2-positive patients had more prevalent weakness in the distal arms (35% versus 20%; P = 0.02), distal legs (25% versus 8%; P < 0.001), and neck (48% versus 23%; P < 0.001). Anti-NXP-2-positive subjects were also more likely to have dysphagia (62% versus 35%; P < 0.001), myalgia (46% versus 25%; P = 0.002), calcinosis (30% versus 17%; P = 0.02), and subcutaneous edema (36% versus 19%; P = 0.01) than anti-NXP-2-negative patients. Five anti-NXP-2-positive subjects (9%) had cancer-associated myositis, representing a 3.68-fold increased risk (95% confidence interval 1.2-8.6) compared to the expected prevalence in the general population. CONCLUSION: In DM, anti-NXP-2 autoantibodies are associated with subcutaneous edema, calcinosis, and a muscle phenotype characterized by myalgia, proximal and distal weakness, and dysphagia. As anti-NXP-2-positive patients have an increased risk of cancer, we suggest that they undergo comprehensive cancer screening.

Pretreatment with morin, a flavonoid, ameliorates adenosine triphosphatases and glycoproteins in isoproterenol-induced myocardial infarction in rats.

The aim of this investigation was to evaluate the preventive role of morin, a flavonoid, on cardiac marker enzymes such as aspartate transaminase, lactate dehydrogenase, creatine kinase and creatine kinase-MB, membrane-bound enzymes such as sodium potassium-dependent adenosine triphosphatase, calcium-dependent adenosine triphosphatase and magnesium-dependent adenosine triphosphatase, and glycoproteins such as hexose, hexosamine, fucose and sialic acid in isoproterenol (ISO)-induced myocardial infarction (MI) in rats. Male albino Wistar rats were pretreated with morin (20, 40 and 80 mg/kg) daily for a period of 30 days. After the treatment period, ISO (85 mg/kg) was subcutaneously injected into the rats at an interval of 24 h for 2 days. ISO-induced rats showed significantly (P < 0.05) increased activities of cardiac marker enzymes in serum and decreased activities in the heart, and increased activities of calcium-dependent adenosine triphosphatase and magnesium-dependent adenosine triphosphatase in the heart, and the activity of sodium potassium-dependent adenosine triphosphatase decreased in the heart. ISO induction also showed a significant increase in the levels of glycoproteins in serum and the heart. Pretreatment with morin (40 mg/kg) daily for a period of 30 days exhibited significant (P < 0.05) effects and altered these biochemical parameters positively compared to the other two doses. Thus, our study shows that morin has a protective role in ISO-induced MI in rats. The observed effects might be due to the free radical-scavenging, antioxidant and membrane-stabilising properties of morin.

N-acetylcysteine and magnesium improve biochemical abnormalities associated with myocardial ischaemic reperfusion in South Indian patients undergoing coronary artery bypass grafting: a comparative analysis.

INTRODUCTION: The clinical presentation of ischaemic reperfusion in postoperative patients correlates with oxidative stress. The limited clinical success of anti-ischaemic reperfusion agents has prompted a comparison of the efficacy of N-acetylcysteine (NAC) and magnesium (Mg) in South Indian patients undergoing coronary artery bypass grafting (CABG). METHODS: In Clinical Trial I, 52 South Indian patients who had undergone CABG surgery (with intraoperative Mg supplementation) and 40 controls (without Mg supplementation) were selected and matched. The control patients underwent the same protocol without Mg. In Clinical Trial II, the study population consisted of 50 patients, where 25 patients received NAC just before the release of the aortic cross clamp. In the NAC untreated group, dextrose solution was administered at the same time as the placebo. Six blood samples were taken at different times during the cardiac surgery and the antioxidant enzymes, ATPase and cardiac markers from the coronary sinus blood samples were analysed. RESULTS: Increased blood lipid peroxidation was observed in patients who were not treated with Mg/NAC. The administration of Mg/NAC just before the release of the aortic cross clamp reduced the lipid peroxidation significantly (p-value is less than 0.05). The above observations were supported by the antioxidant enzyme levels. Significant improvements to the erythrocyte ATPase and cardiac markers in patients treated with Mg/NAC correlated with a reduction in postoperative abnormalities. Based on the biochemical status of the patients, Mg was shown to mediate better recovery from postoperative changes. CONCLUSION: NAC and Mg decreased pump-induced oxidative stress during cardiopulmonary bypass (CPB), suggesting that it could be a novel therapy for assisting in the prevention of CPB-induced oxidative stress.

Influence of Helicteres isora administration for diabetes mellitus: Its effect on erythrocyte membrane and antioxidant status.

In this study the effect of Helicteres isora L. on erythrocyte membrane bound enzymes and antioxidants activity in plasma and erythrocytes of streptozotocin (STZ) induced diabetic model was investigated. The aqueous bark extract of H. isora was administered orally for 30 days to control and STZ induced diabetic rats. The effect of bark extract on glucose, insulin, haemoglobin, glycosylated haemoglobin, TBARS, hydroperoxide, superoxide dismutase (SOD), catalase (CAT), glutathione peroxide (GPx), glutathione-S-transferase (GST), vitamins C and E, reduced glutathione (GSH) and membrane bound enzymes were studied. The levels of glucose, glycosylated haemoglobin, TBARS, hydroperoxide, and vitamin E were increased significantly whereas the level of insulin, haemoglobin, as well as antioxidants, membrane bound total ATPase, Na(+)/K(+)-ATPase, Ca(2+)-ATPase and Mg(2+)-ATPase were decreased significantly in STZ diabetic rats. Administration of bark extract to diabetic rats showed a decrease in the levels of glucose, glycosylated haemoglobin, lipid peroxidation markers and vitamin E. In addition the levels of insulin, haemoglobin, enzymatic antioxidants, vitamin C, and GSH and the activities of membrane bound enzymes also were increased in H. isora treated diabetic rats. The present study indicates that the H. isora possesses a significant favourable effect on erythrocyte membrane bound enzymes and antioxidants defense system in addition to its antidiabetic effect.

Influence of dietary spices on the fluidity of erythrocytes in hypercholesterolaemic rats.

In rats rendered hypercholesterolaemic by maintaining them on a cholesterol-enriched diet (0.5 %) for 8 weeks, as a result of alteration in membrane structural lipids, erythrocytes were observed to be deformed and become more fragile. This deformity and fragility was partially reversed by the two dietary spice principles, curcumin and capsaicin, and the spice, garlic, by virtue of their ability to lower the extent of hypercholesterolaemia. A further insight into the factors that might have reduced the fluidity of erythrocytes in hypercholesterolaemic rats revealed changes in fatty acid profile of the membranes, phospholipid composition of the membrane bilayer, reduced Ca(2+),Mg(2+)-ATPase, and reduction in the sensitivity of erythrocytes to concanavaline A. Dietary capsaicin appeared to counter these changes partially in hypercholesterolaemic rats. Electron spin resonance (ESR) spectra and fluorescence anisotropy parameters also revealed altered fluidity of erythrocytes in hypercholesterolaemic rats. Dietary capsaicin and curcumin significantly reversed this alteration. Scanning electron microscopic examination revealed that the echinocyte population was increased in the erythrocytes of hypercholesterolaemic rats, and this was significantly countered by dietary capsaicin. The membrane protein profile and the active cation efflux appeared to be unaffected in the hypercholesterolaemic situation.

[Immune correction in the therapy of patients with prevalent psoriasis with the help of amino acid complex]. / Immunokorrektsiia v terapii bol'nykh rasprostranennym psoriazom s pomoshch'iu aminokislotnogo kompleksa.

In patients with prevalent psoriasis a positive influence amino acid addition (with the standart therapy) on the clinical status of patients and their immune status induces. As a result of this addition use the lesion area diminished, prolongation of remission periods, reduction of the time spent in hospital.

Lipoic acid decreases lipid peroxidation and protein glycosylation and increases (Na(+) + K(+))- and Ca(++)-ATPase activities in high glucose-treated human erythrocytes.

Lipoic acid supplementation has been found to be beneficial in preventing neurovascular abnormalities in diabetic neuropathy. Insufficient (Na(+) + K(+))-ATPase activity has been suggested as a contributing factor in the development of diabetic neuropathy. This study was undertaken to test the hypothesis that lipoic acid reduces lipid peroxidation and glycosylation and can increase the (Na(+) + K(+))- and Ca(++)-ATPase activities in high glucose-exposed red blood cells (RBC). Washed normal human RBC were treated with normal (6 mM) and high glucose concentrations (45 mM) with 0-0.2 mM lipoic acid (mixture of S and R sterioisomers) in a shaking water bath at 37 degrees C for 24 h. There was a significant stimulation of glucose consumption by RBC in the presence of lipoic acid both in normal and high glucose-treated RBC. Lipoic acid significantly lowered the level of glycated hemoglobin (GHb) and lipid peroxidation in RBC exposed to high glucose concentrations. High glucose treatment significantly lowered the activities of (Na(+) + K(+))- and Ca(++)-ATPases of RBC membranes. Lipoic acid addition significantly blocked the reduction in activities of (Na(+) + K(+))- and Ca(++)-ATPases in high glucose- treated RBC. There were no differences in lipid peroxidation, GHb and (Na(+) + K(+))- and Ca(++)-ATPase activity levels in normal glucose-treated RBC with and without lipoic acid. Thus, lipoic acid can lower lipid peroxidation and protein glycosylation, and increase (Na(+) + K(+))- and Ca(++)-ATPase activities in high-glucose exposed RBC, which provides a potential mechanism by which lipoic acid may delay or inhibit the development of neuropathy in diabetes.

[Occupational aspects of work conditions and assessment of several clinical-biochemical and chemiluminescence parameters in workers of oil processing industry]. / Gigienicheskaia kharakteristika uslovii truda i otsenka nekotorykh pokazatelei u rabotnikov neftepererabatyvaiushchei promyshlennosti.

The authors present materials concerning hygienic evaluation of work conditions and health state in individuals exposed to pyromellitic dianhydride and other aromatic substances detected in the air of workplace. Changes in lipid peroxidation were evaluated through serum and urine chemiluminescence levels, shift of energy metabolism parameters was assessed via dynamics of ATP, ADP, AMP and adenyl system enzymes in RBC. Examinees of groups 2 and 3 demonstrated significant changes in adenyl system parameters of RBC and in serum and urine chemiluminescence. Conclusion is that serum and urine studies using bioenergy and chemiluminescence methods help to evaluate compensatory and metabolic resources, to reveal premorbid condition and to correct it without transitory disablement of the subjects.

[Action of Astragalus membranaceus on left ventricular function of angina pectoris].

The action on left ventricular function of Astragalus Membranaceus (AM), a Qi-tonic, in 20 patients with angina pectoris was studied by means of Doppler Echocardiogram (DEC). It showed that cardiac output increased from 5.09 +/- 0.21 to 5.95 +/- 0.18 L/min 2 weeks after AM was administered (P < 0.01), and no improvement of left ventricular diastolic function appeared. Adenosine triphosphatase activity was not inhibited by using AM, which was different from that of digitalis.

Effect of fish oil and vitamin E on ethanol-induced changes in membrane ATPases.

We evaluated whether fish oil or vitamin E administration affected ethanol-induced changes in membrane ATPases. Male Wistar rats (225-250 g) were fed, through a gastric tube a liquid diet containing fish oil (25% of calories) and ethanol for one month. Another group of animals was given supplemental vitamin E (300 u/kg). In the pair-fed control animals, ethanol-derived calories were replaced with dextrose. The blood ethanol levels were maintained between 150 and 350 mg/dL. At sacrifice, the red cells were immediately washed with ice-cold saline, membranes were prepared and ATPases measured. These was no difference in the Na+K+ ATPase, Ca2+ ATPase and Mg2+ ATPase activities between the fish oil-dextrose and corn oil-dextrose groups. A decrease in Ca2+ ATPase and an increase in Na+K+ ATPase was seen with ethanol feeding; these change are similar to those seen in corn oil-ethanol fed rats. In contrast, Vitamin E administration prevented the ethanol-induced changes in ATPase. This observation provides support for the role of lipid peroxidation in alcohol-induced changes in cell membrane ATPase activities.

[The effect of streptase in hypoxia on the blood and abdominal aorta in rats]. / Vliianie streptazy pri gipoksii na krov' i briushnuiu aortu krys.

In the experiment of albino rats it was shown that hypobaric hypoxia caused a disorders of hemostasis with destabilization of membranes and imbalance of electrolytes in the erythrocyte-plasma-vessel wall system. Streptase administration in a dose of 2500 U/kg in this case events in some degree the changes in the process of the blood coagulation, viscosity-elasticity properties of erythrocytes, calcium levels in plasma and erythrocytes, sodium and magnium levels in the abdominal aorta wall produced by the "altitude rise" in an altitude chamber.

A supplement of Dikanut (Irvingia gabonesis) improves treatment of type II diabetics.

The effects of Dikanut (Irvingia gabonensis), an African viscous preparation, as supplement (4g/day) in the diet of eleven Type II diabetics were studied. Levels of plasma lipids, glucose and erythrocyte ATPases were monitored for one month. The dikanut supplement elicited hypolipidemic activity. The reduction in plasma lipids was primarily due to a decrease in LDL + VLDL-cholesterol and triglycerides levels. HDL-cholesterol was increased. The three ATPases of the erythrocyte membrane of the diabetic patients were significantly lower than in normal subjects. When dikanut was consumed by the diabetics for four weeks, the activities of the enzymes increased significantly. The increases correlated well with significant reduction of plasma glucose levels. These desirable biochemical effects mediated by ingestion of a naturally-occurring dietary fibre were accompanied by improved clinical states.

[Effect of vasodilator preparations on the ATPase activity of the erythrocyte membranes of rabbits with experimental vascular pathology]. / Vliianie sosudorasshiriaiushchikh preparatov na ATFaznuiu aktivnost' membran éritrotsitov krolikov s éksperimental'noi sosudistoi patologiei.

Experiments on rabbits with pituitrin hypertension have demonstrated activation of Na+, K+-ATPase of red cell membranes. Meanwhile ATPase activity declined in vasorenal hypertension. The vasodilatory drugs (papaverine, pentamine, euphylline, nicotinic acid) administered in courses normalized both the activity of transport ATPases of cell membranes and carbohydrate metabolism of blood vessels, which was disturbed in experimental vascular pathology.

An extended model of the glycolysis in erythrocytes.

An extension of a previous model [2] is proposed of the glycolysis of erythrocytes which includes realistic rat laws for the hexokinase-phosphofructokinase system and for the 2,3-P2G phosphatase. Whereas most conclusions previously drawn are reinforced, the mechanism of ATP regulation is different in the present model. The ATP concentration is mainly regulated by the inhibitory action of ATP and the activating effect of AMP on the phosphofructokinase. The role of the 2,3-P2G bypass as a buffer of changes in the ATP demand is of lesser significance than previously thought. Besides the feedback action of the adenine nucleotides on the hexokinase-phosphofructokinase system in the quasisteady state the role of 2,3-P2G as an energy source is important since it can yield ATP for a certain period of time. The present version of the model describes qualitatively the experimental data on the modulation of Na+-K+-ATPase.

Kinetic modifications of the acetylcholinesterase and (Ca2+ + Mg2+)-ATPase in rat erythrocytes by cholesterol feeding.

The influence of cholesterol on the membrane-bound acetylcholinesterase and (Ca2+ + Mg2+)-ATPase was studied in erythrocytes of five groups of male rats fed different fat-supplemented diets. Two groups of rats were fed essential fatty acid (EFA) sufficient diets with 5% lard or corn oil as the dietary fat, and two groups were fed EFA-deficient diets: a basic, fat-free diet and the same diet supplemented with 5% hydrogenated beef fat. One additional group of rats was fed a stock diet. The kinetic changes recorded were in the degree of the cooperativity of the inhibition by F- of the acetylcholinesterase and the activation by Ca2+, and by Mg2+ of the (Ca2+ + Mg2+)-ATPase. The kinetic behavior of the enzymes was only modified by cholesterol feeding when they were bound to a membrane with a high fatty acid fluidity (e.g. derived from rats fed the corn oil-supplemented diet). The enzymes from a membrane with a low fatty acid fluidity (e.g. derived from rats fed a lard-supplemented diet) were not altered by cholesterol feeding. The changes were noticeable after 24 hours of cholesterol feeding. It is suggested that the in vivo cholesterol sites are involved in a regulatory mechanism for mammalian membrane-bound enzymes.

Kinetic changes of the erythrocyte (Mg2+ + Ca2+)-adenosine triphosphatase of rats fed different fat-supplemented diets.

The activation by Mg2+, in the presence of 0.2 mM Ca2+, of the erythrocyte ATPase from rats fed with six different fat-supplemented diets has been studied. A sigmoid kinetic curve was found. The values of the Hill coefficient showed a positive correlation with the membrane fatty acid fluidity, which is expressed as the ratio between double bond index and saturated fatty acid content. The values of the Hill coefficient ranged from 1.0, in animals fed with lard-supplemented diet, to 2.0, in animals fed with corn oil-supplemented diet. When the effect of increasing Ca2+ concentration in these two groups was studied at pH 8.1, an activation with the latter group and an inhibition with the former one were found. The activation by Ca2+ found in corn oil-fed animals was lost after treatment with phospholipase C and restored after the addition of homologous phospholipids. The activation could not be restored by addition of phospholipids from lard-fed animals. In this group, treatment with phospholipase C left the kinetic behavior unmodified, but an activation by Ca2+ could be detected after adding phospholipids from corn oil-fed animals. It is suggested that membrane fatty acid fluidity is involved in the cooperative transitions and cryptic activity of the (Mg2+ + Ca2+)-ATPase.