Current Issue : April - June Volume : 2014 Issue Number : 2 Articles : 9 Articles
Background: Dexmedetomidine is a highly selective central a2-agonist with anesthetic and analgesic properties for\r\npatients in intensive care units. There is little information about the relationship between dosage and plasma\r\nconcentration during long drug infusions of dexmedetomidine in critically ill patients, especially in Asians. In\r\naddition, the administration of dexmedetomidine with a dosage of 0.2ââ?¬â??0.7 Ã?µg/kg/h in Japan is different from that\r\nwith a dosage of 0.2ââ?¬â??1.4 Ã?µg/kg/h in European countries and the USA. There has been concern about obtaining an\r\neffective concentration with a small dosage and estimating the relationship between dosage and plasma\r\nconcentration. We conducted a prospective, observational, cohort study measuring plasma dexmedetomidine\r\nconcentrations.\r\nMethods: Plasma dexmedetomidine concentrations of 67 samples from 34 patients in an intensive care unit for\r\n2 months were measured by ultra performance liquid chromatography coupled with tandem mass spectrometry\r\nusing single-blind method, and the correlation coefficient between dosages and plasma concentrations was\r\nestimated. Exclusion criteria included young patients (<16 years) and samples obtained from patients in which the\r\ndosage of dexmedetomidine was changed within 3 h.\r\nResults: Among the patients, 20 (58.8%) of the 34 received dexmedetomidine at 0.20ââ?¬â??0.83 Ã?µg/kg/h, and in 40 of\r\nthe 67 samples for which dexmedetomidine had been administered, this occurred for a median duration of 18.5 h\r\n(range, 3ââ?¬â??87 h). The range of the dexmedetomidine plasma concentration was 0.22ââ?¬â??2.50 ng/ml. By comparison\r\nwith other studies, with a dosage of 0.2ââ?¬â??0.7 Ã?µg/kg/h, the patients in this setting could obtain an effective\r\ndexmedetomidine concentration. The plasma dexmedetomidine concentration was moderately correlated with the\r\nadministered dosage (r = 0.653, P < 0.01). The approximate linear equation was y = 0.171x + 0.254. The range of\r\nRichmond Agitation-Sedation Scale was 0 to -5.\r\nConclusions: We concluded that, with a dosage of 0.2ââ?¬â??0.83 Ã?µg/kg/h, the patients in this setting could obtain an\r\neffective dexmedetomidine concentration of 0.22ââ?¬â??2.50 ng/ml. In addition, the plasma dexmedetomidine\r\nconcentration was moderately correlated with the administered dosage (r = 0.653, P < 0.01)....
Background: Phenylalanine and tyrosine are precursor amino acids required for the synthesis of dopamine, the main\r\nneurotransmitter implicated in the neurobiology of schizophrenia. Inflammation, increasingly implicated in schizophrenia,\r\ncan impair the function of the enzyme Phenylalanine hydroxylase (PAH; which catalyzes the conversion of phenylalanine to\r\ntyrosine) and thus lead to elevated phenylalanine levels and reduced tyrosine levels. This study aimed to compare\r\nphenylalanine, tyrosine, and their ratio (a proxy for PAH function) in a relatively large sample of schizophrenia patients and\r\nhealthy controls.\r\nMethods: We measured non-fasting plasma phenylalanine and tyrosine in 950 schizophrenia patients and 1000 healthy\r\ncontrols. We carried out multivariate analyses to compare log transformed phenylalanine, tyrosine, and phenylalanine:tyrosine\r\nratio between patients and controls.\r\nResults: Compared to controls, schizophrenia patients had higher phenylalanine (p,0.0001) and phenylalanine: tyrosine\r\nratio (p,0.0001) but tyrosine did not differ between the two groups (p = 0.596).\r\nConclusions: Elevated phenylalanine and phenylalanine:tyrosine ratio in the blood of schizophrenia patients have to be\r\nreplicated in longitudinal studies. The results may relate to an abnormal PAH function in schizophrenia that could become a\r\ntarget for novel preventative and interventional approaches....
Ancient texts of Ayurved describe importance of cow as well as different uses of cow milk and products. Not only milk and its products but also cow urine (Gomutra) is also considered as therapeutically important. Ayurved attributes the importance of Panchagavya means ââ?¬Å?the blend of five products such as milk, curd, ghee, dung and urine obtained from cow. These five products individually called ââ?¬Å?Gavyaââ?¬Â and collectively termed as panchgavya and is said to be curer of all diseases. Acharya Yama has stated a method to prepare Panchagavya, which states that different things should be taken from cows of different colors. The present study was planned to evaluate of cow urine by using modern analytical methods. The parameters used for evaluation were Hippuric acid, phenol and total protein content in cow urine by HPTLC, UV-VIS spectroscopic method respectively. This analytical profile was compared with buffalo and goat urine....
Introduction: IFNa has been largely implicated in the ethiopathogenesis of autoimmune diseases but only recently it has\r\nbeen linked to endothelial damage and accelerated atherosclerosis in autoimmunity. In addition, proinflammatory\r\nconditions are supposed to be implicated in the cardiovascular status of these patients. Since a role for IFNa in endothelial\r\ndamage and impaired Endothelial Progenitor Cell (EPC) number and function has been reported in other diseases, we aimed\r\nto evaluate the potential associations of IFNa serum levels on EPC populations and cytokine profiles in Rheumatoid Arthritis\r\n(RA) patients.\r\nMethods: pre-EPC, EPC and mature EPC (mEPC) populations were quantified by flow cytometry analyzing their differential\r\nCD34, CD133 and VEGFR2 expression in blood samples from 120 RA patients, 52 healthy controls (HC), and 83 systemic\r\nlupus erythematosus (SLE) patients as disease control. Cytokine serum levels were measured by immunoassays and clinical\r\nand immunological data, including cardiovascular (CV) events and CV risk factors, were retrospectively obtained by\r\nreviewing clinical records.\r\nResults: Long-standing, but not recent onset RA patients displayed a significant depletion of all endothelial progenitor\r\npopulations, unless high IFNa levels were present. In fact, the IFNhigh RA patient group (n = 40, 33%), showed increased EPC\r\nlevels, comparable to SLE patients. In addition, high IFNa serum levels were associated with higher disease activity (DAS28),\r\npresence of autoantibodies, higher levels of IL-1b, IL-6, IL-10 and MIP-1a, lower amounts of TGF-b, and increased mEPC/EPC\r\nratio, thus suggesting higher rates of endothelial damage and an endothelial repair failure. Finally, the relationship between\r\nhigh IFNa levels and occurrence of CV events observed in RA patients seems to support this hypothesis.\r\nConclusions: IFNa serum marker could be used to identify a group of RA patients with increased disease activity, EPC\r\nimbalance, enhanced proinflammatory profile and higher cardiovascular risk, probably due, at least in part, to an impaired\r\nendothelial repair....
Background: An emerging data suggested a significant impact of statins on PCSK9 concentration, while the rapid\r\nimpacts of other lipid-lowering drugs such as ezetimibe and xuezhikang alone or in combination on PCSK9 and\r\nlipid profile have not been assessed. This study aims to investigate whether an enhanced PCSK9 concentration by\r\nsingle or combined therapy of lipid-lowering drugs currently used precedes the changes of lipid profile in rats.\r\nMethods: Sixty-three rats were randomly divided into six groups and orally administrated with placebo (N = 13),\r\nezetimibe 10 mg/kg daily, Xuezhikang 1200 mg/kg daily, ezetimibe 10 mg/kg plus Xuezhikang 1200 mg/kg daily,\r\npitavastatin 10 mg/kg daily or pitavastatin 10 mg/kg plus ezetimibe 10 mg/kg daily for 3 days (N = 10 for each\r\ngroup respectively). Blood samples were obtained at day 3 after orally administration. Plasma PCSK9 levels were\r\ndetermined by ELISA and lipid profile were measured by enzymatic assay.\r\nResults: Ezetimibe, Xuezhikang and pitavastatin alone and Xuezhikang plus ezetimibe as well as pitavastatin\r\nplus ezetimibe increased PCSK9 levels by 124%, 56%, 111%, 63% and 204% respectively (p < 0.05 compared with\r\nplacebo). However, Xuezhikang plus ezetimibe did not enhance greater PCSK9 levels compared to monotherapy.\r\nEzetimibe and pitavastatin in combination induced higher PCSK9 levels than pitavastatin monotherapy or\r\nco-therapy with ezetimibe plus Xuezhikang. There was no significant difference between any groups with\r\nregard to lipid profile levels at day 3 (P > 0.05).\r\nConclusions: Elevated PCSK9 concentration by ezetimibe, Xuezhikang and pitavastatin alone or in combination was\r\nfound prior to the alterations of lipid profile in rats. Combination of Xuezhikang and ezetimibe significantly\r\nattenuated increase in PCSK9 compared to ezetimibe plus pitavastatin, suggesting that the former combination\r\nmay be better than the latter in future clinical application....
Background: Zinc deficiency is a major public health problem in many developing countries including Nepal.\r\nThe present study was designed to assess the prevalence of zinc deficiency and to study the association of zinc\r\ndeficiency with anthropometric and socio-demographic variables, in school children of eastern Nepal.\r\nMethods: This cross-sectional study included total 125 school children of age group 6ââ?¬â??12 years from Sunsari and\r\nDhankuta districts of eastern Nepal. Plasma zinc level was estimated by Flame Atomic Absorption Spectroscopy.\r\nResults: The Median interquartile range (IQR) values of zinc in the two districts Sunsari and Dhankuta were 5.9\r\n(4.4, 7.9) Ã?µmol/L and 5.8 (4.3, 8.4) Ã?µmol/L respectively. A total of 55 children (87.3%) in Sunsari and 52 (83.9%) in\r\nDhankuta had zinc deficiency, no significant difference was observed in the Median (IQR) plasma zinc levels\r\n(p = 0.9) and zinc deficiency patterns (p = 0.3) of the two districts. Significant differences were observed in the\r\nplasma zinc levels (p = 0.02) and zinc deficiency patterns (p = 0.001), of the school children having age groups 6ââ?¬â??8\r\nyears than in 9ââ?¬â??10 and 11ââ?¬â??12 years of age, and zinc deficiency patterns between male and female school children\r\n(p = 0.04) respectively.\r\nConclusions: The present study showed higher prevalence of zinc deficiency among school children in eastern\r\nNepal. In our study, zinc deficiency was associated with both sex and age. The findings from the present study will\r\nhelp to populate data for policy implementation regarding consumption and supplementation of zinc....
Background: Early-pregnancy short sleep duration is predictive of gestational diabetes and preeclampsia;\r\nmechanisms for these associations are unknown. Leptin, an adipocyte-derived peptide involved in regulating food\r\nintake and energy expenditure, may play a role in these observed associations. Given inconsistent reports linking\r\nshort sleep duration with leptin, and absence of studies among pregnant women, we examined the association of\r\nmaternal sleep duration with plasma leptin in early pregnancy.\r\nMethods: This cross-sectional study included 830 pregnant women. Plasma leptin was measured in samples\r\ncollected around 13 weeks gestation. Sleep duration was categorized as: =5, 6, 7ââ?¬â??8 (reference), and =9 hours.\r\nDifferences in leptin concentrations across categories were estimated using linear regression. Analyses were\r\ncompleted for lean and overweight/obese women.\r\nResults: Overall, women with long sleep duration had elevated plasma leptin (p-value = 0.04). However, leptin\r\nconcentrations were not statistically significantly elevated in women with a short sleep duration. There was no\r\nassociation of leptin with sleep duration among lean women. Among overweight/obese women, a U-shaped\r\nrelation between leptin and sleep duration was observed: Mean leptin was elevated (Ã?Ÿ = 21.96 ng/ml, P < 0.001)\r\namong women reporting =5 hour of sleep compared with reference group; and women reporting =9 hours of\r\nsleep also had elevated leptin (Ã?Ÿ = 4.29 ng/ml, P = 0.09).\r\nConclusions: Short sleep duration, and to a lesser extent long sleep duration, were associated with elevated leptin\r\namong overweight/obese women. These data add some evidence to help understand mechanistic relationships of\r\nsleep duration with pregnancy complications....
Some studies showed that piperine (the alkaloid of piper nigrum) can change the activities of microsomal enzymes.\r\nMidazolam concentration is applied as a probe to determine the CYP3A enzyme activity. This study was done to\r\ndetermine piperine pretreatment role on midazolam plasma concentration.\r\nTwenty healthy volunteers (14 men and 6 women) received oral dose of piperine (15 mg) or placebo for three days\r\nas pretreatment and midazolam (10 mg) on fourth day of study and the blood samples were taken at 0.5, 2.5 and\r\n5 h after midazolam administration. The midazolam plasma levels were assayed using HPLC method (C18 analytical\r\ncolumn, 75:25 methanol:water as mobile phase, UV detector at 242 nm wavelength and diazepam as internal standard).\r\nData were fit in a ââ?¬Å?one-compartment PK modelââ?¬Â using P-Pharm 1.5 software and analyzed under statistical tests.\r\nThe mean Ã?±SD of the age and body mass index were 24.3 Ã?± 1.83 years (range: 21ââ?¬â??28 years) and 23.46Ã?± 2.85,\r\nrespectively. The duration of sedation in piperine receiving group was greater that the placebo group (188Ã?±59 vs.\r\n102Ã?±43 min, p<0.0001). Half-life and clearance of midazolam were higher in piperine pretreatment group compared to\r\nplacebo [1.88Ã?±0.03 vs. 1.71Ã?± 0.04 h (p<0.0001) and 33.62 Ã?± 0.4 vs. 37.09 Ã?± 1.07 ml/min (p<0.0001), respectively].\r\nAccording to the results, piperine can significantly increases half-life and decreases clearance of midazolam compared\r\nto placebo. It is suggested that piperine can demonstrate those effects by inhibition CYP3A4 enzyme activity in liver\r\nmicrosomal system....
Background: Yakuchinone A has a plethora of beneficial biological effects. However, the pharmacokinetic (PK) data\r\nof yakuchinone A still remain unknown so far. Furthermore, the quantification of yakuchinone A in biological\r\nsamples has not been reported in the literature. Therefore, in the present study we aimed to develop a new\r\nmethod for the fast, efficient and accurate assessment of yakuchinone A concentration in plasma, as a means for\r\nfacilitating the PK evaluation of yakuchinone A.\r\nResults: A liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) method was\r\ndeveloped and validated for the determination of yakuchinone A in rat plasma. Mass spectrometric and chromatographic\r\nconditions were optimized. Plasma samples were pretreated by protein precipitation with methanol. LC separation\r\nwas performed on a Phenomenex Luna C18 column with gradient elution using a mobile phase consisting of\r\nmethanolââ?¬â??water containing 0.5 mM formic acid (HCOOH) at a flow rate of 0.28 mL/min. ESI-MS spectra were\r\nacquired in positive ion multiple reaction monitoring mode (MRM). The precursor-to-product ion pairs used for\r\nMRM of yakuchinone A and yakuchinone B were m/z 313.1?137.0 and 311.2?117.1, respectively. Low concentration\r\nof HCOOH reduced the ion suppression caused by matrix components and clearly improved the analytical sensitivity.\r\nYakuchinone A showed good linearity over a wide concentration range (r > 0.99). The accuracy, precision, stability and\r\nlinearity were found to be within the acceptable criteria. This new method was successfully applied to analyze the rat\r\nplasma concentration of parent yakuchinone A after a single oral administration of SuoQuan capsules. Low systemic\r\nexposure to parent yakuchinone A was observed.\r\nConclusion: The proposed method is sensitive and reliable. It is hoped that this newmethod will prove useful for the\r\nfuture PK studies....
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