Near-normal Concentrations Research Articles

Antidiabetic potential of Amomum dealbatum Roxb. flower and isolation of three bioactive compounds with molecular docking and in vivo study

Amomum dealbatum Roxb. parts have been traditionally used as remedies for joint pain, diabetes, muscular rheumatism, antiseptic, and abscesses in Arunachal Pradesh, Assam, and Tripura. Ethyl acetate sub-fraction E3 had significantly inhibited the α-glucosidase (IC50 5.385 μg/mL). The molecular docking revealed quercetin-3-O-galactoside to be the most potent α-glucosidase inhibitor (binding energy −43.214 kcal/mol). Using the QSAR model, the pIC50 values of myricetin, gallic acid, quercetin-3-O-galactoside, and acarbose were predicted to be 5.65235, 4.39858, 5.65235, and 6.03058, respectively. For the first time, quercetin-3-O-galactoside, myricetin, and gallic acid have been isolated from the flowers of A. dealbatum (ADF). E3 decreased blood glucose level to a near-normal concentration (100.60 ± 2.94 mg/dL) in comparison to diabetic control rats (575.20 ± 24.80 mg/dL). The results have strongly suggested the potential of ADF in treating diabetes. This lesser-known plant has the potential to uncover its full medicinal properties through further in-depth research.

Syndrome of inappropriate antidiuretic hormone associated with aripiprazole

A probable case of aripiprazole-induced syndrome of inappropriate antidiuretic hormone (SIADH) is reported. A 65-year-old Caucasian man arrived in the emergency department (ED) with dizziness, headache, abdominal pain, nausea, and vomiting. There had been no recent additions or changes to the patient's medication regimen except for an increase in the daily dose of aripiprazole (from 10 to 20 mg) about two months prior. On admission, the patient's serum sodium concentration was 108 meq/L, prompting discontinuation of aripiprazole use and fluid restrictions. Over the next 72 hours, the serum sodium level increased to a near-normal concentration (127 meq/L), and the man was discharged back to a nursing facility. Three days later, the patient was readmitted to the ED with recurrent symptoms and a serum sodium concentration of 118 meq/L, a serum osmolality of 254 mOsm/kg, a urine osmolality of 575 mOsm/kg, and a urine sodium concentration of 101 meq/L. It was learned that aripiprazole use had been inappropriately resumed at the nursing facility. Aripiprazole was again discontinued, and fluid restrictions were imposed, with subsequent abatement of hyponatremia over four days. Application of the adverse drug reaction probability scale of Naranjo et al. in this case yielded a score of 7, indicating probable aripiprazole-associated SIADH. A 65-year-old man developed severe hyponatremia after an aripiprazole dosage increase. Hyponatremia resolved promptly with the discontinuation of aripiprazole. After discharge from the hospital, the patient inadvertently received aripiprazole again and was subsequently readmitted with another episode of severe hyponatremia.

To lower or not to lower? Making sense of the latest research on intensive glycaemic control and cardiovascular outcomes

Diabetes is an extremely burdensome and costly chronic disease. It affects an estimated 4–6% of the world’s population, and its prevalence continues to rise.1 2 Diabetes is a major cause...

To lower or not to lower? Making sense of the latest research on intensive glycaemic control and cardiovascular outcomes

Diabetes is an extremely burdensome and costly chronic disease. It affects an estimated 4–6% of the world’s population, and its prevalence continues to rise.1 ,2 Diabetes is a major cause...

Glycated protein update: implications of recent studies, including the diabetes control and complications trial

On the basis of the results of the Diabetes Control and Complications Trial (DCCT), the American Diabetes Association (ADA) now recommends tight control of blood glucose to near-normal concentrations as the primary goal for most eligible insulin-dependent diabetic patients. In the DCCT, intensive therapeutic intervention was based on frequent self-monitoring of blood glucose and monthly measurements of glycohemoglobin. The importance of glycohemoglobin assessments serves to highlight the present inadequacies in laboratory measurements of this analyte, which hinders wide implementation of the ADA recommendations. Clinical interventions aimed at achieving the DCCT's published therapeutic goals may place patients at a significantly increased risk for life-threatening hypoglycemia, if the therapy is based on nonstandardized laboratory results. Clinical laboratories will now be under increasing pressure to provide reproducible, standardized measurements of glycohemoglobin, a goal that recent research has shown to be realistic, if widespread interlaboratory calibration is adopted. Finally, recent advances in measuring glycated serum proteins appear to warrant reevaluation of such assays during future intensive therapy trials, as potentially important tools for fine-tuning tight blood glucose control.

Role of cation gradients in hypercontracture of myocytes during simulated ischemia and reperfusion.

We examined the relationship between transsarcolemmal cation gradients and hypercontracture of cardiac myocytes in ischemia and reperfusion using adult rat ventricular myocytes superfused with buffer mimicking normal or ischemic extracellular fluid. Contractile performance of electrically stimulated cells was recorded by an optical video system simultaneously with measurements of intracellular Ca2+ concentration ([Ca2+]i) using fura-2 or intracellular pH (pHi) using 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein. While cells were exposed to simulated ischemia buffer, the transsarcolemmal H+ gradient was abolished, [Ca2+]i transient stopped, and twitch contraction of myocytes ceased. Upon reperfusion with normal buffer, H+ gradient was quickly restored, Ca2+ transients restarted with transient increase in systolic Ca2+, and twitch contraction restarted with development of hypercontracture, which continued after [Ca2+]i returned to preischemic level even in the presence of near-normal concentrations of high-energy phosphates. When the transsarcolemmal proton, Na+, and Ca2+ gradients were altered so that Na+ entry via Na(+)-H+ exchange and Ca2+ entry via Ca(2+)-Na+ exchange were made less favorable, the transient systolic overshoot of Ca2+ at reperfusion and development of hypercontracture was largely avoided. These results suggest that Na+ and then Ca2+ entry via the Na(+)-H+ and Na(+)-Ca2+ exchangers, respectively, probably contribute to the increase in [Ca2+]i and hypercontracture of myocytes at time of reperfusion in this model.

Effect of Temperature and Dissolved Oxygen Concentration onEdwardsiella ictaluriin Experimentally Infected Channel Catfish

Abstract Channel catfish Ictalurus punctatus were experimentally infected with Edwardsiella ictaluri by immersion exposure. After clinical disease ran its course for 52 d, the surviving fish were exposed to one of the following environmental regimes in troughs: 25°C with aeration, 25°C with no aeration, or variable temperature (18–23°C) with no aeration. After 29 d of exposure to the environmental regimes, various organs and tissues of the fish were assayed to determine the effects of these conditions on E. ictaluri concentrations (colony-forming units/mL of tissue sample). The concentrations of this pathogen were significantly (P < 0.05) higher in all tissues (trunk kidney, liver, head kidney, blood, spleen, gallbladder, muscle, brain, and gonad) 52 d postinfection than 29 d after exposure to any of the environmental regimes (81 d postinfection). Fish exposed to a near-normal concentration of dissolved oxygen (6.4 mg/L) and a constant temperature of 25°C had E. ictaluri concentrations that were significa...

Transient diffusion of ion-implanted B in Si: Dose, time, and matrix dependence of atomic and electrical profiles

The time evolution of B diffusion and electrical activation after ion implantation and annealing at 800 and 900 °C is studied using secondary-ion mass spectrometry and spreading-resistance profiling. The time evolution at 800 °C is observed in both crystalline and post-amorphized samples. Amorphized samples show near-normal concentration enhanced diffusion. Crystalline samples show anomalous transient diffusion, with a rapidly diffusing low-concentration region and a static peak region above a critical concentration Cenh=3.5×1018 cm−3. The peak region above Cenh is shown to be electrically inactive. The static, inactive B is released over a period of many hours, compared with the transient diffusion enhancement which relaxes to near-normal within 30 min. The time evolution of B diffusion at 900 °C is observed as a function of implantation dose. A critical concentration for transient diffusion, Cenh=8×1018 cm−2, independent of dose, is observed at this temperature. The transient diffusion enhancement in the diffusing part of the B profile increases with dose, up to a dose of ∼5×1014 cm−3, and saturates at higher doses. A comparison with published data shows that Cenh∼ni within a factor 2 over the temperature range 550–900 °C. We interpret our observations in terms of a nonequilibrium point-defect model of diffusion and intermediate defect formation.

In utero transplantation of hematopoietic stem cells in sheep: The role of T cells in engraftment and graft-versus-host disease

Transplantation of hematopoietic stem cells (HSC) from adult sheep into fetal lambs results in hematopoietic chimerism and graft-versus-host disease (GVHD). To evaluate the role of T cells in HSC engraftment and GVHD we depleted adult marrow HSC of T cells and observed the incidence of chimerism and GVHD in the fetal recipients. Using a naturally occuring polymorphism of the β-globin locus to detect engraftment, bone marrow obtained from homozygous type A hemoglobin adult sheep were transplanted (2 × 10 9 cells/kg fetal weight) into 90 days' gestation fetal lambs homozygous for type B hemoglobin. Donor HSC were T-cell depleted by treatment with antisera (raised in rabbits against sheep thymocytes) in the presence of complement. T-cell depletion resulted in significant decrease in hematopoietic colony formation by donor HSC in vitro (305 ± 49 v 134 ± 21 colonies/10 5 cells) that normalized by the addition of autologous T cells (433 ± 32 colonies/10 5 cells). Marrow depleted of T cells exhibited reduced engraftment in the recipient fetuses. When T cells were added back to donor HSC (depleted of T cells) at near-normal concentrations, engraftment improved but the lambs also developed GVHD. The addition of T cells to donor HSC (depleted of T cells) at concentrations below that present in unprocessed bone marrow resulted in significant engraftment but not GVHD. T cells play an important role in both the engraftment of adult HSC in fetal recipients and the development of GVHD in chimeric newborns. The elimination of T cells prevents GVHD but markedly reduces engraftment. By the reduction, but not elimination, of T cell number, it is possible to preserve the ability of adult HSC to engraft in the fetus without the development of GVHD.

Cellular abnormalities in chronically denervated myocardium. Implications for the transplanted heart.

Heart transplantation involves chronic effects due to denervation, rejection, and treatment of rejection. The chronically denervated dog heart provides a model for the effects of denervation alone. These hearts have been shown to contain intrinsic neurons with VIP and NPY as possible neurotransmitters. Myocardial tissue noradrenaline concentration falls to very low levels after degeneration of postganglionic sympathetic neurons, but dopamine remains in near-normal concentration and is probably synthesized extraneuronally. ANP is present and released normally; however, the natriuretic response to atrial distension is blunted, suggesting that this response is mainly due to a reflex mechanism. Chronically denervated myocardial tissue exhibits increased oxygen consumption in vitro and increased Na-K, ATPase activity but has normal tissue levels of ATP and creatine phosphate. Glucose oxidation is inhibited in vivo, associated with increased levels of fructose-6-phosphate but normal glucose-6-phosphate, suggesting inhibition of phosphofructokinase activity. However, the enzyme protein concentration of phosphofructokinase, as judged by maximal in vitro activity, is normal. Maximal in vitro activities of succinate dehydrogenase, cytochrome oxidase, monoamine oxidase, calcium-dependent ATPase, and glyceraldehyde-3-dehydrogenase are also normal. From these findings, we would predict that patients with transplanted hearts are likely to show myocardial metabolic inefficiency.

Measurement of near-normal concentrations of erythrocyte protoporphyrin with the hematofluorometer: influence of plasma on "front-surface illumination" assay.

Zinc protoporphyrin in erythrocytes increases in iron depletion. Because the hematofluorometer directly measures zinc protoporphyrin in whole blood, it may therefore be a useful screening instrument for detecting iron deficiency. We evaluated its performance with normal to slightly above-normal zinc protoporphyrin concentrations (0.2 to 2.0 mg/L) in erythrocytes, because this is a critical range for differentiating normal and iron-deficient individuals. There was excellent correlation (r2 = 0.900) between erythrocyte protoporphyrin as measured by an extraction procedure and as measured directly with the hematofluorometer. However, at these concentrations, plasma caused hematofluorometer readings to be spuriously high, by 2.4 to 89.4%, an effect due to the instrument's optical design. The effect can be eliminated by washing the cells free of plasma or by allowing erythrocytes to displace plasma by settling to the illuminated surface before the measurement. The interference does not affect the hematofluorometer's sensitivity, but abnormal results obtained for whole blood should be confirmed with more-specific tests, and interlaboratory precision may be influenced if whole-blood samples are used. A 1-min delay from sample placement to measurement decreased zinc protoporphyrin values by 2.6 to 36.9%. We also describe the use of cryopreserved control erythrocytes, for which the CV is 2.3% for a concentration of 0.96 mg per liter of erythrocytes, which are not affected by time of measurement, and which are stable for three months.

Thymic activity in severe combined immunodeficiency diseases.

Thymic function was evaluated by quantitation of circulating thymic factor in patients with several forms of severe infantile immunodeficiency diseases. Direct quantitation of thymic factor in serum of patients with severe combined immunodeficiency revealed heterogeneity of this syndrome by this parameter, as was also shown by study of susceptibility of the marrow cells to differentiation in vitro. Thymic factor was not detectable in one patient with severe combined immunodeficiency, but was present in normal or near-normal concentrations in three others. Circulating levels of this hormonal activity were also not detectable in a patient with DiGeorge athymic syndrome. Following marrow or fetal liver transplantation, which corrected the severe combined immunodeficiency thymic factor levels either increased slightly or did not change appreciably. Fetal thymic transplantation, which together with fetal liver transplantation corrected the immunodeficiency in one patient with severe combined immunodeficiency, was associated with increase of thymic factor to normal levels. Fetal thymus transplantation alone, which was employed to correct the immunodeficiency of DiGeorge athymic syndrome, caused an increase in thymic factor activity to normal or near normal levels in this patient.