Abstract We determined the total activity and isoenzyme distribution of lactate dehydrogenase and creatine kinase in serum and biopsy specimens from skeletal muscle of nine normal individuals and nine patients with Duchenne muscular dystrophy (I), five with collagen disease (II), and four with non-progressive unclassified myopathy (III). Mean total serum creatine kinase in patients with Duchenne muscular dystrophy (867 U/liter, SD = 197) was 31-fold that in the control group (28 U/liter, SD = 14). There was also a small (3.3-fold) increase in the mean total serum creatine kinase of patients with III, but none in the serum from patients with II. Changes in the creatine kinase isoenzyme distribution of skeletal muscle were primarily in the MB isoenzyme. The mean percentage of creatine kinase-MB activity in muscle from patients with I (2.81, SD = 1.15) and patients with III (1.69, SD = 1.07) significantly (P less than 0.005) exceeded that of the control group (0.43, SD = 0.18). Muscle from patients with II showed little change. The most striking changes in lactate dehydrogenase were also observed in patients with I, in whom the mean total serum activity (356 U/liter, SD = 115) was 3.4-fold that of serum from the control group (105 U/liter, SD = 19). Skeletal muscle from these patients also showed a significant decrease in mean percent isoenzyme 5 activity (from 50 to 23) and an increase in that of isoenzymes 1 and 2 (from 1 to 9 and 8 to 20, respectively). These changes in the distribution of these two sets of isoenzymes in muscle were reflected in the serum.
Malaria continues to be one of the most devastating global health problems due to the high morbidity and mortality it causes in endemic regions. The search for new antimalarial targets is vital because of the increasing prevalence of drug resistance in malaria parasites. Malarial proteases constitute promising therapeutic targets as they play important roles in the parasite life cycle. The inhibition of these enzymes has pharmacological and therapeutic significance since they are involved in numerous processes, including the development, invasion, egress, and breakdown of host hemoglobin to release amino acids for parasite sustenance. In this study, <i>in silico</i> techniques were used to shed light on the mechanisms underlying the inhibitory effects of prenylated quercetin isolated from <i>Globimetula oreophila</i> on plasmepsin I and II, falciparum 2 and 3, <i>Plasmodium falciparum</i> calcium-dependent protein kinase 2, dihydrofolate reductase-thymidylate synthase, and serine repeat antigen 5. The test compound significantly interacts with key enzyme binding pockets through hydrogen bonds, van der Waals, and hydrophobic interactions, influencing protease specificity control. Crucial ligand features like carbonyl and hydroxyl groups were identified as essential for receptor interactions. Comparative analysis revealed the test compound's strong binding affinities with energies ranging from -6.4 Kcal/mol to -9.4 Kcal/mol, indicating competitive potential against various enzymes, particularly excelling against <i>Pf</i>DHFR-TS, plasmepsin-I, and SERA5 compared to native ligands. This suggests the compound's ability to competitively inhibit enzyme activity by targeting co-factor binding sites, especially with specific proteases, holding promise for therapeutic applications as potent inhibitors for the prevention and treatment of malaria.
A dexamethasone suppression test (DST) was performed on 8 schizoaffective depressed men. Cross-sectional comparisons were made with three groups: schizophrenics (n = 10), unipolar major depressives (n = 23) and healthy controls (n = 43). All were drug-free and similar in age and body weight. Evaluations utilized the Research Diagnostic Criteria (RDC) for diagnosis, and the Hamilton Rating Scale for Depression for depressive symptom rating. DST nonsuppression, defined as a blood cortisol level of greater than or equal to 5.0 micrograms/dl at 16.00 h postdexamethasone, was observed in 43.5% of the major depressive disorder patients. This was different from the other three groups: 12.5% in schizoaffective depressed, 10.0% in schizophrenics and 9.3% in healthy controls (p less than 0.01, p less than 0.01, and p less than 0.001 respectively). Although schizoaffective depressed patients were significantly different from major depressive disorder patients in their DST responses, both groups were similar in their total HRSD scores and different from the schizophrenics (p less than 0.01 for each). These results, together with others previously reported by us on the thyrotropin-releasing hormone challenge in the same diagnostic groups, may be taken to mean that schizoaffective disorder, depressed type, is biologically distinct from major depressive disorder but not schizophrenia. On the other hand, until further corroborated, they should probably be considered a reflection of the heterogeneity of the schizoaffective syndrome and the nonspecificity of the DST.
Abstract Background Insomnia affects the energy metabolism components which may alter the body’s metabolic functions. Sleep disturbances, both quantitative and qualitative, may increase the risk of developing chronic conditions, such as obesity, metabolic disorders, diabetes, and cardiovascular disease. Aim This study was carried out to investigate the effect of insomnia on glucose homeostasis in aged female rats, and to elucidate the possible underlying mechanism(s), as well as the potential metabolic recovery after retrieval to the normal sleep pattern. Methods 60 Sprague Dawley aged female rats were randomly divided into two main groups: Control group (C) and Insomnia group (I). The latter was further subdivided into two subgroups, 10 rats each: Group Iins. which was subjected to insomnia four hours daily, five days /week for 4 weeks, and Group Іins, Rec. that was subjected to insomnia like Iins. group with retrieval to normal sleep for two weeks. Rats in all groups were subjected to estimation of Body weight (BW), Body mass index (BMI) and Waist circumference at the beginning of the study. The intraperitoneal glucose tolerance test (IPGTT) was measured at the beginning of the study and was monitored every two weeks. By the end of fourth week (for groups C and Iins.) & By the end of the sixth week (for group Iins.rec). BW, BMI, Waist circumference, intraperitoneal glucose tolerance test (IPGTT), peak glycemia (PG) and area under the curve (AUC), Fasting blood glucose (FBG), Insulin, Homeostatic Model Assessment for Insulin Resistance (HOMA- IR), Total cholesterol (TC), Triglycerides (TG), Low density lipoprotein cholesterol (LDL-C), High density lipoprotein cholesterol (HDL-C), Adiponectin, IL6 and Caspase 3 were estimated. Results After four weeks, Iins. rats exhibited a significantly higher change in BW, BMI, WC, FBG, blood glucose levels at 30 min., 60 min, 90 min., 120 min, PG and AUC of IPGGT, insulin level and HOMA-IR, serum (TGs), (TC), (LDL-C), serum IL6 & caspase3 but showed significant decrease in serum level of (HDL-C) and adiponectin in comparison to C rats, After two week recovery from insomnia, Iins.rec. rats exhibited a significantly lower values of WC, FBG, insulin, HOMA-IR, (TGs), (TC), (LDL-C), serum IL6 & caspase3 with insignificant change in BW, BMI, blood glucose levels at 30 min., 60 min, 90 min., 120 min, PG, AUC of IPGGT & serum (HDL-C) with significantly higher values of adiponectin when compared to Iins.rats, and exhibited insignificant change in BW, BMI, WC, FBG, blood glucose levels at 60 min. and at 90 min, (TC), (LDL-C) and adiponectin with significantly higher values of blood glucose levels at 30 min., 120 min, PG and AUC of IPGGT insulin level, HOMA-IR, serum (TGs), serum IL6 & caspase3 with significantly lower values serum (HDL-C) in comparison to the C rats. Conclusion Four-week insomnia in aged female rats resulted in increased blood glucose, insulin resistance, dyslipidemia and enhanced inflammatory and apoptotic states. Retrieval of normal sleep for two weeks normalized body adiposity, fasting blood glucose, total cholesterol and LDL-C and minimized the insulin resistance, hypertriglyceridemia and the decrease in HDL-C as well as inflammation and apoptosis.
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