Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Earlier studies had failed to show the presence of capillaries between the white fibres of pigeon pectoralis muscle. In this paper, data are reported for the first time documenting that these capillaries occur in both intra- and inter-fasicular areas of the muscle. Fresh frozen sections of pigeon pectoralis major muscle were incubated for alkaline ATPase reaction following pretreatment with different EDTA solutions (4.3 mM, pH 4.3). The results showed the existence of an inherent heterogeneity of capillaries. The capillaries of white fibres stained intensely for K+/Mg2+-EDTA or Mg2+-EDTA pre-incubated ATPase; the capillaries of red fibres stained poorly. Both white fibre and red fibre capillaries were examined ultrastructurally in the non-perfused pigeon pectoralis muscle. It is suggested that a possible correlation exists between the distinctive metabolic and mechanical characteristics of the Type II white, glycolytic, fast-twitch fast-fatigue muscle fibres and the high ATPase activity of their capillaries.
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PMID:On the heterogeneity of capillaries of pigeon pectoralis muscle: a histoenzymatic and ultrastructural study. 15 80

Whole cytosol isolated from human neutrophils was found to accelerate the Ca(2+)-dependent fusion of phospholipid vesicles with neutrophil plasma membranes as measured by several fluorescence resonance energy transfer lipid dilution assays or by the fate of an encapsulated aqueous soluble fluorophore. The Ca2+ (threshold of 2-10 microM) and protein concentration dependencies for fusion mediated by purified human neutrophil annexin I (lipocortin I), recombinant annexin I and des(1-9)annexin I showed behavior similar to that of whole cytosol. A monoclonal antibody against the N-terminal region of annexin I strongly inhibited the action of isolated annexins as well as whole cytosol, indicating that annexin I is the major activity of this type in whole neutrophil cytosol and that it functions even in this complex mixture of proteins. Residual Ca(2+)-dependent fusion activity in the absence of cytosol or annexin I was not inhibited by several antibodies against annexin I, implicating an as yet unknown protein. Kinetic analysis of liposomal fusion showed that annexin I, as in the case of synexin, accelerates aggregation of vesicles but not the actual fusion event per se. The disposition of annexin I in liposomal aggregates was studied by monitoring binding of the protein with a pyrene-phospholipid and by simultaneously monitoring vesicular aggregation by turbidity. An antibody to the N-terminus of annexin I inhibited vesicular aggregation but not binding, suggesting that initial binding of annexin I is similar to that of annexin V. A relatively small proportion of the bound annexin was involved in intervesicular linkage, and no exchange of bound annexin to subsequently added vesicles was observed. The lack of extensive contact between lipids of aggregated vesicles was supported by a lack of energy transfer between phospholipid probes on separate aggregating vesicles. Covalent linkage of maleimidyl or photoaffinity phospholipid derivatives with annexin I in vesicular aggregates did not allow complete disaggregation of vesicles by EDTA, suggesting that monomers of annexin I can contact two membranes simultaneously at the point of intervesicular linkage. These data are discussed in terms of possible models for the structure of this site.
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PMID:Annexin I-mediated vesicular aggregation: mechanism and role in human neutrophils. 138 75

There is increasing evidence that platelets play an important role in the pathogenesis of acute ischemic heart disease. Therefore an understanding of factors that influence platelet performance is important. This study was undertaken (1) to characterize during evolving myocardial infarction platelet activity in the peripheral circulation and across the ischemic/infarcting myocardial compartment, the locus of presumed platelet hyperactivity, and (2) to evaluate the effects of prostacyclin (PGI2), a most potent antiplatelet agent and vasodilator. A total of 59 patients with evolving myocardial infarction were studied. Twenty-two patients were instrumented with arterial and coronary sinus catheters and received intravenous infusion of PGI2, 13 +/- 4.5 ng/kg/min (mean +/- SD), for 90 min. In 15 patients with anterior myocardial infarction, transcardiac platelet function and response to PGI2 were studied. Plasma levels of beta-thromboglobulin (beta-TG) and of thromboxane B2 (TxB2), in vivo measures of platelet activity, were elevated three- and 10-fold. 6-Keto-prostaglandin F 1 alpha, the stable end product of PGI2, was less than 10 pg/ml, reflecting a leftward shift of the TxB2/PGI2 ratio. Platelets circulating during evolving myocardial infarction ("ischemic platelets") were hyperaggregable in response to ADP and relatively resistant to PGI2, both in vivo and in vitro. Concentrations of platelet cyclic AMP and the cyclic AMP response to PGI2 were diminished. The platelet hyperreactivity, expressed by plasma beta-TG, platelet aggregation, and PGI2-induced inhibition of aggregation, was most intense early during infarct evolution and decreased with time. The increased platelet performance resulted in "platelet fatigue," indicated by decreased contents of beta-TG of the ischemic platelet and decreased TxA2 production in response to collagen. However, the ischemic platelet produced twice normal TxA2 in response to arachidonic acid (stimulus and substrate), demonstrating a heightened metabolic capacity. TxA2 was produced across the ischemic/infarcting compartment in 10 of 15 patients with anterior myocardial infarction. The antiplatelet effect of PGI2 was greatly diminished. In summary, the data define an abnormal pattern of platelet behavior during evolving myocardial infarction, characterized by a proaggregatory environment, heightened platelet reactivity in both the peripheral and coronary circulation, and relative resistance to PGI2. The clinical consequences of the data are that the patient in the acute phase of myocardial infarction may benefit from suppression of platelet function and requires significantly greater doses of PGI2 than normal subjects.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Systemic and transcardiac platelet activity in acute myocardial infarction in man: resistance to prostacyclin. 293 81

The quianazoline antifolate N10-propargyl-5,8-dideazafolic acid (ICI 155,387), an inhibitor of thymidylate synthetase (TS), was evaluated for clinical toxicity in a phase I trial. The compound was given once every week as a bolus injection. Fourteen patients with advanced cancer were treated at doses of 10-30 mg/m3. Four patients from the lowest to the highest dose developed severe renal toxicity, detected by a reversible decrease in the Cr-EDTA clearance. Hepatotoxicity was observed with transient elevations of alanine aminotransferase (ALT) in 10 patients and alkaline phosphatase in nine patients. Neither the incidence nor the severity of these toxicities was dose related. Two patients developed feelings of fatigue, which in one patient coincided with a decrease in Cr-EDTA clearance. No myelotoxicity, dermatological, gastrointestinal toxicity or mucositis was seen. No tumour responses due to ICI 155,387 occurred. The severity and the erratic nature of the renal side-effects suggest that this schedule cannot be recommended for further development of this compound in Phase II trials.
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PMID:A phase I evaluation of N10-propargyl-5,8-dideazafolic acid. 335 7

The aim of the present study was to investigate the metabolic base of psychoneurological symptoms, most notably tiredness and loss of concentration ability, appearing after carbohydrate-rich meals and during oral glucose tolerance tests. Such metabolic changes may be the cause of many accidents attributed to the "human factor". Oral glucose tolerance tests (OGTT) were performed in healthy volunteers, divided into symptomatic (n = 21) and symptom-free (n = 15) groups. Since the symptoms arising during OGTT simulate those in alcohol intoxication, a method for clinical examination of alcohol intoxication was used to separate symptom-free from symptomatic subjects. Comparison of blood glucose concentrations during OGTT revealed the symptomatic group to have higher concentrations in blood samples taken 15 min (p less than 0.05), 30 min (p less than 0.01), 45, 60 and 90 min (p less than 0.05) after intake of glucose than those having no symptoms. The symptoms began when the glucose concentration was at maximum, some 38 min (mean value) following the ingestion of glucose. The symptomatic subjects demonstrated a normal assimilation rate of glucose (mean 1.7 %/min) as tested with intravenous glucose tolerance tests and the differences in blood glucose concentrations between the groups is concluded to depend on the rate of absorption of glucose from the intestinal tract. The enterochromaffine cells of the intestinal tract are the site of biosynthesis, storage and release of 5-hydroxytryptamine (5-HT) (serotonin). In whole blood practically all of the 5-HT is of thrombocytic origin. Thrombocytes are thought to be peripheral models of 5-HT neurons in regard to 5-HT uptake, storage release and metabolism. Thrombocytes have a mechanism for 5-HT uptake analogous to the reuptake mechanism for 5-HT in the serotonergic nerve terminals. The whole blood 5-HT changes parallel changes in the 5-HT concentrations of the neurons. In this work 5-HT concentrations were measured during OGTT in whole blood to ascertain the possible relation between 5-HT changes and glucose absorption. For this purpose a reliable, fluorometric method for 5-HT was developed with the following improvements: In whole EDTA-blood the oxidation of 5-HT was prevented with ascorbic acid. The oxidation of hemoglobin iron to ferri-iron was prevented with carbon monoxide, because 5-HT, being a phenol, will otherwise form a complex with ferri-iron. Proteins were precipitated with perchloric acid and the supernatant neutralized before purification of 5-HT by cation exchange.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Role of 5-hydroxytryptamine (serotonin) in oral glucose intolerance. 658 28

We report a case of anemia due to chronic lead poisoning. A 46-year-old female was admitted to our hospital because of general fatigue and anemia. A peripheral blood smear showed basophilic stippling. There was basophilic stippling and nuclear dysplasia of erythroblasts in the bone marrow. Laboratory findings were as follows: RBC 296 X 10(4)/microliter, Hb 8.5 g/dl, blood lead concentration 67 micrograms/dl, urinary lead concentration 309 micrograms/l, blood delta-ALA dehydrase 0.03 mumol/ml, urinary delta-ALA 25.2 mg/l, urinary coproporphyrin 8,810 micrograms/g.Cr, and blood protoporphyrin 612 micrograms/dl. Chronic lead poisoning was diagnosed and she was treated with Ca-EDTA.
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PMID:[Anemia due to chronic lead poisoning]. 896 Jun 71

Mechanical loading contributes to the structural deterioration of bioprosthetic heart valves. The influence of stress state during fixation may play a substantial role in their failure, linking fatigue damage caused by buckling and tension and the enzymatic degradation of glutaraldehyde-crosslinked collagen. Bovine pericardia were obtained immediately postmortem and 100 mm x 15 mm samples were cut in the base-to-apex direction. Half the samples were subjected to a uniaxial tensile stress of 250 kPa and half remained unloaded during a crosslinking treatment in 0.5% glutaraldehyde. Tissue samples were rinsed and cut into 16 mm x 4 mm test strips. Half of these strips were exposed to cyclic compressive buckling and alternating tension at 30 Hz for 20 million cycles (approx. 7.5 days) using a custom-built multi-sample fatigue system. Fatigue-damaged and non-damaged samples were subsequently incubated at 37 C for 48 hrs in: (i) Type I bacterial collagenase (20 U/ml) buffered in 0.05 M Tris, 10 mM CaCl2 2H2O (pH 7.4) or (ii) 0.05 M Tris buffer (pH 7.4) only. In both cases, the samples were loaded sinusoidally between 40 and 80 g using a previously described microtensile culture system. Tissue removed from the bath was rinsed in 0.1 M EDTA solution and mounted in a servo-hydraulic mechanical testing system (MTS). Ultimate tensile strength (UTS), maximum tissue modulus, and fracture strain were determined. The percent collagen solubilized was assessed by a colourmetric hydroxyproline assay of the enzyme bath and tissue sample. All data were analyzed by analysis of variance (ANOVA). The results confirmed the synergy between fatigue damage and collagenase proteolysis in these materials; however, there were no significant differences in this effect between simple fixation and stress-fixation up to 20 million cycles. There were significant decreases in the mechanical properties and an increase in the amount of collagen solubilized with increased exposure to fatigue cycling.
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PMID:Stress state during fixation determines susceptibility to fatigue-linked biodegradation in bioprosthetic heart valve materials. 1208 92

C-reactive protein (CRP) is an acute-phase reactant whose levels increase in response to a variety of inflammatory stimuli. Elevated levels in serum are observed after trauma, tissue necrosis, infection, surgery, and myocardial infarction and are associated with an increased risk of cardiovascular disease. CRP levels are also elevated in noninflammatory states, such as obesity, sleep disturbances, depression, chronic fatigue, aging, and physical inactivity. In this study, the performance of a highly sensitive CRP enzyme immunoassay was evaluated, along with common laboratory variables (specimen type, processing time, and storage conditions) that may influence measured blood concentrations of CRP. The measurement range of the assay was from 0.4 to 50 microg/liter. Total imprecision (coefficient of variation) ranged from 8.1 to 11.4%. CRP levels obtained with the enzyme immunoassay were highly correlated with those obtained with an automated immunonephelometric assay. Comparable results were obtained for plasma (heparin and EDTA treated) and serum samples, and levels were unaffected by delays in sample processing and storage temperature. CRP levels were also unaffected by up to seven freeze-thaw cycles. The median CRP concentration in healthy adults was determined to be 0.94 mg/liter, with a 95% working reference interval of 0 to 6.9 mg/liter. In view of these data, we recommend that serial serum or plasma samples for CRP should be stored at 4 degrees C for short periods of time or at -70 degrees C for longer periods and tested within the same run to minimize interassay variability.
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PMID:Analytical performance of a highly sensitive C-reactive protein-based immunoassay and the effects of laboratory variables on levels of protein in blood. 1285

Breast cancer is the most common cancer among women worldwide. Discomfort and fatigue are usually arisen from anticancer therapy such as surgery, radiotherapy, chemotherapy, hormonal therapy, or combination therapy, because of the suppressed immunological functions. Yunzhi (Coriolus versicolor) can modulate various immunological functions in vitro, in vivo, and in human clinical trials. Danshen (Salvia miltiorrhiza) has been shown to benefit the circulatory system by its vasodilating and anti-dementia activity. The purpose of this clinical trial was to evaluate the immunomodulatory effects of Yunzhi-Danshen capsules in post-treatment breast cancer patients. Eighty-two patients with breast cancer were recruited to take Yunzhi [50 mg/kg body weight, 100% polysaccharopeptide (PSP)] and Danshen (20 mg/kg body weight) capsules every day for a total of 6 months. EDTA blood samples were collected every 2 months for the investigation of immunological functions. Flow cytometry was used to assess the percentages and absolute counts of human lymphocyte subsets in whole blood. Plasma level of soluble interleukin-2 receptor (sIL-2R) was measured by enzyme-linked immunosorbent assay (ELISA). Results showed that the absolute counts of T-helper lymphocytes (CD4+), the ratio of T-helper (CD4+)/T suppressor and cytotoxic lymphocytes (CD8+), and the percentage and the absolute counts of B-lymphocytes were significantly elevated in patients with breast cancer after taking Yunzhi-Danshen capsules, while plasma slL-2R concentration was significantly decreased (all p < 0.05). Therefore, the regular oral consumption of Yunzhi-Danshen capsules could be beneficial for promoting immunological function in post-treatment of breast cancer patients.
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PMID:Immunomodulatory activities of Yunzhi and Danshen in post-treatment breast cancer patients. 1604 56

Rats have inherent licking behavior and responses to good and aversive tasting stimuli, which are comparable to humans. Taste masking of chewable and orodispersible tablets of an iron EDTA complex salt was evaluated using rat behavioral avoidance model, brief access test. Taste-masked chewable and orodispersible tablets of iron EDTA complex were prepared using various flavors and sweeteners as taste-masking agents. These formulations were presented to rats and their responses were recorded in terms of licking frequency and other avoidance responses. Formulations were also presented to human volunteers and a correlation between responses of humans and rats was tried to be established. Taste responses of rats were found to be similar to those of humans. A high correlation between the taste responses of rats and humans was observed. Evaluation of taste masking using human panels presents several difficulties such as ethical concerns, fatigue and subjectivity. Thus, rat behavioral avoidance model can be considered as a good alternative to taste assessment by human volunteers for further such investigations.
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PMID:In vivo evaluation of taste masking for developed chewable and orodispersible tablets in humans and rats. 2351 23


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