Increased Serum Alkaline Phosphatase and Serum Phosphate as Predictors of Mortality after Stroke

PubMed Central

S, Pratibha; JB, Agadi

2014-01-01

Context: Serum Alkaline phosphatase (ALP) & phosphate are considered to be indicators of vascular calcification. Link between bone metabolism, vascular calcification, cardiovascular events have been well studied in chronic kidney disease and ischemic heart disease. Aims: To determine that increased serum phosphate and alkaline phosphatase are predictors of mortality rates and recurrent vascular events in stroke. Materials and Methods: Sixty patients admitted with acute stroke (ischemic & haemorrhagic) were included in the study. Their baseline clinical characteristics and biochemical parameters including serum ALP and phosphate were noted. All patients were followed up for a period of one year. The all- cause mortality, the mortality due to cardiovascular events and recurrent vascular events without death were noted during the follow up. Statistical analyses were done to look for any correlation between mortality and baseline levels of serum ALP and phosphate. Results: Of the 60 patients, 8 (13.3%) patients were lost for follow up. Fourteen (26.9%) patients died; of which 12 deaths were due to vascular causes and 2 deaths were due to non vascular causes. Increasing levels of serum ALP and phosphate correlated with all cause mortality and recurrent vascular events without death Conclusion: Serum ALP and phosphate prove to be cost effective prognostic indicator of mortality and recurrent vascular events in stroke. This finding has to be confirmed with studies including larger population. Further research on ALP inhibitors, Vitamin D analogues and phosphate binders to improve mortality in stroke population can be encouraged. PMID:25300293

Increased serum alkaline phosphatase and serum phosphate as predictors of mortality after stroke.

PubMed

S, Pratibha; S, Praveen-Kumar; Jb, Agadi

2014-08-01

Serum Alkaline phosphatase (ALP) & phosphate are considered to be indicators of vascular calcification. Link between bone metabolism, vascular calcification, cardiovascular events have been well studied in chronic kidney disease and ischemic heart disease. To determine that increased serum phosphate and alkaline phosphatase are predictors of mortality rates and recurrent vascular events in stroke. Sixty patients admitted with acute stroke (ischemic & haemorrhagic) were included in the study. Their baseline clinical characteristics and biochemical parameters including serum ALP and phosphate were noted. All patients were followed up for a period of one year. The all- cause mortality, the mortality due to cardiovascular events and recurrent vascular events without death were noted during the follow up. Statistical analyses were done to look for any correlation between mortality and baseline levels of serum ALP and phosphate. Of the 60 patients, 8 (13.3%) patients were lost for follow up. Fourteen (26.9%) patients died; of which 12 deaths were due to vascular causes and 2 deaths were due to non vascular causes. Increasing levels of serum ALP and phosphate correlated with all cause mortality and recurrent vascular events without death Conclusion: Serum ALP and phosphate prove to be cost effective prognostic indicator of mortality and recurrent vascular events in stroke. This finding has to be confirmed with studies including larger population. Further research on ALP inhibitors, Vitamin D analogues and phosphate binders to improve mortality in stroke population can be encouraged.

Effects of routine prophylactic vaccination or administration of aluminum adjuvant alone on allergen-specific serum IgE and IgG responses in allergic dogs.

PubMed

Tater, Kathy C; Jackson, Hilary A; Paps, Judy; Hammerberg, Bruce

2005-09-01

To determine the acute corn-specific serum IgE and IgG, total serum IgE, and clinical responses to s.c. administration of prophylactic vaccines and aluminum adjuvant in corn-allergic dogs. 20 allergic and 8 nonallergic dogs. 17 corn-allergic dogs were vaccinated. Eight clinically normal dogs also were vaccinated as a control group. Serum corn-specific IgE, corn-specific IgG, and total IgE concentrations were measured in each dog before vaccination and 1 and 3 weeks after vaccination by use of an ELISA. The corn-allergic dogs also had serum immunoglobulin concentrations measured at 8 and 9 weeks after vaccination. Twenty allergic dogs received a s.c. injection of aluminum adjuvant, and serum immunoglobulin concentrations were measured in each dog 1, 2, 3, 4, and 8 weeks after injection. The allergic dogs were examined during the 8 weeks after aluminum administration for clinical signs of allergic disease. The allergic dogs had significant increases in serum corn-specific IgE and IgG concentrations 1 and 3 weeks after vaccination but not 8 or 9 weeks after vaccination. Control dogs did not have a significant change in serum immunoglobulin concentrations after vaccination. After injection of aluminum adjuvant, the allergic dogs did not have a significant change in serum immunoglobulin concentrations or clinical signs. Allergen-specific IgE and IgG concentrations increase after prophylactic vaccination in allergic dogs but not in clinically normal dogs. Prophylactic vaccination of dogs with food allergies may affect results of serologic allergen-specific immunoglobulin testing performed within 8 weeks after vaccination.

Steady-State Serum T3 Concentrations for 48 Hours Following the Oral Administration of a Single Dose of 3,5,3'-Triiodothyronine Sulfate (T3S).

PubMed

Santini, Ferruccio; Giannetti, Monica; Ricco, Ilaria; Querci, Giorgia; Saponati, Giorgio; Bokor, Daniela; Rivolta, Giovanni; Bussi, Simona; Braverman, Lewis E; Vitti, Paolo; Pinchera, Aldo

2014-07-01

Sulfate conjugation of thyroid hormones is an alternate metabolic pathway that facilitates the biliary and urinary excretion of iodothyronines and enhances their deiodination rate, leading to the generation of inactive metabolites. A desulfating pathway reverses this process, and thyromimetic effects have been observed following the parenteral administration of 3,5,3'-triiodothyronine (T3) sulfate (T3S) in rats. The present study investigated whether T3S is absorbed after oral administration in humans and if it represents a source of T3. Twenty-eight hypothyroid patients (7 men and 21 women; mean age, 44 ± 11 years) who had a thyroidectomy for thyroid carcinoma were enrolled. Replacement thyroid hormone therapy was withdrawn (42 days for thyroxine, 14 days for T3) prior to 131I remnant ablation. A single oral dose of 20, 40, 80 (4 patients/group), or 160 μg (16 patients/group) of T3S was administered 3 days before the planned administration of 131I. Blood samples for serum T3S and total T3 (TT3) concentrations were obtained at various times up to 48 hours after T3S administration. At all T3S doses, serum T3S concentrations increased, reaching a peak at 2 to 4 hours and progressively returning to basal levels within 8 to 24 hours. The T3S maximum concentration (Cmax) and area under the 0- to 48-hour concentration-time curve (AUC0-48h) were directly and significantly related to the administered dose. An increase in serum TT3 concentration was observed (significant after 1 hour), and the concentration increased further at 2 and 4 hours and then remained steady up to 48 hours after T3S administration. There was a significant direct correlation between the TT3 AUC0-48h and the administered dose of T3S. No changes in serum free thyroxine (T4) concentrations during the entire study period were observed, whereas serum thyroid-stimulating hormone levels increased slightly at 48 hours, but this was not related to the dose of T3S. No adverse events were reported. (1) T3S is

Increased serum bicarbonate in critically ill patients: a retrospective analysis.

PubMed

Libório, Alexandre Braga; Noritomi, Danilo Teixeira; Leite, Tacyano Tavares; de Melo Bezerra, Candice Torres; de Faria, Evandro Rodrigues; Kellum, John A

2015-03-01

Although metabolic alkalosis is a common occurrence, no study has evaluated its prevalence, associated factors or outcomes in critically ill patients. This is a retrospective study from the Multiparameter Intelligent Monitoring in Intensive Care II database. From 23,529 adult patient records, 18,982 patients met the inclusion criteria. Serum bicarbonate levels demonstrated a U-shaped association with mortality with knots at 25 and 30 mEq/l. Of the total included patients, 5,565 (29.3 %) had at least one serum bicarbonate level measurement >30 mEq/l. The majority were exposed to multiple factors that are classically associated with metabolic alkalosis (mainly diuretic use, hypernatremia, hypokalemia and high gastric output). Patients with increased serum bicarbonate exhibited increased ICU LOS, more days on mechanical ventilation and higher hospital mortality. After multivariate adjustment, each 5-mEq/l increment in the serum bicarbonate level above 30 mEq/l was associated with an odds ratio of 1.21 for hospital mortality. The association between increased serum bicarbonate levels and mortality occurs independently of its possible etiologies. An increased serum bicarbonate level is common in critically ill patients; this can be attributed to multiple factors in the majority of cases, and its presence and duration negatively influence patient outcomes.

Increased serum soluble corin in dyslipidemia: A cross-sectional study.

PubMed

Wang, Xiaolei; Chen, Shi; Zhang, Qiu; Liu, Yan; Liu, Lu; Li, Huiling; Peng, Hao

2015-10-23

Natriuretic peptides have been associated with dyslipidemia. As a physiological activator of natriuretic peptides, corin might also be associated with dyslipidemia. However, this association has not yet been studied in Chinese populations. Serum soluble corin and blood lipid profiles were determined for 2496 participants aged above 30y. A logistic regression model was applied to evaluate the association between serum soluble corin and dyslipidemia. Serum soluble corin was significantly increased in participants with dyslipidemia in both men (P<0.001) and women (P<0.001). After controlling for the confounding factors, OR of dyslipidemia positively increased with increasing levels of serum soluble corin in men (P for trend=0.011) and women (P for trend=0.043). Participants with a high corin level were more likely to have dyslipidemia than those with a low corin level in men (OR, 95% CI: 1.45, 1.07-1.97) and women (OR, 95% CI: 1.33, 1.04-1.70). Serum soluble corin was significantly and positively associated with dyslipidemia. Our findings suggested that serum soluble corin may be a marker or risk factor for dyslipidemia. Copyright © 2015 Elsevier B.V. All rights reserved.

Time-Dependent Decline in Serum Phenytoin Concentration with Heightened Convulsive Seizure Risk by Prolonged Administration of Fosphenytoin in Japanese: A Retrospective Study.

PubMed

Ohno, Yuta; Niwa, Takashi; Hirai, Keita; Suzuki, Keiko; Yamada, Yuto; Hayashi, Yuichi; Hayashi, Hideki; Suzuki, Akio; Itoh, Yoshinori

2018-04-20

Because clinical data to confirm the safety and effectiveness of fosphenytoin, a prodrug of phenytoin, are insufficient, the length of administration of fosphenytoin is restricted. Nevertheless, some cases require fosphenytoin administration for more than a few days. The aim of this study was to retrospectively investigate the serum concentration of phenytoin in adult Japanese patients who received intravenous fosphenytoin therapy for more than 3 days. Patients injected with intravenous fosphenytoin for more than 3 days at Gifu University Hospital between January 2012 and September 2014 were enrolled. Individual pharmacokinetic parameters were predicted by Bayesian estimation using NONMEM software, and the maintenance dose of fosphenytoin required to maintain the therapeutic trough concentration (10-20 μg/mL) was calculated from the parameters. Among a total of 8 patients, the serum trough concentration of phenytoin decreased with each day after repeated injection of fosphenytoin. The incidence rate of significant convulsive seizures was increased time-dependently (0% on day 1, 12.5% on day 2, 25% on day 3, and 66.7% on day 4 and after). Phenytoin clearance showed a time-dependent increase. The maintenance dose of fosphenytoin required to maintain the therapeutic trough concentration was simulated to be 779.8 ± 316.8 mg/day, a dose that was markedly higher than the actual maintenance dose (414.1 ± 55.7 mg/day). Prolonged use of fosphenytoin for such patients as those with autoimmune-mediated encephalopathy accompanied with reflux disease and/or ileus time-dependently decreased the serum concentration of phenytoin and increased the risk of convulsion. Therefore, the maintenance dose should be increased to maintain the therapeutic serum concentration.

Oral administration of L-arginine in patients with angina or following myocardial infarction may be protective by increasing plasma superoxide dismutase and total thiols with reduction in serum cholesterol and xanthine oxidase

PubMed Central

Tripathi, Pratima; Chandra, M

2009-01-01

Administration of L-arginine has been shown to control ischemic injury by producing nitric oxide which dilates the vessels and thus maintains proper blood flow to the myocardium. In the present study attempt has been made to determine whether oral administration of L-arginine has any effect on oxidant/antioxidant homeostasis in ischemic myocardial patients [represented by the patients of acute angina (AA) and acute myocardial infarction (MI)]. L-arginine has antioxidant and antiapoptotic properties, decreases endothelin-1 expression and improves endothelial function, thereby controlling oxidative injury caused during myocardial ischemic syndrome. Effect of L-arginine administration on the status of free radical scavenging enzymes, pro-oxidant enzyme and antioxidants viz. total thiols, carbonyl content and plasma ascorbic acid levels in the patients has been evaluated. We have observed that L-arginine administration (three grams per day for 15 days) resulted in increased activity of free radical scavenging enzyme superoxide dismutase (SOD) and increase in the levels of total thiols (T-SH) and ascorbic acid with concomitant decrease in lipid per-oxidation, carbonyl content, serum cholesterol and the activity of proxidant enzyme, xanthine oxidase (XO). These findings suggest that the supplementation of L-arginine along with regular therapy may be beneficial to the patients of ischemic myocardial syndromes. PMID:20716909

Increase in serum magnesium level in haemodialysis patients receiving sevelamer hydrochloride.

PubMed

Mitsopoulos, Efstathios; Griveas, Ioannis; Zanos, Stavros; Anagnostopoulos, Konstantinos; Giannakou, Anastasia; Pavlitou, Aikaterini; Sakellariou, Georgios

2005-01-01

Clinical studies have shown that sevelamer hydrochloride improves lipid profiles and attenuates the progression of the cardiovascular calcifications in haemodialysis patients. It is known that both of these properties are associated with increased magnesium levels. The effect of sevelamer on serum magnesium level is not well documented. The aim of this study was to determine the effects of sevelamer treatment on serum magnesium in haemodialysis patients and to assess the association of magnesium levels with lipid profiles and intact parathyroid hormone (iPTH). Phosphate binders were discontinued during a two week washout period. Forty-seven patients, whose serum phosphate was greater than 6.0 mg/dl at the end of washout, received sevelamer hydrochloride for eight weeks. The patients were then washed off sevelamer for another two weeks. Mean serum phosphorus concentration declined from 7.5 +/- 1.3 to 6.4 +/- 1.2 mg/dl (P < 0.001), mean serum magnesium levels increased from 2.75 +/- 0.35 to 2.90 +/- 0.41 mg/dl (P < 0.001) and median serum iPTH levels decreased from 297 to 213 pg/ml (P=0.001) during the eight weeks of sevelamer treatment. After the two week post-treatment washout phosphorus levels increased to 7.3 +/- 1.3 mg/dl (P < 0.001), magnesium levels were reduced to 2.77 +/- 0.39 mg/dl (P < 0.001) and iPTH levels increased to 240 pg/ml (P=0.012). No change was observed in serum calcium levels during the sevelamer treatment period and the subsequent washout period. The mean decline in total and low density lipoprotein (LDL) cholesterol during sevelamer treatment was 16.3 and 28.3 (P < 0.001), respectively. The mean increase in high density lipoprotein (HDL) cholesterol and in apolipoprotein A1 was 2.9 +/- 5.8 mg/dl (P=0.004) and 6.8 +/- 11.1 mg/dl (P=0.001), respectively. Multivariate analysis showed that the rise in serum magnesium concentration significantly correlated with reductions in iPTH levels (r=-0.40, P=0.016), but did not have any significant

Effects of stress on serum triglycerides, nonsterified fatty acids, and total cholesterol levels in male rats after ethanol administration

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hershock, D.; Vogel, W.H.

1989-02-09

Serum triglycerides, nonesterified fatty acids (NEFA), and total cholesterol were determined during one hour immobilization stress in adult male Sprague-Dawley rats after ethanol administration (2g/kg, i.p.). Stress and ethanol effects were evaluated in two experiments: (1) rats maintained on Purina Rodent Chow for six weeks and fasted for 24 hours; and (2) rats maintained on the same diet supplemented with 1% cholesterol and 10% peanut oil for six weeks and nonfasted prior to experimentation. Blood was obtained from indwelling jugular catheters. In each experiment, differences were seen in triglyceride and NEFA levels but not in total cholesterol. In the regularmore » diet-fed rats (1), serum triglyceride levels were not affected by either stress or ethanol. However, NEFA levels did show differences in the response to ethanol and stress. A 63% decrease from baseline after 5{prime} of stress was partially abolished by ethanol; instead, a 24% increase was observed. Also, a stress-induced increase in NEFA which occurred after 15{prime} was not observed in the ethanol treated rats; rather, a decrease in NEFA was noted. Total cholesterol did not change in response to stress or ethanol. In the high cholesterol diet-fed rats (2), ethanol did not suppress a stress-induced increase in triglyceride levels. NEFA levels in ethanol-treated rats were higher during the first 15{prime} of stress as compared to stress alone. A decrease in NEFA was however seen in the ethanol-treated rats after 30{prime} of stress and these levels remained lower than the stress alone group. A diet-induced increase in total cholesterol levels was observed; however, no changes were seen due to either or ethanol. Thus, ethanol administration prior to acute immobilization stress did affect serum triglyceride and NEFA levels but did not change total cholesterol.« less

Effects of escitalopram, R-citalopram, and reboxetine on serum levels of tumor necrosis factor-α, interleukin-10, and depression-like behavior in mice after lipopolysaccharide administration.

PubMed

Dong, Chao; Zhang, Ji-chun; Yao, Wei; Ren, Qian; Yang, Chun; Ma, Min; Han, Mei; Saito, Ryo; Hashimoto, Kenji

2016-05-01

Inflammation plays a role in the pathophysiology of depression. The purpose of this study is to examine whether the selective serotonin reuptake inhibitor (SSRI) escitalopram, its inactive enantiomer R-citalopram, and selective noradrenaline reuptake inhibitor (NRI) reboxetine, show anti-inflammatory and antidepressant effects in an inflammation-induced model of depression. Pretreatment with escitalopram (1, 3, or 10mg/kg, i.p.) markedly blocked an increase in the serum levels of pro-inflammatory cytokine, tumor necrosis factor-α (TNF-α), after a single administration of lipopolysaccharide (LPS; 0.5mg/kg). Furthermore, escitalopram (3 or 10mg/kg) significantly increased the serum levels of the anti-inflammatory cytokine interleukin-10 (IL-10) by a single administration of LPS. In contrast, pretreatment with R-citalopram (10mg/kg, i.p.) or reboxetine (10mg/kg, i.p.) did not affect the alterations in serum levels of TNF-α and IL-10 after LPS administration. Co-administration of reboxetine with escitalopram did not show anti-inflammatory effects. Pretreatment with escitalopram (10mg/kg) significantly attenuated LPS-induced increase of the immobility time in the tail-suspension test (TST) and forced swimming test (FST). In contrast, pretreatment with R-citalopram (10mg/kg), or reboxetine (10mg/kg) did not alter LPS-induced increase of immobility time of TST and FST. Interestingly, co-administration of reboxetine with escitalopram did not show antidepressant effect in this model. These findings suggest that escitalopram, but not R-citalopram and reboxetine, has anti-inflammatory and antidepressant effects in LPS-treated model of depression, and that reboxetine can antagonize the effects of escitalopram in the inflammation model. Therefore, it is likely that serotonergic system plays a key role in the pathophysiology of inflammation-induced depression. Copyright © 2016 Elsevier Inc. All rights reserved.

Time-dependent alterations in serum NO concentration after oral administration of l-arginine, l-NAME, and allopurinol in intestinal ischemia/reperfusion

PubMed Central

Yanni, Amalia E; Margaritis, Eleutherios; Liarakos, Nikolaos; Pantopoulou, Alkisti; Poulakou, Maria; Kostakis, Maria; Perrea, Despoina; Kostakis, Alkis

2008-01-01

Objective To study the effect of oral administration of a nitric oxide (NO) donor l-arginine (l-Arg), a NO synthase inhibitor NG-nitro-l-arginine methyl ester (l-NAME) and an inhibitor of xanthine oxidase, allopurinol (Allo), on serum NO concentration and catalase activity after intestinal ischemia/reperfusion (I/R) in rats. Methods Male Wistar rats received per os l-Arg (800 mg/kg) or l-NAME (50 mg/kg) or Allo (100 mg/kg) 24 hrs, 12 hrs and 1 hr before underwent 1 hr occlusion of superior mesenteric artery followed by 1 hr of reperfusion (l-Arg(IR1), l-NAME(IR1) and Allo(IR1) respectively) or 1 hr occlusion followed by 8 hrs of reperfusion (l-Arg(IR8), l-NAME(IR8) and Allo(IR8) respectively). There was one group underwent 1 hr occlusion (I), a group underwent 1 hr occlusion followed by 1 hr reperfusion (IR1), a group subjected to 1 hr occlusion followed by 8 hrs of reperfusion (IR8) and a last group that served as control (C). Serum NO concentration and catalase activity were measured. Results After 1 hr of reperfusion serum NO concentration was elevated in IR1 and l-Arg(IR1) groups compared with group C but not in l-NAME(IR1) and Allo(IR1) group. Catalase activity was enhanced in l-NAME(IR1) group. Interestingly, serum NO concentration was increased after 8 hrs of reperfusion in all groups (IR8, l-Arg(IR8), l-NAME(IR8) and Allo(IR8)) compared with control while catalase activity did not show significant difference in any group. Conclusions The results of the present study show that NO concentration is elevated in serum after intestinal I/R and the elevation sustained after administration of l-Arg but not after administration of l-NAME or Allo after 1 hr reperfusion. However, after 8 hrs of reperfusion NO concentration was increased in all groups studied, focusing attention on its possible important role in a complicated situation such as intestinal I/R that involves intestine and other organs. Serum catalase activity does not seem to be affected by per os

Increased androgen response to follicle-stimulating hormone administration in women with polycystic ovary syndrome.

PubMed

Wachs, Deborah S; Coffler, Mickey S; Malcom, Pamela J; Shimasaki, Shunichi; Chang, R Jeffrey

2008-05-01

In women with polycystic ovary syndrome (PCOS), excess ovarian androgen production is driven by increased LH secretion. Studies conducted in animals suggest that the granulosa cell may influence LH-stimulated theca cell androgen production. The objective of this study was to determine whether FSH enhances androgen production in women with PCOS compared with that of normal women. A prospective study was conducted to compare androgen production in response to FSH in two groups of women. The study was conducted in a General Clinical Research Center in a tertiary academic medical center. Women with PCOS, 18-35 yr (n = 20), and normal ovulatory controls, 18-35 yr (n = 10), were recruited for study. Serial blood samples were obtained over a 24-h period after an iv injection of recombinant human FSH (150 IU). The main outcome measures were serum 17-hydroxyprogesterone (17-OHP), androstenedione (A), dehydroepiandrosterone (DHEA), testosterone (T), and inhibin B (Inh B) responses after FSH administration. Basal serum 17-OHP, A, and T levels were markedly increased in women with PCOS compared with that observed in normal women. Basal DHEA and Inh B levels were similar to those of normal controls. After FSH injection, PCOS women demonstrated enhanced production of 17-OHP, A, DHEA, and Inh B, whereas in normal women no increases were observed. T levels declined slightly in both groups. These findings provide evidence that, in PCOS women, theca cell androgen production is enhanced by FSH administration and suggest a granulosa-theca cell paracrine mechanism.

Changes in hepatic gene expression and serum metabolites after oral administration of overdosed vitamin-E-loaded nanoemulsion in rats.

PubMed

Park, Chae Young; Jang, Chul Ho; Lee, Do Yup; Cho, Hyung Taek; Kim, Young Jun; Park, Yoo Heon; Imm, Jee-Young

2017-11-01

Vitamin-E-loaded nanoemulsion (Vit E-NE) was produced, and the effects of repeated oral administration of Vit E-NE (2 g/kg/day) for five days on hepatic gene expression and serum metabolites were investigated in rats. The mean particle diameter and zeta potential of Vit E-NE was 112 nm and 56 mV, respectively. Vit E-NE administered rats showed significantly higher triglyceride content than of standard diet (control) or Vit E control emulsion (Vit E-CE) group but no toxicity symptoms were found in blood biochemical analysis. Next generation sequencing analysis of rat liver revealed that several genes related to energy and xenobiotic metabolism (CYP1A1 and glutathione S-transferase) were significantly altered. Serum metabolites (B-hydroxybutyrate and palmitoleic acid) indicating ketone body production and activation of stearoyl-CoAdesaturase were significantly increased by administration of Vit E-NE. The results of this study suggest that excessive consumption of edible nano-sized food ingredients can possibly cause adverse effects. Copyright © 2017 Elsevier Ltd. All rights reserved.

Response of the antioxidant enzymes of the erythrocyte and alterations in the serum biomarkers in rats following oral administration of nanoparticles.

PubMed

Canli, Esin G; Atli, Gülüzar; Canli, Mustafa

2017-03-01

In this study, Al 2 O 3 , CuO and TiO 2 nanoparticles (NPs) were administered to mature female rats (Rattus norvegicus var. albinos) via oral gavage (0, 0.5, 5, 50mg/kg b.w./day) for 14days to investigate their effects on 14 serum biomarkers and 4 antioxidant enzyme (catalase, superoxide dismutase, glutathione peroxidase, glutathione S-transferase) activities in the erythrocyte. Data showed that Al 2 O 3 did not cause any significant (P>0.05) change in the parameters, except few cases, while CuO and TiO 2 caused significant alterations in antioxidant system parameters of the erythrocytes. Activities of catalase and superoxide dismutase significantly decreased in CuO and TiO 2 administered rats. Oppositely, glutathione peroxidase activity increased in CuO and TiO 2 administered rats. There were no significant alterations in the activity of glutathione S-transferase in the erythrocytes. Levels of glucose, cholesterol, bilirubin, triglyceride, triiodothyronine (T3), estradiol, prolactin and immunoglobulin M (IgM) in the serum altered after some of NP administrations, whereas cortisol, protein, creatinine, blood urea nitrogen (BUN), thyroxine (T4) and immunoglobulin G (IgG) levels in the serum did not change significantly after any of NP administration. There were outstanding increases in the levels of bilirubin and prolactin and decreases in the levels of triglyceride and estradiol. The present study demonstrated that the antioxidant enzymes in the erythrocyte were generally affected from copper and titanium NPs, while aluminium and copper NPs caused more significant alterations in serum biomarkers. Copyright © 2017 Elsevier B.V. All rights reserved.

Increase in tiagabine serum concentration with coadministration of gemfibrozil.

PubMed

Burstein, Aaron H; Boudreau, Eilis A; Theodore, William H

2009-02-01

To report a case of possible acute tiagabine toxicity secondary to administration of gemfibrozil. A 39-year-old male was taking tiagabine 16 mg orally 3 times per day and carbamazepine 500 mg orally twice per day for complex partial seizures secondary to mesial temporal sclerosis. He was found to have type IV hypertriglyceridemia and was prescribed gemfibrozil. Because he reported severe confusion and altered consciousness shortly after a single 600-mg dose of gemfibrozil, he was admitted for controlled challenge with that drug. A single 300-mg dose of gemfibrozil resulted in lightheadedness and led to a 59% and 75% increase in total tiagabine serum concentrations at 2 and 5 hours, respectively, without significant change in baseline carbamazepine concentrations. This is the first report of an interaction between the widely used antihyperlipidemic drug gemfibrozil and tiagabine. Since tiagabine, which was originally developed as an antiepileptic medication, is now being used widely for a variety of other indications such as anxiety and depression, there is an increased risk for clinically significant interactions with gemfibrozil. Increased total and unbound tiagabine concentrations following a single 300-mg dose of gemfibrozil and reproduction of clinical symptoms with gemfibrozil rechallenge suggests the toxicity our patient experienced was due to a pharmacokinetic drug interaction. Use of the Horn Drug Interaction Probability Scale showed a probable interaction between gemfibrozil and tiagabine.

Effects of long-term oral administration of levothyroxine sodium on serum thyroid hormone concentrations, clinicopathologic variables, and echocardiographic measurements in healthy adult horses.

PubMed

Frank, Nicholas; Buchanan, Benjamin R; Elliott, Sarah B

2008-01-01

To determine the effects of long-term oral levothyroxine sodium (L-T(4)) administration on serum thyroid hormone concentrations, thyroid gland function, clinicopathologic variables, and echocardiographic examination measurements in adult euthyroid horses. 6 healthy adult mares. Horses received L-T(4) (48 mg/d) orally for 48 weeks. Every 4 weeks, physical examinations were performed; blood samples were collected for CBC, plasma biochemical analyses, and assessments of serum total triiodothyronine (tT(3)) and thyroxine (tT(4)) concentrations. Plasma creatine kinase MB activity and cardiac troponin I concentration were also measured. Echocardiographic examinations were performed before and at 16, 32, and 48 weeks during the treatment period. During the treatment period, mean body weight decreased significantly; heart rate varied significantly, but the pattern of variation was not consistent. Significant time effects were detected for certain clinicopathologic variables, but mean values remained within reference ranges. Cardiac troponin I was only detectable in 8 of 24 plasma samples (concentration range, 0.01 to 0.03 ng/mL). Serum creatine kinase MB activity did not change significantly over time. Compared with the pretreatment value, 5.4-, 4.0-, and 3.7-fold increases in mean serum tT(4) concentrations were detected at 16, 32, and 48 weeks, respectively. Some cardiac measurements changed significantly over time, but mean values remained within published reference ranges. Mean fractional shortening was lower than the pretreatment mean value at 16 and 32 weeks. In horses, long-term oral administration of 48 mg of L-T(4)/d significantly increased serum tT(4) concentrations and did not appear to adversely affect health.

Serum elevation of B lymphocyte stimulator does not increase regulatory B cells in glioblastoma patients undergoing immunotherapy.

PubMed

Saraswathula, Anirudh; Reap, Elizabeth A; Choi, Bryan D; Schmittling, Robert J; Norberg, Pamela K; Sayour, Elias J; Herndon, James E; Healy, Patrick; Congdon, Kendra L; Archer, Gerald E; Sanchez-Perez, Luis; Sampson, John H

2016-02-01

Regulatory B cells that secrete IL-10 (IL-10(+) Bregs) represent a suppressive subset of the B cell compartment with prominent anti-inflammatory capacity, capable of suppressing cellular and humoral responses to cancer and vaccines. B lymphocyte stimulator (BLyS) is a key regulatory molecule in IL-10(+) Breg biology with tightly controlled serum levels. However, BLyS levels can be drastically altered upon chemotherapeutic intervention. We have previously shown that serum BLyS levels are elevated, and directly associated, with increased antigen-specific antibody titers in patients with glioblastoma (GBM) undergoing lymphodepletive temozolomide chemotherapy and vaccination. In this study, we examined corresponding IL-10(+) Breg responses within this patient population and demonstrate that the IL-10(+) Breg compartment remains constant before and after administration of the vaccine, despite elevated BLyS levels in circulation. IL-10(+) Breg frequencies were not associated with serum BLyS levels, and ex vivo stimulation with a physiologically relevant concentration of BLyS did not increase IL-10(+) Breg frequency. However, BLyS stimulation did increase the frequency of the overall B cell compartment and promoted B cell proliferation upon B cell receptor engagement. Therefore, using BLyS as an adjuvant with therapeutic peptide vaccination could promote humoral immunity with no increase in immunosuppressive IL-10(+) Bregs. These results have implications for modulating humoral responses in human peptide vaccine trials in patients with GBM.

Serum lipocalin-2 levels are increased in patients with psoriasis.

PubMed

Kamata, M; Tada, Y; Tatsuta, A; Kawashima, T; Shibata, S; Mitsui, H; Asano, Y; Sugaya, M; Kadono, T; Kanda, N; Watanabe, S; Sato, S

2012-04-01

The protein lipocalin (LCN)-2 is known to be related to insulin resistance, obesity and atherosclerotic diseases. Psoriasis is an inflammatory skin disease related to metabolic syndrome. The aim of this study was to examine the relationship between serum LCN2 levels and indicators for metabolic syndrome and inflammatory cytokine levels in patients with psoriasis. Serum LCN2 levels were measured in patients with psoriasis, atopic dermatitis (AD) or bullous pemphigoid (BP), and compared with those of healthy controls. Serum LCN2 levels were also compared with several indicators for metabolic syndrome, and with serum levels of interleukin (IL)-6 and tumour necrosis factor (TNF)-α, two markers of inflammation. Serum LCN2 levels in patients with psoriasis were significantly higher than those of healthy controls, but there was no significant correlation between serum LCN2 and body mass index. Serum LCN2 levels also correlated with serum IL-6 and TNF-α levels in patients with psoriasis. Serum LCN2 levels are a general indicator for increased inflammation in the patients with psoriasis. © The Author(s). CED © 2012 British Association of Dermatologists.

Effect of antacid and ascorbic acid on serum salicylate concentration.

PubMed

Hansten, P D; Hayton, W L

1980-01-01

To determine the effect of antacid or ascorbic acid administration on plateau serum salicylate concentrations, nine healthy subjects were given each of the following treatments by balanced block design: choline salicylate (equivalent to 3.76 or 5.62 Gm/day of aspirin); choline salicylate plus magnesium-aluminum hydroxide (120 ml/day); or choline salicylate plus ascorbic acid (3 Gm/day). In subjects developing a control serum salicylate level above 10 mg/dl, antacid administration produced a decrease in serum salicylate level (mean 19.8 mg/dl vs. 15.8 mg/dl) (P less than 0.01). Ascorbic acid administration was not associated with a significant change in serum salicylate. The reduction in serum salicylate following antacid appears to be due to antacid-induced alkalinization of the urine with resultant increase in renal salicylate clearance. Antacid administration should be considered a potential cause of altered serum salicylate concentration in patients receiving large doses of salicylate.

Therapeutic serum phenobarbital concentrations obtained using chronic transdermal administration of phenobarbital in healthy cats.

PubMed

Delamaide Gasper, Joy A; Barnes Heller, Heidi L; Robertson, Michelle; Trepanier, Lauren A

2015-04-01

Seizures are a common cause of neurologic disease, and phenobarbital (PB) is the most commonly used antiepileptic drug. Chronic oral dosing can be challenging for cat owners, leading to poor compliance. The purpose of this study was to determine if the transdermal administration of PB could achieve serum PB concentrations of between 15 and 45 μg/ml in healthy cats. Nineteen healthy cats were enrolled in three groups. Transdermal PB in pluronic lecithin organogel (PLO) was applied to the pinnae for 14 days at a dosage of 3 mg/kg q12h in group 1 (n = 6 cats) and 9 mg/kg q12h in group 2 (n = 7 cats). Transdermal PB in Lipoderm Activemax was similarly applied at 9 mg/kg q12h for 14 days in group 3 (n = 6 cats). Steady-state serum PB concentrations were measured at trough, and at 2, 4 and 6 h after the morning dose on day 15. In group 1, median concentrations ranged from 6.0-7.5 μg/ml throughout the day (observed range 0-11 μg/ml). Group 2 median concentrations were 26.0 μg/ml (observed range 18.0-37.0 μg/ml). For group 3, median concentrations ranged from 15.0-17.0 μg/ml throughout the day (range 5-29 μg/ml). Side effects were mild. One cat was withdrawn from group 2 owing to ataxia and sedation. These results show therapeutic serum PB concentrations can be achieved in cats following chronic transdermal administration of PB in PLO at a dosage of 9 mg/kg q12h. More individual variation was noted using Lipoderm Activemax. Transdermal administration may be an alternative for cats that are difficult to medicate orally. © ISFM and AAFP 2014.

Effects of Oral Prednisone Administration on Serum Cystatin C in Dogs.

PubMed

Muñoz, J; Soblechero, P; Duque, F J; Macías-García, B; Ruiz, P; Zaragoza, C; Barrera, R

2017-11-01

Oral administration of glucocorticoid alters serum cystatin C (sCysC) concentration in humans. To determine if oral administration of prednisone alters sCysC in dogs without pre-existing renal disease. Forty six dogs were included: 10 dogs diagnosed with steroid responsive meningitis arteritis (SRMA; group A), 20 dogs diagnosed of pituitary-dependent hyperadrenocorticism (PDH; group B), and 16 healthy control dogs (group C). Retrospective observational study. SRMA diagnosed dogs were administered prednisone 4 mg/kg/24 h PO 7 days, reducing the dose to 2 mg/kg/24 h 7 days before medication withdrawal. In group A, sampling was performed at days 0, 7, 14 and a final control at day 21. Blood and urine samples were collected in the 3 groups, and in group A, sampling was performed at all time points (days 1, 7, 14, and 21). In group A, sCysC was significantly higher at day 7 compared to the control group (0.4 ± 0.04 mg/L vs. 0.18 ± 0.03 mg/L mean ± SEM respectively P < 0.01); sCysC values decreased to basal at day 14 when the dose was decreased and after 1 week of withdrawal of prednisone (0.27 ± 0.03 mg/L for group A at day 14 and 0.15 ± 0.02 mg/L at day 21; P > 0.05). Dogs with PDH included in group B did not have significant differences in sCysC (0.22 ± 0.03 mg/L) compared to control (P > 0.05). Oral administration of prednisone unlike altered endogenous glucocorticoid production, increases sCysC in dogs in a dose-dependent fashion. Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Effects of antidepressants on alternations in serum cytokines and depressive-like behavior in mice after lipopolysaccharide administration.

PubMed

Ohgi, Yuta; Futamura, Takashi; Kikuchi, Tetsuro; Hashimoto, Kenji

2013-02-01

Accumulating evidence suggests that inflammation may play a role in the pathophysiology of major depressive disorder (MDD). Antidepressants, including selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs), possess anti-inflammatory effects in vitro. Here, we examined the effects of SSRIs and SNRIs on lipopolysaccharide (LPS)-induced inflammation and depressive-like behavior in male mice. A single administration of LPS (0.5mg/kg, i.p.) increased serum levels of the pro-inflammatory cytokine, tumor necrosis factor-α (TNFα) and the anti-inflammatory cytokine, interleukin-10 (IL-10) in mice. Pretreatment with SSRIs (fluoxetine and paroxetine), SNRIs (venlafaxine and duloxetine), or 5-hydroxytryptophan (5-HTP), a precursor of serotonin, attenuated LPS-induced increases in TNFα, whereas it increased serum levels of IL-10, in mice treated with LPS. In the tail suspension test (TST), LPS increased the immobility time without affecting spontaneous locomotor activity, suggesting that LPS induced depressive-like behavior in mice. Treatment with fluoxetine (30 mg/kg) or paroxetine (10mg/kg) significantly shortened LPS-induced increases of immobility time. These results suggested that antidepressants exert anti-inflammatory effects in vivo, and that the serotonergic system may partially mediate these effects. In addition, the anti-inflammatory effects of antidepressants may help alleviate the symptoms of LPS-induced depression in mice. Copyright © 2012 Elsevier Inc. All rights reserved.

Effect of quantity and route of administration of manganese monoxide on feed intake and serum manganese in ruminants

DOE Office of Scientific and Technical Information (OSTI.GOV)

Black, J.R.; Ammerman, C.B.; Henry, P.R.

1985-02-01

The experiment investigated effects of high quantities of manganese and route of administration (diet versus capsule-dosed) on feed intake and blood characteristics in sheep. Twenty-four Florida native or Florida native by St. Croix crossbred wethers, 47 kg initially, were assigned randomly to eight treatments including basal diet supplemented with 0, 3000, 6000, or 9000 ppm manganese as a reagent grade manganese monoxide or basal diet plus gelatin capsules containing the equivalent of 0, 3000, 6000, or 9000 ppm manganese based on intake of the previous day. Three sheep per treatment were provided feed and tap water for ad libitum intake.more » Sheep were fed basal diet for 7 days followed by a 21-day experimental period, then placed back on the basal diet for 7 days. Average daily feed intake was reduced by increasing supplemental manganese, regardless of route. Animals dosed by capsule consumed less feed than those administered manganese in the diet. Serum manganese increased as manganese supplementation increased, but route of administration had no effect.« less

A study of the prevalence of significant increases in serum creatinine following angiotension-converting enzyme inhibitor administration.

PubMed

Thorp, M L; Ditmer, D G; Nash, M K; Wise, R; Jaderholm, P L; Smith, J D; Chan, W

2005-05-01

Angiontension-converting enzyme inhibitors (ACEIs) are beneficial in the treatment of diabetic and nondiabetic kidney disease, coronary artery disease and congestive heart failure. One adverse effect of ACEIs use is a rise in serum creatinine and potential renal failure. This paper attempts to quantify this risk and assess the need for pre- and post-ACEI serum creatinine measurements. A computerized search of Kaiser Permanente Northwest's electronic medical record was conducted to find patients over the age of 40 years taking lisinopril between July 1, 2000 and June 30, 2002. Patient demographic information and presence in diabetes and coronary artery disease registries was collected. A subsequent search for pre- and postlisinopril serum creatinine levels within 6 months of initial lisinopril prescription was conducted. Patients with prelisinopril creatinine < or = 1.2 mg/dl and postlisinopril creatinine > 2.5 mg/dl underwent chart review to discern adverse events associated with the rise in serum creatinine. A total of 18,977 patients were prescribed lisinopril between July 1, 2000 and June 30, 2002. In all 13 166 patients had a pre- and postlisinopril creatinine checked. In all, 31 patients had a rise in creatinine from < or = 1.2 mg/dl to > 2.5 mg/dl (0.2%). Possible contributors to rise in creatinine included congestive heart failure, dehydration and infection. No patients developed end-stage renal disease, although three died. In conclusion, end-stage renal disease is an unlikely outcome among patients prescribed lisinopril and is most likely associated with other events.

Increased serum butyrylcholinesterase activity in type IIb hyperlipidaemic patients.

PubMed

Kálmán, János; Juhász, Anna; Rakonczay, Zoltán; Abrahám, György; Zana, Marianna; Boda, Krisztina; Farkas, Tibor; Penke, Botond; Janka, Zoltán

2004-07-23

The inheritance of the apolipoprotein E4 (APOE4) allele has been shown to increase the plasma cholesterol level, but little information is as concerns the association of the APOE genotype and hyperlipidaemia and the activities of two serum enzymes, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Blood samples from 55 type IIb hyperlipidaemic, non-demented patients and 55 age- and sex-matched controls were therefore examined in this pilot study. A significantly increased BChE activity was found in the serum of type IIb hyperlipidaemic patients, but the AChE activity did not differ significantly as compared with that in the control group. The APOE4 allele was significantly overrepresented among the hyperlipidaemic probands, but neither serum cholinesterase activity was affected by the dosage of the APOE4 gene. Our results point to a possible association between an abnormal lipid metabolism and the BChE activity and might have implications as regards the pathomechanism of both Alzheimer's and vascular dementias and the cholinesterase inhibitor therapy of dementing disorders.

Serum and tissue concentrations of gallium after oral administration of gallium nitrate and gallium maltolate to neonatal calves.

PubMed

Monk, Caroline S; Sweeney, Raymond W; Bernstein, Lawrence R; Fecteau, Marie-Eve

2016-02-01

To determine serum and tissue concentrations of gallium (Ga) after oral administration of gallium nitrate (GaN) and gallium maltolate (GaM) to neonatal calves. 8 healthy neonatal calves. Calves were assigned to 1 of 2 groups (4 calves/group). Gallium (50 mg/kg) was administered as GaN or GaM (equivalent to 13.15 mg of Ga/kg for GaN and 7.85 mg of Ga/kg for GaM) by oral gavage once daily for 5 days. Blood samples were collected 0, 0.25, 0.5, 1, 2, 4, 8, 12, and 24 hours after Ga administration on day 1; 4 and 24 hours after Ga administration on days 2, 3, and 4; and 4, 12, and 24 hours after Ga administration on day 5. On day 6, calves were euthanized and tissue samples were obtained. Serum and tissue Ga concentrations were measured by use of mass spectrometry. Data were adjusted for total Ga dose, and comparisons were made between the 2 groups. Calves receiving GaM had a significantly higher dose-adjusted area under the curve and dose-adjusted maximum serum Ga concentration than did calves receiving GaN. Despite receiving less Ga per dose, calves receiving GaM had tissue Ga concentrations similar to those for calves receiving GaN. In this study, calves receiving GaM had significantly higher Ga absorption than did calves receiving GaN. These findings suggested that GaM might be useful as a prophylactic agent against Mycobacterium avium subsp paratuberculosis infection in neonatal calves.

Antenatal retinoic acid administration increases trophoblastic retinol-binding protein dependent retinol transport in the nitrofen model of congenital diaphragmatic hernia.

PubMed

Kutasy, Balazs; Friedmacher, Florian; Pes, Lara; Coyle, David; Doi, Takashi; Paradisi, Francesca; Puri, Prem

2016-04-01

Low pulmonary retinol levels and disrupted retinoid signaling pathway (RSP) have been implicated in the pathogenesis of congenital diaphragmatic hernia (CDH) and associated pulmonary hypoplasia (PH). It has been demonstrated that nitrofen disturbs the main retinol-binding protein (RBP)-dependent trophoblastic retinol transport. Several studies have demonstrated that prenatal treatment with retinoic acid (RA) can reverse PH in the nitrofen-induced CDH model. We hypothesized that maternal administration of RA can increase trophoblastic RBP-dependent retinol transport in a nitrofen model of CDH. Pregnant rats were treated with nitrofen or vehicle on gestational day 9 (D9) and sacrificed on D21. RA was given i.p. on D18, D19, and D20. Retinol and RA levels were measured using high-performance liquid chromatography. Immunohistochemistry was performed to evaluate trophoblastic expression of RBP. Expression levels of the primary RSP genes were determined using quantitative real-time PCR and immunohistochemistry. Markedly increased trophoblastic RBP immunoreactivity was observed in CDH+RA compared to CDH. Significantly increased serum and pulmonary retinol and RA levels were detected in CDH+RA compared to CDH. Pulmonary expression of RSP genes and proteins were increased in CDH+RA compared to CDH. Increased trophoblastic RBP expression and retinol transport after antenatal administration of RA suggest that retinol-triggered RSP activation may attenuate CDH-associated PH by elevating serum and pulmonary retinol levels.

Increased serum concentrations of adiponectin in canine hypothyroidism.

PubMed

Mazaki-Tovi, Michal; Abood, Sarah K; Kol, Amir; Farkas, Amnon; Schenck, Patricia A

2015-02-01

Serum concentrations of adiponectin were compared between sex-matched hypothyroid (n = 18) and euthyroid (n = 18) client-owned dogs with comparable ages and body condition scores (BCS). Concentrations of adiponectin (mean; 95% confidence interval) were significantly (P < 0.01) higher in hypothyroid (17.2 µg/mL; 12.1-20.5 µg/mL) than healthy (8.0 µg/mL; 5.6-11.4 µg/mL) dogs following adjustment for potential confounders (BCS, age and sex). Serum concentrations of adiponectin were significantly negatively associated with concentrations of total thyroxine (P <0.05) and positively correlated with concentrations of cholesterol (r = 0.6, P <0.01) in hypothyroid dogs. In conclusion, this study demonstrated increased serum concentrations of adiponectin in dogs with hypothyroidism. Suggestive of the presence of resistance to adiponectin that could have contributed to development of hyperlipidemia and insulin resistance in these dogs or alternatively, could be a consequence of these metabolic alterations. Copyright © 2014 Elsevier Ltd. All rights reserved.

Increased Serum Oxidative Stress Markers in Women with Uterine Leiomyoma

PubMed Central

Santulli, Pietro; Borghese, Bruno; Lemaréchal, Herve; Leconte, Mahaut; Millischer, Anne-Elodie; Batteux, Frédéric

2013-01-01

Background Uterine leiomyomas (fibroids) are the most common gynaecological benign tumors in premenopausal women. Evidences support the role of oxidative stress in the development of uterine leiomyoma. We have analysed oxidative stress markers (thiols, advanced oxidized protein products (AOPP), protein carbonyls and nitrates/nitrites) in preoperative sera from women with histologically proven uterine leiomyoma. Methodology/Principal Findings We conducted a laboratory study in a tertiary-care university hospital. Fifty-nine women with histologically proven uterine leiomyoma and ninety-two leiomyoma-free control women have been enrolled in this study. Complete surgical exploration of the abdominopelvic cavity was performed in each patient. Preoperative serum samples were obtained from all study participants to assay serum thiols, AOPP, protein carbonyls and nitrates/nitrites. Concentrations of serum protein carbonyl groups and AOPP were higher in leiomyoma patients than in the control group (p=0.005 and p<0.001, respectively). By contrast, serum thiol levels were lower in leiomyoma patients (p<0.001). We found positive correlations between serum AOPP concentrations and total fibroids weight (r=0.339; p=0.028), serum AOPP and serum protein carbonyls with duration of infertility (r=0.762; p=0.006 and r=0.683; p=0.021, respectively). Conclusions/Significance This study, for the first time, reveals a significant increase of protein oxidative stress status and reduced antioxidant capacity in sera from women with uterine leiomyoma. PMID:23951284

Influence of human body composition on serum peak thyrotropin (TSH) after recombinant human TSH administration in patients with differentiated thyroid carcinoma.

PubMed

Castagna, Maria Grazia; Pinchera, Aldo; Marsili, Alessandro; Giannetti, Monica; Molinaro, Eleonora; Fierabracci, Paola; Grasso, Lucia; Pacini, Furio; Santini, Ferruccio; Elisei, Rossella

2005-07-01

In this study, we evaluated the influence of height, weight, body mass index (BMI), body surface area, and body composition [total lean body mass (LBM) and fat body mass] on serum peak TSH levels obtained after recombinant human (rh)TSH. Furthermore, to verify whether the serum peak TSH influenced the efficacy of radioiodine ((131)I), we compared the rate of thyroid remnant ablation according to the patients' BMI. We studied 105 patients with differentiated thyroid carcinoma who underwent rhTSH stimulation test. Serum TSH measurements were performed before and 24, 48, and 72 h after rhTSH administration. We also compared the rate of thyroid remnant ablation among 70 differentiated thyroid carcinoma patients with different BMI. The serum peak TSH after rhTSH was significantly lower in overweight and obese subjects compared with normal-weight subjects (92.1 +/- 41.8, 82.4 +/- 24.2, and 112.7 +/- 46.3 microU/ml, respectively; P = 0.01) and in males compared with females (74.6 +/- 22.3 and 105.0 +/- 43.0 microU/ml, respectively; P = 0.0002). By univariate analysis, serum peak TSH was negatively related to weight, height, body surface area, BMI, LBM, and fat body mass, but only LBM was independently associated with serum peak TSH levels. Although it was confirmed that overweight and obese patients had a lower serum peak TSH, the rate of ablation did not differ among normal-weight, overweight, and obese patients. With this study we demonstrated that LBM is the only parameter independently associated with serum peak TSH after rhTSH administration. However, the serum peak TSH does not influence the rate of (131)I remnant ablation.

Increased serum concentrations of soluble ST2 predict mortality after burn injury.

PubMed

Hacker, Stefan; Dieplinger, Benjamin; Werba, Gregor; Nickl, Stefanie; Roth, Georg A; Krenn, Claus G; Mueller, Thomas; Ankersmit, Hendrik J; Haider, Thomas

2018-06-27

Large burn injuries induce a systemic response in affected patients. Soluble ST2 (sST2) acts as a decoy receptor for interleukin-33 (IL-33) and has immunosuppressive effects. sST2 has been described previously as a prognostic serum marker. Our aim was to evaluate serum concentrations of sST2 and IL-33 after thermal injury and elucidate whether sST2 is associated with mortality in these patients. We included 32 burn patients (total body surface area [TBSA] >10%) admitted to our burn intensive care unit and compared them to eight healthy probands. Serum concentrations of sST2 and IL-33 were measured serially using an enzyme-linked immunosorbent assay (ELISA) technique. The mean TBSA was 32.5%±19.6%. Six patients (18.8%) died during the hospital stay. Serum analyses showed significantly increased concentrations of sST2 and reduced concentrations of IL-33 in burn patients compared to healthy controls. In our study cohort, higher serum concentrations of sST2 were a strong independent predictor of mortality. Burn injuries cause an increment of sST2 serum concentrations with a concomitant reduction of IL-33. Higher concentrations of sST2 are associated with increased in-hospital mortality in burn patients.

Effects of oral administration of levothyroxine sodium on serum concentrations of thyroid gland hormones and responses to injections of thyrotropin-releasing hormone in healthy adult mares.

PubMed

Sommardahl, Carla S; Frank, Nicholas; Elliott, Sarah B; Webb, Latisha L; Refsal, Kent R; Denhart, Joseph W; Thompson, Donald L

2005-06-01

To determine the effects of levothyroxine sodium (L-T4) on serum concentrations of thyroid gland hormones and responses to injections of thyrotropin-releasing hormone (TRH) in euthyroid horses. 12 healthy adult mares. 8 horses received an incrementally increasing dosage of L-T4 (24, 48, 72, or 96 mg of L-T4/d) for weeks 1 to 8. Each dose was provided for 2 weeks. Four additional horses remained untreated. Serum concentrations of total triiodothyronine (tT3), total thyroxine (tT4), free T3 (fT3), free T4 (fT4), and thyroid-stimulating hormone (TSH) were measured in samples obtained at weeks 0, 2, 4, 6, and 8; 1.2 mg of TRH was then administered i.v., and serum concentrations of thyroid gland hormones were measured 2 and 4 hours after injection. Serum reverseT3 (rT3) concentration was also measured in the samples collected at weeks 0 and 8. Treated horses lost a significant amount of weight (median, 19 kg). Significant treatment-by-time effects were detected for serum tT3, tT4, fT3, fT4, and TSH concentrations, and serum tT4 concentrations were positively correlated (r, 0.95) with time (and therefore dosage) in treated horses. Mean +/- SD serum rT3 concentration significantly increased in treated horses (3.06 +/- 0.51 nmol/L for week 8 vs 0.74 +/- 0.22 nmol/L for week 0). Serum tT3, tT4, fT3, and TSH concentrations in response to TRH injections differed significantly between treated and untreated horses. Administration of levothyroxine sodium increased serum tT4 concentrations and blunted responses toTRH injection in healthy euthyroid horses.

Why Block Grants Should Increase Administrative Costs.

ERIC Educational Resources Information Center

Baker, Keith

1983-01-01

Federal education programs increase costs because they attach fewer strings to funds than state or local grants, and this is likely to lead to administrative empire-building. Bureaucracy tends pathologically as it grows to generate more work for itself independent of true administrative needs. Some policy implications are drawn. (MJL)

Clinical significance of increased serum levels of FGF-23 in fibrous dysplasia.

PubMed

Florez, Helena; Mandelikova, Stanislava; Filella, Xavier; Monegal, Ana; Guañabens, Núria; Peris, Pilar

2017-12-30

Fibrous dysplasia (FD) can be associated with the development of hypophosphatemic osteomalacia, caused by the production of FGF-23 by dysplastic bone tissue. This study analysed FGF-23 levels in patients with FD, and their association with disease activity and serum phosphate values. Twelve adult patients with FD were included in the study. Clinical history, disease extension and activity and treatments received were reviewed, and the relationship of those values with FGF-23 and serum P levels was analysed. FGF-23 was elevated in 6/12 patients (50%). Patients with high FGF-23 levels had similar age and disease activity and extension than those who did not. No differences were observed in serum phosphate values between both groups (increased FGF-23: 3.9±0.9 mg/dl vs. decreased FGF-23: 3.5±0.6 mg/dl). In fact, none of the patients with increased FGF-23 had low serum phosphate values. Adult FD patients frequently present elevated FGF-23 values with no serum phosphate level repercussion, suggesting an alteration in the processing of this protein in the dysplastic bone tissue for this pathology. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

Analysis of serum corticosteroid-induced alkaline phosphatase isoenzyme in dogs with hepatobiliary diseases.

PubMed

Kojima, K; Ohno, K; Kanemoto, H; Goto-Koshino, Y; Fukushima, K; Tsujimoto, H

2017-05-01

To reveal the relationship between canine corticosteroid-induced alkaline phosphatase isoenzyme activity and hepatobiliary diseases. Retrospective analysis of the relationship between serum corticosteroid-induced alkaline phosphatase activity and diagnosis, serum cortisol concentration and alanine transferase activity in dogs with hepatobiliary diseases. Dogs with a history of glucocorticoid administration were excluded. Seventy-two dogs with hepatobiliary diseases were analysed. The serum corticosteroid-induced alkaline phosphatase concentration was increased in dogs with hepatobiliary diseases. There was no correlation between serum cortisol concentration and serum corticosteroid-induced alkaline phosphatase percentage or activity. Dogs with hepatobiliary disease can exhibit high serum alkaline phosphatase activity even if the dogs have not been administrated glucocorticoids and the serum cortisol concentration is normal. © 2017 British Small Animal Veterinary Association.

Increased serum serotonin improves parturient calcium homeostasis in dairy cows.

PubMed

Hernández-Castellano, Lorenzo E; Hernandez, Laura L; Weaver, Samantha; Bruckmaier, Rupert M

2017-02-01

Hypocalcemia in dairy cows is caused by the sudden increase in calcium demand by the mammary gland for milk production at the onset of lactation. Serotonin (5-HT) is a key factor for calcium homeostasis, modulating calcium concentration in blood. Therefore, it is hypothesized that administration of 5-hydroxy-l-tryptophan (5-HTP), a 5-HT precursor, can increase 5-HT concentrations in blood and, in turn, induce an increase in blood calcium concentration. In this study, 20 Holstein dairy cows were randomly assigned to 2 experimental groups. Both groups received a daily i.v. infusion of 1 L of either 0.9% NaCl (C group; n = 10) or 0.9% NaCl containing 1 mg of 5-HTP/kg of BW (5-HTP group, n = 10). Infusions started d 10 before the estimated parturition and ceased the day of parturition, resulting in at least 4 d of infusion (8.37 ± 0.74 d of infusion). Until parturition, blood samples were collected every morning before the infusions, after parturition samples were taken daily until d 7, and a final sample was collected on d 30. Milk yield was recorded during this period. No differences between groups were observed for blood glucose, magnesium, and β-hydroxybutyrate. Cows receiving the 5-HTP infusion showed an increase in fatty acid concentrations from d -3 to -1 before parturition. Serum 5-HT concentrations were increased at d -4 related to parturition until d 5 postpartum in the 5-HTP group compared with the C group. In addition, cows from the 5-HTP group had increased 5-HT concentrations in colostrum, but not in mature milk, on d 7 postpartum. Serum calcium concentrations decreased in both groups around parturition; however, calcium remained higher in the 5-HTP group than in controls, with a significant difference between groups on d 1 (1.62 ± 0.08 vs. 1.93 ± 0.09 mmol/L in control and 5-HTP groups, respectively) and d 2 (1.83 ± 0.06 vs. 2.07 ± 0.07 mmol/L in control and 5-HTP groups, respectively). Additionally, colostrum yield (first milking) was lower in the

Minocycline reduces inflammatory parameters in the brain structures and serum and reverses memory impairment caused by the administration of amyloid β (1-42) in mice.

PubMed

Garcez, Michelle Lima; Mina, Francielle; Bellettini-Santos, Tatiani; Carneiro, Franciellen Gonçalves; Luz, Aline Pereira; Schiavo, Gustavo Luis; Andrighetti, Matheus Scopel; Scheid, Maylton Grégori; Bolfe, Renan Pereira; Budni, Josiane

2017-07-03

Alzheimer's disease (AD) is a neurodegenerative disorder and the most common type of age-related dementia. Cognitive decline, beta-amyloid (Aβ) accumulation, neurofibrillary tangles, and neuroinflammation are the main pathophysiological characteristics of AD. Minocycline is a tetracycline derivative with anti-inflammatory properties that has a neuroprotective effect. The aim of this study was to evaluate the effect of minocycline on memory, neurotrophins and neuroinflammation in an animal model of AD induced by the administration of Aβ (1-42) oligomer. Male BALB/c mice were treated with minocycline (50mg/kg) via the oral route for a total of 17days, 24h after intracerebroventricular administration of Aβ (1-42) oligomer. At the end of this period, was performed the radial maze test, and 24h after the last minocycline administration, serum was collected and the cortex and hippocampus were dissected for biochemical analysis. The administration of minocycline reversed the memory impairment caused by Aβ (1-42). In the hippocampus, minocycline reversed the increases in the levels of interleukin (IL-1β), Tumor Necrosis Factor- alpha (TNF-α) and, IL-10 caused by Aβ (1-42). In the cortex, AD-like model increase the levels of IL-1β, TNF-α and, IL-4. Minocycline treatment reversed this. In the serum, Aβ (1-42) increased the levels of IL-1β and IL-4, and minocycline was able to reverse this action, but not to reverse the decrease of IL-10 levels. Minocycline also reversed the increase in the levels of Brain-derived neurotrophic factor (BDNF) in the hippocampus caused by Aβ (1-42), and reduced Nerve Growth Factor (NGF) increases in the total cortex. Therefore, our results indicate that minocycline causes improvements in the spatial memory, and cytokine levels were correlated with this effect in the brain it. Besides this, minocycline reduced BDNF and NGF levels, highlighting the promising effects of minocycline in treating AD-like dementia. Copyright © 2017

Deficits in serum amyloid A contribute to increased neonatal mortality during murine listeriosis.

PubMed

Hawkins, J Seth; Wu, Qingqing; Wang, Yanxia; Lu, Christopher Y

2013-12-01

To understand the increased susceptibility of preterm neonates to infection. A murine listeriosis model using immunohistochemistry, microarray technology, and real-time polymerase chain reaction (PCR). We report that recombinant serum amyloid A (SAA) administered prophylactically 18 h before intraperitoneal (i.p.) inoculation with Listeria monocytogenes conferred a dramatic survival benefit compared with administration of only vehicle in neonatal mice. Neonates that received the recombinant SAA protein had significantly fewer Listeria colony counts on plating of infected liver and showed significantly more activated macrophages, but SAA did not affect postnatal growth. Real-time PCR was used to confirm the microarray findings that gene expression levels for the SAA proteins 1 (Saa1) and 2 (Saa2), in addition to that for orosomucoid-2 (Orm2), were strikingly elevated in the adult compared with those in the neonate. Real-time PCR analysis showed that of the acute phase cytokines, tumor necrosis factor (TNF) gene expression increased exponentially with time in the infected adult, whereas neonates did not show similar increases. The increased susceptibility of neonatal mice to listeriosis is in part mediated by a deficiency in the acute phase response, specifically expression of SAA, and that prophylactic SAA protein before neonatal murine listeriosis results in more macrophage activation, lower Listeria counts, and greater survival.

Incidence of immediate hypersensitivity reaction and serum sickness following administration of Crotalidae polyvalent immune Fab antivenom: a meta-analysis.

PubMed

Schaeffer, Tammi H; Khatri, Vaishali; Reifler, Liza M; Lavonas, Eric J

2012-02-01

  Crotalidae polyvalent immune Fab (ovine) (FabAV) is commonly used in the treatment of symptomatic North American crotaline snake envenomation. When approved by the U.S. Food and Drug Administration in 2000, the incidences of immediate hypersensitivity reactions and serum sickness were reported as 0.14 and 0.18, respectively. The objective of this meta-analysis was to evaluate the incidence of immediate hypersensitivity reactions and serum sickness reported in studies of patients treated with FabAV therapy after North American crotaline envenomation.   The authors searched PubMed, Ovid MEDLINE, and EMBASE from January 1, 1997, to September 20, 2010, for English-language medical literature and cross-referenced bibliographies of reviewed articles. The published abstracts of the major toxicology conferences were also searched. All prospective and retrospective cohort studies with patients receiving FabAV therapy for North American crotaline envenomations were eligible for data abstraction. Two content experts reviewed full-text articles and extracted relevant study design and outcome data. Proportions of immediate hypersensitivity and serum sickness for each study were analyzed in a random-effects model to produce an overall estimate of immediate hypersensitivity and serum sickness incidence associated with FabAV administration.   The literature search revealed 11 unique studies of patients who received FabAV that contained information on immediate hypersensitivity reactions and serum sickness. The meta-analysis produced a combined estimate of the incidence of immediate hypersensitivity of 0.08 (95% confidence interval [CI] = 0.05 to 0.11) and a combined estimate of the incidence of serum sickness of 0.13 (95% CI = 0.07 to 0.21).   In this systematic literature review and meta-analysis, the combined estimates of the incidence of immediate hypersensitivity reactions and serum sickness from FabAV in the treatment of symptomatic North American crotaline

Increased Serum Sodium and Serum Osmolarity Are Independent Risk Factors for Developing Chronic Kidney Disease; 5 Year Cohort Study.

PubMed

Kuwabara, Masanari; Hisatome, Ichiro; Roncal-Jimenez, Carlos A; Niwa, Koichiro; Andres-Hernando, Ana; Jensen, Thomas; Bjornstad, Petter; Milagres, Tamara; Cicerchi, Christina; Song, Zhilin; Garcia, Gabriela; Sánchez-Lozada, Laura G; Ohno, Minoru; Lanaspa, Miguel A; Johnson, Richard J

2017-01-01

Epidemics of chronic kidney disease (CKD) not due to diabetes mellitus (DM) or hypertension have been observed among individuals working in hot environments in several areas of the world. Experimental models have documented that recurrent heat stress and water restriction can lead to CKD, and the mechanism may be mediated by hyperosmolarity that activates pathways (vasopressin, aldose reductase-fructokinase) that induce renal injury. Here we tested the hypothesis that elevated serum sodium, which reflects serum osmolality, may be an independent risk factor for the development of CKD. This study was a large-scale, single-center, retrospective 5-year cohort study at Center for Preventive Medicine, St. Luke's International Hospital, Tokyo, Japan, between 2004 and 2009. We analyzed 13,201 subjects who underwent annual medical examination of which 12,041 subjects (age 35 to 85) without DM and/or CKD were enrolled. This analysis evaluated age, sex, body mass index, abdominal circumference, hypertension, dyslipidemia, hyperuricemia, fasting glucose, BUN, serum sodium, potassium, chloride and calculated serum osmolarity. Elevated serum sodium was an independent risk factor for development of CKD (OR: 1.03, 95% CI, 1.00-1.07) after adjusted regression analysis with an 18 percent increased risk for every 5 mmol/L change in serum sodium. Calculated serum osmolarity was also an independent risk factor for CKD (OR: 1.04; 95% CI, 1.03-1.05) as was BUN (OR: 1.08; 95% CI, 1.06-1.10) (independent of serum creatinine). Elevated serum sodium and calculated serum osmolarity are independent risk factors for developing CKD. This finding supports the role of limiting salt intake and preventing dehydration to reduce risk of CKD.

Thiazide increases serum calcium in anuric patients: the role of parathyroid hormone.

PubMed

Vasco, Raquel F V; Reis, Eduardo T; Moyses, Rosa M A; Elias, Rosilene M

2017-12-01

We evaluated the effect of hydrochlorothiazide in a sample of anuric patients on hemodialysis and found an increase in serum calcium, which occurred only in those with parathyroid hormone >300 pg/ml. This finding highlights the extra-renal effect of this diuretic and a possible role of parathyroid hormone in the mechanism. Thiazide diuretics are commonly used in patients with chronic kidney disease to treat hypertension. Their effects on calcium and bone metabolism are not well established, once calciuria may not fully explain levels of calcium and parathyroid hormone (PTH) in this population. A previous study has suggested that thiazides require the presence of PTH as a permissive condition for its renal action. In anuric patients, however, the role of PTH, if any, in the thiazide effect is unknown. To assess thiazide extra renal effect on serum calcium and whether such an effect is reliant on PTH, hydrochlorothiazide (HCTZ) 100 mg was given orally once a day to a sample of 19 anuric patients on hemodialysis for 2 weeks. Laboratories' analyses were obtained in three phases: baseline, after diuretic use, and after a 2-week washout phase. We demonstrated that serum calcium (Ca) increased in ten patients (52.6%) after HCTZ use, returning to previous levels after the washout period. Out of the 19 patients, ten presented PTH ≥ 300 pg/ml, and Ca has increased in eight of them, whereas in the other nine patients with PTH < 300 pg/ml, serum Ca has increased only in two individuals (RR risk of increase Ca 3.9; p = 0.012). HCTZ was capable of increasing serum Ca in a sample of anuric patients on hemodialysis and seems this effect is highly dependent on PTH levels. Caution is required while interpreting this result, as the small sample size might implicate in a finding caused by chance.

Epidermal Dysfunction Leads to an Age-Associated Increase in Levels of Serum Inflammatory Cytokines.

PubMed

Hu, Lizhi; Mauro, Theodora M; Dang, Erle; Man, George; Zhang, Jing; Lee, Dale; Wang, Gang; Feingold, Kenneth R; Elias, Peter M; Man, Mao-Qiang

2017-06-01

Even though elderly populations lack visible or other clinical signs of inflammation, their serum cytokine and C-reactive protein levels typically are elevated. However, the origin of age-associated systemic inflammation is unknown. Our previous studies showed that abnormalities in epidermal function provoke cutaneous inflammation, and because intrinsically aged skin displays compromised permeability barrier homeostasis and reduced stratum corneum hydration, we hypothesized here that epidermal dysfunction could contribute to the elevations in serum cytokines in the elderly. Our results show first that acute disruption of the epidermal permeability barrier in young mice leads not only to a rapid increase in cutaneous cytokine mRNA expression but also an increase in serum cytokine levels. Second, cytokine levels in both the skin and serum increase in otherwise normal, aged mice (>12 months). Third, expression of tumor necrosis factor-α and amyloid A mRNA levels increased in the epidermis, but not in the liver, in parallel with a significant elevation in serum levels of cytokines. Fourth, disruption of the permeability barrier induced similar elevations in epidermal and serum cytokine levels in normal and athymic mice, suggesting that T cells play a negligible role in the elevations in cutaneous and serum inflammatory cytokines induced by epidermal dysfunction. Fifth, correction of epidermal function significantly reduced cytokine levels not only in the skin but also in the serum of aged mice. Together, these results indicate that the sustained abnormalities in epidermal function in chronologically aged skin contribute to the elevated serum levels of inflammatory cytokines, potentially predisposing the elderly to the subsequent development or exacerbation of chronic inflammatory disorders. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Serum S100B level increases after running but not cycling exercise.

PubMed

Stocchero, Cintia Mussi Alvim; Oses, Jean Pierre; Cunha, Giovani Santos; Martins, Jocelito Bijoldo; Brum, Liz Marina; Zimmer, Eduardo Rigon; Souza, Diogo Onofre; Portela, Luis Valmor; Reischak-Oliveira, Alvaro

2014-03-01

The objective of this study was to investigate the effect of running versus cycling exercises upon serum S100B levels and typical markers of skeletal muscle damage such as creatine kinase (CK), aspartate aminotransferase (AST) and myoglobin (Mb). Although recent work demonstrates that S100B is highly expressed and exerts functional properties in skeletal muscle, there is no previous study that tries to establish a relationship between muscle damage and serum S100B levels after exercise. We conducted a cross-sectional study on 13 male triathletes. They completed 2 submaximal exercise protocols at anaerobic threshold intensity. Running was performed on a treadmill with no inclination (RUN) and cycling (CYC) using a cycle-simulator. Three blood samples were taken before (PRE), immediately after (POST) and 1 h after exercise for CK, AST, Mb and S100B assessments. We found a significant increase in serum S100B levels and muscle damage markers in RUN POST compared with RUN PRE. Comparing groups, POST S100B, CK, AST and Mb serum levels were higher in RUN than CYC. Only in RUN, the area under the curve (AUC) of serum S100B is positively correlated with AUC of CK and Mb. Therefore, immediately after an intense exercise such as running, but not cycling, serum levels of S100B protein increase in parallel with levels of CK, AST and Mb. Additionally, the positive correlation between S100B and CK and Mb points to S100B as an acute biomarker of muscle damage after running exercise.

Identification of a Hemolysis Threshold That Increases Plasma and Serum Zinc Concentration.

PubMed

Killilea, David W; Rohner, Fabian; Ghosh, Shibani; Otoo, Gloria E; Smith, Lauren; Siekmann, Jonathan H; King, Janet C

2017-06-01

Background: Plasma or serum zinc concentration (PZC or SZC) is the primary measure of zinc status, but accurate sampling requires controlling for hemolysis to prevent leakage of zinc from erythrocytes. It is not established how much hemolysis can occur without changing PZC/SZC concentrations. Objective: This study determines a guideline for the level of hemolysis that can significantly elevate PZC/SZC. Methods: The effect of hemolysis on PZC/SZC was estimated by using standard hematologic variables and mineral content. The calculated hemolysis threshold was then compared with results from an in vitro study and a population survey. Hemolysis was assessed by hemoglobin and iron concentrations, direct spectrophotometry, and visual assessment of the plasma or serum. Zinc and iron concentrations were determined by inductively coupled plasma spectrometry. Results: A 5% increase in PZC/SZC was calculated to result from the lysis of 1.15% of the erythrocytes in whole blood, corresponding to ∼1 g hemoglobin/L added into the plasma or serum. Similarly, the addition of simulated hemolysate to control plasma in vitro caused a 5% increase in PZC when hemoglobin concentrations reached 1.18 ± 0.10 g/L. In addition, serum samples from a population nutritional survey were scored for hemolysis and analyzed for changes in SZC; samples with hemolysis in the range of 1-2.5 g hemoglobin/L showed an estimated increase in SZC of 6% compared with nonhemolyzed samples. Each approach indicated that a 5% increase in PZC/SZC occurs at ∼1 g hemoglobin/L in plasma or serum. This concentration of hemoglobin can be readily identified directly by chemical hemoglobin assays or indirectly by direct spectrophotometry or matching to a color scale. Conclusions: A threshold of 1 g hemoglobin/L is recommended for PZC/SZC measurements to avoid increases in zinc caused by hemolysis. The use of this threshold may improve zinc assessment for monitoring zinc status and nutritional interventions.

Muscle enzyme and fiber type-specific sarcomere protein increases in serum after inertial concentric-eccentric exercise.

PubMed

Carmona, G; Guerrero, M; Cussó, R; Padullés, J M; Moras, G; Lloret, M; Bedini, J L; Cadefau, J A

2015-12-01

Muscle damage induced by inertial exercise performed on a flywheel device was assessed through the serum evolution of muscle enzymes, interleukin 6, and fiber type-specific sarcomere proteins such as fast myosin (FM) and slow myosin (SM). We hypothesized that a model of muscle damage could be constructed by measuring the evolution of serum concentration of muscle proteins following inertial exercise, according to their molecular weight and the fiber compartment in which they are located. Moreover, by measuring FM and SM, the type of fibers that are affected could be assessed. Serum profiles were registered before and 24, 48, and 144 h after exercise in 10 healthy and recreationally active young men. Creatine kinase (CK) and CK-myocardial band isoenzyme increased in serum early (24 h) and returned to baseline values after 48 h. FM increased in serum late (48 h) and remained elevated 144 h post-exercise. The increase in serum muscle enzymes suggests increased membrane permeability of both fast and slow fibers, and the increase in FM reveals sarcomere disruption as well as increased membrane permeability of fast fibers. Consequently, FM could be adopted as a fiber type-specific biomarker of muscle damage. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Effects of psychological stress on serum iron and erythropoiesis.

PubMed

Wei, Chunlan; Zhou, Jian; Huang, Xueqiang; Li, Min

2008-07-01

There are about one billion patients with iron deficiency anaemia all over the world. Recently, researchers have reported successively that stress can cause decrease of serum iron, in consistent with our studies showing that heat exposure and acceleration stress led to significant decrease of serum iron in rats. However, so far whether pure psychological stress can cause decrease of serum iron and consequently affect erythropoiesis has not been reported. To study the characteristic effects of psychological stress on serum iron and erythropoiesis, and to establish an useful experimental basis for further study involving how sufficient intake of dietary iron causes decrease of serum iron and the consequent effects on physiological function of the human body. Psychological stress was administered to 20 rats with Communication Box system. On the 7th and 14th day after administration, 10 rats were executed, respectively, and the rat blood and femoral bone marrow were collected for analysis of serum iron (SI), serum ferritin (SF), serum transferrin receptor (sTfR), haemoglobin (Hb), red blood cell count (RBC), RBC distribution width (RDW), mean corpuscular volume (MCV), serum erythropoietin (EPO) and bone marrow iron. Experimental data were statistically analysed with SPSS 11.0. For rats analysed on the 7th and 14th day in psychological stress group, (1) femoral bone marrow iron was significantly decreased; (2) serum iron was decreased by 28.6% (P < 0.01) and 27.5% (P < 0.01); (3) Hb was decreased by 10.0% (P < 0.01) and 12.8% (P < 0.01), RBC count was decreased by 5.1% (P < 0.05) and 9.8% (P < 0.01), MCV was decreased by 1.7% (P < 0.05) and 7.3% (P < 0.01), RDW was increased by 10.7 and 22.5%; (4) serum ferritin, transferrin receptor and EPO showed no significant changes in comparison with controls after 7-day administration, but serum ferritin and EPO were decreased by 23.8 and 12.3% while transferrin receptor increased by 31.5% after 14-day administration. For rats

Effect of Enterococcus faecium SF68 on serum cobalamin and folate concentrations in healthy dogs.

PubMed

Lucena, R; Olmedilla, A B; Blanco, B; Novales, M; Ginel, P J

2018-04-17

To study the effect of a 14-day administration of the probiotic Enterococcus faecium SF68 on serum concentrations of cobalamin and folate in healthy dogs. Thirty-six healthy dogs were randomly allocated between probiotic and control groups. Enterococcus faecium SF68 was administered to the probiotic group for 14 days whereas the control group did not receive any product. A blood sample was taken from all dogs when starting the administration (day 1), when the administration ended (day 14) and 14 days later (day 28). Serum cobalamin and folate concentrations and the canine inflammatory bowel disease activity index scores were determined at each time point. There was a progressive reduction of mean serum cobalamin in the probiotic group during the 28-day study, with significantly lower concentration at day 28 compared to baseline and day 14 concentrations. Moderate hypocobalaminaemia was observed in eight dogs at day 28. Probiotic administration was associated with a non-significant increase in mean serum folate concentration at day 14, and a significant decrease at day 28 compared with day 1. The canine inflammatory bowel disease activity index score remained unaltered during the study. Short-term Enterococcus faecium SF68 administration caused a significant reduction of mean cobalamin concentration and moderate hypocobolaminaemia in eight of 18 dogs. Monitoring serum folate appears unnecessary because the probiotic caused a non-significant increase that returned to baseline values after administration was discontinued. © 2018 British Small Animal Veterinary Association.

Increased (/sup 125/I)trypsin-binding in serum from cystic fibrosis patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cox, K.L.; Frates, R.C. Jr.; Sheikholislam, B.M.

1982-01-01

The capacities of normal and cystic fibrosis (CF) sera to bind to exogenous human (/sup 125/I)trypsin were compared. Sera from eight older CF patients bound significantly more exogenous human (/sup 125/I)trypsin than did sera from eight normal subjects (p less than 0.001). Disregarding the increased trypsin-binding (TB) of CF sera, serum immunoreactive trypsinogen (SIRT) levels were not detectable in these eight older CF patients. However, when SIRT levels were corrected for TB, four CF patients had normal SIRT concentrations and four had low but detectable SIRT levels. As compared to five normal newborns' sera, serum from a newborn with CFmore » had normal TB and the SIRT levels were very high. In conclusion, increased TB in CF serum lowers results of SIRT assays. Therefore, unless SIRT levels are corrected for TB, results obtained from currently available SIRT kits may be invalid.« less

Serum gamma-glutamyltransferase activity is increased in patients with calcific aortic valve stenosis.

PubMed

Bozbas, Huseyin; Yildirir, Aylin; Demir, Ozlem; Cakmak, Abdulkadir; Karacaglar, Emir; Yilmaz, Mustafa; Eroglu, Serpil; Pirat, Bahar; Ozin, Bulent; Muderrisoglu, Haldun

2008-07-01

A growing body of data indicates an independent association between serum gamma-glutamyltransferase (GGT) activity, a marker of increased oxidative stress, and cardiovascular diseases. The process of calcific aortic valve disease has been shown to present characteristics of atherosclerosis. The study aim was to evaluate the possible role of serum GGT in patients with calcific aortic valve disease. The results of patients' echocardiography studies from 2005 for the presence of calcific aortic valve disease in the forms of aortic stenosis (AS) and aortic valve calcification (AVC) without significant valve stenosis, were retrospectively evaluated. Age-and gender-matched patients with normal aortic valve morphology were selected at random as a control group. A total of 383 patients was enrolled into the study (126 with AS, 133 with AVC, 124 controls). Serum GGT activity, along with other liver enzyme analyses and laboratory results, were determined and compared among the groups. Age, gender and clinical and laboratory results were similar among the three groups. Median serum GGT levels in the AS, AVC and control groups were 23.0 U/1 (mean 31.5 +/- 24.9 U/1), 22.0 U/1 (mean 27.6 +/- 18.6 U/) and 18.0 U/l (mean 22.4 +/- 16.4 U/l), respectively. Compared to controls, AS patients had significantly higher serum GGT and C-reactive protein levels, while the differences between AVC patients and controls for these parameters were not significant. The study results suggest that serum GGT activity is increased in patients with calcific AS. These increases seem to occur in advanced rather than milder forms of calcific aortic valve disease.

Sibutramine administration decreases serum anti-Müllerian hormone (AMH) levels in women with polycystic ovary syndrome.

PubMed

Vosnakis, Christos; Georgopoulos, Neoklis A; Armeni, Anastasia K; Papadakis, Efstathios; Roupas, Nikolaos D; Katsikis, Ilias; Panidis, Dimitrios

2012-08-01

To investigate the effect of diet, physical exercise and sibutramine administration on serum anti-Müllerian hormone (AMH) levels, hormonal and metabolic parameters in overweight and obese patients with polycystic ovary syndrome (PCOS). Prospective clinical study, in an outpatient clinic setting, of 76 overweight and obese women with PCOS. All patients were placed on a hypocaloric diet, physical exercise plus sibutramine (10 mg per day) for the first month and then on either a hypocaloric diet, physical exercise plus sibutramine (10 mg per day) or a hypocaloric diet and physical exercise for the subsequent 6 months. Serum AMH levels, body composition, hormonal and metabolic features and insulin sensitivity indices were evaluated at baseline and at 4 and 7 months of treatment. Body weight reduction was greater in the sibutramine group. Moreover, serum FSH and testosterone levels decreased, and SHBG, free androgen index and all indices of insulin resistance significantly improved at 4 and 7 months. Serum AMH levels decreased only in PCOS women who received sibutramine, at both 4 and 7 months of treatment. A hypocaloric diet and a diet plus sibutramine both resulted in significant weight loss in overweight and obese women with PCOS. Patients who received sibutramine showed greater weight loss and improvement in hyperandrogenemia and insulin sensitivity after 7 months of treatment. Serum AMH levels significantly decreased at both 4 and 7 months of treatment only in PCOS women who received sibutramine, indicating a possible direct, gonadotropin independent effect of sibutramine on the ovarian production of AMH. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

The effect of two different doses comprising the simultaneous administration of intravenous B-complex vitamins and oral folic acid on serum homocysteine levels in hemodialysis patients.

PubMed

Sombolos, Kostas; Papaioannou, Anna; Christidou, Fotini; Natse, Taisir; Bamichas, Gerasimos; Gionanlis, Lazaros; Katsaris, George; Progia, Evagelia

2006-01-01

Several regimens using different doses of folic acid (FA) alone or supplemented with B-complex vitamins (BCVs) have been tested for their ability to reduce total homocysteine (tHcy) serum levels in hemodialysis (HD) patients. In the present study, we assessed the effect of two different doses comprising the simultaneous administration of intravenous (IV) BCVs and an oral FA supplementation on serum tHCy levels in HD patients. In a cohort of 49 patients (31 male, 18 female) undergoing chronic HD treatment for a mean of 40.0+/-40.7 months, serum concentrations of tHcy, folate and vitamin-B12 (vB12) were determined at the end of three sequential periods as follows: 20 weeks without any BCV and/or FA supplementation (period A), 20 weeks with a dose comprising the simultaneous administration of IV BCVs and an oral supplementation of 5 mg of FA once a week (period B), and 20 weeks with a dose comprising the simultaneous administration of IV BCVs and an oral supplementation of 5 mg of FA thrice a week (period C). An IV dose of BCVs consisting of a 5 mL solution containing vitamin B1 (250 mg), vitamin B6 (250 mg) and vitamin B12 (1.5 mg) was administered at the end of hemodialysis. Mean serum tHcy levels were significantly higher at the end of period A relative to levels at the end of periods B and C (35.8+/-23 micromol/L vs. 22.0+/-17.6 and 15.0+/-4.5 micromol/L, respectively; p<0.000001). Mean serum folate levels and mean serum vB12 levels were significantly lower at the end of period A relative to levels at the end of periods B and C (p<0.000001). Mean serum tHcy levels were lowest at the end of period C (p<0.000001 in comparison to periods A and B), and 26 of the 49 HD patients (67.3%) possessed tHcy levels below 16 micromol/L. In HD patients, high doses consisting of the simultaneous administration of IV BCVs and an oral FA supplementation resulted in the efficient reduction of serum tHcy levels.

Central irisin administration suppresses thyroid hormone production but increases energy consumption in rats.

PubMed

Tekin, Suat; Erden, Yavuz; Ozyalin, Fatma; Onalan, Ebru Etem; Cigremis, Yilmaz; Colak, Cemil; Tekedereli, Ibrahim; Sandal, Suleyman

2018-05-01

Irisin, which is secreted from the skeletal muscle in response to physical exercise and defined as a thermogenic peptide, may play an important role in energy metabolism. Thyroid hormones, which are one of the other influential factors on the metabolic status, increase heat production and are the main regulators of energy metabolism. This study was conducted to determine the possible effects of irisin administration on thyroid hormones. Forty adult male Wistar albino rats were used in the study. The rats were equally divided into 4 groups (n = 10). The brain infusion kit was implanted in the groups, and irisin (or solvent as control) was centrally administered to the rats via osmotic mini pumps for 7 days. During the experiment, food consumption, body weights, and body temperatures of the animals were recorded. Food intake was significantly increased in the groups treated with irisin (p < 0.05), but their body weights were not changed. Hypothalamic TRH gene expression, serum TSH, fT3, and fT4 levels were significantly lower in the groups treated with irisin as compared to the naive and control groups (p < 0.05). In addition, irisin increased UCP1 mRNA expression in white and brown adipose tissue and UCP3 mRNA expression in muscle tissue in rats and also raised their body temperature (p < 0.05). Consequently, although central irisin administration has inhibitory effects on the hypothalamic-pituitary-thyroid axis, it seems to be an important agent in the regulation of food intake and energy metabolism. Copyright © 2018 Elsevier B.V. All rights reserved.

Influence of sildenafil and donepezil administration on the serum redox balance in experimentally induced lower limb critical ischemia.

PubMed

Constantinescu, Mihaela Ioana; Constantinescu, Dan Petru; Andercou, Aurel; Mironiuc, Ion Aurel

2013-01-01

Chronic lower limb ischemia (CLLI) leads to endothelial cell dysfunctions and endothelial lesions. The use of substances that release nitric oxide and activate endothelial nitric oxide synthase has proved to be useful in increasing angiogenesis and arteriogenesis under critical ischemia conditions. To investigate the therapeutic effect of Sildenafil and Donepezil with a vasodilating action in experimentally induced CLLI and on serum redox homeostasis. The research was performed in 3 groups of rats (n=10 animals/group) with experimentally induced CLLI: group I - control group; group II - animals treated postoperatively with a therapeutic dose of sildenafil, and group III - animals treated postoperatively with a therapeutic dose of donepezil. Oxidative stress (OS) indicators (malondialdehyde - MDA, protein carbonyls - PC), antioxidant (AO) defense indicators (reduced glutathione - GSH and oxidized glutathione - GSSH), and ceruloplasmin (CP) were determined on days 7, 14, 21 and 30. Statistical processing was performed using the Excel application (Microsoft Office 2007), with the StatsDirect v.2.7.2 software. Changes in OS were evidenced in all groups on account of a decrease in MDA and PC. The greatest OS decrease in all groups was on day 30. AO defence changes were represented by decreased levels of GSH and GSSG in all groups, at the studied moments. Intracellular AO defense in the cytosol, nucleus and mitochondria was similar in all groups, (decreased GSH, GSSG and GSH/GSSG ratio). We found increased extracellular levels of GSH, GSSG, and CP and increased extracellular GSH/GSSG ratio at level compared to values on day 7. 1) The administration of sildenafil (group II) and donepezil (group III) has favorable effects on reducing OS in experimentally induced CLLI. 2) Sildenafil and Donepezil administration stimulates extracellular AO defense on account of CP. 3) Sildenafil and Donepezil administration influences intracellular redox homeostasis on account of the GSH

Identification of a Hemolysis Threshold That Increases Plasma and Serum Zinc Concentration123

PubMed Central

Otoo, Gloria E; Smith, Lauren; Siekmann, Jonathan H

2017-01-01

Background: Plasma or serum zinc concentration (PZC or SZC) is the primary measure of zinc status, but accurate sampling requires controlling for hemolysis to prevent leakage of zinc from erythrocytes. It is not established how much hemolysis can occur without changing PZC/SZC concentrations. Objective: This study determines a guideline for the level of hemolysis that can significantly elevate PZC/SZC. Methods: The effect of hemolysis on PZC/SZC was estimated by using standard hematologic variables and mineral content. The calculated hemolysis threshold was then compared with results from an in vitro study and a population survey. Hemolysis was assessed by hemoglobin and iron concentrations, direct spectrophotometry, and visual assessment of the plasma or serum. Zinc and iron concentrations were determined by inductively coupled plasma spectrometry. Results: A 5% increase in PZC/SZC was calculated to result from the lysis of 1.15% of the erythrocytes in whole blood, corresponding to ∼1 g hemoglobin/L added into the plasma or serum. Similarly, the addition of simulated hemolysate to control plasma in vitro caused a 5% increase in PZC when hemoglobin concentrations reached 1.18 ± 0.10 g/L. In addition, serum samples from a population nutritional survey were scored for hemolysis and analyzed for changes in SZC; samples with hemolysis in the range of 1–2.5 g hemoglobin/L showed an estimated increase in SZC of 6% compared with nonhemolyzed samples. Each approach indicated that a 5% increase in PZC/SZC occurs at ∼1 g hemoglobin/L in plasma or serum. This concentration of hemoglobin can be readily identified directly by chemical hemoglobin assays or indirectly by direct spectrophotometry or matching to a color scale. Conclusions: A threshold of 1 g hemoglobin/L is recommended for PZC/SZC measurements to avoid increases in zinc caused by hemolysis. The use of this threshold may improve zinc assessment for monitoring zinc status and nutritional interventions. PMID

Increased serum level of homocysteine correlates with retinal nerve fiber layer thinning in diabetic retinopathy

PubMed Central

Srivastav, Khushboo; Mahdi, Abbas A.; Shukla, Rajendra K.; Meyer, Carsten H.; Akduman, Levent; Khanna, Vinay K.

2016-01-01

Purpose To study the correlation between serum levels of vitamin B12, folic acid, and homocysteine and the severity of diabetic retinopathy and the correlation with retinal nerve fiber layer (RNFL) thinning on spectral domain optical coherence tomography (SD-OCT). Methods In a tertiary care center–based prospective cross-sectional study, 60 consecutive cases and 20 healthy controls in the age group of 40–65 years were included. The eyes of the cases were divided into three groups according to Early Treatment Diabetic Retinopathy Study (ETDRS) classification: diabetes mellitus without retinopathy (n = 20), non-proliferative diabetic retinopathy with macular edema (n = 20), and proliferative diabetic retinopathy with macular edema (n = 20). The serum levels of vitamin B12 and folic acid were measured using a standard protocol. The serum homocysteine assay was performed using an enzyme-linked immunosorbent assay (ELISA) kit. Average RNFL thickness was measured using SD-OCT. Statistical analysis was used to assess the correlations between the study variables. Results Increased severity of diabetic retinopathy was found to correlate with an increase in the serum levels of homocysteine (F = 53.79; p<0.001). The mean serum levels of vitamin B12 and folic acid were found to be within the normal reference range. A positive correlation was found between retinal nerve fiber layer thinning and serum levels of homocysteine (p<0.001). Conclusions This study, for the first time, demonstrated a correlation between increased homocysteine with a decrease in RNFL thickness and increased severity of diabetic retinopathy. PMID:27994434

[Subacute sclerosing panencephalitis cases diagnosed by increased CSF/serum measles antibody indices].

PubMed

Samlıoğlu, Pınar; Unalp, Aycan; Gökçay, Ahmet; Altuğlu, Imre; Oztürk, Aysel; Zeytinoğlu, Ayşın

2012-10-01

Subacute sclerosing panencephalitis (SSPE) caused by persistent defective measles virus strains, is a progressive neurological disorder of children and adolescents. The aim of this letter was to share the data from SSPE-suspected cases who were definitely diagnosed by the detection of increased antibody index in serum and cerebrospinal fluid (CSF) samples. A total of 11 patients (mean age: 14.3 years) with suspected SSPE between February 2006 to August 2008, were included in the study. Simultaneously obtained serum and CSF samples from patients were analyzed in terms of albumin, total IgG and measles-specific IgG levels (Measles Virus IgG ELISA for CSF Diagnostics, Euroimmun, Germany). The value of CSQrel (relative CSF/serum quotient) ≥ 1.5 was accepted indicative for intrathecal measles antibody synthesis. Seven (63.6%) of the 11 patients' diagnosis were confirmed with the demonstration of elevated CSF/serum indices (CSQrel range: 2.3-36.9; mean: 12.9). Mean age of those seven cases was 12.3 years (age range: 7-21) and four of them were male. The history of patients with high antibody indices indicated that three of four patients who had measles infection had not been vaccinated against measles. These three unvaccinated patients had measles infection at 3rd, 8th and 30th months of age, respectively, and the period of SSPE development were 15, 6 and 4.5 years, respectively. With this letter we would like to emphasize once more that effective measles vaccination is the only way for the prevention of measles and SSPE and the demonstration of increased measles antibody index in simultaneously obtained serum and CSF samples is crucial for the diagnosis of SSPE.

Serum cortisol concentration with exploratory cut-off values do not predict the effects of hydrocortisone administration in children with low cardiac output after cardiac surgery.

PubMed

Verweij, E J; Hogenbirk, Karin; Roest, Arno A W; van Brempt, Ronald; Hazekamp, Mark G; de Jonge, Evert

2012-10-01

Low cardiac output syndrome is common after paediatric cardiac surgery. Previous studies suggested that hydrocortisone administration may improve haemodynamic stability in case of resistant low cardiac output syndrome in critically ill children. This study was set up to test the hypothesis that the effects of hydrocortisone on haemodynamics in children with low cardiac output syndrome depend on the presence of (relative) adrenal insufficiency. A retrospective study was done on paediatric patients who received hydrocortisone when diagnosed with resistant low cardiac output syndrome after paediatric cardiac surgery in the period from 1 November 2005 to 31 December 2008. We studied the difference in effects of treatment with hydrocortisone administration between patients with adrenal insufficiency defined as an exploratory cut-off value of total cortisol of <100 nmol/l and patients with a serum total cortisol of ≥ 100 nmol/l. A total of 62 of patients were enrolled, meeting the inclusion criteria for low cardiac output syndrome. Thirty-two patients were assigned to Group 1 (<100 nmol/l) and 30 were assigned to Group 2 (≥ 100 nmol/l). Haemodynamics improved after hydrocortisone administration, with an increase in blood pressure, a decrease in administered vasopressors and inotropic drugs, an increase in urine production and a decrease in plasma lactate concentrations. The effects of treatment with hydrocortisone in children with low cardiac output after cardiac surgery was similar in patients with a low baseline serum cortisol concentration and those with normal baseline cortisol levels. A cortisol value using an exploratory cut-off value of 100 nmol/l for adrenal insufficiency should not be used as a criterion to treat these patients with hydrocortisone.

Serum butyrylcholinesterase and paraoxonase 1 in a canine model of endotoxemia: effects of choline administration.

PubMed

Tvarijonaviciute, Asta; Kocaturk, Meric; Cansev, Mehmet; Tecles, Fernando; Ceron, Jose J; Yilmaz, Zeki

2012-10-01

Butyrylcholinesterase (BChE) and paraoxonase 1 (PON1) are two serum enzymes synthesized by the liver that are related with inflammation. The main objectives of this study were to determine changes in serum BChE and PON1 by using a canine model of endotoxemia, and to evaluate whether choline alters BChE and PON1 activities during inflammation. For this purpose, a total of 20 mongrel dogs were divided into four groups: control, choline (C), lipopolysaccharide (LPS), and LPS+C. Dogs in the control group were injected with 0.9% NaCl (0.2 ml/kg, i.v.). Dogs in C and LPS+C groups received choline chloride (20 mg/kg, i.v., three times with 4 h intervals). Endotoxin was injected (0.02 mg/kg, i.v., once) to the dogs of LPS and LPS+C groups. Statistically significant decreases in BChE and PON1 activities in LPS group were detected 24 and 48 h post injection, respectively. No statistically significant changes in BChE and PON1 activities at different times were detected in control, C, or LPS+C groups. In conclusion, the data obtained in present study revealed a decrease in serum BChE and PON1 activities in dogs during experimentally induced endotoxemia and that choline administration attenuates these changes. Copyright © 2011 Elsevier Ltd. All rights reserved.

Chronic administration of nandrolone increases susceptibility to morphine dependence without correlation with LVV-hemorphin 7 in rats.

PubMed

Huang, Eagle Yi-Kung; Chen, Yuan-Hao; Huang, Tzu-Ying; Chen, Ying-Jie; Chow, Lok-Hi

2016-10-01

LVV-hemorphin 7 (LVVYPWTQRF; LVV-H7), an N-terminal fragment of the β-chain of hemoglobin cleaved by cathepsin D/pepsin, is an atypical endogenous opioid peptide that is found in high concentration in blood. LVV-H7 acts as a μ-opioid agonist and an inhibitor of insulin-regulated aminopeptidase. Subchronic administration of anabolic androgenic steroids (AAS) has been clinically proven to induce the synthesis of erythrocytes and increase hemoglobin concentrations. Patients with a history of AAS abuse are more susceptible to opioid abuse. We hypothesized that this association could be at least partially attributed to the sensitization of the mesocorticolimbic dopaminergic pathway by LVV-H7. Using the conditioned place preference test and neurochemical analysis, we investigated the possible mechanism underlying the effect of chronic nandrolone administration on morphine-induced reward and its correlation with LVV-H7 in rats. Either LVV-H7 may not sensitize the rewarding neural circuits or its inhibition on locomotor activity could mask reward-related behaviors. Chronic nandrolone pretreatment indeed caused a significant reward by low dose morphine, which did not cause any reward in control rats. However, coadministration of anti-LVV-H7 antiserum with nandrolone did not block this effect. This may rule out the possibility of the involvement of LVV-H7 in the action of nandrolone to intensify morphine-induced reward. Moreover, the serum level of LVV-H7 was mildly increased in response to chronic nandrolone administration in our animal model. According to the current clinical observations, we may conclude that the chronic administration of nandrolone can increase susceptibility to morphine dependence, but that this effect is not related to elevated LVV-H7. Copyright © 2016 Elsevier Ltd. All rights reserved.

Metabolic control may influence the increased superoxide generation in diabetic serum.

PubMed

Ceriello, A; Giugliano, D; Quatraro, A; Dello Russo, P; Lefèbvre, P J

1991-07-01

Superoxide anion (O2-) generation in serum from 10 Type 1 diabetic patients and 10 normal subjects was measured ex vivo. The amount of O2- production was significantly increased in diabetic serum 0.41 +/- 0.04 (+/- SD) vs 0.14 +/- 0.04 mumol l-1 min-1, p less than 0.001) and correlated with fasting plasma glucose and glycosylated protein levels in both diabetic (r = 0.72, p less than 0.01, and r = 0.62, p less than 0.05) and normal r = 0.75, p less than 0.01 and r = 0.64, p less than 0.05) subjects. Improved metabolic control in the diabetic patients was associated with a reduction of serum O2- production (0.28 +/- 0.06 mumol l-1 min-1, p less than 0.01), but the correlation between O2- levels and fasting plasma glucose and glycosylated protein concentrations was retained (r = 0.86 and r = 0.72, respectively, both p less than 0.01).

Value of antirabies vaccine with and without serum against severe challenges.

PubMed

VEERARAGHAVAN, N; SUBRAHMANYAN, T P

1960-01-01

Earlier studies with antirabies serum and vaccine have been extended to determine the value of serum, vaccine, or serum and vaccine combined against rabies challenges of increasing degrees of severity. While serum alone was not found to have any protective effect, vaccine alone was sufficient against mild challenges, the superiority of combined therapy with both serum and vaccine becoming evident at a challenge of about 50 LD(50). With challenges of over 300 LD(50) no treatment was of any value. It was also found that with a recommended optimum dose of serum, the usual vaccine dose could be halved-a matter of importance in countries with a high incidence of neuroparalytic accidents following administration of nervous tissue vaccine.

Increased serum thrombomodulin level is associated with disease severity and mortality in pediatric sepsis.

PubMed

Lin, Jainn-Jim; Hsiao, Hsiang-Ju; Chan, Oi-Wa; Wang, Yu; Hsia, Shao-Hsuan; Chiu, Cheng-Hsun

2017-01-01

Endothelial dysfunction plays an important role in the pathophysiology of sepsis. As previously reported, the serum thrombomodulin is elevated in diseases associated with endothelial injury. The aim of this study was to investigate the association of serum thrombomodulin level in different pediatric sepsis syndromes and evaluate the relationship with disease severity and mortality. We prospectively collected cases of sepsis treated in a pediatric intensive care unit from June 2012 to July 2015 at Chang Gung Children's Hospital in Taoyuan, Taiwan. Clinical characteristics and serum thrombomodulin levels were analyzed. Increased serum thrombomodulin levels on days 1 and 3 of the diagnosis of sepsis were found in different pediatric sepsis syndromes. Patients with septic shock had significantly increased serum thrombomodulin levels on days 1 and 3 [day 1: median, 6.9 mU/ml (interquartile range (IQR): 5.8-12.8) and day 3: median, 5.8 mU/ml (IQR: 4.6-10.8)] compared to healthy controls [median, 3.4 mU/ml (IQR: 2.3-4.2)] (p = <0.001 and 0.001, respectively) and those with sepsis [day 1: median, 2.9 mU/ml (IQR: 1.8-4.7) and day 3: median, 3 mU/ml (IQR: 1.5-3.5)] and severe sepsis [day 1: median, 3.3 mU/ml (IQR: 1.3-8.6) and day 3: median, 4.4 mU/ml (IQR: 0.5-6)] (p = <0.001 and 0.001, respectively). There was also a significant positive correlation between serum thrombomodulin level on day 1 and day 1 PRISM-II, PELOD, P-MOD and DIC scores. The patients who died had significantly higher serum thrombomodulin levels on days 1 and 3 [day 1: median, 9.9 mU/ml (IQR: 6.2-15.6) and day 3: median, 10.4 mU/ml (IQR: 9.2-11.7)] than the survivors [day 1; median, 4.4 mU/ml (IQR: 2.2-7.5) and day 3: [median, 3.5 mU/ml (IQR: 1.6-5.7)] (p = 0.046 and 0.012, respectively). Increased serum thrombomodulin levels were found in different pediatric sepsis syndromes and correlated with disease severity and mortality.

Midlevel Administrators' Pay Increases Slightly but Doesn't Match Inflation

ERIC Educational Resources Information Center

Fuller, Andrea

2012-01-01

Salaries for midlevel administrators rose by a median of 2 percent this year over last year, matching the median pay increase for senior administrators and coming in slightly higher than the 1.9-percent median increase for faculty members, says an annual report released by the College and University Professional Association for Human Resources.…

[Evaluation of the increasing serum lactate dehydrogenase caused by recombinant human granulocyte-colony stimulating factor].

PubMed

Sawa, Toshiyuki; Yoshida, Tsutomu; Ikoma, Tetsuroh; Toyoda, Miki; Ohno, Yasushi; Fujiwara, Hisayoshi

2003-01-01

Increasing serum lactate dehydrogenase (LDH) is often caused by granulocyte-colony stimulating factor (G-CSF) for leukopenia following chemotherapy in patients with lung cancer. To evaluate the increase in LDH, we investigated the significance of its elevation and LDH isozyme during chemotherapy supported by recombinant human G-CSF (rhG-CSF). To exclude effects of liver diseases and chemotherapy-induced liver dysfunction, only patients in whom laboratory findings concerning liver function were within normal range were entered in this study. If leukocyte or neutrophil counts were less than grade 3, subcutaneous injection of 50 micrograms/m2 of filgrastim was given daily until leukocyte counts increased to more than 10,000/mm3. Sixty patients with unresectable lung cancer were enrolled in this study and the LDH isozyme was evaluable in 54 patients. Increasing LDH was observed in 38 patients(70.4%), and LDH isozyme was measured in these 38 patients. Increases in granulocytes and LDH isozymes were found to have a positive correlation. LDH2, LDH3, LDH4 and LDH5 increased significantly after rhG-CSF administration, although LDH 1 did not increase. It was found that a rapid increase in leukocytes by rhG-CSF induced an increase in LDH, especially LDH 3.4. Considering the results of principal component analysis and the distribution ratio of LDH isozymes in neutrophils, it is thought that elevation of LDH is reflected in the rapid production and consumption of neutrophils.

Apelin-13 increased food intake with serum ghrelin and leptin levels in male rats.

PubMed

Saral, S; Alkanat, M; Sumer, A; Canpolat, S

2018-01-01

In this study, we aimed to explain the role of apelin-13 on body weight, food and water intake with serum leptin, ghrelin, neuropeptid Y (NPY) and peptid YY (PYY) levels in male rat. Thirty-two Sprague-Dawley male rats were used for the study. The rats were injected SP (0.9 %) intraperitoneally (i.p) in the control group and 30 (AP30), 100 (AP100) and 300 (AP300) µg/kg apelin-13 in the study groups, respectively, 10 min before the transition to dark period, for 10 days. During the experimental period, with light and dark periods of food and water intake, body weights were recorded in rats. Rats were euthanized and serum samples were obtained. In serum samples leptin, ghrelin, NPY and PYY levels were measured with specific ELISA kit. Apelin-13 was increased body weights in all three (AP30, AP100 and AP300) groups compared with the control group. AP100 and AP300 groups had increased food intake in the dark and the cumulative period, but in the light period food intake values were not significantly increased (p > 0.05). As for the value of water intake, compared with the control group, all dose of apelin-13 increased water intake during the dark and the cumulative period. There was no significant change in water intake in the light period. On the other hand, compared with the control group, serum leptin levels were found to increase in the groups administered 100 and 300 µg/kg of apelin-13 (p < 0.05). Ghrelin levels were found high in all groups treated with apelin-13. Serum levels of NPY decreased only in the 300 µg/kg apelin-13 treated group (p 0.05). Apelin-13 increases body weight in rats as well as food and water intake (dark and cumulative period). Additionally, ghrelin can mediate the orexigenic effect of apelin-13 in the regulation of food intake (Fig. 4, Ref. 37).

Increased serum cortisol on oral food challenge in infants with food protein-induced enterocolitis syndrome.

PubMed

Shimomura, Masaki; Ito, Yasunori; Tanaka, Hiroki; Meguro, Takaaki; Kimura, Mitsuaki

2018-01-01

An increase in absolute neutrophil count (ANC) is seen after oral food challenge test (OFC) in patients with food protein-induced enterocolitis syndrome (FPIES). Although it has been suggested that interleukin (IL)-8 is involved in this phenomenon, a possible role for cortisol has not yet been studied. Six positive OFC in five patients with FPIES due to cows' milk (CM) proteins, and two negative OFC in two patients with suspected FPIES were analyzed. Absolute neutrophil count, serum IL-8, and serum cortisol were measured before OFC, 6 and 24 h after the ingestion of CM formula. For the positive OFC, ANC measured 6 h after the ingestion of CM formula was significantly higher than that measured before the OFC (median, 8,761 versus 2,297/μL; P < 0.05). Significant increases in serum cortisol and IL-8 were observed 6 h after OFC (cortisol, median 1,119 pg/mL before versus 2,141 pg/mL after, P < 0.05; IL-8, median 15.5 pg/mL before versus 165.3 pg/mL after, P < 0.05). The change ratio (i.e. ratio of that after OFC to that before OFC) of ANC was significantly correlated not only with that of serum IL-8 (r = 0.90, P < 0.01) but also with that of serum cortisol (r = 0.76, P < 0.05). Moreover, the serum cortisol change ratio was significantly higher in subjects with vomiting than in those without (median, 2.5 versus 1.0, P < 0.05). Serum cortisol, in combination with IL-8, affects the increase in ANC after OFC. © 2017 Japan Pediatric Society.

Prenatal administration of retinoic acid increases the trophoblastic insulin-like growth factor 2 protein expression in the nitrofen model of congenital diaphragmatic hernia.

PubMed

Kutasy, Balazs; Friedmacher, Florian; Duess, Johannes W; Puri, Prem

2014-02-01

The high mortality rate in congenital diaphragmatic hernia (CDH) is attributed to pulmonary hypoplasia (PH). Insulin-like growth factor 2 (IGF2) is an important regulator of fetal growth. The highest levels of IGF2 expression are found in the placenta, which are negatively regulated by decidual retinoid acid receptor alpha (RARα). It has been demonstrated that prenatal administration of retinoic acid (RA) suppresses decidual RARα expression. Previous studies have further shown that prenatal administration of RA can reverse PH in nitrofen-induced CDH model. In IGF2 knockout animals, low levels of IGF2 are associated with decreased placental growth and PH. We therefore hypothesized that nitrofen decreases trophoblastic IGF2 expression and prenatal administration of RA increases it through decidual RARα in the nitrofen-induced CDH model. Pregnant rats were exposed to either olive oil or nitrofen on day 9 of gestation (D9). RA was given intraperitoneally on D18, D19 and D20. Fetuses were harvested on D21 and divided into three groups: control, CDH and nitrofen+RA. Immunohistochemistry was performed to evaluate decidual RARα and trophoblastic IGF2 expression. Protein levels of IGF2 in serum, intra-amniotic fluid and left lungs were measured by enzyme-linked immunosorbent assay. Significant growth retardation of placenta and left lungs was observed in the CDH group compared to control and nitrofen+RA group. Markedly increased decidual RARα and decreased IGF2 immunoreactivity were found in the CDH group compared to control and nitrofen+RA group. Significantly decreased IGF2 protein levels were detected in serum, intra-amniotic fluid and left lungs in the CDH group compared to control and nitrofen+RA group. Our findings suggest that nitrofen may disturb trophoblastic IGF2 expression through decidual RARα resulting in retarded placental growth and PH in the nitrofen-induced CDH. Prenatal administration of RA may promote lung and placental growth by increasing

Possible Increase in Serum FABP4 Level Despite Adiposity Reduction by Canagliflozin, an SGLT2 Inhibitor.

PubMed

Furuhashi, Masato; Matsumoto, Megumi; Hiramitsu, Shinya; Omori, Akina; Tanaka, Marenao; Moniwa, Norihito; Yoshida, Hideaki; Ishii, Junnichi; Miura, Tetsuji

2016-01-01

Fatty acid-binding protein 4 (FABP4/A-FABP/aP2) is secreted from adipocytes in association with catecholamine-induced lipolysis, and elevated serum FABP4 level is associated with obesity, insulin resistance and atherosclerosis. Secreted FABP4 as a novel adipokine leads to insulin resistance via increased hepatic glucose production (HGP). Sodium-glucose cotransporter 2 (SGLT2) inhibitors decrease blood glucose level via increased urinary glucose excretion, though HGP is enhanced. Here we investigated whether canagliflozin, an SGLT2 inhibitor, modulates serum FABP4 level. Canagliflozin (100 mg/day) was administered to type 2 diabetic patients (n = 39) for 12 weeks. Serum FABP4 level was measured before and after treatment. At baseline, serum FABP4 level was correlated with adiposity, renal dysfunction and noradrenaline level. Treatment with canagliflozin significantly decreased adiposity and levels of fasting glucose and HbA1c but increased average serum FABP4 level by 10.3% (18.0 ± 1.0 vs. 19.8 ± 1.2 ng/ml, P = 0.008), though elevation of FABP4 level after treatment was observed in 26 (66.7%) out of 39 patients. Change in FABP4 level was positively correlated with change in levels of fasting glucose (r = 0.329, P = 0.044), HbA1c (r = 0.329, P = 0.044) and noradrenaline (r = 0.329, P = 0.041) but was not significantly correlated with change in adiposity or other variables. Canagliflozin paradoxically increases serum FABP4 level in some diabetic patients despite amelioration of glucose metabolism and adiposity reduction, possibly via induction of catecholamine-induced lipolysis in adipocytes. Increased FABP4 level by canagliflozin may undermine the improvement of glucose metabolism and might be a possible mechanism of increased HGP by inhibition of SGLT2. UMIN-CTR Clinical Trial UMIN000018151.

Increased levels of serum matrix metalloproteinase-3 in haemodialysis patients with dialysis-related amyloidosis.

PubMed

Naganuma, Toshihide; Sugimura, Kazunobu; Uchida, Junji; Tashiro, Koichiro; Yoshimura, Rikio; Takemoto, Yoshiaki; Nakatani, Tatsuya

2008-04-01

It is recognized that matrix metalloproteinase-3 (MMP-3) is abundantly expressed in active rheumatoid synovium, and that serum level of MMP-3 is a useful marker for diagnosis of rheumatoid arthritis and for evaluation of prognosis in joint destruction. Little is known about serum MMP-3 levels in haemodialysis (HD) patients, and thus, the association between serum MMP-3 and dialysis-related amyloidosis (DRA) has yet to be elucidated. Serum levels of MMP-3 were measured by enzyme immunoassay in 150 HD patients, 90 without DRA and 60 with DRA, before HD. Simple regression analysis was performed to investigate the relationship between serum level of MMP-3 and clinical parameters, including age, HD duration, C-reactive protein and beta2 microglobulin (BMG). Serum levels of MMP-3 were significantly higher in HD patients with DRA than in HD patients without DRA (258.2 +/- 118.1 vs 201.5 +/- 98.4 pg/mL, P = 0.0017), and both levels were significantly higher than those of healthy subjects (45.6 +/- 13.4 pg/mL, P < 0.0001). Serum MMP-3 levels significantly correlated with serum levels of BMG (r = 0.197, P = 0.0164) and HD duration (r = 0.168, P = 0.0427). Moreover, serum MMP-3 levels significantly correlated with serum BMG levels in HD patients without DRA (r = 0.341, P = 0.0012), but not in HD patients with DRA. Our results suggest that matrix metalloproteinase activity increases in HD patients, which may be associated with BMG and DRA.

High serum ALP level is associated with increased risk of denosumab-related hypocalcemia in patients with bone metastases from solid tumors.

PubMed

Kinoshita, Yuka; Arai, Makoto; Ito, Nobuaki; Takashi, Yuichi; Makita, Noriko; Nangaku, Masaomi; Shinoda, Yusuke; Fukumoto, Seiji

2016-05-31

Metastatic bone disease is one of the most common complications of advanced cancers. Pathological fractures, spinal cord compression, and radiotherapy or surgery to the bone are collectively called skeletal-related events (SREs), which cause severe pain, increase hospitalization rates, and impair the quality of life (QOL) of patients with bone metastases. The receptor activator of nuclear factor-kB ligand (RANKL)/RANK pathway is critical in the progression of bone metastases. Previous studies have demonstrated that an anti-RANKL antibody (denosumab) was superior to zoledronic acid in prolonging time to first SRE in patients with bone metastases from prostate and breast cancers. However, severe hypocalcemic events occur more frequently after treatment with denosumab compared with zoledronic acid. In this study, 368 administrations of denosumab in 219 patients with metastatic bone disease from solid tumors were analyzed to clarify the risk factors for developing hypocalcemia. The results showed that grade 2/3 hypocalcemia was observed in 10.4% of the total number of denosumab administrations. Patients with higher baseline serum ALP, higher performance status (PS), or gastric cancer were at higher risk for developing hypocalcemia. The cut-off value for ALP to predict denosumab-related hypocalcemia was 587 U/L with a sensitivity of 0.77 and a specificity of 0.81. Close monitoring of serum calcium, especially after the first treatment with denosumab, is strongly recommended in these patients.

Approach to the evaluation of a patient with an increased serum osmolal gap and high-anion-gap metabolic acidosis.

PubMed

Kraut, Jeffrey A; Xing, Shelly Xiaolei

2011-09-01

An increase in serum osmolality and serum osmolal gap with or without high-anion-gap metabolic acidosis is an important clue to exposure to one of the toxic alcohols, which include methanol, ethylene glycol, diethylene glycol, propylene glycol, or isopropanol. However, the increase in serum osmolal gap and metabolic acidosis can occur either together or alone depending on several factors, including baseline serum osmolal gap, molecular weight of the alcohol, and stage of metabolism of the alcohol. In addition, other disorders, including diabetic or alcoholic ketoacidosis, acute kidney injury, chronic kidney disease, and lactic acidosis, can cause high-anion-gap metabolic acidosis associated with an increased serum osmolal gap and therefore should be explored in the differential diagnosis. It is essential for clinicians to understand the value and limitations of osmolal gap to assist in reaching the correct diagnosis and initiating appropriate treatment. In this teaching case, we present a systematic approach to diagnosing high serum osmolality and increased serum osmolal gap with or without high-anion-gap metabolic acidosis. Published by Elsevier Inc.

Increased serum leptin and insulin concentrations in canine hypothyroidism.

PubMed

Mazaki-Tovi, Michal; Feuermann, Yonatan; Segev, Gilad; Klement, Eyal; Yas-Natan, Einat; Farkas, Amnon; Kol, Amir; Shamay, Avi

2010-01-01

Serum concentrations of leptin and insulin were compared between gender-matched hypothyroid (n=25) and healthy (n=25) client-owned dogs within comparable age and body condition score (BCS) ranges. Fasted blood samples were collected from each dog and analysed for glucose, cholesterol, triglyceride, leptin and insulin concentrations. Leptin and insulin concentrations were significantly higher in the hypothyroid compared to normal dogs (P=0.006 and P=0.001, respectively) following adjustment for potential confounders. A nearly significant (P=0.051) interaction with BCS was found in the association between hypothyroidism and leptin. Leptin concentrations were significantly higher in hypothyroid dogs compared to normal dogs, in separate analyses for BCS 6 (P=0.036) and 7 (P=0.049). There was no significant difference in glucose concentration between the hypothyroid and normal groups (P=0.84) following adjustment for BCS. This study showed that canine hypothyroidism is associated with increased serum leptin and insulin concentrations, neither of which may be attributed to obesity alone. Copyright 2008 Elsevier Ltd. All rights reserved.

Long-term administration of tolvaptan increases myocardial remodeling and mortality via exacerbation of congestion in mice heart failure model after myocardial infarction.

PubMed

Eguchi, Akiyo; Iwasaku, Toshihiro; Okuhara, Yoshitaka; Naito, Yoshiro; Mano, Toshiaki; Masuyama, Tohru; Hirotani, Shinichi

2016-10-15

In contrast to loop diuretics, tolvaptan does not cause neurohormonal activation in several animal heart failure models. However, it remains unknown whether chronic vasopressin type 2 receptor blockade exerts beneficial effects on mortality in murine heart failure after myocardial infarction (MI). In an experimental heart failure model, we tested the hypothesis that tolvaptan reduces myocardial remodeling and mortality. MI was induced in 9-week-old male C57Bl6/J by the left coronary artery ligation. In study 1, animals were randomly assigned to treatment with placebo or tolvaptan starting 14days post-MI. In study 2, animals were randomized to tolvaptan or furosemide+tolvaptan starting 14days post-MI. Interestingly, results showed lower survival rate in tolvaptan group compared to placebo. Tolvaptan group had higher serum osmolality, heavier body weight, more severe myocardial remodeling, and lung congestion at day 28 of drug administration compared to placebo. In study 2, addition of furosemide significantly reduced mortality rate seen with tolvaptan, and presented with decreased osmolality, myocardial remodeling, and lung congestion compared to tolvaptan-treated mice. Increase in proximal tubular expression of aquaporin 1, Angiotensin II, and vasopressin seen with tolvaptan treatments were normalized to basal levels, similar to levels in placebo-treated mice. Contrary to our hypothesis, tolvaptan was associated with increased mortality in murine heart failure after MI. This increase in lung congestion, myocardial remodeling, could be prevented by co-administration of furosemide, which resulted in normalized serum osmolality, neurohormonal activation, and renal aquaporin 1 expression, and hence decreased mortality post-MI. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Elevated basal serum tryptase identifies a multisystem disorder associated with increased TPSAB1 copy number.

PubMed

Lyons, Jonathan J; Yu, Xiaomin; Hughes, Jason D; Le, Quang T; Jamil, Ali; Bai, Yun; Ho, Nancy; Zhao, Ming; Liu, Yihui; O'Connell, Michael P; Trivedi, Neil N; Nelson, Celeste; DiMaggio, Thomas; Jones, Nina; Matthews, Helen; Lewis, Katie L; Oler, Andrew J; Carlson, Ryan J; Arkwright, Peter D; Hong, Celine; Agama, Sherene; Wilson, Todd M; Tucker, Sofie; Zhang, Yu; McElwee, Joshua J; Pao, Maryland; Glover, Sarah C; Rothenberg, Marc E; Hohman, Robert J; Stone, Kelly D; Caughey, George H; Heller, Theo; Metcalfe, Dean D; Biesecker, Leslie G; Schwartz, Lawrence B; Milner, Joshua D

2016-12-01

Elevated basal serum tryptase levels are present in 4-6% of the general population, but the cause and relevance of such increases are unknown. Previously, we described subjects with dominantly inherited elevated basal serum tryptase levels associated with multisystem complaints including cutaneous flushing and pruritus, dysautonomia, functional gastrointestinal symptoms, chronic pain, and connective tissue abnormalities, including joint hypermobility. Here we report the identification of germline duplications and triplications in the TPSAB1 gene encoding α-tryptase that segregate with inherited increases in basal serum tryptase levels in 35 families presenting with associated multisystem complaints. Individuals harboring alleles encoding three copies of α-tryptase had higher basal serum levels of tryptase and were more symptomatic than those with alleles encoding two copies, suggesting a gene-dose effect. Further, we found in two additional cohorts (172 individuals) that elevated basal serum tryptase levels were exclusively associated with duplication of α-tryptase-encoding sequence in TPSAB1, and affected individuals reported symptom complexes seen in our initial familial cohort. Thus, our findings link duplications in TPSAB1 with irritable bowel syndrome, cutaneous complaints, connective tissue abnormalities, and dysautonomia.

Value of antirabies vaccine with and without serum against severe challenges

PubMed Central

Veeraraghavan, N.; Subrahmanyan, T. P.

1960-01-01

Earlier studies with antirabies serum and vaccine have been extended to determine the value of serum, vaccine, or serum and vaccine combined against rabies challenges of increasing degrees of severity. While serum alone was not found to have any protective effect, vaccine alone was sufficient against mild challenges, the superiority of combined therapy with both serum and vaccine becoming evident at a challenge of about 50 LD50. With challenges of over 300 LD50 no treatment was of any value. It was also found that with a recommended optimum dose of serum, the usual vaccine dose could be halved—a matter of importance in countries with a high incidence of neuroparalytic accidents following administration of nervous tissue vaccine. PMID:13841546

Increasing insulin resistance accentuates the effect of triglyceride-associated loci on serum triglycerides during 5 years.

PubMed

Justesen, Johanne M; Andersson, Ehm A; Allin, Kristine H; Sandholt, Camilla H; Jørgensen, Torben; Linneberg, Allan; Jørgensen, Marit E; Hansen, Torben; Pedersen, Oluf; Grarup, Niels

2016-12-01

Blood concentrations of triglycerides are influenced by genetic factors as well as a number of environmental factors, including adiposity and glucose homeostasis. The aim was to investigate the association between a serum triglyceride weighted genetic risk score (wGRS) and changes in fasting serum triglyceride level over 5 years and to test whether the effect of the wGRS was modified by 5 year changes of adiposity, insulin resistance, and lifestyle factors. A total of 3,474 nondiabetic individuals from the Danish Inter99 cohort participated in both the baseline and 5 year follow-up physical examinations and had information on the wGRS comprising 39 genetic variants. In a linear regression model adjusted for age, sex, and baseline serum triglyceride, the wGRS was associated with increased serum triglyceride levels over 5 years [per allele effect = 1.3% (1.0-1.6%); P = 1.0 × 10 -17 ]. This triglyceride-increasing effect of the wGRS interacted with changes in insulin resistance (P interaction = 1.5 × 10 -6 ). This interaction indicated that the effect of the wGRS was stronger in individuals who became more insulin resistant over 5 years. In conclusion, our findings suggest that increased genetic risk load is associated with a larger increase in fasting serum triglyceride levels in nondiabetic individuals during 5 years of follow-up. This effect of the wGRS is accentuated by increasing insulin resistance. Copyright © 2016 by the American Society for Biochemistry and Molecular Biology, Inc.

Increased serum thrombomodulin level is associated with disease severity and mortality in pediatric sepsis

PubMed Central

Lin, Jainn-Jim; Hsiao, Hsiang-Ju; Chan, Oi-Wa; Wang, Yu

2017-01-01

Background Endothelial dysfunction plays an important role in the pathophysiology of sepsis. As previously reported, the serum thrombomodulin is elevated in diseases associated with endothelial injury. Objective The aim of this study was to investigate the association of serum thrombomodulin level in different pediatric sepsis syndromes and evaluate the relationship with disease severity and mortality. Methods We prospectively collected cases of sepsis treated in a pediatric intensive care unit from June 2012 to July 2015 at Chang Gung Children’s Hospital in Taoyuan, Taiwan. Clinical characteristics and serum thrombomodulin levels were analyzed. Results Increased serum thrombomodulin levels on days 1 and 3 of the diagnosis of sepsis were found in different pediatric sepsis syndromes. Patients with septic shock had significantly increased serum thrombomodulin levels on days 1 and 3 [day 1: median, 6.9 mU/ml (interquartile range (IQR): 5.8–12.8) and day 3: median, 5.8 mU/ml (IQR: 4.6–10.8)] compared to healthy controls [median, 3.4 mU/ml (IQR: 2.3–4.2)] (p = <0.001 and 0.001, respectively) and those with sepsis [day 1: median, 2.9 mU/ml (IQR: 1.8–4.7) and day 3: median, 3 mU/ml (IQR: 1.5–3.5)] and severe sepsis [day 1: median, 3.3 mU/ml (IQR: 1.3–8.6) and day 3: median, 4.4 mU/ml (IQR: 0.5–6)] (p = <0.001 and 0.001, respectively). There was also a significant positive correlation between serum thrombomodulin level on day 1 and day 1 PRISM-II, PELOD, P-MOD and DIC scores. The patients who died had significantly higher serum thrombomodulin levels on days 1 and 3 [day 1: median, 9.9 mU/ml (IQR: 6.2–15.6) and day 3: median, 10.4 mU/ml (IQR: 9.2–11.7)] than the survivors [day 1; median, 4.4 mU/ml (IQR: 2.2–7.5) and day 3: [median, 3.5 mU/ml (IQR: 1.6–5.7)] (p = 0.046 and 0.012, respectively). Conclusion Increased serum thrombomodulin levels were found in different pediatric sepsis syndromes and correlated with disease severity and mortality. PMID

Visceral fat obesity increases serum DPP-4 levels in men with type 2 diabetes mellitus.

PubMed

Tanaka, Sayuri; Kanazawa, Ippei; Notsu, Masakazu; Sugimoto, Toshitsugu

2016-06-01

The relationship between serum DPP-4 level and visceral fat mass is still unclear in type 2 diabetes mellitus (T2DM). This study thus aimed to examine the association of visceral fat accumulation and metabolic syndrome with serum DPP-4 levels in T2DM. Visceral and subcutaneous fat areas were evaluated by performing computed tomography scan in 135 men with T2DM, who had never taken DPP-4 inhibitors or GLP-1 receptor agonists. We investigated the association between serum DPP-4 levels and visceral fat area as well as the presence of metabolic syndrome. Multiple regression analysis adjusted for age, duration of T2DM, body mass index, serum creatinine, and HbA1c showed that serum DPP-4 levels were positively associated with visceral fat area (β=0.25, p=0.04), but not subcutaneous fat area (β=-0.18, p=0.13). In logistic regression analyses adjusted for the confounding factors described above, serum DPP-4 levels were positively associated with visceral fat obesity and metabolic syndrome [odds ratio (OR)=1.63, 95% confidence interval (CI)=1.00-2.66 per standard deviation (SD) increase, p=0.04; OR=1.77, 95%CI=1.09-2.88 per SD increase, p=0.02, respectively]. The present study showed that serum DPP-4 level was positively and specifically associated with accumulation of visceral fat and the presence of metabolic syndrome in men with T2DM. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The effects of programmed administration of human parathyroid hormone fragment (1-34) on bone histomorphometry and serum chemistry in rats

NASA Technical Reports Server (NTRS)

Dobnig, H.; Turner, R. T.

1997-01-01

PTH treatment can result in dramatic increases in cancellous bone volume in normal and osteopenic rats. However, this potentially beneficial response is only observed after pulsatile treatment; continuous infusion of PTH leads to hypercalcemia and bone abnormalities. The purpose of these studies was to determine the optimal duration of the PTH pulses. A preliminary study revealed that human PTH-(1-34) (hPTH) is cleared from circulation within 6 h after sc administration of an anabolic dose of the hormone (80 microg/kg). To establish the effects of gradually extending the duration of exposure to hPTH without increasing the daily dose, we programmed implanted Alzet osmotic pumps to deliver the 80 microg/kg x day dose of the hormone during pulses of 1, 2, and 6 h/day, or 40 microg/kg x day continuously. Discontinuous infusion was accomplished by alternate spacing of external tubing with hPTH solution and sesame oil. After 6 days of treatment, we evaluated serum chemistry and bone histomorphometry. As negative and positive controls, groups of rats received pumps that delivered vehicle only and 80 microg/kg x day hPTH by daily sc injection, respectively. Dynamic and static bone histomorphometry revealed that the daily sc injection and 1 h/day infusion dramatically increased osteoblast number and bone formation in the proximal tibial metaphysis, whereas longer infusion resulted in systemic side-effects, including up to a 10% loss in body weight, hypercalcemia, and histological changes in the proximal tibia resembling abnormalities observed in patients with chronic primary hyperparathyroidism, including peritrabecular marrow fibrosis and focal bone resorption. Infusion for as little as 2 h/day resulted in minor weight loss and changes in bone histology that were intermediate between sc and continuous administration. The results demonstrate that the therapeutic interval for hPTH exposure is brief, but that programmed administration of implanted hormone is a feasible

Intrahippocampal administration of anandamide increases REM sleep.

PubMed

Rueda-Orozco, Pavel Ernesto; Soria-Gómez, Edgar; Montes-Rodríguez, Corinne Jennifer; Pérez-Morales, Marcel; Prospéro-García, Oscar

2010-04-05

A nascent literature has postulated endocannabinoids (eCBs) as strong sleep-inducing lipids, particularly rapid-eye-movement sleep (REMs), nevertheless the exact mechanisms behind this effect remain to be determined. Anandamide and 2-arachidonyl glycerol, two of the most important eCBS, are synthesized in the hippocampus. This structure also expresses a high concentration of cannabinoid receptor 1 (CB1). Recent extensive literature supports eCBs as important regulators of hippocampal activity. It has also been shown that these molecules vary their expression on the hippocampus depending on the light-dark cycle. In this context we decided to analyze the effect of intrahippocampal administration of the eCB anandamide (ANA) on the sleep-waking cycle at two points of the light-dark cycle. Our data indicate that the administration of ANA directly into the hippocampus increases REMs in a dose dependent manner during the dark but not during the light phase of the cycle. The increase of REMs was blocked by the CB1 antagonist AM251. This effect was specific for the hippocampus since ANA administrations in the surrounding cortex did not elicit any change in REMs. These results support the idea of a direct relationship between hippocampal activity and sleep mechanisms by means of eCBs. The data presented here show, for the first time that eCBs administered into the hippocampus trigger REMs and support previous studies where chemical stimulation of limbic areas triggered sleep.

Restoration of parathyroid function after change of phosphate binder from calcium carbonate to lanthanum carbonate in hemodialysis patients with suppressed serum parathyroid hormone.

PubMed

Inaba, Masaaki; Okuno, Senji; Nagayama, Harumi; Yamada, Shinsuke; Ishimura, Eiji; Imanishi, Yasuo; Shoji, Shigeichi

2015-03-01

Control of phosphate is the most critical in the treatment of chronic kidney disease with mineral and bone disorder (CKD-MBD). Because calcium-containing phosphate binder to CKD patients is known to induce adynamic bone disease with ectopic calcification by increasing calcium load, we examined the effect of lanthanum carbonate (LaC), a non-calcium containing phosphate binder, to restore bone turnover in 27 hemodialysis patients with suppressed parathyroid function (serum intact parathyroid hormone [iPTH] ≦ 150 pg/mL). At the initiation of LaC administration, the dose of calcium-containing phosphate binder calcium carbonate (CaC) was withdrawn or reduced based on serum phosphate. After initiation of LaC administration, serum calcium and phosphate decreased significantly by 4 weeks, whereas whole PTH and iPTH increased. A significant and positive correlation between decreases of serum calcium, but not phosphate, with increases of whole PTH and iPTH, suggested that the decline in serum calcium with reduction of calcium load by LaC might increase parathyroid function. Serum bone resorption markers, such as serum tartrate-resistant acid phosphatase 5b, and N-telopeptide of type I collagen increased significantly by 4 weeks after LaC administration, which was followed by increases of serum bone formation markers including serum bone alkaline phosphatase, intact procollagen N-propeptide, and osteocalcin. Therefore, it was suggested that LaC attenuated CaC-induced suppression of parathyroid function and bone turnover by decreasing calcium load. In conclusion, replacement of CaC with LaC, either partially or totally, could increase parathyroid function and resultant bone turnover in hemodialysis patients with serum iPTH ≦ 150 pg/mL. Copyright © 2015 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Nicergoline increases serum substance P levels in patients with an ischaemic stroke.

PubMed

Nishiyama, Yasuhiro; Abe, Arata; Ueda, Masayuki; Katsura, Ken-ichiro; Katayama, Yasuo

2010-01-01

Aspiration pneumonia is one of the most important complications following ischaemic stroke, and a leading cause of mortality in stroke patients. This is particularly prevalent in patients with involvement of the basal ganglia, which may be due to impaired neurotransmission through lack of production of substance P. Consecutive patients in the chronic stage, 1-3 months after cerebral ischaemic infarction, were assessed for basal ganglia involvement by magnetic resonance imaging. The patients were randomised to 4 weeks of treatment with (n = 25) or without (n = 25) nicergoline (15 mg t.i.d.). Serum concentration of substance P was measured by radioimmunoassay. At entry to the study, mean concentration of substance P was significantly (p < 0.001) lower in patients with bilateral basal ganglia lesions than in patients with no or unilateral basal ganglia involvement. Nicergoline administration caused a significant (p = 0.021) increase from baseline in mean substance P concentration. No significant change was seen in the nicergoline-untreated patients (p = 0.626). Among the patients who received nicergoline, 11 patients had bilateral basal ganglia involvement and there was no significant mean change in substance P in these patients, whereas there was a significant increase (p = 0.032) in the 14 nicergoline-treated patients with no or unilateral basal ganglia involvement. The present study suggests a possible effect of nicergoline to increase substance P level in ischaemic stroke patients with partial damage to basal ganglia, who have a decreased swallowing response and consequent risk of aspiration pneumonia. Further trials of nicergoline treatment in patients at risk for aspiration pneumonia are warranted. (c) 2009 S. Karger AG, Basel.

Polydatin administration improves serum biochemical parameters and oxidative stress markers during chronic alcoholism: a pilot study.

PubMed

Pace, Maria Caterina; Passavanti, Maria Beatrice; Aurilio, Caterina; Sansone, Pasquale; Aurilio, Rossella; DE Maria, Salvatore; Lama, Stefania; Federico, Alessandro; Ravagnan, Gianpietro; Caraglia, Michele; Stiuso, Paola

2015-01-01

Polydatin, a hydroxystilbene derived from the rhizome of Polygonum cuspidatum, elicits hepatoprotective and neuroprotective effects through its anti-oxidant properties. The present study aimed to determine the effects of oral administration of polydatin in alcoholic patients in order to improve liver biochemical parameters, serum oxidative stress and mental state. We enrolled 20 chronic alcoholic patients hospitalized for rehabilitative therapy. The patients were divided into two groups receiving the following treatment regimes for two weeks: administration of an anti-oxidant nutritional supplement containing glutathione and vitamin C (group 1), or glutathione, vitamin C and polydatin (group 2). The results of the present study show that elevated plasma aspartate aminotransferase and alanine aminotransferase levels in patients after two weeks of alcohol withdrawal were significantly reduced by polydatin (group 2), when compared to group 1. Polydatin also significantly reduced lipid peroxidation levels. Finally, our preliminary data resulting from the analysis of the Mini-Mental Status suggest that polydatin improves cognitive performance. Daily dietary administration of polydatin should be considered for prevention and treatment of liver disease and cognitive impairment in alcoholic patients. Copyright © 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Serum thioredoxin reductase is highly increased in mice with hepatocellular carcinoma and its activity is restrained by several mechanisms.

PubMed

Zhang, Le; Cheng, Qing; Zhang, Longjie; Wang, Yijun; Merrill, Gary F; Ilani, Tal; Fass, Deborah; Arnér, Elias S J; Zhang, Jinsong

2016-10-01

Increased thioredoxin reductase (TrxR) levels in serum were recently identified as possible prognostic markers for human prostate cancer or hepatocellular carcinoma. We had earlier shown that serum levels of TrxR protein are very low in healthy mice, but can in close correlation to alanine aminotransferase (ALT) increase more than 200-fold upon chemically induced liver damage. We also found that enzymatic TrxR activity in serum is counteracted by a yet unidentified oxidase activity in serum. In the present study we found that mice carrying H22 hepatocellular carcinoma tumors present highly increased levels of TrxR in serum, similarly to that reported in human patients. In this case ALT levels did not parallel those of TrxR. We also discovered here that the TrxR-antagonistic oxidase activity in serum is due to the presence of quiescin Q6 sulfhydryl oxidase 1 (QSOX1). We furthermore found that the chemotherapeutic agents cisplatin or auranofin, when given systemically to H22 tumor bearing mice, can further inhibit TrxR activities in serum. The TrxR serum activity was also inhibited by endogenous electrophilic inhibitors, found to increase in tumor-bearing mice and to include protoporphyrin IX (PpIX) and 4-hydroxynonenal (HNE). Thus, hepatocellular carcinoma triggers high levels of serum TrxR that are not paralleled by ALT, and TrxR enzyme activity in serum is counteracted by several different mechanisms. The physiological role of TrxR in serum, if any, as well as its potential value as a prognostic marker for tumor progression, needs to be studied further. Copyright © 2016 Elsevier Inc. All rights reserved.

Vitamin D increases serum levels of the soluble receptor for advanced glycation end products in women with PCOS.

PubMed

Irani, Mohamad; Minkoff, Howard; Seifer, David B; Merhi, Zaher

2014-05-01

Elevation of serum proinflammatory advanced glycation end products (AGEs) is involved in the pathogenesis of polycystic ovary syndrome (PCOS). The soluble receptor for AGEs (sRAGE) acts as a decoy by binding circulating AGEs. Vitamin D supplementation attenuates the deposition of AGEs in the vascular system of diabetic animals and improves some metabolic aspects of vitamin D-deficient women with PCOS. Additionally, serum anti-Mullerian hormone (AMH) is elevated in women with PCOS, reflecting abnormal ovarian folliculogenesis. The objective of the study was to evaluate the effect of 1,25 dihydroxyvitamin D3 (vit D3) supplementation on serum sRAGE and AMH in vitamin D-deficient women with PCOS. DESIGN, SETTINGS, PARTICIPANTS, AND INTERVENTION: Sixty-seven women with (n = 22) or without (control; n = 45) PCOS who were diagnosed with vitamin D deficiency were enrolled. Fifty-one women were replaced with oral vit D3 for 8 weeks (16 with PCOS and 35 controls) and 16 women were not treated (six with PCOS and 10 controls). Serum 25-hydroxyvitamin D (25 OH-D), sRAGE, and AMH concentrations were measured at baseline and after vit D3 supplementation in the treated group and 8 weeks apart in the nontreated group. Changes in serum sRAGE and AMH concentrations after vit D3 replacement were measured. In all participants, there was a negative correlation between body mass index and serum sRAGE levels (r = -0.3, P = .01). In women with PCOS, but not in controls, vit D3 increased serum sRAGE (P = .03) and decreased serum AMH levels (P < .001). The increase in serum sRAGE positively correlated with the increase in serum 25 OH-D after supplementation in women with PCOS (r = 0.6, P = .01). In women with PCOS, vit D3 might exert a protective effect against the inflammatory action of AGEs by increasing circulating sRAGE. The normalization in serum AMH induced by vit D3 replacement suggests an improvement in folliculogenesis.

Biochemical changes in the kidney and liver of rats following administration of ethanolic extract of Psidium guajava leaves.

PubMed

Adeyemi, O S; Akanji, M A

2011-09-01

Furtherance to a previous report on the anti-trypanosomal properties of Psidium guajava aqueous leaf extract in rats experimentally infected with Trypanosoma brucei brucei, we have evaluated the effects of the daily intraperitoneal administration of P. guajava leaf extract to rats on the activities of alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT) and acid phosphatase (ACP) in the kidney, liver and serum. The results obtained revealed that the administration of the extract produced significant increase in the serum activities of AST, ALT, ALP and ACP when compared with the control (p < 0.05). Also AST, ALT and ALP and ACP activities in the tissues of animals administered the extract revealed inconsistent changes (p < 0.05) relative to control. The increase in the serum activity of ALP may be an indicator that there was a likely compromise to the integrity of the plasma membrane as a result of the ethanolic extract administration. This could have caused leakages of the other enzymes investigated, which may explain the corresponding increases in the serum activities of AST, ALT and ACP observed.

[Serum non-esterified fatty acids to albumin ratio increased significantly in children with nephrotic syndrome].

PubMed

Fan, Chun-Li; Wu, Jia; Bu, Xiao-Min; Wan, Shu-Jun; Guo, Peng-Tao; Ma, Yan-Juan; Wang, Jun-Jun

2016-10-20

To analyze serum levels of non-esterified fatty acids (NEFA) and albumin (ALB) in children with nephrotic syndrome (NS) and investigate the clinical significance of altered serum NEFA to ALB ratio in children with NS in acute and remission phases. Serum levels of NEFA and ALB were measured in 55 NS children in acute phase, in 33 NS children in remission and in 122 healthy control children, and the ratio of NEFA to ALB was calculated. The other lipid/lipoprotein and renal function parameters were also analyzed in these children. Compared with the healthy control children, children with NS had a significantly decreased serum ALB level (t=11.152, P<0.001) and a significantly increased NEFA to ALB ratio (t=4.991, P<0.001). Compared with NS children in remission, those in acute phase showed a significantly decreased ALB (Z=7.822, P<0.001) and an increased NEFA to ALB ratio (t=4.991, P<0.001). In all the NS children, NEFA to ALB ratio was positively correlated with the levels of TC (r=0.564, P<0.001), TG (r=0.444, P<0.001), LDL-C (r=0.625, P<0.001), urea (r=0.437, P<0.001), creatinine (r=0.278, P=0.013), and uric acid (r=0.397, P<0.001), while negatively correlated with the level of total protein (r=-0.461, P<0.001). Multiple linear regression analyses showed that NEFA to ALB ratio was independently associated with serum urea levels (β=0.703, P=0.001; adjusted R 2 =0.494) after adjustment of other related factors. Serum NEFA to ALB ratio is significantly increased in NS children in close association with impaired kidney function, and may function as a novel parameter for assessing the development of NS.

Serum S-adenosylmethionine, but not methionine, increases in response to overfeeding in humans.

PubMed

Elshorbagy, A K; Jernerén, F; Samocha-Bonet, D; Refsum, H; Heilbronn, L K

2016-01-25

Plasma concentration of the methyl donor S-adenosylmethionine (SAM) is linearly associated with body mass index (BMI) and fat mass. As SAM is a high-energy compound and a sensor of cellular nutrient status, we hypothesized that SAM would increase with overfeeding. Forty normal to overweight men and women were overfed by 1250 kcal per day for 28 days. Serum SAM increased from 106 to 130 nmol/l (P=0.006). In stratified analysis, only those with weight gain above the median (high-weight gainers; average weight gain 3.9±0.3 kg) had increased SAM (+42%, P=0.001), whereas low-weight gainers (weight gain 1.5±0.2 kg) did not (Pinteraction=0.018). Overfeeding did not alter serum concentrations of the SAM precursor, methionine or the products, S-adenosyl-homocysteine and homocysteine. The SAM/SAH (S-adenosylhomocysteine) ratio was unchanged in the total population, but increased in high-weight gainers (+52%, P=0.006, Pinteraction =0.005). Change in SAM correlated positively with change in weight (r=0.33, P=0.041) and fat mass (r=0.44, P=0.009), but not with change in protein intake or plasma methionine, glucose, insulin or low-density lipoprotein (LDL)-cholesterol. Overfeeding raised serum SAM in proportion to the fat mass gained. The increase in SAM may help stabilize methionine levels, and denotes a responsiveness of SAM to nutrient state in humans. The role of SAM in human energy metabolism deserves further attention.

Effect of co-administration of cassava (Manihot esculenta Crantz) rich diet and alcohol in rats.

PubMed

Boby, R G; Indira, M

2004-01-01

The effects of co-administration of a cassava rich diet and alcohol in rats were investigated. The animals were divided into four groups (1) Control, (2) Alcohol, (3) Cassava and (4) Alcohol + Cassava. Consumption of alcohol along with cassava reduced the alcohol induced toxicity which was evidenced by the lower activities of GOT, GPT, GGT, acid phosphatase and alkaline phosphatase in the liver and serum of co-administered group. The pyruvate content in the blood increased while the lactate content, lactate/pyruvate ratio and the activity of LDH decreased in the blood due to co-administration. The blood cyanide content, serum thiocyanate content and the activities of rhodanase and beta-glucuronidase increased on co-administration. The histopathological studies also revealed that co-administration reduced the alcohol induced toxicity.

Increased serum APRIL differentially correlates with distinct cytokine profiles and disease activity in systemic lupus erythematosus patients.

PubMed

Boghdadi, Ghada; Elewa, Enass A

2014-09-01

Cytokines play an important role in the pathogenesis of systemic lupus erythematosus (SLE). Among the cytokines that regulate B cell homeostasis is a proliferation-inducing ligand (APRIL). This study aimed to determine whether serum levels of APRIL are raised in patients with SLE and correlate with disease activity or proinflammatory cytokines production, or both. Serum APRIL, interleukin-17 (IL-17), IL-4 and interferon gamma (IFN-γ) levels were measured in forty patients with SLE and 30 healthy controls. Disease activity was assessed by SLE disease activity index (SLEDAI), and results were correlated with serum APRIL levels. Serum APRIL levels were significantly higher in patients with SLE than in healthy controls. Positive correlation was found between serum APRIL levels and total SLEDAI score and anti-dsDNA antibody titers. Moreover, serum APRIL levels was significantly higher in patients with arthritis, mucocutaneous manifestations and proteinuria. APRIL is increased in patients with active SLE accompanying the increase of IL-17 and IFN-γ. Significant positive correlations between serum levels of APRIL and IL-17 and IFN-γ and a negative correlation between serum levels of APRIL and IL-4 were found. The results suggest that APRIL may be an important marker of disease activity in patients with SLE. We provide the analyses of APRIL levels in patients with SLE, suggesting new tools for the diagnosis, prognosis and possible therapeutic management of SLE.

Sex differences in the effect of acute peripheral IL-1β administration on the brain and serum BDNF and VEGF expression in rats.

PubMed

Obuchowicz, Ewa; Nowacka, Marta; Paul-Samojedny, Monika; Bielecka-Wajdman, Anna M; Małecki, Andrzej

2017-02-01

The present study was designed to evaluate, for the first time, the potential sex differences in BDNF and VEGF systems under normal conditions and in response to IL-1β given ip. Peripheral overproduction of this cytokine mediates the pathophysiology of various acute neuroinflammatory states. Until now, the effect of IL-1β on VEGF expression in rat brain structures and its serum level has not been examined. In male and female rats, the BDNF and VEGF mRNA expression, and BDNF level were evaluated in the amygdala, hippocampus, hypothalamus and pituitary gland. The VEGF levels were determined in the pituitary. Serum BDNF and VEGF levels were also measured. The pituitary BDNF mRNA, and BDNF and VEGF levels were higher in females than in male rats whereas in males, the BDNF levels were higher in the other brain structures. The serum BDNF concentration was similar in both groups but VEGF levels were enhanced in females. Following IL-1β (50μg/kg ip.) administration, a higher serum IL-1β level was detected in females than in males. In male rats, IL-1β decreased BDNF mRNA in all the brain structures, except for the pituitary, and VEGF mRNA in the amygdala. In opposite, IL-1β challenge in females increased the pituitary VEGF mRNA and serum BDNF and VEGF levels. These results suggest that in females BDNF and VEGF may play a more important role in the pituitary function. In males, amygdala trophic system seems to be especially sensitive to the enhanced peripheral IL-1β production. Our findings point to the need to consider sex-related differences to be able to draw reliable conclusions about changes in BDNF and VEGF levels during inflammation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Aripiprazole maintenance increases smoked cocaine self-administration in humans

PubMed Central

Rubin, Eric; Foltin, Richard W.

2011-01-01

Rationale Partial dopamine receptor agonists have been proposed as candidate pharmacotherapies for cocaine dependence. Objective This 42-day, within-subject, human laboratory study assessed how maintenance on aripiprazole, a partial D2 receptor agonist, influenced smoked cocaine self-administration, cardiovascular measures, subjective effects, and cocaine craving in nontreatment-seeking, cocaine-dependent volunteers. Methods In order to achieve steady-state concentrations, participants (n=8 men) were administered placebo and aripiprazole (15 mg/day) capsules in counter-balanced order for 21 days. A smoked cocaine dose–response curve (0, 12, 25, 50 mg) was determined twice under placebo and aripiprazole maintenance. Sessions comprised a “sample” trial, when participants smoked the cocaine dose available that session, and five choice trials, when they responded on a progressive-ratio schedule of reinforcement to receive the cocaine dose or receive $5.00. Results Cocaine’s reinforcing, subjective, and cardiovascular effects were dose-dependent. Aripiprazole significantly increased cocaine (12, 25 mg) self-administration. Following a single administration of cocaine (25 mg), aripiprazole decreased ratings of how much participants would pay for that dose. Following repeated cocaine (50 mg) self-administration, aripiprazole decreased ratings of cocaine quality, craving, and good drug effect as compared to placebo. Conclusions These data suggest that aripiprazole may have increased self-administration to compensate for a blunted subjective cocaine effect. Overall, the findings do not suggest aripiprazole would be useful for treating cocaine dependence. PMID:21373790

Exercise increases serum brain-derived neurotrophic factor in patients with major depressive disorder.

PubMed

Kerling, A; Kück, M; Tegtbur, U; Grams, L; Weber-Spickschen, S; Hanke, A; Stubbs, B; Kahl, K G

2017-06-01

Brain derived neurotrophic factor (BDNF) has been implicated in the pathogenesis of major depressive disorder (MDD). Existing data on exercise treatment in people with MDD are inconsistent concerning the effect of exercise on BDNF pointing either to increased or unaltered BDNF concentrations. However, studies in non-depressed persons demonstrated a significant effect on resting peripheral BDNF concentrations in aerobic training interventions. Given the lack of clarity mentioned above, the current study aimed at examining the effect of adjunctive exercise on serum BDNF levels in guideline based treated patients with MDD. 42 depressed inpatients were included, and randomized either to a 6 week structured and supervised exercise intervention plus treatment as usual (EXERCISE, n=22), or to treatment as usual (TAU, n=20). BDNF serum concentrations were assessed before and after the intervention in both study groups with established immunoassays. Serum BDNF slightly decreased in the TAU group, whilst there was an increase in BDNF levels in the exercise group. There was a significant time x group effect concerning sBDNF (p=0.030) with repeated ANOVA measures with age and BMI as covariates, suggesting an increase in BDNF concentrations in the EXERCISE group compared to TAU. Though there was no statistic difference in the antidepressant medication between EXERCISE and TAU potential interactions between exercise and medication on the effects of exercise in BDNF cannot be excluded. Gender was not considered as a covariate in ANOVA due to the small number of objects. Exercise training given as adjunct to standard guideline based treatment appears to have additional effects on BDNF serum concentrations in people with MDD. Our results add further evidence to the beneficial effects of exercise in the treatment of MDD. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

High incidence of hypocalcemia and serum creatinine increase in patients with bone metastases treated with zoledronic acid.

PubMed

Zuradelli, Monica; Masci, Giovanna; Biancofiore, Giuseppe; Gullo, Giuseppe; Scorsetti, Marta; Navarria, Pierina; Tancioni, Flavio; Berlusconi, Marco; Giordano, Laura; Santoro, Armando

2009-05-01

Zoledronic acid belongs to the new generation of bisphosphonates with demonstrated clinical benefit for the treatment of bone metastases from different kinds of neoplasms. Hypocalcemia and serum creatinine elevation are expected adverse events during this therapy. The monitoring of serum calcium and creatinine is therefore recommended. The primary aim of this study was to establish the actual incidence of hypocalcemia and serum creatinine elevation during treatment with zoledronic acid. Skeletal-related events and side effects were also assessed. Serum creatinine and calcium levels were evaluated in 240 consecutive patients (83 males, 157 females; mean age, 62 years) with metastatic bone lesions from different solid tumors treated with zoledronic acid. Overall, 93 of 240 patients (38.8%) developed hypocalcemia, which was grade (G)1 in 45 patients (48.4%), G2 in 37 patients (39.8%), G3 in 10 patients (10.8%), and G4 in one patient (1.1%). The median time to occurrence of hypocalcemia (any grade) was 2.3 months after the beginning of the treatment (range, 0-34.9 months). Increased serum creatinine was observed in 33 of 240 patients (13.7%), of whom 19 had G1 (57.6%), 11 had G2 (33.3%), and three had G3 (9.1%). The median time to serum creatinine increase (for any grade) was 4.7 months (range, 0-29.2 months). Our analysis shows a high incidence of hypocalcemia and increased serum creatinine level during treatment with zoledronic acid. These results strongly support the need for accurate monitoring of plasma calcium and creatinine levels.

Increasing insulin resistance accentuates the effect of triglyceride-associated loci on serum triglycerides during 5 years[S

PubMed Central

Justesen, Johanne M.; Andersson, Ehm A.; Allin, Kristine H.; Sandholt, Camilla H.; Jørgensen, Torben; Linneberg, Allan; Jørgensen, Marit E.; Hansen, Torben; Pedersen, Oluf; Grarup, Niels

2016-01-01

Blood concentrations of triglycerides are influenced by genetic factors as well as a number of environmental factors, including adiposity and glucose homeostasis. The aim was to investigate the association between a serum triglyceride weighted genetic risk score (wGRS) and changes in fasting serum triglyceride level over 5 years and to test whether the effect of the wGRS was modified by 5 year changes of adiposity, insulin resistance, and lifestyle factors. A total of 3,474 nondiabetic individuals from the Danish Inter99 cohort participated in both the baseline and 5 year follow-up physical examinations and had information on the wGRS comprising 39 genetic variants. In a linear regression model adjusted for age, sex, and baseline serum triglyceride, the wGRS was associated with increased serum triglyceride levels over 5 years [per allele effect = 1.3% (1.0–1.6%); P = 1.0 × 10−17]. This triglyceride-increasing effect of the wGRS interacted with changes in insulin resistance (Pinteraction = 1.5 × 10−6). This interaction indicated that the effect of the wGRS was stronger in individuals who became more insulin resistant over 5 years. In conclusion, our findings suggest that increased genetic risk load is associated with a larger increase in fasting serum triglyceride levels in nondiabetic individuals during 5 years of follow-up. This effect of the wGRS is accentuated by increasing insulin resistance. PMID:27777317

Short-term cooling increases serum triglycerides and small high-density lipoprotein levels in humans.

PubMed

Hoeke, Geerte; Nahon, Kimberly J; Bakker, Leontine E H; Norkauer, Sabine S C; Dinnes, Donna L M; Kockx, Maaike; Lichtenstein, Laeticia; Drettwan, Diana; Reifel-Miller, Anne; Coskun, Tamer; Pagel, Philipp; Romijn, Fred P H T M; Cobbaert, Christa M; Jazet, Ingrid M; Martinez, Laurent O; Kritharides, Leonard; Berbée, Jimmy F P; Boon, Mariëtte R; Rensen, Patrick C N

Cold exposure and β3-adrenergic receptor agonism, which both activate brown adipose tissue, markedly influence lipoprotein metabolism by enhancing lipoprotein lipase-mediated catabolism of triglyceride-rich lipoproteins and increasing plasma high-density lipoprotein (HDL) levels and functionality in mice. However, the effect of short-term cooling on human lipid and lipoprotein metabolism remained largely elusive. The objective was to assess the effect of short-term cooling on the serum lipoprotein profile and HDL functionality in men. Body mass index-matched young, lean men were exposed to a personalized cooling protocol for 2 hours. Before and after cooling, serum samples were collected for analysis of lipids and lipoprotein composition by 1 H-nuclear magnetic resonance. Adenosine triphosphate-binding cassette A1 (ABCA1)-mediated cholesterol efflux capacity of HDL was measured using [ 3 H]cholesterol-loaded ABCA1-transfected Chinese hamster ovary cells. Short-term cooling increased serum levels of free fatty acids, triglycerides, and cholesterol. Cooling increased the concentration of large very low-density lipoprotein (VLDL) particles accompanied by increased mean size of VLDL particles. In addition, cooling enhanced the concentration of small LDL and small HDL particles as well as the cholesterol levels within these particles. The increase in small HDL was accompanied by increased ABCA1-dependent cholesterol efflux in vitro. Our data show that short-term cooling increases the concentration of large VLDL particles and increases the generation of small LDL and HDL particles. We interpret that cooling increases VLDL production and turnover, which results in formation of surface remnants that form small HDL particles that attract cellular cholesterol. Copyright © 2017 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Increased serum phosphate concentrations in patients with advanced chronic kidney disease treated with diuretics.

PubMed

Caravaca, Francisco; García-Pino, Guadalupe; Martínez-Gallardo, Rocío; Ferreira-Morong, Flavio; Luna, Enrique; Alvarado, Raúl; Ruiz-Donoso, Enrique; Chávez, Edgar

2013-01-01

Serum phosphate concentrations usually show great variability in patients with advanced chronic kidney disease (ACKD) not on dialysis. Diuretics treatment can have an influence over the severity of mineral-bone metabolism alterations related to ACKD, but their effect on serum phosphate levels is less known. This study aims to determine whether diuretics are independently associated with serum phosphate levels, and to investigate the mechanisms by which diuretics may affect phosphate metabolism. 429 Caucasian patients with CKD not on dialysis were included in this cross-sectional study. In addition to conventional serum biochemical measures, the following parameters of renal phosphate excretion were assessed: 24-hours urinary phosphate excretion, tubular maximum phosphate reabsorption (TmP), and fractional excretion of phosphate (FEP). 58% of patients were on treatment with diuretics. Patients on diuretics showed significantly higher mean serum phosphate concentration (4.78 ± 1.23 vs. 4.24 ± 1.04 mg/dl; P<.0001), and higher TmP per GFR (2.77 ± 0.72 vs. 2.43 ± 0.78 mg/dl; P<.0001) than those not treated with diuretics. By multivariate linear and logistic regression, significant associations between diuretics and serum phosphate concentrations or hyperphosphataemia remained after adjustment for potential confounding variables. In patients with the highest phosphate load adjusted to kidney function, those treated with diuretics showed significantly lower FEP than those untreated with diuretics. Treatment with diuretics is associated with increased serum phosphate concentrations in patients with ACKD. Diuretics may indirectly interfere with the maximum renal compensatory capacity to excrete phosphate. Diuretics should be considered in the studies linking the relationship between serum phosphate concentrations and cardiovascular alterations in patients with CKD.

Apolipoprotein E-knockout mice show increased titers of serum anti-nuclear and anti-dsDNA antibodies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Yuehai; Huang, Ziyang, E-mail: huangziyang666@126.com; Lu, Huixia

2012-07-13

Highlights: Black-Right-Pointing-Pointer Titers of ANA and anti-dsDNA antibodies were higher in ApoE{sup -/-} than C57B6/L mice. Black-Right-Pointing-Pointer Spleen was greater and splenocyte apoptosis lower in ApoE{sup -/-} than B6 mice. Black-Right-Pointing-Pointer Level of TLR4 was lower in spleen tissue of ApoE{sup -/-} than B6 mice. Black-Right-Pointing-Pointer The TLR4 pathway may participate in maintaining the balance of splenocyte apoptosis. Black-Right-Pointing-Pointer The TLR4 pathway may participate in antibody production in spleen tissue. -- Abstract: Apolipoprotein E-knockout (ApoE{sup -/-}) mice, atherosclerosis-prone mice, show an autoimmune response, but the pathogenesis is not fully understood. We investigated the pathogenesis in female and male ApoE{sup -/-}more » mice. The spleens of all ApoE{sup -/-} and C57BL/6 (B6) mice were weighed. The serum IgG level and titers of anti-nuclear antibody (ANA) and anti-double-stranded DNA (anti-dsDNA) antibody were assayed by ELISA. Apoptosis of spleen tissue was evaluated by TUNEL. TLR4 level in spleen tissue was tested by immunohistochemistry and Western blot analysis. Levels of MyD88, p38, phosphorylated p38 (pp38), interferon regulatory factor 3 (IRF3) and Bcl-2-associated X protein (Bax) in spleen tissue were detected by Western blot analysis. We also survey the changes of serum autoantibodies, spleen weight, splenocyte apoptosis and the expressions of TLR4, MyD88, pp38, IRF3 and Bax in spleen tissue in male ApoE{sup -/-} mice after 4 weeks of lipopolysaccharide (LPS), Toll-like receptor 4 ligand, administration. ApoE{sup -/-} mice showed splenomegaly and significantly increased serum level of IgG and titers of ANA and anti-dsDNA antibody as compared with B6 mice. Splenocyte apoptosis and the expression of TLR4, MyD88, pp38, IRF3 and Bax in spleen tissue were significantly lower in ApoE{sup -/-} than B6 mice. The expression of TLR4, MyD88, IRF3, pp38, and Bax differed by sex in ApoE{sup -/-} spleen

One year B-vitamins increases serum and whole blood folate forms and lowers plasma homocysteine in older Germans.

PubMed

Kirsch, Susanne H; Herrmann, Wolfgang; Kruse, Vera; Eckert, Rudolf; Gräber, Stefan; Geisel, Jürgen; Obeid, Rima

2015-02-01

We aimed to study the effect of long-term supplementation of B-vitamins on folate forms in serum and whole blood (WB) in elderly German subjects. 59 participants (mean age 67 years) were randomized to daily receive either vitamin D3 (1200 IU), folic acid (500 μg), vitamin B12 (500 μg), vitamin B6 (50 mg), and calcium carbonate (456 mg) or vitamin D3 plus calcium carbonate. Serum and WB folate forms were measured before and after 6 and 12 months. B-vitamins supplementation for 6 months led to higher concentrations of 5-methyltetrahydrofolate (5-methylTHF) in serum (mean 49.1 vs. 19.6 nmol/L) and WB (1332 vs. 616 nmol/L). Also non-methyl-folate concentrations in serum and WB were higher after 6 months with B-vitamins supplementation. Unmetabolized folic acid (UFA) increased after supplementation. tHcy concentration was lowered after 1 year of B-vitamin supplementation (mean 13.1 vs. 9.6 μmol/L). A stronger reduction of tHcy after 1 year was found in participants who had baseline level >12.5 μmol/L (mean 17.0 vs. 11.9 μmol/L) compared to those with baseline tHcy lower than this limit (mean 9.1 vs. 7.4 μmol/L). In contrast, the increases in serum and WB 5-methylTHF were comparable between the two groups. One year B-vitamins supplementation increased the levels of 5-methylTHF and non-methyl-folate in serum and WB, normalized tHcy, but caused an increase in the number of cases with detectable UFA in serum. Lowering of tHcy was predicted by baseline tHcy, but not by baseline serum or WB 5-methylTHF.

Creatine metabolism and safety profiles after six-week oral guanidinoacetic acid administration in healthy humans.

PubMed

Ostojic, Sergej M; Niess, Barbara; Stojanovic, Marko; Obrenovic, Milos

2013-01-01

Guanidinoacetic acid (GAA) is a natural precursor of creatine, yet the potential use of GAA as a nutritional additive for restoring creatine availability in humans has been limited by unclear efficacy and safety after exogenous GAA administration. The present study evaluated the effects of orally administered GAA on serum and urinary GAA, creatine and creatinine concentration, and on the occurrence of adverse events in healthy humans. Twenty-four healthy volunteers were randomized in a double-blind design to receive either GAA (2.4 grams daily) or placebo (PLA) by oral administration for 6 weeks. www.clinicaltrials.gov, identification number NCT01133899. Serum creatine and creatinine increased significantly from before to after administration in GAA-supplemented participants (P < 0.05). The proportion of participants who reported minor side effects was 58.3% in the GAA group and 45.5% in the placebo group (P = 0.68). A few participants experienced serum creatine levels above 70 µmol/L. Exogenous GAA is metabolized to creatine, resulting in a significant increase of fasting serum creatine after intervention. GAA had an acceptable side-effects profile with a low incidence of biochemical abnormalities.

Creatine Metabolism and Safety Profiles after Six-Week Oral Guanidinoacetic Acid Administration in Healthy Humans

PubMed Central

Ostojic, Sergej M.; Niess, Barbara; Stojanovic, Marko; Obrenovic, Milos

2013-01-01

Objectives; Guanidinoacetic acid (GAA) is a natural precursor of creatine, yet the potential use of GAA as a nutritional additive for restoring creatine availability in humans has been limited by unclear efficacy and safety after exogenous GAA administration. The present study evaluated the effects of orally administered GAA on serum and urinary GAA, creatine and creatinine concentration, and on the occurrence of adverse events in healthy humans. Methods and Results; Twenty-four healthy volunteers were randomized in a double-blind design to receive either GAA (2.4 grams daily) or placebo (PLA) by oral administration for 6 weeks. Clinical trial registration: www.clinicaltrials.gov, identification number NCT01133899. Serum creatine and creatinine increased significantly from before to after administration in GAA-supplemented participants (P < 0.05). The proportion of participants who reported minor side effects was 58.3% in the GAA group and 45.5% in the placebo group (P = 0.68). A few participants experienced serum creatine levels above 70 µmol/L. Conclusion; Exogenous GAA is metabolized to creatine, resulting in a significant increase of fasting serum creatine after intervention. GAA had an acceptable side-effects profile with a low incidence of biochemical abnormalities. PMID:23329885

The impact of high progesterone levels on the day of HCG administration in assisted human reproduction treatments.

PubMed

Tanada, Michelli S; Yoshida, Ivan H; Santos, Monise; Berton, Caroline Z; Souto, Elen; Carvalho, Waldemar P de; Cordts, Emerson B; Barbosa, Caio P

2018-06-01

Progesterone is a steroid hormone that acts on the endometrium. It is known for producing physical and mood-related side effects. Few studies have looked into how progesterone levels affect embryo development and quality. This study aimed to find a cutoff level for serum progesterone on the day of HCG administration from which embryo quality is impaired. The study included 145 cycles, from which 885 oocytes and 613 embryos were obtained. All patients had their serum progesterone levels measured on the day of HCG administration. Data sets were collected from patient medical records. The chi-square test was used to assess qualitative variables and the Mann-Whitney test to evaluate quantitative variables. Statistical analysis revealed that serum progesterone levels and reproductive variables were not significantly associated. In regards to oocyte maturity, however, when progesterone levels were greater than 1.3 ng/mL the probability of oocytes being immature increased by 12.7%. The fragmentation rate of embryos categorized as "top quality" in D3 increased proportionately to increases in progesterone levels (12.23%). High progesterone levels appeared to be correlated with increased embryo fragmentation rates, but high serum levels of the hormone on the day of HCG administration had no impact on reproductive variables and were not associated with impaired embryo development.

Metabolic changes in rat serum after administration of suberoylanilide hydroxamic acid and discriminated by SVM.

PubMed

Yu, J; Wu, H; Lin, Z; Su, K; Zhang, J; Sun, F; Wang, X; Wen, C; Cao, H; Hu, L

2017-12-01

Suberoylanilide hydroxamic acid (SAHA) exerts marked anticancer effects via promotion of apoptosis, cell cycle arrest, and prevention of oncogene expression. In this study, serum metabolomics and artificial intelligence recognition were used to investigate SAHA toxicity. Forty rats (220 ± 20 g) were randomly divided into control and three SAHA groups (low, medium, and high); the experimental groups were treated with 12.3, 24.5, or 49.0 mg kg -1 SAHA once a day via intragastric administration. After 7 days, blood samples from the four groups were collected and analyzed by gas chromatography-mass spectrometry, and pathological changes in the liver were examined using microscopy. The results showed that increased levels of urea, oleic acid, and glutaconic acid were the most significant indicators of toxicity. Octadecanoic acid, pentadecanoic acid, glycerol, propanoic acid, and uric acid levels were lower in the high SAHA group. Microscopic observation revealed no obvious damage to the liver. Based on these data, a support vector machine (SVM) discrimination model was established that recognized the metabolic changes in the three SAHA groups and the control group with 100% accuracy. In conclusion, the main toxicity caused by SAHA was due to excessive metabolism of saturated fatty acids, which could be recognized by an SVM model.

Comparison between preoperative administration of methylprednisolone with its administration before and during congenital heart surgery on serum levels of IL-6 and IL-10.

PubMed

Abbasi Tashnizi, Mohammad; Soltani, Ghasem; Moeinipour, Ali Asghar; Ayatollahi, Hossein; Tanha, Amir Saber; Jarahi, Lida; Sepehri Shamloo, Alireza; Zirak, Nahid

2013-02-01

Steroid administration during cardiopulmonary bypass is considered to improve cardiopulmonary function by modulating inflammations caused by bypass. This study was performed to compare effectiveness of preoperative and intraoperative methylprednisolone (MP) to preoperative methylprednisolone alone in post bypass inflammatory (IL-6) and anti-inflammatory (IL-10) factors. Fifty pediatric patients undergoing cardiopulmonary bypass surgery from August 2011 to 2012 in the cardiac surgery department of Imam Reza Hospital, the major center for CPB, in Mashhad, Iran were randomly assigned to receive preoperative and intraoperative MP (30 mg/kg, 4 hours before bypass and in bypass prime, number 25) or preoperative MP only (30 mg/kg, number 25). Before and after bypass, four and 24 hours after bypass, serum IL-6 and IL-10 were measured by ELISA. In both groups, no significant difference with variation of expression for IL-6 (inflammatory factor) and IL-10 (anti-inflammatory factor) in different times after bypass was observed. No significant difference in reducing post bypass inflammation between preoperative steroid treatment and combined preoperative and intraoperative steroid administration reported and they had the same effects.

[Severely increased serum lipid levels in diabetic ketoacidosis - case report].

PubMed

Stefansson, Hrafnkell; Sigvaldason, Kristinn; Kjartansson, Hilmar; Sigurjonsdottir, Helga Águsta

2017-01-01

Severe hypertriglyceridemia is a known, but uncommon complication of diabetic ketoacidosis. We discuss the case of a 23-year-old, previously healthy, woman who initially presented to the emergency department with abdominal pain. Grossly lipemic serum due to extremely high triglyceride (38.6 mmol/L) and cholesterol (23.2 mmol/L) levels were observed with a high blood glucose (23 mmol/L) and a low pH of 7.06 on a venous blood gas. She was treated successfully with fluids and insulin and had no sequale of pancreatitis or cerebral edema. Her triglycerides and cholesterol was normalized in three days and she was discharged home on insulin therapy after five days. Further history revealed a recent change in diet with no meat, fish or poultry consumption in the last 12 months and concomitantly an increase in carbohydrate intake which might have contributed to her extremely high serum lipid levels. This case demonstrates that clinicians should be mindful of the different presentations of diabetic ketoacidosis. Key words: diabetic ketoacidosis, hypertriglyceridemia, hyperlipidemia, vegan diet, carbohydrate diet. Correspondence: Hrafnkell Stefansson, hrafnkell.stefans@gmail.com.

Increased serum triglycerides and reduced HDL cholesterol in male rats after intake of ammonium chloride for 3 weeks

PubMed Central

2013-01-01

Background Previous data suggested that intake of sodas and other acid beverages might be associated with increased levels of serum triglycerides, lowered HDL cholesterol, and increased formation of mono unsaturated fatty acids, which are the preferred ones for triglyceride synthesis. The present work is an extension of these studies. Methods Thirty male rats were divided into 3 groups. All groups were given the same food, but various beverages: water (W), ammonium chloride, 200 mmol/L (AC), or sodium bicarbonate, 200 mmol/L (SB). Serum triglycerides, HDL cholesterol, and the fatty acid distribution in total serum lipids were determined. Delta9-desaturase in serum lipids was estimated by the ratio of palmitoleic to palmitic acid, and by the oleic/stearic acid ratio. Correlation and ANOVA were used to study associations and group differences. Results After 3 weeks, the AC group had higher triglyceride concentration and higher Delta9 desaturase indexes, but lower serum HDL and body weight as compared with the SB and W groups. In each of the groups, the oleic acid/stearic acid ratio correlated positively with serum triglycerides; in the pooled group the correlation coefficient was r = 0.963, p<0.01. Conclusions Rats ingesting ammonium chloride as compared with sodium bicarbonate responded with increased desaturase indexes, increased serum triglycerides, and lowered HDL cholesterol concentration, thereby possibly contributing to explain the increased triglyceride concentration previously observed in subjects with a frequent intake of acid beverages, such as sodas containing carbonic acid, citric acid, and phosphoric acid. PMID:23800210

Acute effects of intravenous cocaine administration on serum concentrations of ghrelin, amylin, glucagon-like peptide-1, insulin, leptin and peptide YY and relationships with cardiorespiratory and subjective responses.

PubMed

Bouhlal, Sofia; Ellefsen, Kayla N; Sheskier, Mikela B; Singley, Erick; Pirard, Sandrine; Gorelick, David A; Huestis, Marilyn A; Leggio, Lorenzo

2017-11-01

Food intake and use of drugs of abuse like cocaine share common central and peripheral physiological pathways. Appetitive hormones play a major role in regulating food intake; however, little is known about the effects of acute cocaine administration on the blood concentrations of these hormones in cocaine users. We evaluated serum concentrations of six appetitive hormones: ghrelin (total and acyl-ghrelin), amylin, glucagon-like peptide-1 (GLP-1), insulin, leptin and peptide YY (PYY), as well as acute cardiorespiratory and subjective responses of 8 experienced cocaine users who received 25mg intravenous (IV) cocaine. Serum concentrations of GLP-1 (p=0.014) and PYY (p=0.036) were significantly decreased one hour following IV cocaine administration; there was a trend towards a decrease for insulin (p=0.055) and amylin (p=0.063) concentrations, while no significant IV cocaine effect was observed for ghrelin (total or acyl-ghrelin) or leptin concentrations (p's≫>0.5). We also observed associations between hormone concentrations acutely affected by IV cocaine (GLP-1, PYY, insulin, amylin) and some cocaine-related cardiorespiratory and subjective responses (e.g., increased heart and respiratory rates; feeling high and anxious). These findings show a significant effect of acute IV cocaine administration on some appetitive hormones and suggest potential associations between these hormones and cocaine-related cardiorespiratory and subjective responses. Additional research is needed to further investigate the potential mechanisms underlining these associations. Published by Elsevier B.V.

Increased serum enzyme levels associated with kupffer cell reduction with no signs of hepatic or skeletal muscle injury.

PubMed

Radi, Zaher A; Koza-Taylor, Petra H; Bell, Rosonald R; Obert, Leslie A; Runnels, Herbert A; Beebe, Jean S; Lawton, Michael P; Sadis, Seth

2011-07-01

Macrophage colony-stimulating factor (M-CSF) is a hematopoietic growth factor that is responsible for the survival and proliferation of monocytes and the differentiation of monocytes into macrophages, including Kupffer cells (KCs) in the liver. KCs play an important role in the clearance of several serum enzymes, including aspartate aminotransferase and creatine kinase, that are typically elevated as a result of liver or skeletal muscle injury. We used three distinct animal models to investigate the hypothesis that increases in the levels of serum enzymes can be the result of decreases in KCs in the apparent absence of hepatic or skeletal muscle injury. Specifically, neutralizing M-CSF activity via a novel human monoclonal antibody reduced the CD14(+)CD16(+) monocyte population, depleted KCs, and increased aspartate aminotransferase and creatine kinase serum enzyme levels in cynomolgus macaques. In addition, the treatment of rats with clodronate liposomes depleted KCs and led to increased serum enzyme levels, again without evidence of tissue injury. Finally, in the osteopetrotic (Csf1(op)/Csf1(op)) mice lacking functional M-CSF and having reduced levels of KCs, the levels of serum enzymes are higher than in wild-type littermates. Together, these findings support a mechanism for increases in serum enzyme levels through M-CSF regulation of tissue macrophage homeostasis without concomitant histopathological changes in either the hepatic or skeletal system. Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Increase in serum albumin concentration is associated with prediabetes development and progression to overt diabetes independently of metabolic syndrome.

PubMed

Jun, Ji Eun; Lee, Seung-Eun; Lee, You-Bin; Jee, Jae Hwan; Bae, Ji Cheol; Jin, Sang-Man; Hur, Kyu Yeon; Lee, Moon-Kyu; Kim, Jae Hyeon

2017-01-01

Serum albumin concentration is associated with both type 2 diabetes and metabolic syndrome (MetS). We sought to investigate whether baseline serum albumin and change in serum albumin could be independent risk factors for prediabetes in subjects without MetS. We further examined the effect of serum albumin on progression to overt diabetes in subjects who developed prediabetes. Among 10,792 participants without diabetes and MetS who consecutively underwent yearly health check-ups over six years, 9,807 subjects without incident MetS were enrolled in this longitudinal retrospective study. The risk of developing prediabetes (impared fasting glucose or hemoglobin A1c) was analyzed according to baseline and percent change in serum albumin concentration using Cox regression analysis. Serial changes in serum albumin concentration were measured from baseline to one year before prediabetes diagnosis, and then from the time of prediabetes diagnosis to progression to overt diabetes or final follow-up. A total of 4,398 incident cases of prediabetes developed during 35,807 person-years (median 3.8 years). The hazard ratio for incident prediabetes decreased as percent change in serum albumin concentration (quartiles and per 1%) increased in a crude and fully adjusted model. However, baseline serum albumin concentration itself was not associated with prediabetic risk. Serum albumin levels kept increasing until the end of follow-up in prediabetic subjects who returned to normal glycemic status, whereas these measures did not change in prediabetic subjects who developed type 2 diabetes. Serum albumin concentration measured at the end of follow-up was the highest in the regression group, compared to the stationary (p = 0.014) or progression groups (p = 0.009). Increase in serum albumin concentration might protect against early glycemic deterioration and progression to type 2 diabetes even in subjects without MetS.

Increase in serum albumin concentration is associated with prediabetes development and progression to overt diabetes independently of metabolic syndrome

PubMed Central

Jun, Ji Eun; Lee, Seung-Eun; Lee, You-Bin; Jee, Jae Hwan; Bae, Ji Cheol; Jin, Sang-Man; Hur, Kyu Yeon; Lee, Moon-Kyu

2017-01-01

Aim Serum albumin concentration is associated with both type 2 diabetes and metabolic syndrome (MetS). We sought to investigate whether baseline serum albumin and change in serum albumin could be independent risk factors for prediabetes in subjects without MetS. We further examined the effect of serum albumin on progression to overt diabetes in subjects who developed prediabetes. Methods Among 10,792 participants without diabetes and MetS who consecutively underwent yearly health check-ups over six years, 9,807 subjects without incident MetS were enrolled in this longitudinal retrospective study. The risk of developing prediabetes (impared fasting glucose or hemoglobin A1c) was analyzed according to baseline and percent change in serum albumin concentration using Cox regression analysis. Serial changes in serum albumin concentration were measured from baseline to one year before prediabetes diagnosis, and then from the time of prediabetes diagnosis to progression to overt diabetes or final follow-up. Results A total of 4,398 incident cases of prediabetes developed during 35,807 person-years (median 3.8 years). The hazard ratio for incident prediabetes decreased as percent change in serum albumin concentration (quartiles and per 1%) increased in a crude and fully adjusted model. However, baseline serum albumin concentration itself was not associated with prediabetic risk. Serum albumin levels kept increasing until the end of follow-up in prediabetic subjects who returned to normal glycemic status, whereas these measures did not change in prediabetic subjects who developed type 2 diabetes. Serum albumin concentration measured at the end of follow-up was the highest in the regression group, compared to the stationary (p = 0.014) or progression groups (p = 0.009). Conclusions Increase in serum albumin concentration might protect against early glycemic deterioration and progression to type 2 diabetes even in subjects without MetS. PMID:28430803

A possible mechanism for the decrease in serum thyroxine level by phenobarbital in rodents

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kato, Yoshihisa, E-mail: kato@kph.bunri-u.ac.jp; Suzuki, Hiroshi; Haraguchi, Koichi

2010-12-15

Effects of phenobarbital (PB) on the levels of serum thyroid hormones such as total thyroxine (T{sub 4}) and triiodothyronine were examined in male mice, hamsters, rats, and guinea pigs. One day after the final administration of PB (80 mg/kg, intraperitoneal, once daily for 4 days), significant decreases in the levels of the serum total T{sub 4} and free T{sub 4} occurred in mice, hamsters, and rats, while a significant decrease in the level of serum triiodothyronine was observed in hamsters and rats among the animals examined. In addition, a significant decrease in the level of serum thyroid-stimulating hormone was observedmore » in only hamsters among the rodents examined. Significant increases in the level and activity of hepatic T{sub 4}-UDP-glucuronosyltransferase (UGT1A) after the PB administration occurred in mice, hamsters, and rats, while the increase in the amount of biliary [{sup 125}I]T{sub 4}-glucuronide after an intravenous injection of [{sup 125}I]T{sub 4} to the PB-pretreated animals occurred only in rats. In mice, rats, and hamsters, but not guinea pigs, PB pretreatment promoted the clearance of [{sup 125}I]T{sub 4} from the serum, led to a significant increase in the steady-state distribution volumes of [{sup 125}I]T{sub 4}, and raised the concentration ratio (Kp value) of the liver to serum and the liver distribution of [{sup 125}I]T{sub 4}. The present findings indicate that the PB-mediated decreases in the serum T{sub 4} level in mice, hamsters, and rats, but not guinea pigs, occur mainly through an increase in the accumulation level of T{sub 4} in the liver.« less

Increased serum level of prolactin is related to autoantibody production in systemic lupus erythematosus.

PubMed

Yang, J; Li, Q; Yang, X; Li, M

2016-04-01

Prolactin (PRL) is known to aid effector B cells and augment autoimmunity, but the role of PRL in systemic lupus erythematosus (SLE) is not fully elucidated. The aim of this study was to determine the correlation between the serum levels of PRL and autoantibody production in SLE. Blood levels of PRL, anti-double-stranded DNA (ds-DNA) antibody, immunoglobulin M (IgM) and immunoglobulin G (IgG) were determined in samples from 30 adult patients with SLE and 25 healthy controls. The relationships between the serum level of PRL and SLE disease activity, as well as the titres of the ds-DNA antibody, IgM and IgG were determined. The serum level of PRL was higher in the SLE patients than in the healthy controls. PRL concentration increased during SLE flares-ups and decreased following disease remission. There was a positive correlation between the PRL concentration and serum levels of IgM, IgG and ds-DNA antibody titre. These data suggest that the serum level of PRL was closely related to the antibody production and disease activity of SLE patients. PRL concentration was dramatically reduced upon the remission of disease activity, indicating that PRL levels might be a promising predictor of SLE disease severity. © The Author(s) 2015.

Increase in swimming endurance capacity of mice by capsaicin-induced adrenal catecholamine secretion.

PubMed

Kim, K M; Kawada, T; Ishihara, K; Inoue, K; Fushiki, T

1997-10-01

Increase in endurance swimming capacity caused by capsaicin (CAP), a pungent component of red pepper, -induced increase of fat metabolism in mice was investigated using an adjustable-current water pool. The mice administered CAP via a stomach tube, showed longer swimming time until exhaustion than the control group of mice, in a dose-dependent manner. The maximal effect was observed at a dose of 10 mg/kg while more than 15 mg/kg had no effect. The increase of endurance was observed only when CAP was administered two hours before swimming. After the administration of CAP, the serum glucose concentration rapidly increased and then decreased within 60 min, while the concentration of serum-free fatty acids gradually increased through 3 hours. The residual glycogen concentration of the gastrocnemius muscle after 30 min of swimming was significantly higher in the CAP-administered mice than in control mice, suggesting that use of the serum free fatty acids spared muscle glycogen consumption. The serum adrenaline concentration significantly increased with twin peaks at 30 min and two hours after administration of CAP. An experiment using adrenalectomized mice was done to confirm that the effect of CAP is due to increased energy metabolism through the secretion of adrenaline from the adrenal gland. The swimming endurance capacity of the adrenalectomized mice was not increased by CAP administration, although adrenaline injection induced a 58% increase in the endurance time. These results suggest that the increase of swimming endurance induced by CAP in mice is caused by an increase in fatty acid utilization due to CAP-induced adrenal catecholamine secretion.

Agomelatine Increases BDNF Serum Levels in Depressed Patients in Correlation with the Improvement of Depressive Symptoms

PubMed Central

Pettorruso, Mauro; De Berardis, Domenico; Varasano, Paola Annunziata; Lucidi Pressanti, Gabriella; De Remigis, Valeria; Valchera, Alessandro; Ricci, Valerio; Di Nicola, Marco; Janiri, Luigi; Biggio, Giovanni; Di Giannantonio, Massimo

2016-01-01

Background: Agomelatine modulates brain-derived neurotrophic factor expression via its interaction with melatonergic and serotonergic receptors and has shown promising results in terms of brain-derived neurotrophic factor increase in animal models. Methods: Twenty-seven patients were started on agomelatine (25mg/d). Venous blood was collected and brain-derived neurotrophic factor serum levels were measured at baseline and after 2 and 8 weeks along with a clinical assessment, including Hamilton Depression Rating Scale and Snaith-Hamilton Pleasure Scale. Results: Brain-derived neurotrophic factor serum concentration increased after agomelatine treatment. Responders showed a significant increase in brain-derived neurotrophic factor levels after 2 weeks of agomelatine treatment; no difference was observed in nonresponders. Linear regression analysis showed that more prominent brain-derived neurotrophic factor level variation was associated with lower baseline BDNF levels and greater anhedonic features at baseline. Conclusions: Patients affected by depressive disorders showed an increase of brain-derived neurotrophic factor serum concentration after a 2-week treatment with agomelatine. The increase of brain-derived neurotrophic factor levels was found to be greater in patients with lower brain-derived neurotrophic factor levels and marked anhedonia at baseline. PMID:26775293

Development of Spexin-based Human Galanin Receptor Type II-Specific Agonists with Increased Stability in Serum and Anxiolytic Effect in Mice.

PubMed

Reyes-Alcaraz, Arfaxad; Lee, Yoo-Na; Son, Gi Hoon; Kim, Nam Hoon; Kim, Dong-Kyu; Yun, Seongsik; Kim, Dong-Hoon; Hwang, Jong-Ik; Seong, Jae Young

2016-02-24

The novel neuropeptide spexin (SPX) was discovered to activate galanin receptor 2 (GALR2) and 3 (GALR3) but not galanin receptor 1 (GALR1). Although GALR2 is known to display a function, particularly in anxiety, depression, and appetite regulation, the further determination of its function would benefit from a more stable and selective agonist that acts only at GALR2. In the present study, we developed a GALR2-specific agonist with increased stability in serum. As galanin (GAL) showed a low affinity to GALR3, the residues in SPX were replaced with those in GAL, revealing that particular mutations such as Gln5 → Asn, Met7 → Ala, Lys11 → Phe, and Ala13 → Pro significantly decreased potencies toward GALR3 but not toward GALR2. Quadruple (Qu) mutation of these residues still retained potency to GALR2 but totally abolished the potency to both GALR3 and GALR1. The first amino acid modifications or D-Asn1 substitution significantly increased the stability when they are incubated in 100% fetal bovine serum. Intracerebroventricular administration of the mutant peptide with D-Asn1 and quadruple substitution (dN1-Qu) exhibited an anxiolytic effect in mice. Taken together, the GALR2-specific agonist with increased stability can greatly help delineation of GALR2-mediated functions and be very useful for treatments of anxiety disorder.

The Effect of Different Carbapenem Antibiotics (Ertapenem, Imipenem/Cilastatin, and Meropenem) on Serum Valproic Acid Concentrations.

PubMed

Wu, Chien-Chih; Pai, Tsung-Yu; Hsiao, Fei-Yuan; Shen, Li-Jiuan; Wu, Fe-Lin Lin

2016-10-01

Carbapenem antibiotics (CBPMs) may significantly reduce the serum concentration of valproic acid (VPA), but the extent of this effect among various CBPMs is unknown. This study compared the extent and onset of the interactions among ertapenem, imipenem/cilastatin, and meropenem. A 5-year retrospective study was performed. Hospitalized patients over 18 years old who received VPA and a CBPM concurrently were enrolled via the pharmacy computer system. Patients who lacked VPA serum concentration measurements before or during CBPMs' use, had concurrent medication(s) that might interfere with VPA metabolism, or had a history of liver cirrhosis were excluded. Total VPA serum concentrations before and during CBPMs' use and after its discontinuation were recorded, and differences among various CBPMs were analyzed. Fifty-two patients were included in this analysis. Irrespective of the route of administration, VPA serum concentrations were subtherapeutic in 90% of the subjects during CBPMs' use. There was a significant decrease (P < 0.001) in VPA serum concentrations during the use of CBPMs: 72% ± 17%, 42% ± 22%, and 67% ± 19% in the ertapenem (N = 9), imipenem/cilastatin (N = 17), and meropenem (N = 26) groups, respectively. The effect of ertapenem and meropenem on VPA was significantly more expressed than that of imipenem/cilastatin (P < 0.005). The onset of this drug interaction occurred within 24 hours of CBPMs' administration, and VPA serum concentrations returned to 90% of baseline within 7 days of CBPMs' discontinuation along with a 20% increase in VPA dose. Increasing VPA dose during the use of ertapenem or meropenem did not result in elevating VPA serum concentrations to therapeutic levels during the combined therapy period. CBPMs reduced VPA serum concentration within 24 hours of administration by approximately 60%. Ertapenem and meropenem had a greater effect on VPA serum concentration than imipenem/cilastatin. Because of the dramatic reduction of VPA serum

The influence of chosen metals administration in drinking water on magnesium balance in rats.

PubMed

Kiełczykowska, Małgorzata; Pasternak, Kazimierz; Boguszewska, Anna; Musik, Irena

2004-01-01

The aim of our study was to estimate the influence of chromium, lead and aluminium on the magnesium level in serum and tissues of rats. Male Wistar rats received Cr, Pb and Al at the concentration of 500 mg of metal x dm(-3) in the form of drinking water for three or six weeks. After the period of administration the animals were sacrificed under ketamine narcosis and blood from the heart as well as the tissues of the liver, kidney, brain, spleen, femoral muscle and heart muscle were collected. Magnesium concentration was measured in serum and tissue homogenates. Chromium caused the increase of Mg level in some tissues after six weeks and no changes in serum. Lead influenced Mg level in serum and tissues mainly after six weeks but the changes were more diverse and depending on the tissue. After six weeks' administration aluminium caused the magnesium release from serum and its storage in tissues.

Effect of ethanolic extract of Lepidium meyenii Walp on serum hormone levels in ovariectomized rats.

PubMed

Zhang, Yongzhong; Yu, Longjiang; Jin, Wenwen; Ao, Mingzhang

2014-01-01

To evaluate the effect of long-term ethanol extract of Lepidium meyenii (Maca) on serum hormone levels in ovariectomized (OVX) rats and compare them with the effect of diethylstilbestrol. Fifty female Sprague-Dawley rats were ovariectomized or sham operated. Both sham and OVX control groups (n = 10, respectively) received the vehicle. The remaining OVX rats were oral administrated with ethanol extract of Maca (0.096, or 0.24g/kg; n = 10, respectively) and diethylstilbestrol (0.05 mg/kg; n = 10). The treatment continued for 28 weeks. At week 12 and week 28, the blood of rats was collected and serum hormone levels, including estradiol (E2), testosterone (T) and follicle-stimulating hormone (FSH) were measured by radioimmunoassay. At week 12, the levels of serum E2 were slightly higher in Maca groups than that in OVX group; T levels were significantly decreased; and FSH levels were advanced slightly in Maca groups than that in sham group. After 28 weeks administration, serum E2 levels in Maca-treated animals did not differ significantly from sham control, the low dose of Maca increased serum E2 levels, and Maca prevented increase in serum FSH levels compared with OVX group. Long-term Maca supply modulates endocrine hormone balance in OVX rats, especially it decreases enhanced FSH levels. It is proposed that Maca may become a potential choice for postmenopausal women.

Repeated administration of fresh garlic increases memory retention in rats.

PubMed

Haider, Saida; Naz, Nosheen; Khaliq, Saima; Perveen, Tahira; Haleem, Darakhshan J

2008-12-01

Garlic (Allium sativum) is regarded as both a food and a medicinal herb. Increasing attention has focused on the biological functions and health benefits of garlic as a potentially major dietary component. Chronic garlic administration has been shown to enhance memory function. Evidence also shows that garlic administration in rats affects brain serotonin (5-hydroxytryptamine [5-HT]) levels. 5-HT, a neurotransmitter involved in a number of physiological functions, is also known to enhance cognitive performance. The present study was designed to investigate the probable neurochemical mechanism responsible for the enhancement of memory following garlic administration. Sixteen adult locally bred male albino Wistar rats were divided into control (n = 8) and test (n = 8) groups. The test group was orally administered 250 mg/kg fresh garlic homogenate (FGH), while control animals received an equal amount of water daily for 21 days. Estimation of plasma free and total tryptophan (TRP) and whole brain TRP, 5-HT, and 5-hydroxyindole acetic acid (5-HIAA) was determined by high-performance liquid chromatography with electrochemical detection. For assessment of memory, a step-through passive avoidance paradigm (electric shock avoidance) was used. The results showed that the levels of plasma free TRP significantly increased (P < .01) and plasma total TRP significantly decreased (P < .01) in garlic-treated rats. Brain TRP, 5-HT, and 5-HIAA levels were also significantly increased following garlic administration. A significant improvement in memory function was exhibited by garlic-treated rats in the passive avoidance test. Increased brain 5-HT levels were associated with improved cognitive performance. The present results, therefore, demonstrate that the memory-enhancing effect of garlic may be associated with increased brain 5-HT metabolism in rats. The results further support the use of garlic as a food supplement for the enhancement of memory.

Serum creatine kinase isoenzymes in children with osteogenesis imperfecta.

PubMed

D'Eufemia, P; Finocchiaro, R; Zambrano, A; Lodato, V; Celli, L; Finocchiaro, S; Persiani, P; Turchetti, A; Celli, M

2017-01-01

This study evaluates serum creatine kinase isoenzyme activity in children with osteogenesis imperfecta to determine its usefulness as a biochemical marker during treatment with bisphosphonate. The changes of creatine kinase (CK) isoenzyme activity during and after discontinuation therapy were observed. These results could be useful in addressing over-treatment risk prevention. The brain isoenzyme of creatine kinase (CKbb) is highly expressed in mature osteoclasts during osteoclastogenesis, thus plays an important role in bone resorption. We previously identified high serum CKbb levels in 18 children with osteogenesis imperfect (OI) type 1 treated for 1 year with bisphosphonate (neridronate). In the present study, serum CK isoenzymes were evaluated in the same children with continuous versus discontinued neridronate treatment over a further 2-year follow-up period. This study included 18 children with OI type 1, 12 with continued (group A) and 6 with ceased (group B) neridronate treatment. Auxological data, serum biochemical markers of bone metabolism, bone mineral density z-score, and serum total CK and isoenzyme activities were determined in both groups. Serum CKbb was progressively and significantly increased in group A (p < 0.004) but rapidly decreased to undetectable levels in group B. In both groups, the cardiac muscle creatine kinase isoenzyme (CKmb) showed a marked decrease, while serum C-terminal telopeptide (CTx) levels were almost unchanged. This study provides evidence of the cumulative effect of neridronate administration in increasing serum CKbb levels and the reversible effect after its discontinuation. This approach could be employed for verifying the usefulness of serum CKbb as a biochemical marker in patients receiving prolonged bisphosphonate treatment. Moreover, the decreased serum CKmb levels suggest a systemic effect of these drugs.

Significance and prognostic value of increased serum direct bilirubin level for lymph node metastasis in Chinese rectal cancer patients.

PubMed

Gao, Chun; Fang, Long; Li, Jing-Tao; Zhao, Hong-Chuan

2016-02-28

To determine the significance of increased serum direct bilirubin level for lymph node metastasis (LNM) in Chinese rectal cancer patients, after those with known hepatobiliary and pancreatic diseases were excluded. A cohort of 469 patients, who were treated at the China-Japan Friendship Hospital, Ministry of Health (Beijing, China), in the period from January 2003 to June 2011, and with a pathological diagnosis of rectal adenocarcinoma, were recruited. They included 231 patients with LNM (49.3%) and 238 patients without LNM. Follow-up for these patients was taken through to December 31, 2012. The baseline serum direct bilirubin concentration was (median/inter-quartile range) 2.30/1.60-3.42 μmol/L. Univariate analysis showed that compared with patients without LNM, the patients with LNM had an increased level of direct bilirubin (2.50/1.70-3.42 vs 2.10/1.40-3.42, P = 0.025). Multivariate analysis showed that direct bilirubin was independently associated with LNM (OR = 1.602; 95%CI: 1.098-2.338, P = 0.015). Moreover, we found that: (1) serum direct bilirubin differs between male and female patients; a higher concentration was associated with poor tumor classification; (2) as the baseline serum direct bilirubin concentration increased, the percentage of patients with LNM increased; and (3) serum direct bilirubin was associated with the prognosis of rectal cancer patients and higher values indicated poor prognosis. Higher serum direct bilirubin concentration was associated with the increased risk of LNM and poor prognosis in our rectal cancers.

Significance and prognostic value of increased serum direct bilirubin level for lymph node metastasis in Chinese rectal cancer patients

PubMed Central

Gao, Chun; Fang, Long; Li, Jing-Tao; Zhao, Hong-Chuan

2016-01-01

AIM: To determine the significance of increased serum direct bilirubin level for lymph node metastasis (LNM) in Chinese rectal cancer patients, after those with known hepatobiliary and pancreatic diseases were excluded. METHODS: A cohort of 469 patients, who were treated at the China-Japan Friendship Hospital, Ministry of Health (Beijing, China), in the period from January 2003 to June 2011, and with a pathological diagnosis of rectal adenocarcinoma, were recruited. They included 231 patients with LNM (49.3%) and 238 patients without LNM. Follow-up for these patients was taken through to December 31, 2012. RESULTS: The baseline serum direct bilirubin concentration was (median/inter-quartile range) 2.30/1.60-3.42 μmol/L. Univariate analysis showed that compared with patients without LNM, the patients with LNM had an increased level of direct bilirubin (2.50/1.70-3.42 vs 2.10/1.40-3.42, P = 0.025). Multivariate analysis showed that direct bilirubin was independently associated with LNM (OR = 1.602; 95%CI: 1.098-2.338, P = 0.015). Moreover, we found that: (1) serum direct bilirubin differs between male and female patients; a higher concentration was associated with poor tumor classification; (2) as the baseline serum direct bilirubin concentration increased, the percentage of patients with LNM increased; and (3) serum direct bilirubin was associated with the prognosis of rectal cancer patients and higher values indicated poor prognosis. CONCLUSION: Higher serum direct bilirubin concentration was associated with the increased risk of LNM and poor prognosis in our rectal cancers. PMID:26937145

Effect of oral calcium bolus administration on milk production, concentrations of minerals and metabolites in serum, early-lactation health status, and reproductive performance of Holstein dairy cows.

PubMed

Jahani-Moghadam, M; Chashnidel, Y; Teimouri-Yansari, A; Mahjoubi, E; Dirandeh, E

2018-05-01

To determine the effects of oral Ca bolus administration in the early postpartum period of cows on milk yield and composition, blood metabolites, early-lactation health status, and reproductive performance. Multiparous Holstein dry cows (n=66) with a mean parity of 3.1 (SD 0.35) were fed a diet with a positive dietary cation-anion difference (DCAD) prior to calving. They were randomly assigned to receive no treatment (Control; n=33) or two oral Ca boluses (n=33, 45 g of Ca per bolus); one was administered immediately after calving (Day 0) and the second 24 hours (±30 minutes) later. Blood samples were collected at calving, and on Days 2 and 7 to determine concentrations in serum of Ca, P, Mg, glucose, non-esterified fatty acids (NEFA), and β-hydroxybutyric acid (BHBA). Milk yield was recorded daily and milk composition was determined weekly from calving until 28 day postpartum. Health and outcomes were determined during the first 30 days postpartum and reproductive outcomes to 180 days postpartum. Mean milk yields and composition over the first month of lactation were similar between cows in the two treatment groups (p>0.1). Mean concentrations of Ca in serum were not different between treatment groups on Day 0, but were higher on Day 2 for cows that received oral Ca boluses (1.77 (SE 0.07)) compared with Control cows (1.54 (SE 0.08)) (p=0.04). Concentrations in serum of P, Mg, glucose, NEFA and ΒHBA did not differ between treatment groups on any day of measurement. Fewer cows that received oral Ca were diagnosed with hypocalcaemia (total concentrations of Ca in serum <1.5 mmol/L) by Day 2 (2/33; 6%) compared with Control cows (12/33; 36%) (p=0.01). There was no difference in the prevalence of other health outcomes between treatment groups. The proportion of cows conceiving to first insemination was greater in cows that received an oral Ca bolus (19/29; 65%) than Control cows (12/29; 41%) (p=0.01). Oral Ca bolus administration increased concentrations of Ca

Leptin protects cardiomyocytes from serum-deprivation-induced apoptosis by increasing anti-oxidant defence.

PubMed

Zheng, Juan; Fang, Ji; Yin, Yuan-Jun; Wang, Xiao-Chen; Ren, An-Jing; Bai, Jie; Sun, Xue-Jun; Yuan, Wen-Jun; Lin, Li

2010-10-01

1. Leptin, an important adipose-derived hormone, can be associated with cardiac pathophysiology; however, the role of leptin in cardiomyocyte apoptosis is poorly understood. The present study examines serum-deprivation-induced apoptosis in primary cultured cardiomyocytes treated with leptin. 2. Cardiomyocytes were subjected to serum deprivation in the presence or absence of leptin (5 or 50 nmol/L) for 48 h. Apoptosis was determined by Hoechst 33258 and Annexin V-FITC/propidium iodide dual staining. Cell viability, malondialdehyde (MDA) content, caspase 3 activation, and the expression and enzyme activity of superoxide dismutase (SOD) were measured. Small interference RNA (siRNA) targeting SOD1 and SOD2 were used to knockdown their expression and measure apoptosis. 3. Serum deprivation caused nearly 30% of apoptosis in cardiomyocytes, and an approximately 60% decrease in cell viability. The mRNA levels and the activated form of caspase 3 were greatly increased. In the presence of leptin, the apoptotic rate was reduced to approximately 15%, cell viability was increased and the activation of caspase 3 was partially inhibited. Additionally, the augmented lipid peroxidation (MDA formation) was abolished, and the impaired activities of SOD1 and SOD2 were restored by leptin. The mRNA expression of SOD2, but not SOD1, was stimulated by leptin. Transfection with siRNA that cause deficiency of either SOD1 or SOD2 attenuated the anti-apoptotic effects of leptin. 4. The results suggest that leptin inhibits serum-deprivation-induced apoptosis in cardiomyocytes by activating SOD. The present study outlines the direct actions of leptin in cardiac disorders that are related to elevated leptin levels. © 2010 The Authors. Clinical and Experimental Pharmacology and Physiology © 2010 Blackwell Publishing Asia Pty Ltd.

Comparison Between Preoperative Administration of Methylprednisolone With its Administration Before and During Congenital Heart Surgery on Serum Levels of IL-6 And IL-10

PubMed Central

Abbasi Tashnizi, Mohammad; Soltani, Ghasem; Moeinipour, Ali Asghar; Ayatollahi, Hossein; Tanha, Amir Saber; Jarahi, Lida; Sepehri Shamloo, Alireza; Zirak, Nahid

2013-01-01

Background Steroid administration during cardiopulmonary bypass is considered to improve cardiopulmonary function by modulating inflammations caused by bypass. Objectives This study was performed to compare effectiveness of preoperative and intraoperative methylprednisolone (MP) to preoperative methylprednisolone alone in post bypass inflammatory (IL-6) and anti-inflammatory (IL-10) factors. Patients and Methods Fifty pediatric patients undergoing cardiopulmonary bypass surgery from August 2011 to 2012 in the cardiac surgery department of Imam Reza Hospital, the major center for CPB, in Mashhad, Iran were randomly assigned to receive preoperative and intraoperative MP (30 mg/kg, 4 hours before bypass and in bypass prime, number 25) or preoperative MP only (30 mg/kg, number 25). Before and after bypass, four and 24 hours after bypass, serum IL-6 and IL-10 were measured by ELISA. Results In both groups, no significant difference with variation of expression for IL-6 (inflammatory factor) and IL-10 (anti-inflammatory factor) in different times after bypass was observed. Conclusions No significant difference in reducing post bypass inflammation between preoperative steroid treatment and combined preoperative and intraoperative steroid administration reported and they had the same effects. PMID:23682327

Serum thyroxine concentrations after radioactive iodine therapy in cats with hyperthyroidism

DOE Office of Scientific and Technical Information (OSTI.GOV)

Meric, S.M.; Hawkins, E.C.; Washabau, R.J.

Thirty-one cats with hyperthyroidism were given one dose of radioactive iodine (131I) IV. Serum thyroxine (T4) concentrations were measured before treatment in all cats, at 12-hour intervals after treatment in 10 cats, and at 48-hour intervals after treatment in 21 cats. Serum T4 concentrations also were measured one month after /sup 131/I therapy in 29 cats. Activity of 131I administered was 1.5 to 6.13 mCi, resulting in a dose of 20,000 rads to the thyroid. Serum T4 concentrations before /sup 131/I administration were 5.3 to 51.0 micrograms/dl, with a median T4 concentration of 11.0 micrograms/dl. Serum T4 decreased most rapidlymore » during the first 3 to 6 days after treatment. Sixteen cats (55%) had normal serum thyroxine concentrations by day 4 after 131I administration, and 23 cats (74%) were euthyroxinemic by day 8 after treatment. One month after administration of 131I, the 29 cats evaluated were clinically improved, and 24 (83%) of the 29 cats evaluated had normal serum T4 concentrations, 3 cats (10%) remained hyperthyroxinemic, and 2 cats (7%) were hypothyroxinemic. Therefore, administration of 131I was a safe and effective method to quickly decrease serum T4 concentrations in hyperthyroid cats.« less

Intranasal administration of oxytocin increases human aggressive behavior.

PubMed

Ne'eman, R; Perach-Barzilay, N; Fischer-Shofty, M; Atias, A; Shamay-Tsoory, S G

2016-04-01

Considering its role in prosocial behaviors, oxytocin (OT) has been suggested to diminish levels of aggression. Nevertheless, recent findings indicate that oxytocin may have a broader influence on increasing the salience of social stimuli and may therefore, under certain circumstances, increase antisocial behaviors such as aggression. This controversy led to the following speculations: If indeed oxytocin promotes primarily prosocial behavior, administration of OT is expected to diminish levels of aggression. However, if oxytocin mainly acts to increase the salience of social stimuli, it is expected to elevate levels of aggression following provocation. In order to test this assumption we used the Social Orientation Paradigm (SOP), a monetary game played against a fictitious partner that allows measuring three types of responses in the context of provocation: an aggressive response - reducing a point from the fictitious partner, an individualistic response - adding a point to oneself, and a collaborative response - adding half a point to the partner and half a point to oneself. In the current double-blind, placebo-controlled, within-subject study design, 45 participants completed the SOP task following the administration of oxytocin or placebo. The results indicated that among subjects naïve to the procedure oxytocin increased aggressive responses in comparison with placebo. These results support the saliency hypothesis of oxytocin and suggest that oxytocin plays a complex role in the modulation of human behavior. Copyright © 2016 Elsevier Inc. All rights reserved.

IL-33 circulating serum levels are increased in patients with non-segmental generalized vitiligo.

PubMed

Vaccaro, Mario; Cicero, Francesca; Mannucci, Carmen; Calapai, Gioacchino; Spatari, Giovanna; Barbuzza, Olga; Cannavò, Serafinella P; Gangemi, Sebastiano

2016-09-01

IL-33 is a recently identified cytokine, encoded by the IL-33 gene, which is a member of the IL-1 family that drives the production of T-helper-2 (Th-2)-associated cytokines. Serum levels of IL-33 have been reported to be up-regulated in various T-helper (Th)-1/Th-17-mediated diseases, such as psoriasis, rheumatoid arthritis, and inflammatory bowel. To investigate whether cytokine imbalance plays a role in the pathogenesis of vitiligo, we performed a case-control association study by enzyme-linked immunosorbent assay of IL-33 in our patients. IL-33 serum levels were measured by a quantitative enzyme immunoassay technique in patients with non-segmental generalized vitiligo and compared with those of healthy controls. IL-33 serum levels in patients with vitiligo were significantly increased than those in healthy controls. There was a positive correlation of IL-33 serum levels with extension of vitiligo and disease activity. This study suggests a possible systemic role of IL-33 in the pathogenesis of vitiligo. Inhibiting IL-33 activity might be a novel therapeutic strategy in the treatment of autoimmune inflammatory disease, like vitiligo.

Increased serum alkaline phosphatase levels correlate with high disease activity and low bone mineral density in patients with axial spondyloarthritis.

PubMed

Kang, Kwi Young; Hong, Yeon Sik; Park, Sung-Hwan; Ju, Ji Hyeon

2015-10-01

Recent studies report an association between serum alkaline phosphatase (ALP) levels and inflammation. The present study examined the relationship between ALP and disease activity, bone mineral density (BMD), and radiological damage in axial spondyloarthritis (SpA). A total of 115 patients who fulfilled the ASAS axial SpA criteria were enrolled. Serum ALP, bone-specific ALP (BALP), serum cross-linked telopeptide of type-I collagen (sCTX), and inflammatory markers were measured. Clinical parameters, BMD, grade of sacroiliitis, and the modified Stoke AS Spinal Score (mSASSS) were also assessed. The Ankylosing Spondylitis Disease Activity Score (ASDAS) was also calculated. The associations between serum ALP, disease activity score, BMD, and radiologic damage were evaluated. The mean serum ALP level was 77 ± 26 U/l. Serum ALP levels increased in 14 patients (13%). Serum ALP levels increased along with ASDAS-CRP after adjusting for age and sex (p = 0.004), and were significantly correlated with ASDAS-ESR and ASDAS-CRP (p = 0.001 and p < 0.001, respectively), negatively correlated with BMD in the lumbar spine and femoral neck (p = 0.003 and 0.046, respectively), and positively correlated with sacroiliitis grade and the mSASSS (p < 0.001 and p < 0.002, respectively). BALP and sCTX were not associated with disease activity or BMD. Multivariate analysis showed that serum ALP was independently associated with ASDAS-CRP (p = 0.010). Increased serum ALP levels were associated with high disease activity, low BMD, and higher structural damage scores in SpA patients. Copyright © 2015 Elsevier Inc. All rights reserved.

Effect of recombinant human thyroid stimulating hormone on serum thyroxin and thyroid scintigraphy in euthyroid cats.

PubMed

van Hoek, Ingrid M; Peremans, Kathelijne; Vandermeulen, Eva; Duchateau, Luc; Gommeren, Kris; Daminet, Sylvie

2009-04-01

This study investigated the thyroidal response to administration of recombinant human thyroid stimulating hormone (rhTSH) by means of serum total thyroxine (TT(4)) concentration and pertechnetate uptake by the thyroid gland in six healthy euthyroid spayed female cats. A pertechnetate scan was performed on day 1 to calculate thyroid/salivary gland (T/S) uptake ratio. On day 3, 25 microg rhTSH was injected intravenously. Six hours later the thyroid scan was repeated as on day 1. Blood was drawn for serum TT(4) measurement prior to injection of rhTSH and performance of the pertechnetate scan. Statistically significant differences in mean serum TT(4) concentration, T/S uptake ratio before and 6h after rhTSH administration and T/S uptake ratio between left and right lobes were noted. We can conclude that 25 microg rhTSH increases pertechnetate uptake in the thyroid glands of cats, this should be taken into account when thyroid scintigraphy after rhTSH administration is interpreted.

Nutrient supplemented serum-free medium increases cardiomyogenesis efficiency of human pluripotent stem cells.

PubMed

Ting, Sherwin; Lecina, Marti; Chan, Yau-Chi; Tse, Hung Fat; Reuveny, Shaul; Oh, Steve Kw

2013-07-26

To development of an improved p38 MAPK inhibitor-based serum-free medium for embryoid body cardiomyocyte differentiation of human pluripotent stem cells. Human embryonic stem cells (hESC) differentiated to cardiomyocytes (CM) using a p38 MAPK inhibitor (SB203580) based serum-free medium (SB media). Nutrient supplements known to increase cell viability were added to SB medium. The ability of these supplements to improve cardiomyogenesis was evaluated by measurements of cell viability, total cell count, and the expression of cardiac markers via flow cytometry. An improved medium containing Soy hydrolysate (HySoy) and bovine serum albumin (BSA) (SupSB media) was developed and tested on 2 additional cell lines (H1 and Siu-hiPSC). Characterization of the cardiomyocytes was done by immunohistochemistry, electrophysiology and quantitative real-time reverse transcription-polymerase chain reaction. hESC cell line, HES-3, differentiating in SB medium for 16 d resulted in a cardiomyocyte yield of 0.07 ± 0.03 CM/hESC. A new medium (SupSB media) was developed with the addition of HySoy and BSA to SB medium. This medium resulted in 2.6 fold increase in cardiomyocyte yield (0.21 ± 0.08 CM/hESC). The robustness of SupSB medium was further demonstrated using two additional pluripotent cell lines (H1, hESC and Siu1, hiPSC), showing a 15 and 9 fold increase in cardiomyocyte yield respectively. The age (passage number) of the pluripotent cells did not affect the cardiomyocyte yields. Embryoid body (EB) cardiomyocytes formed in SupSB medium expressed canonical cardiac markers (sarcomeric α-actinin, myosin heavy chain and troponin-T) and demonstrated all three major phenotypes: nodal-, atrial- and ventricular-like. Electrophysiological characteristics (maximum diastolic potentials and action potential durations) of cardiomyocytes derived from SB and SupSB media were similar. The nutrient supplementation (HySoy and BSA) leads to increase in cell viability, cell yield and cardiac

Accumulation of cholesterol and increased demand for zinc in serum-deprived RPE cells

PubMed Central

Mishra, Sanghamitra; Peterson, Katherine; Yin, Lili; Berger, Alan; Fan, Jianguo

2016-01-01

Purpose Having observed that confluent ARPE-19 cells (derived from human RPE) survive well in high-glucose serum-free medium (SFM) without further feeding for several days, we investigated the expression profile of RPE cells under the same conditions. Methods Expression profiles were examined with microarray and quantitative PCR (qPCR) analyses, followed by western blot analysis of key regulated proteins. The effects of low-density lipoprotein (LDL) and zinc supplementation were examined with qPCR. Immunofluorescence was used to localize the LDL receptor and to examine LDL uptake. Cellular cholesterol levels were measured with filipin binding. Expression patterns in primary fetal RPE cells were compared using qPCR. Results Microarray analyses of gene expression in ARPE-19, confirmed with qPCR, showed upregulation of lipid and cholesterol biosynthesis pathways in SFM. At the protein level, the cholesterol synthesis control factor SRBEF2 was activated, and other key lipid synthesis proteins increased. Supplementation of SFM with LDL reversed the upregulation of lipid and cholesterol synthesis genes, but not of cholesterol transport genes. The LDL receptor relocated to the plasma membrane, and LDL uptake was activated by day 5–7 in SFM, suggesting increased demand for cholesterol. Confluent ARPE-19 cells in SFM accumulated intracellular cholesterol, compared with cells supplemented with serum, over 7 days. Over the same time course in SFM, the expression of metallothioneins decreased while the major zinc transporter was upregulated, consistent with a parallel increase in demand for zinc. Supplementation with zinc reversed expression changes for metallothionein genes, but not for other zinc-related genes. Similar patterns of regulation were also seen in primary fetal human RPE cells in SFM. Conclusions ARPE-19 cells respond to serum deprivation and starvation with upregulation of the lipid and cholesterol pathways, accumulation of intracellular cholesterol, and

Effect of ethanolic extract of Lepidium meyenii Walp on serum hormone levels in ovariectomized rats

PubMed Central

Zhang, Yongzhong; Yu, Longjiang; Jin, Wenwen; Ao, Mingzhang

2014-01-01

Objective: To evaluate the effect of long-term ethanol extract of Lepidium meyenii (Maca) on serum hormone levels in ovariectomized (OVX) rats and compare them with the effect of diethylstilbestrol. Materials and Methods: Fifty female Sprague-Dawley rats were ovariectomized or sham operated. Both sham and OVX control groups (n = 10, respectively) received the vehicle. The remaining OVX rats were oral administrated with ethanol extract of Maca (0.096, or 0.24g/kg; n = 10, respectively) and diethylstilbestrol (0.05 mg/kg; n = 10). The treatment continued for 28 weeks. At week 12 and week 28, the blood of rats was collected and serum hormone levels, including estradiol (E2), testosterone (T) and follicle-stimulating hormone (FSH) were measured by radioimmunoassay. Results: At week 12, the levels of serum E2 were slightly higher in Maca groups than that in OVX group; T levels were significantly decreased; and FSH levels were advanced slightly in Maca groups than that in sham group. After 28 weeks administration, serum E2 levels in Maca-treated animals did not differ significantly from sham control, the low dose of Maca increased serum E2 levels, and Maca prevented increase in serum FSH levels compared with OVX group. Conclusions: Long-term Maca supply modulates endocrine hormone balance in OVX rats, especially it decreases enhanced FSH levels. It is proposed that Maca may become a potential choice for postmenopausal women. PMID:25097281

Imatinib Increases Serum Creatinine by Inhibiting Its Tubular Secretion in a Reversible Fashion in Chronic Myeloid Leukemia.

PubMed

Vidal-Petiot, Emmanuelle; Rea, Delphine; Serrano, Fidéline; Stehlé, Thomas; Gardin, Claude; Rousselot, Philippe; Peraldi, Marie-Noëlle; Flamant, Martin

2016-03-01

Monitoring renal function is important in imatinib-treated patients with chronic myeloid leukemia because serum creatinine may increase during the course of therapy. The mechanism of this increase and its reversibility on treatment cessation have never been investigated. We retrospectively analyzed data from imatinib-treated patients explored in our renal physiology unit with measurement of glomerular filtration rate (urinary clearance of (51)CrEDTA) and of urinary clearance and tubular secretion of creatinine. Results were compared with those of controls matched for measured glomerular filtration rate, age, gender, and ethnicity. We also analyzed variations of serum creatinine before and during imatinib cessation and after imatinib resumption in patients enrolled in imatinib discontinuation studies. In 4 imatinib-treated patients who underwent thorough renal exploration, the part of creatinine clearance due to tubular secretion was negligible (2.4, 3.1, -1.3, and 2.8 mL/min) and significantly lower than that measured in their respective controls (17.7 ± 5.6, 43.0 ± 18.0, 23.1 ± 6.7, and 18.6 ± 5.6 mL/min, P < .001). In 1 patient, exploration was repeated after imatinib discontinuation and evidenced a recovery of creatinine tubular secretion (20.3 vs. 17.9 ± 5.2 mL/min in the control population, P = .2). In 15 patients of imatinib discontinuation studies, a median decrease in serum creatinine of 17.9% was observed after imatinib cessation. Resumption of treatment in 6 patients led to a median increase in serum creatinine of 18.8%. Imatinib completely blunts tubular secretion of creatinine, a previously unreported pharmacologic property. This inhibition increases serum creatinine independently of any glomerular dysfunction and is fully reversible on imatinib cessation. Copyright © 2016 Elsevier Inc. All rights reserved.

Resveratrol Increases Serum BDNF Concentrations and Reduces Vascular Smooth Muscle Cells Contractility via a NOS-3-Independent Mechanism

PubMed Central

Malinowski, Bartosz; Grześk, Elżbieta; Grześk, Grzegorz

2017-01-01

Resveratrol is a polyphenol that presents both antineuroinflammatory properties and the ability to interact with NOS-3, what contributes to vasorelaxation. Brain-derived neurotrophic factor (BNDF), a molecule associated with neuroprotection in many neurodegenerative disorders, is considered as an important element of maintaining stable cerebral blood flow. Vascular smooth muscle cells (VSMCs) are considered to be an important element in the pathogenesis of neurodegeneration and a potential preventative target by agents which reduce the contractility of the vessels. Our main objectives were to define the relationship between serum and long-term oral resveratrol administration in the rat model, as well as to assess the effect of resveratrol on phenylephrine- (PHE-) induced contraction of vascular smooth muscle cells (VSMCs). Moreover, we attempt to define the dependence of contraction mechanisms on endothelial NO synthase. Experiments were performed on Wistar rats (n = 17) pretreated with resveratrol (4 weeks; 10 mg/kg p.o.) or placebo. Serum BDNF levels were quantified after 2 and 4 weeks of treatment with ELISA. Contraction force was measured on isolated and perfused tail arteries as the increase of perfusion pressure with a constant flow. Values of serum BNDF in week 0 were 1.18 ± 0.12 ng/mL (treated) and 1.17 ± 0.13 ng/mL (control) (p = ns). After 2 weeks of treatment, BDNF in the treatment group was higher than in controls, 1.52 ± 0.23 ng/mL and 1.24 ± 0.13 ng/mL, respectively. (p = 0.02) Following 4 weeks of treatment, BDNF values were higher in the resveratrol group compared to control 1.64 ± 0.31 ng/mL and 1.32 ± 0.26 ng/mL, respectively (p = 0.031). EC50 values obtained for PHE in resveratrol pretreated arteries were significantly higher than controls (5.33 ± 1.7 × 10−7 M/L versus 4.53 ± 1.2 × 10−8 M/L, p < 0.05). These results show a significant increase in BDNF concentration in the resveratrol pretreated group. The

The regulation of pituitary-thyroid abnormalities by peripheral administration of levothyroxine increased brain-derived neurotrophic factor and reelin protein expression in an animal model of Alzheimer's disease.

PubMed

Shabani, Sahreh; Farbood, Yaghoob; Mard, Seyyed Ali; Sarkaki, Alireza; Ahangarpour, Akram; Khorsandi, Layasadat

2018-03-01

Alzheimer's disease (AD) is associated with decreased serum levels of thyroid hormones (THs), increased levels of thyroid-stimulating hormone (TSH), and decreased protein expression of brain-derived neurotrophic factor (BDNF) and reelin in the hippocampus. In this study, we have evaluated the effect of subcutaneous administration of levothyroxine (L-T 4 ) on levels of THs and TSH as well as protein expression of BDNF and reelin in AD rats. To make an animal model of AD, amyloid-beta peptide (Aβ) plus ibotenic acid were infused intrahippocampally, and rats were treated with L-T 4 and (or) saline for 10 days. The levels of THs and TSH were measured by ELISA kits. Protein synthesis was detected by Western blotting method. Results have been shown that serum level of THs, BDNF, and reelin protein expression in the hippocampus were significantly decreased (P < 0.001) in AD animals and elevated significantly in AD rats treated with L-T 4 (P < 0.01). Data showed that TSH level significantly decreased in AD rats treated with L-T 4 (P < 0.05). These findings indicated that L-T 4 increased BDNF and reelin protein expression by regulation of serum THs and TSH level in Aβ-induced AD rats.

In etanercept-treated psoriatic arthritis patients clinical improvement correlated with an increase of serum cortisol relative to other adrenal hormones.

PubMed

Atzeni, F; Sarzi-Puttini, P; DePortu, S; Cutolo, M; Carrabba, M; Straub, R H

2008-01-01

In patients with rheumatoid arthritis (RA), long-term therapy with anti-tumor necrosis factor (TNF) antibodies sensitizes the pituitary gland and improves adrenal androgen secretion in prednisolone-naïve patients. However, whether this is similar in psoriatic arthritis (PsA) is not known. The aim of this study was to assess the effect of 12 weeks of etanercept treatment upon the function of the HPA axis in patients with PsA. Eleven prednisolone-naïve patients (mean age 47.3+/-8.9 years) with PsA were included. We measured serum levels of adrenocorticotropic hormone (ACTH), 17-hydroxyprogesterone (17OHP), cortisol, and androstenedione (ASD), at baseline and at 4 and 12 weeks after initiation of anti-TNF therapy (etanercept, 50 mg every week as a single dose by sc. injection). Clinical improvement was assessed using the Disease Activity Score-28 (DAS-28). Mean levels of serum ACTH, serum cortisol, serum 17OHP and serum ASD did not markedly change during 12 weeks of etanercept treatment. Similarly, the ratio of serum cortisol divided by serum ACTH did not change during 12 weeks of anti-TNF treatment. However, an increase of serum cortisol relative to serum 17OHP or ASD was related to clinical improvement. This indicates that improvement was linked to higher serum cortisol levels relative to others adrenal hormones. This is the first study to demonstrate baseline serum levels and the course of HPA axis-related hormones in patients with PsA. An increase of serum cortisol relative to others adrenocortical hormones (i.e., androstenedione and ACTH) was accompanied by clinical improvement.

Frequency of laboratory measurement and hyperkalaemia in hospitalised patients using serum potassium concentration increasing drugs.

PubMed

Uijtendaal, Esther V; Zwart-van Rijkom, Jeannette E F; van Solinge, Wouter W; Egberts, Toine C G

2011-09-01

Although, drug-drug interactions (DDIs) between potassium-increasing drugs (PIDs) are known risk factors for developing hyperkalaemia, not much is known about their risk and management strategies during hospitalisation. This study examines the frequency of serum potassium measurements and hyperkalaemia in hospitalised patients, based on the use of one or more PIDs, and the determinants thereof. Adult patients hospitalised in the University Medical Centre Utrecht between 2006 and 2008 were included in this cross-sectional study. The frequency of serum potassium measurements and of hyperkalaemia were compared between patients using only one PID at a time (monotherapy group) and patients using two or more PIDs concomitantly (interaction group). The determinants studied were renal failure, diabetes mellitus, use of diuretics, type of DDI, start of the PIDs within the hospital versus continued home medication and medical speciality. Serum potassium was measured more frequently in the interaction group than in the monotherapy group [67 vs. 56%; relative risk (RR) 1.19, 95% confidence interval (CI) 1.14-1.24] and the risk of hyperkalaemia was also increased in the interaction group (9.9 vs. 5.9%, RR 1.7, 95% CI 1.3-2.1). The combination of potassium-sparing diuretics plus a potassium supplement, start of the PID within the hospital and hospitalisation in non-internal medicine departments was associated with higher relative risk estimates for hyperkalaemia. Among our patient cohort, even when physicians received a direct pop-up to monitor serum potassium levels when prescribing two PIDs concomitantly, serum potassium levels were not measured in 33% of patients, and 10% of patients developed hyperkalaemia. Improved management strategies and/or clinical decision-support systems are needed to decrease the frequency of hyperkalaemia following DDIs.

Increased cancer cell proliferation in prostate cancer patients with high levels of serum folate

USDA-ARS?s Scientific Manuscript database

Introduction: A recent clinical trial revealed that folic acid supplementation is associated with an increased incidence of prostate cancer (1). The present study evaluates serum and prostate tissue folate levels in men with prostate cancer, compared to histologically normal prostate glands from can...

Co-administration of α-lipoic acid and glutathione is associated with no significant changes in serum bilirubin, alkaline phosphatase or γ-glutamyltranspeptidase levels during the treatment of neuroborreliosis with intravenous ceftriaxone.

PubMed

Puri, Basant K; Hakkarainen-Smith, Jaana S; Derham, Anne; Monro, Jean A

2015-09-01

While pharmacotherapy with intravenous ceftriaxone, a third-generation cephalosporin, is a potential treatment of Lyme neuroborreliosis, there is concern that it can cause the formation of biliary sludge, leading to hepatobiliary complications such as biliary colic, jaundice and cholelithiasis, which are reflected in changes in serum levels of bilirubin and markers of cholestatic liver injury (alkaline phosphatase and γ-glutamyltranspeptidase). It has been suggested that the naturally occurring substances α-lipoic acid and glutathione may be helpful in preventing hepatic disease. α-Lipoic acid exhibits antioxidant, anti-inflammatory and anti-apoptotic activities in the liver, while glutathione serves as a sulfhydryl buffer. The aim of this study was to determine whether co-administration of α-lipoic acid and glutathione is associated with significant changes in serum levels of bilirubin, alkaline phosphatase and γ-glutamyltranspeptidase during the treatment of Lyme neuroborreliosis with long-term intravenous ceftriaxone. Serum levels of bilirubin, alkaline phosphatase and γ-glutamyltranspeptidase were measured in 42 serologically positive Lyme neuroborreliosis patients before and after long-term treatment with intravenous ceftriaxone (2-4 g daily) with co-administration of oral/intravenous α-lipoic acid (600 mg daily) and glutathione (100 mg orally or 0.6-2.4 g intravenously daily). None of the patients developed biliary colic and there were no significant changes in serum bilirubin, alkaline phosphatase or γ-glutamyltranspeptidase levels over the course of the intravenous ceftriaxone treatment (mean length 75.0 days). Co-administration of α-lipoic acid and glutathione is associated with no significant changes in serum bilirubin, alkaline phosphatase or γ-glutamyltranspeptidase levels during the treatment of neuroborreliosis with intravenous ceftriaxone.

Mendelian randomization analysis associates increased serum urate, due to genetic variation in uric acid transporters, with improved renal function.

PubMed

Hughes, Kim; Flynn, Tanya; de Zoysa, Janak; Dalbeth, Nicola; Merriman, Tony R

2014-02-01

Increased serum urate predicts chronic kidney disease independent of other risk factors. The use of xanthine oxidase inhibitors coincides with improved renal function. Whether this is due to reduced serum urate or reduced production of oxidants by xanthine oxidase or another physiological mechanism remains unresolved. Here we applied Mendelian randomization, a statistical genetics approach allowing disentangling of cause and effect in the presence of potential confounding, to determine whether lowering of serum urate by genetic modulation of renal excretion benefits renal function using data from 7979 patients of the Atherosclerosis Risk in Communities and Framingham Heart studies. Mendelian randomization by the two-stage least squares method was done with serum urate as the exposure, a uric acid transporter genetic risk score as instrumental variable, and estimated glomerular filtration rate and serum creatinine as the outcomes. Increased genetic risk score was associated with significantly improved renal function in men but not in women. Analysis of individual genetic variants showed the effect size associated with serum urate did not correlate with that associated with renal function in the Mendelian randomization model. This is consistent with the possibility that the physiological action of these genetic variants in raising serum urate correlates directly with improved renal function. Further studies are required to understand the mechanism of the potential renal function protection mediated by xanthine oxidase inhibitors.

[Interaction between fluorine and zinc after long-term oral administration into the digestive system of rats].

PubMed

Mazurek-Mochol, Małgorzata

2002-01-01

Drug interactions are the side effect of administration of two or more drugs or a drug-food combination. Although some drug interactions are intentional and beneficial to the patient, the majority are unintentional and associated with a potentially harmful effect. The aim of this study was to search for interactions in rats between fluoride and zinc administered orally for 12 weeks and to elucidate any potential toxicological and therapeutic consequences. 60 male Wistar rats were divided into six groups of ten rats each and exposed to: 1. controls (distilled water); 2. sodium fluoride (NaF); 3. low-dose zinc (Zn); 4. high-dose zinc; 5. NaF + low-dose Zn; 6. NaF + high-dose Zn. At the end of the experiment the content of F- and Zn+ in serum, urine, incisors, femur and mandible was measured and densitometry of femoral bones was performed. Serum alkaline phosphatase, alanine and aspartate aminotransferase activities, as well as bilirubin and creatinine concentrations were determined to confirm non-toxicity of fluoride dose. Animals receiving NaF only demonstrated higher content of fluorine in serum, urine bones and teeth. Zinc concentrations in serum, urine, bones and teeth were elevated in rats receiving zinc with or without NaF. Fluorine accumulation in bones and teeth was reduced by Zn, but in general the effect lacked statistical significance. Zinc slightly reduced the concentrations of fluorine in serum and urine. Sodium fluoride slightly reduced the concentration of zinc in serum and urine. Bone mineral content (BMC) was significantly increased by NaF and was not further increased by co-administration of zinc. No changes in serum alkaline phosphatase, alanine and aspartate aminotransferase activities, bilirubin and creatinine concentrations were detected. In conclusion, simultaneous administration of fluorine and zinc may be beneficial for prevention and treatment of pathologic conditions in bones and teeth and is not accompanied by an increase in fluorine

Serum Penicillin G Levels Are Lower Than Expected in Adults within Two Weeks of Administration of 1.2 Million Units

PubMed Central

Hansen, Christian J.; Russell, Kevin L.; Blumer, Jeffrey L.

2011-01-01

When introduced in the 1950s, benzathine penicillin G (BPG) was shown to be effective in eradicating group A beta-hemolytic streptococcus (GAS) for at least 3 weeks after administration. Several studies since the 1990s suggest that at 3–4 weeks serum penicillin G levels are less than adequate (below MIC90 of 0.016 µg/ml). We studied these levels for 4 weeks after the recommended dose of BPG in military recruits, for whom it is used as prophylaxis against GAS. The 329 subjects (mean age 20 years) each received 1.2 million units BPG IM and gave sera 1 day post injection and twice more at staggered time points over 4 weeks. Serum penicillin G levels were measured by liquid chromatography/tandem mass spectometry. The half-life of serum penicillin G was 4.1 days. By day 11, mean levels were <0.02 µg/ml, and by day 15<0.01 µg/ml. Levels in more than 50% of the subjects were below 0.02 µg/ml on day 9, and <.01 µg/ml on day 16. There was no demonstrable effect of subject body-surface area nor of the four different lots of BPG used. These data indicate that in healthy young adults serum penicillin G levels become less than protective <2½ weeks after injection of 1.2 million units of BPG. The findings require serious consideration in future medical and public health recommendations for treatment and prophylaxis of GAS upper respiratory tract infections. PMID:21991307

Increased serum nonesterified fatty acid and low ionised calcium concentrations are associated with post partum colic in mares.

PubMed

Holcombe, S J; Embertson, R M; Kurtz, K A; Roessner, H A; Wismer, S E; Geor, R J; Kaneene, J B

2016-01-01

Increased serum nonesterified fatty acids (NEFA) and decreased serum electrolytes are linked to abdomasal displacements in post partum dairy cattle. Post partum colic in mares may be associated with metabolic changes specific to pregnancy and the periparturient period. To determine if fluctuations in serum NEFA, ionised calcium (iCa) and magnesium (iMg) occurred in periparturient mares and if these alterations were associated with post partum colic. Longitudinal observational study. Mares from 3 farms in central Kentucky were enrolled. Blood samples were collected 14 days prior to the estimated foaling date, within 4 days post parturition, and 14 and 28 days after foaling for batch analysis of serum NEFA, iCa and iMg. Health information was provided by farm managers and veterinarians. Data were analysed using Kruskal-Wallis χ(2) statistic for nonparametric data and a matched case/control approach. Repeated measures logistic regression models were developed. Serum NEFAs were higher at 14-1 day before foaling (mean ± s.d., mmol/l), 0.28 ± 0.12, P = 0.04 and from foaling to 4 days after foaling, 0.29 ± 0.20 (P = 0.05) in mares that developed colic compared with those that did not colic, 0.19 ± 0.05 and 0.21 ± 0.14, respectively. Ionised calcium was lower at 15-28 days post foaling in mares that showed colic, 1.50 ± 0.17 compared to mares that did not colic, 1.60 ± 0.12, P = 0.02. Risk of colic in post partum mares increased 38% for each 0.1 mmol/l increase in serum NEFA (odds ratio = 1.38, 95% confidence interval 1.06-1.81, P = 0.02). Mares with post partum colic had significantly higher serum NEFA and lower iCa prior to the colic episode compared with mares that did not develop colic. Monitoring these metabolic alterations may lead to predictive and preventive colic strategies for post partum mares. © 2015 EVJ Ltd.

The usefulness of administrative databases for identifying disease cohorts is increased with a multivariate model.

PubMed

van Walraven, Carl; Austin, Peter C; Manuel, Douglas; Knoll, Greg; Jennings, Allison; Forster, Alan J

2010-12-01

Administrative databases commonly use codes to indicate diagnoses. These codes alone are often inadequate to accurately identify patients with particular conditions. In this study, we determined whether we could quantify the probability that a person has a particular disease-in this case renal failure-using other routinely collected information available in an administrative data set. This would allow the accurate identification of a disease cohort in an administrative database. We determined whether patients in a randomly selected 100,000 hospitalizations had kidney disease (defined as two or more sequential serum creatinines or the single admission creatinine indicating a calculated glomerular filtration rate less than 60 mL/min/1.73 m²). The independent association of patient- and hospitalization-level variables with renal failure was measured using a multivariate logistic regression model in a random 50% sample of the patients. The model was validated in the remaining patients. Twenty thousand seven hundred thirteen patients had kidney disease (20.7%). A diagnostic code of kidney disease was strongly associated with kidney disease (relative risk: 34.4), but the accuracy of the code was poor (sensitivity: 37.9%; specificity: 98.9%). Twenty-nine patient- and hospitalization-level variables entered the kidney disease model. This model had excellent discrimination (c-statistic: 90.1%) and accurately predicted the probability of true renal failure. The probability threshold that maximized sensitivity and specificity for the identification of true kidney disease was 21.3% (sensitivity: 80.0%; specificity: 82.2%). Multiple variables available in administrative databases can be combined to quantify the probability that a person has a particular disease. This process permits accurate identification of a disease cohort in an administrative database. These methods may be extended to other diagnoses or procedures and could both facilitate and clarify the use of

Proteolysis inhibition by hibernating bear serum leads to increased protein content in human muscle cells.

PubMed

Chanon, Stéphanie; Chazarin, Blandine; Toubhans, Benoit; Durand, Christine; Chery, Isabelle; Robert, Maud; Vieille-Marchiset, Aurélie; Swenson, Jon E; Zedrosser, Andreas; Evans, Alina L; Brunberg, Sven; Arnemo, Jon M; Gauquelin-Koch, Guillemette; Storey, Kenneth B; Simon, Chantal; Blanc, Stéphane; Bertile, Fabrice; Lefai, Etienne

2018-04-03

Muscle atrophy is one of the main characteristics of human ageing and physical inactivity, with resulting adverse health outcomes. To date, there are still no efficient therapeutic strategies for its prevention and/or treatment. However, during hibernation, bears exhibit a unique ability for preserving muscle in conditions where muscle atrophy would be expected in humans. Therefore, our objective was to determine whether there are components of bear serum which can control protein balance in human muscles. In this study, we exposed cultured human differentiated muscle cells to bear serum collected during winter and summer periods, and measured the impact on cell protein content and turnover. In addition, we explored the signalling pathways that control rates of protein synthesis and degradation. We show that the protein turnover of human myotubes is reduced when incubated with winter bear serum, with a dramatic inhibition of proteolysis involving both proteasomal and lysosomal systems, and resulting in an increase in muscle cell protein content. By modulating intracellular signalling pathways and inducing a protein sparing phenotype in human muscle cells, winter bear serum therefore holds potential for developing new tools to fight human muscle atrophy and related metabolic disorders.

Serum levels of osteopontin are increased in SIRS and sepsis.

PubMed

Vaschetto, Rosanna; Nicola, Stefania; Olivieri, Carlo; Boggio, Elena; Piccolella, Fabio; Mesturini, Riccardo; Damnotti, Federica; Colombo, Davide; Navalesi, Paolo; Della Corte, Francesco; Dianzani, Umberto; Chiocchetti, Annalisa

2008-12-01

In sepsis, dysregulation of the immune response leads to rapid multiorgan failure and death. Accurate and timely diagnosis is lifesaving and should discriminate sepsis from the systemic inflammatory response syndrome (SIRS) caused by non-infectious agents. Osteopontin acts as an extracellular matrix component or a soluble cytokine in inflamed tissues. Its exact role in immune response and sepsis remains to be elucidated. Therefore, we investigated the role of osteopontin in SIRS and sepsis. Prospective, observational study. Intensive care unit of a university hospital. Fifty-six patients with SIRS or sepsis and 56 healthy subjects were enrolled. We analyzed the serum levels of osteopontin and TH1-TH2 cytokines and investigated the role of osteopontin on interleukin 6 secretion by monocytes. Serum osteopontin levels were strikingly higher in patients than in controls and in sepsis than in SIRS, and decreased during the resolution of both the disorders. Receiver operating characteristic curves showed that osteopontin levels have discriminative power between SIRS and sepsis with an area under the curve of 0.796. Osteopontin levels directly correlated with those of interleukin 6 and in vitro, recombinant osteopontin increased interleukin 6 secretion by monocytes in both the absence and presence of high doses of lipopolysaccharide. These data suggest that osteopontin might be a mediator involved in the pathogenesis of SIRS and sepsis, possibly by supporting interleukin 6 secretion. 45. SIRS/Sepsis: clinical studies.

Neurotensin is increased in serum of young children with autistic disorder.

PubMed

Angelidou, Asimenia; Francis, Konstantinos; Vasiadi, Magdalini; Alysandratos, Konstantinos-Dionysios; Zhang, Bodi; Theoharides, Athanasios; Lykouras, Lefteris; Sideri, Kyriaki; Kalogeromitros, Dimitrios; Theoharides, Theoharis C

2010-08-23

Autism spectrum disorders (ASD) are a group of pervasive neurodevelopmental disorders diagnosed in early childhood. They are associated with a set of "core symptoms" that include disabilities in social interaction skills, verbal and non-verbal communication, as well as repetitive and stereotypic behaviors. There is no definite pathogenetic mechanism or diagnostic tests. Many children with ASD also have "allergic-like" symptoms, but test negative implying mast cell activation by non-allergic triggers. We measured by Milliplex arrays serum levels of 3 neuropeptides that could stimulate mast cells in children with autistic disorder (n = 19; 16 males and 3 females; mean age 3.0 ± 0.4 years) and healthy, unrelated controls (n = 16; 13 males and 3 females; mean age 3 ± 1.2 years). Only neurotensin (NT) was significantly increased from 60.5 ± 6.0 pg/ml in controls to 105.6 ± 12.4 pg/ml in autistic disorder (p = 0.004). There was no statistically significant difference in the serum levels of β-endorphin or substance P (SP). NT could stimulate immune cells, especially mast cells, and/or have direct effects on brain inflammation and ASD.

Effects of zinc and cholesterol/choleate on serum lipoproteins and the liver in rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cho, C.H.; Chen, S.M.; Ogle, C.W.

1989-01-01

The effects of short-term treatment with orally-administered zinc sulfate and/or a mixture of cholesterol/choleate on serum lipoprotein and hepatic enzyme levels were studied. Administration of graded doses of zinc sulfate for 5 days, dose-dependently increased serum and hepatic zinc levels but depressed the serum high-density lipoprotein-cholesterol (HDL-C) concentration and liver cytochrome P-450 activity. However, it did not affect hepatic concentrations of malondialdehyde and free {beta}-glucuronidase. Cholesterol/choleate treatment for 5 days markedly damaged the liver, as reflected by elevations of hepatic concentrations of malondialdehyde (both in the mitochondrial and microsomal fractions) and of free {beta}-glucuronidase; total cholesterol and low-density lipoprotein-cholesterol inmore » the blood were increased, whereas HDL-C was decreased significantly. Concomitant administration of zinc sulfate with cholesterol/choleate further lowered HDL-C levels, but reversed the high hepatic concentrations of both malondialdehyde and free {beta}-glucuronidase. The present study indicates that both zinc ions and cholesterol can decrease circulatory HDL-C levels and that zinc protects against cholesterol-induced hepatic damage by reducing lysosomal enzyme release and preventing lipid peroxidation in the liver.« less

Red palm oil supplementation does not increase blood glucose or serum lipids levels in Wistar rats with different thyroid status.

PubMed

Rauchová, H; Vokurková, M; Pavelka, S; Vaněčková, I; Tribulová, N; Soukup, T

2018-05-04

Red palm oil (RPO) is a rich natural source of antioxidant vitamins, namely carotenes, tocopherols and tocotrienols. However, it contains approximately 50 % saturated fatty acids the regular consumption of which could negatively modify lipid profile. The aim of our study was to test whether 7 weeks of RPO supplementation (1 g/kg body weight/day) would affect blood glucose and lipid metabolism in adult male Wistar rats with altered thyroid status. We induced hypothyroidism and hyperthyroidism in rats by oral administration of either methimazole or mixture of thyroid hormones. Different thyroid status (EU - euthyroid, HY - hypothyroid and HT - hyperthyroid) was characterized by different serum thyroid hormones levels (total and free thyroxine and triiodothyronine), changes in the activity of a marker enzyme of thyroid status - liver mitochondrial glycerol-3-phosphate dehydrogenase, and altered absolute and relative heart weights. Fasting blood glucose levels were higher in HT rats in comparison with EU and HY rats, but the changes caused by RPO supplementation were not significant. The achievement of the HY status significantly increased serum levels of total cholesterol, as well as with high-density lipoprotein-cholesterol and low-density lipoprotein-cholesterol: 2.43+/-0.15, 1.48+/-0.09, 0.89+/-0.08 mmol/l, compared to EU: 1.14+/-0.06, 0.77+/-0.06, 0.34+/-0.05 mmol/l and HT: 1.01+/-0.06, 0.69+/-0.04, 0.20+/-0.03 mmol/l, respectively. RPO supplementation did not increase significantly levels of blood lipids but tended to increase glutathione levels in the liver. In conclusion, RPO supplementation did not induce the presumed deterioration of glucose and lipid metabolism in rats with three well-characterized alterations in thyroid status.

The effects of chronic testosterone administration on body weight, food intake, and fat weight were age-dependent.

PubMed

Iwasa, Takeshi; Matsuzaki, Toshiya; Yiliyasi, Mayila; Yano, Kiyohito; Irahara, Minoru

2017-11-01

Previously, we showed that chronic testosterone administration increased body weight (BW) and food intake (FI), but did not alter fat weight, in young female rats. To examine our hypothesis that the effects of androgens on BW, FI and body composition might be age-dependent, the effects of chronic testosterone administration were evaluated in rats of different ages; i.e., young and middle-aged rats. Although chronic testosterone administration increased BW gain, FI, and feed efficiency in both young and middle-aged rats, it increased visceral fat weight in middle-aged rats, but not in young rats. Therefore, it is possible that testosterone promotes the conversion of energy to adipose tissue and exacerbates fat accumulation in older individuals. In addition, although the administration of testosterone increased the serum leptin level, it did not alter hypothalamic neuropeptide Y mRNA expression in middle-aged rats. On the contrary, the administration of testosterone did not affect the serum leptin levels of young rats. Thus, testosterone might induce hypothalamic leptin resistance, which could lead to fat accumulation in older individuals. Testosterone might disrupt the mechanisms that protect against adiposity and hyperphagia and represent a risk factor for excessive body weight and obesity, especially in older females. Copyright © 2017 Elsevier Inc. All rights reserved.

Olive Leaf Extract Elevates Hepatic PPAR α mRNA Expression and Improves Serum Lipid Profiles in Ovariectomized Rats.

PubMed

Yoon, Leena; Liu, Ya-Nan; Park, Hyunjin; Kim, Hyun-Sook

2015-07-01

We hypothesized that olive leaf extract might alleviate dyslipidemia resulting from estrogen deficiency. Serum lipid profile and mRNA expression of the related genes in the liver and adipose tissue were analyzed after providing olive leaf extract (200 or 400 mg/kg body weight; n=7 for each group) to ovariectomized rats for 10 weeks. After 10 weeks' administration, the rats in the olive leaf extract-administered groups showed significantly lower levels of serum triglyceride and very-low-density lipoprotein (VLDL)-cholesterol compared with the rats in the control group, whereas the administration of olive leaf extract did not significantly change the elevated low-density lipoprotein cholesterol levels. In addition, administration of high dose of olive leaf extract significantly decreased the liver triglyceride and increased serum estradiol levels. mRNA expressions of peroxisome proliferator-activated receptor alpha (PPAR α) and acyl-CoA oxidase (ACO) were not affected by ovariectomy, however, administration of olive leaf extract significantly increased both PPAR α and ACO mRNA expression. Expression of adiponectin mRNA in adipose tissue was significantly decreased in the ovariectomized control group. Rats administered low-dose olive leaf extract showed significantly elevated adiponectin mRNA expression compared with rats in the ovariectomized control group. Even though dose-dependent effects were not observed in most of the measurements, these results suggest that genes involved in lipid metabolism may be regulated by olive leaf extract administration in ovariectomized rats.

Tolerating increases in the serum creatinine following aggressive treatment of chronic kidney disease, hypertension and proteinuria: pre-renal success.

PubMed

Hirsch, Sheldon; Hirsch, Jackie; Bhatt, Udayan; Rovin, Brad H

2012-01-01

Blood pressure (BP) reduction in patients with chronic kidney disease (CKD), particularly with a renin-angiotensin system inhibitor (RASI), commonly leads to an initial decrease in glomerular filtration rate. The current clinical guideline, based on studies with single RASIs, is to tolerate an increase in the serum creatinine only up to 30%. This guideline has aptly guided CKD care for over a decade, but should be updated in the contemporary context of more aggressive RASI and diuretic use. This study is a retrospective review of 48 mostly African-American patients with CKD treated with multiple and/or high-dose renin-angiotensin system (RAS) inhibition and diuretics, targeting both low BP and reduction of urine protein. RASI was not reduced in response to initial increases in serum creatinine greater than 30%. A clinically well-tolerated increase in serum creatinine over 30% during the first year occurred in 41% of the patients. Treatment was unaltered, and target goals for BP and urine protein were typically achieved. After the point of maximal serum creatinine in the first year, these patients had minimal progression of disease over the next 6 years, with a long-term estimated glomerular filtration rate slope of only -0.52 ml/min/year/1.73 m(2). Only 25% progressed to end-stage renal disease or death. The 30% limitation to initial increases in the serum creatinine still pertains for single RASI at usual doses. However, favorable long-term outcomes suggest that initial increases over 30% should be tolerated in the context of dual goal-directed, more aggressive RASI and diuretic use. Copyright © 2012 S. Karger AG, Basel.

Serum trypsin, alpha-amylase and lipase during bombesin stimulation in normal subjects and patients with pancreatic insufficiency.

PubMed

Hafkenscheid, J C; Hessels, M; Jansen, J B; Lamers, C B

1984-01-31

The effect of infusion of bombesin (60 pmol/kg 20 min) on pancreatic enzymes in serum was studied in 13 normal subjects and 12 patients with pancreatic insufficiency. In normal subjects administration of bombesin induced large increases in serum trypsin (p less than 0.01), while serum total alpha-amylase and pancreatic alpha-amylase did not change and serum lipase showed only a modest rise (0.01 less than p less than 0.05). Patients with pancreatic insufficiency had significantly lower serum concentrations of all enzymes studied (p less than 0.01) and in such patients bombesin did not change the concentrations of pancreatic enzymes in serum. It is concluded that determination of the serum trypsin response to bombesin may be of help in the diagnosis of pancreatic insufficiency.

Association between increased serum d-serine and cognitive gains induced by intensive cognitive training in schizophrenia.

PubMed

Panizzutti, Rogerio; Fisher, Melissa; Garrett, Coleman; Man, Wai Hong; Sena, Walter; Madeira, Caroline; Vinogradov, Sophia

2018-04-23

Neuroscience-guided cognitive training induces significant improvement in cognition in schizophrenia subjects, but the biological mechanisms associated with these changes are unknown. In animals, intensive cognitive activity induces increased brain levels of the NMDA-receptor co-agonist d-serine, a molecular system that plays a role in learning-induced neuroplasticity and that may be hypoactive in schizophrenia. Here, we investigated whether training-induced gains in cognition were associated with increases in serum d-serine in outpatients with schizophrenia. Ninety patients with schizophrenia and 53 healthy controls were assessed on baseline serum d-serine, l-serine, and glycine. Schizophrenia subjects performed neurocognitive tests and were assigned to 50 h of either cognitive training of auditory processing systems (N = 47) or a computer games control condition (N = 43), followed by reassessment of cognition and serum amino acids. At study entry, the mean serum d-serine level was significantly lower in schizophrenia subjects vs. healthy subjects, while the glycine levels were significantly higher. There were no significant changes in these measures at a group level after the intervention. However, in the active training group, increased d-serine was significantly and positively correlated with improvements in global cognition and in Verbal Learning. No such associations were observed in the computer games control subjects, and no such associations were found for glycine. d-Serine may be involved in the neurophysiologic changes induced by cognitive training in schizophrenia. Pharmacologic strategies that target d-serine co-agonism of NMDA-receptor functioning may provide a mechanism for enhancing the behavioral effects of intensive cognitive training. Copyright © 2017 Elsevier B.V. All rights reserved.

Long-term parenteral administration of 2-hydroxypropyl-β-cyclodextrin causes bone loss.

PubMed

Kantner, Ingrid; Erben, Reinhold G

2012-07-01

Cyclodextrins are oligosaccharides which are used in the pharmaceutical industry and research as vehicles for application of apolar substances such as steroids. The aim of this study was to examine the long-term effects of parenteral administration of 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) on bone. Sham-operated (SHAM) or ovariectomized (OVX) adult rats were subcutaneously injected with physiological saline, 50, or 200 mg/kg HP-β-CD daily. After 4 months, body weight in OVX rats and uterine weight in SHAM rats were significantly lower after administration of 200 mg/kg HP-β-CD, relative to vehicle controls. At 200 mg/kg, HP-β-CD was hepatotoxic as measured by increased serum transaminases, and reduced serum albumin. Moreover, 200 mg/kg HP-β-CD led to decreased vertebral and tibial bone mineral density (BMD), and to cortical thinning at the tibial shaft. Bone loss in HP-β-CD-treated rats was associated with increased bone resorption as measured by increased renal deoxypyridinoline excretion. Although 50 mg/kg HP-β-CD was devoid of overt signs of organ toxicity and did not impair BMD, bone resorption was already increased. In summary, subcutaneous long-term administration of HP-β-CD at a daily dose of 200 mg/kg led to increased bone resorption and subsequent bone loss. Minor alterations in bone metabolism were also seen at 50 mg/kg.

Supplemental vitamin D increases serum cytokines in those with initially low 25-hydroxyvitamin D: a randomized, double blind, placebo-controlled study.

PubMed

Barker, Tyler; Rogers, Victoria E; Levy, Mark; Templeton, Jenna; Goldfine, Howard; Schneider, Erik D; Dixon, Brian M; Henriksen, Vanessa T; Weaver, Lindell K

2015-02-01

The purpose of this study was to determine if vitamin D status before supplementation influences the cytokine response after supplemental vitamin D. Forty-six reportedly healthy adults (mean(SD); age, 32(7) y; body mass index (BMI), 25.3(4.5) kg/m(2); serum 25-hydroxyvitamin D (25(OH)D), 34.8(12.2) ng/mL) were randomly assigned (double blind) to one of three groups: (1) placebo (n=15), or supplemental vitamin D (cholecalciferol) at (2) 4000 (n=14) or (3) 8000IU (n=17). Supplements were taken daily for 35days. Fasting blood samples were obtained before (Baseline, Bsl) and 35-days after (35-d) supplementation. Serum 25(OH)D, 1,25-dihydroxyvitamin D (1,25(OH)D), cytokines, and intact parathyroid hormone with calcium were measured in each blood sample. Supplemental vitamin D increased serum 25(OH)D (4000IU, ≈29%; 8000IU, ≈57%) and 1,25(OH)D (4000IU, ≈12%; 8000IU, ≈38%) without altering intact parathyroid hormone or calcium. The vitamin D metabolite increases in the supplemental vitamin D groups (n=31) were dependent on initial levels as serum 25(OH)D (r=-0.63, p<0.05) and 1,25(OH)D (r=-0.45, p<0.05) at Bsl correlated with their increases after supplementation. Supplemental vitamin D increased interferon (IFN)-γ and interleukin (IL)-10 in subjects that were vitamin D insufficient (serum 25(OH)D<29ng/mL) compared to sufficient (serum 25(OH)D⩾30ng/mL) at Bsl. We conclude that supplemental vitamin D increase a pro- and anti-inflammatory cytokine in those with initially low serum 25(OH)D. Copyright © 2014 Elsevier Ltd. All rights reserved.

[Effect of repeated cycles of tetraolean and oleandomycin administration on the indices of nonspecific resistence of the body in experimental staphylococcal sepsis].

PubMed

Plaksin, A I; Plaksina, A N

1975-02-01

The effect of repeated cycles of tetracycline and oleandomycin administration on the complement titer, content of lysozyme and bactericidal properties of the serum in rabbits with experimental staphylococcal sepsis was studied. It was shown that the septic process induced by intravenous inoculation of staphylococci was accompanied by stimulation of the host nonspecific resistance. However, repeated inoculations of the animals resulted in exhaustion of the host protective forces and decreased non-specific resistance. The use of tetracycline in experimental staphylococcal sepsis was accompanied by an increase in the complement titer, lysozyme content and bactericidal properties of the serum after both the 1st and 2nd cycles of the drug administration. The use of oleaudomycin induced an increase in the contents of the complement, lysozyme and bactericidal properties of the serum at the background of staphylococcal sepsis only after the 1st cycle. The repeated cycle of oleandomycin administration was accompanied by a decrease in the above indices. Such conditions should be taken into account in choosing the antibiotic for treatment of septic cases especially when repeated cycles of the drug administration are used.

Increased serum cholesterol esterification rates predict coronary heart disease and sudden death in a general population.

PubMed

Tanaka, Shin-ichiro; Yasuda, Tomoyuki; Ishida, Tatsuro; Fujioka, Yoshio; Tsujino, Takeshi; Miki, Tetsuo; Hirata, Ken-ichi

2013-05-01

Lecithin:cholesterol acyltransferase (LCAT) is thought to be important in reverse cholesterol transport. However, its association with coronary heart disease (CHD) and sudden death is controversial. We prospectively studied 1927 individuals from the general population. Serum concentrations of apolipoprotein A-I, A-II, B, C-II, C-III, E, and LCAT activity measured as a serum cholesterol esterification rate were evaluated. We documented 61 events of CHD and sudden death during 10.9 years of follow-up. After adjustment for age and sex, LCAT activity was significantly associated with the risk of CHD and sudden death (hazard ratio, 3.02; 95% confidence interval, 1.49-6.12; P=0.002). In multivariate analysis adjusted for age, sex, current smoking status, history of diabetes mellitus, body mass index, systolic blood pressure, serum total cholesterol, and serum high-density lipoprotein cholesterol concentrations, the hazard ratio of LCAT activity for the risk of CHD and sudden death remained significant (hazard ratio, 3.07; 95% confidence interval, 1.35-7.01; P=0.008). However, when it was analyzed for men and women separately, this association remained significant only in women. Increased LCAT activity measured as a serum cholesterol esterification rate was a risk for CHD and sudden death in a Japanese general population.

Anti-tau antibody administration increases plasma tau in transgenic mice and patients with tauopathy

PubMed Central

Yanamandra, Kiran; Patel, Tirth K.; Jiang, Hong; Schindler, Suzanne; Ulrich, Jason D.; Boxer, Adam L.; Miller, Bruce L.; Kerwin, Diana R.; Gallardo, Gilbert; Stewart, Floy; Finn, Mary Beth; Cairns, Nigel J.; Verghese, Philip B.; Fogelman, Ilana; West, Tim; Braunstein, Joel; Robinson, Grace; Keyser, Jennifer; Roh, Joseph; Knapik, Stephanie S.; Hu, Yan; Holtzman, David M.

2017-01-01

Tauopathies are a group of disorders in which the cytosolic protein tau aggregates and accumulates in cells within the brain, resulting in neurodegeneration. A promising treatment being explored for tauopathies is passive immunization with anti-tau antibodies. We previously found that administration of an anti-tau antibody to human tau transgenic mice increased the concentration of plasma tau. We further explored the effects of administering an anti-tau antibody on plasma tau. After peripheral administration of an anti-tau antibody to human patients with tauopathy and to mice expressing human tau in the central nervous system, there was a dose-dependent increase in plasma tau. In mouse plasma, we found that tau had a short half-life of 8 min that increased to more than 3 hours after administration of anti-tau antibody. As tau transgenic mice accumulated insoluble tau in the brain, brain soluble and interstitial fluid tau decreased. Administration of anti-tau antibody to tau transgenic mice that had decreased brain soluble tau and interstitial fluid tau resulted in an increase in plasma tau, but this increase was less than that observed in tau transgenic mice without these brain changes. Tau transgenic mice subjected to acute neuronal injury using 3-nitropropionic acid showed increased interstitial fluid tau and plasma tau. These data suggest that peripheral administration of an anti-tau antibody results in increased plasma tau, which correlates with the concentration of extracellular and soluble tau in the brain. PMID:28424326

Serum sterol responses to increasing plant sterol intake from natural foods in the Mediterranean diet.

PubMed

Escurriol, Verónica; Cofán, Montserrat; Serra, Mercè; Bulló, Mónica; Basora, Josep; Salas-Salvadó, Jordi; Corella, Dolores; Zazpe, Itziar; Martínez-González, Miguel A; Ruiz-Gutiérrez, Valentina; Estruch, Ramón; Ros, Emilio

2009-09-01

Phytosterols in natural foods are thought to inhibit cholesterol absorption. The Mediterranean diet is rich in phytosterol-containing plant foods. To assess whether increasing phytosterol intake from natural foods was associated with a cholesterol-lowering effect in a substudy of a randomized trial of nutritional intervention with Mediterranean diets for primary cardiovascular prevention (PREDIMED study). One hundred and six high cardiovascular risk subjects assigned to two Mediterranean diets supplemented with virgin olive oil (VOO) or nuts, which are phytosterol-rich foods, or advice on a low-fat diet. Outcomes were 1-year changes in nutrient intake and serum levels of lipids and non-cholesterol sterols. Average phytosterol intake increased by 76, 158 and 15 mg/day in participants assigned VOO, nuts and low-fat diets, respectively. Compared to participants in the low-fat diet group, changes in outcome variables were observed only in those in the Mediterranean diet with nuts group, with increases in intake of fibre, polyunsaturated fatty acids and phytosterols (P < 0.020, all) and significant (P < 0.05) reductions of LDL-cholesterol (0.27 mmol/l or 8.3%) and the LDL/HDL-cholesterol ratio (0.29 mmol/l or 11.5%). Variations in saturated fat, cholesterol or fibre intake were unrelated to LDL-cholesterol changes. In the whole group, changes in serum sitosterol-to-cholesterol, which reflect those of dietary phytosterol intake and absorption, correlated inversely to LDL-cholesterol changes (r = -0.256; P = 0.008). In multivariate analyses, baseline LDL-cholesterol, increases in serum sitosterol ratios and statin use were independently associated with LDL-cholesterol reductions. Small amounts of phytosterols in natural foods appear to be bioactive in cholesterol lowering.

Effect of bombesin on serum immunoreactive trypsin in healthy subjects and in patients with chronic pancreatitis.

PubMed

Labò, G; Vezzadini, P; Gullo, L; Sternini, C; Bonora, G

1983-08-01

We studied the effect of bombesin (9 ng/kg X min for 30 min by intravenous infusion) on serum immunoreactive trypsin in healthy subjects and in chronic pancreatitis patients. Bombesin administration caused a marked and significant increase of serum immunoreactive trypsin concentration in healthy subjects. The increase occurred in the first 15 min after the beginning of bombesin infusion and persisted for the duration of the study (2 h). In patients with chronic pancreatitis, the increase was much less pronounced. In these patients, the integrated immunoreactive trypsin response to bombesin was significantly correlated with bicarbonate, lipase, and chymotrypsin outputs into the duodenum. The response of serum immunoreactive trypsin to bombesin stimulation seems to vary according to the degree of pancreatic exocrine dysfunction and to reflect the functional capacity of acinar cell mass.

Minimal dose interferon suppository treatment suppresses viral replication with platelet counts and serum albumin levels increased in chronically hepatitis C virus-infected patients: a phase 1b, placebo-controlled, randomized study.

PubMed

Haruna, Yoshimichi; Inoue, Atsuo

2014-02-01

Animal studies have shown that rectally administrated interferon (IFN) is transferred into the lymphatic system via the rectal mucous membrane, suggesting that an IFN suppository could serve as another drug delivery method. We developed an IFN suppository and administered it to patients with chronic hepatitis C to evaluate its efficacy and safety. Twenty-eight patients with chronic hepatitis C participated in the study. The low-dose IFN suppository containing 1,000 international units (IU) of lymphoblastoid IFNα was administered to 14 patients daily for 24 weeks. Others had a placebo dosing. In 13 of the 14 IFN suppository-treated patients, viral load decreased at week 4. The serum hepatitis C virus (HCV) RNA levels (Log IU/mL, mean±standard error) were 5.65±0.18 before the treatment and 5.17±0.27 at week 4 (P=0.01). The 2'-5' oligoadenylate synthetase activity increased, while the CD4/CD8 ratio decreased significantly. Interestingly, platelet counts and serum albumin levels were significantly increased during and after the treatment. No serious adverse events were observed. The low-dose IFN suppository treatment suppressed HCV replication, modifying host immunity, with increased platelet counts and serum albumin levels. The IFN suppository could be considered a new drug delivery method to preserve the quality of life of patients.

High serum copper level is associated with an increased risk of preeclampsia in Asians: A meta-analysis.

PubMed

Song, Xingxing; Li, Bingrong; Li, Zongyao; Wang, Jiantao; Zhang, Dongfeng

2017-03-01

Epidemiological studies evaluating the associations between serum copper and ratios of Cu/Zn and the preeclampsia (PE) risk in Asian population have produced inconsistent results. Therefore, we conducted a meta-analysis to summarize the relationships. We hypothesize that higher serum copper and ratios of Cu/Zn may increase the PE risk. A systematic literature search was performed in PubMed, Web of Science, Embase, Chinese National Knowledge Infrastructure (CNKI), VIP (Database of Chinese Scientific and Technical Periodicals) and Wangfang databases for relevant studies up to November 2016. Pooled standardized mean difference (SMD) was calculated with random effects model. The results showed that PE patients had a higher serum copper level [SMD (95% CI): 1.05 (0.34, 1.77), Z=2.88, P for Z=0.004; I 2 =96.9%, P for I 2 <0.0001] compared with healthy pregnancy controls. In subgroup analyses, a higher serum copper level in PE patients was observed in case-control studies [SMD (95% CI): 1.39 (0.44, 2.34)]. No significant difference was found between PE patients and healthy pregnancy controls for ratios of Cu/Zn [(SMD (95% CI): 0.26 (-0.77, 1.29), Z=0.49, P for Z=0.625; I 2 =95.8%, P for I 2 <0.0001)]. In conclusion, our meta-analysis indicates that a higher serum copper level is associated with an increased risk of PE. Further studies are needed to confirm these results in future research. Copyright © 2017 Elsevier Inc. All rights reserved.

Increased serum levels of high mobility group box 1 protein in patients with autistic disorder.

PubMed

Emanuele, Enzo; Boso, Marianna; Brondino, Natascia; Pietra, Stefania; Barale, Francesco; Ucelli di Nemi, Stefania; Politi, Pierluigi

2010-05-30

High mobility group box 1 (HMGB1) is a highly conserved, ubiquitous protein that functions as an activator for inducing the immune response and can be released from neurons after glutamate excitotoxicity. The objective of the present study was to measure serum levels of HMGB1 in patients with autistic disorder and to study their relationship with clinical characteristics. We enrolled 22 adult patients with autistic disorder (mean age: 28.1+/-7.7 years) and 28 age- and gender-matched healthy controls (mean age: 28.7+/-8.1 years). Serum levels of HMGB1 were measured by enzyme-linked immunosorbent assay (ELISA). Compared with healthy subjects, serum levels of HMGB1 were significantly higher in patients with autistic disorder (10.8+/-2.6 ng/mL versus 5.6+/-2.5 ng/mL, respectively, P<0.001). After adjustment for potential confounders, serum HMGB1 levels were independently associated with their domain A scores in the Autism Diagnostic Interview-Revised, which reflects their impairments in social interaction. These results suggest that HMGB1 levels may be affected in autistic disorder. Increased HMGB1 may be a biological correlate of the impaired reciprocal social interactions in this neurodevelopmental disorder. Copyright 2010 Elsevier Inc. All rights reserved.

Radiotherapy for Rectal Cancer Is Associated With Reduced Serum Testosterone and Increased FSH and LH

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bruheim, Kjersti; Svartberg, Johan; Department of Medicine, University Hospital of North Norway, Tromso

Purpose: It is known that scattered radiation to the testes during pelvic radiotherapy can affect fertility, but there is little knowledge on its effects on male sex hormones. The aim of this study was to determine whether radiotherapy for rectal cancer affects testosterone production. Methods and Materials: All male patients who had received adjuvant radiotherapy for rectal cancer from 1993 to 2003 were identified from the Norwegian Rectal Cancer Registry. Patients treated with surgery alone were randomly selected from the same registry as control subjects. Serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone, and sex hormone bindingmore » globulin (SHBG) were analyzed, and free testosterone was calculated (N = 290). Information about the radiotherapy treatment was collected from the patient hospital charts. Results: Serum FSH was 3 times higher in the radiotherapy group than in the control group (median, 18.8 vs. 6.3 IU/L, p <0.001), and serum LH was 1.7 times higher (median, 7.5 vs. 4.5 IU/l, p <0.001). In the radiotherapy group, 27% of patients had testosterone levels below the reference range (8-35 nmol/L), compared with 10% of the nonirradiated patients (p <0.001). Irradiated patients had lower serum testosterone (mean, 11.1 vs. 13.4 nmol/L, p <0.001) and lower calculated free testosterone (mean, 214 vs. 235 pmol/L, p <0.05) than control subjects. Total testosterone, calculated free testosterone, and gonadotropins were related to the distance from the bony pelvic structures to the caudal field edge. Conclusions: Increased serum levels of gonadotropins and subnormal serum levels of testosterone indicate that curative radiotherapy for rectal cancer can result in permanent testicular dysfunction.« less

High levels of serum fibroblast growth factor (FGF)-23 are associated with increased mortality in long haemodialysis patients.

PubMed

Jean, Guillaume; Terrat, Jean-Claude; Vanel, Thierry; Hurot, Jean-Marc; Lorriaux, Christie; Mayor, Brice; Chazot, Charles

2009-09-01

Fibroblast growth factor (FGF)-23, a novel bone-derived phosphaturic factor involved in mineral metabolism, is increased in chronic kidney disease (CKD); in dialysis patients, it has been linked to increased mortality rates and vascular calcification (VC). The present investigation aimed to study the factors associated with elevated serum FGF-23 levels in patients treated with long haemodialysis (LHD) sessions and to determine whether a relationship exists between serum FGF-23 levels and patient survival. All patients treated in one haemodialysis centre from September 2006 were included in the study. Standard laboratory values, medical history, cardiovascular events and risk factors, medication and FGF-23 levels [ELISA (C-Term) Immutopics] were recorded. Patients received haemodialysis three times a week, on a 5- to 8-h schedule. Patient data were analysed according to FGF-23 quartiles. The effect of FGF-23 on the 2-year survival rate was assessed using the Cox proportional hazard model, adjusted for confounding variables and according to the serum phosphate tertiles. The study included 219 patients. Serum FGF-23 levels were high: 7060 +/- 13 500 RU/mL (median, 2740 RU/mL). In logistical regressions, only calcaemia (P = 0.002), phosphataemia (P = 0.008) and warfarin use (P = 0.04) were associated with the highest FGF-23 quartile. In the subgroup of patients with an estimated VC score, the third and fourth quartiles of the FGF-23 levels were associated with more severe VC. In multivariate linear regressions, only phosphataemia remained significantly correlated with FGF-23 (P = 0.04). The 2-year mortality rate was significantly higher for haemodialysis patients with serum FGF-23 levels in the higher quartile [P = 0.007; hazard ratio, 2.5 (1.3-5)] than in the first quartile, whereas within the phosphataemia tertiles, the lowest serum FGF-23 quartile was associated with lowered mortality. This study demonstrated a high level of circulating FGF-23 in LHD patients

Assessment of the effects of epinephrine and insulin on plasma and serum biochemical variables in llamas and alpacas.

PubMed

Cebra, Christopher K; Tornquist, Susan J

2004-12-01

To describe the metabolic effects of epinephrine administration in New World camelids and investigate whether these effects are influenced by administration of insulin. 6 llamas and 8 alpacas (all adult castrated males). Prior to each experiment, food was withheld from camelids for 8 hours. On each of 2 consecutive days, alpacas were administered epinephrine (10 mg/kg, IM; time 0); alpacas were randomly assigned to receive regular insulin (0.2 U/kg, IV) immediately after epinephrine administration on one of those days. In llamas, the experiment was performed once after administration of epinephrine only. At 0, 30, 60, 90, 120, 150, 180, 210, and 240 minutes after treatment, blood samples were collected and several serum or plasma biochemical variables were assessed; in addition, plasma samples from llamas were assessed for insulin concentrations. Data were compared between days (alpacas only) and between time points. Administration of epinephrine induced mobilization of glucose, triglycerides, nonesterified fatty acids, and beta-hydroxybutyrate. A small increase in endogenous insulin concentration was detected in epinephrine-treated llamas, compared with baseline values. Overall, insulin administration decreased, negated, or delayed the epinephrine-associated increases in serum or plasma concentrations of circulating energy substrates, except that it augmented the epinephrine-associated increase in concentration of triglycerides. Epinephrine appeared to mobilize energy substrates in camelids and hence may be involved in the pathogenesis of disorders of glucose and fat metabolism. Insulin appeared to antagonize most of these effects, and its administration may have therapeutic value in camelids.

Interferon-Free Treatment of Hepatitis C Virus in HIV/Hepatitis C Virus-Coinfected Subjects Results in Increased Serum Low-Density Lipoprotein Concentration

PubMed Central

Townsend, Kerry; Meissner, Eric G.; Sidharthan, Sreetha; Sampson, Maureen; Remaley, Alan T.; Tang, Lydia; Kohli, Anita; Osinusi, Anu; Masur, Henry

2016-01-01

Abstract Chronic hepatitis C virus (HCV) infection is associated with lower serum concentration of low-density lipoprotein (LDL-C), the primary cholesterol metabolite targeted pharmaceutically to modulate cardiovascular risk. Chronic infection with human immunodeficiency virus (HIV) and treatment with antiretrovirals (ARVs) are associated with dyslipidemia and increased risk of cardiovascular disease. In subjects coinfected with HIV and HCV, lipid abnormalities associated with either infection alone are often attenuated. Treatment of chronic HCV infection in HIV/HCV-coinfected subjects is now possible with interferon (IFN)-free regimens composed of directly acting antivirals (DAAs). We previously observed a marked increase in serum LDL-C in HCV-monoinfected subjects treated with sofosbuvir and ribavirin (SOF/RBV) that correlated with viral decline in serum, suggesting a direct influence of HCV clearance on serum cholesterol. In the present study, we assessed longitudinal changes in cholesterol in HIV/HCV-coinfected subjects during treatment of HCV genotype-1 (GT1) infection with combination DAA therapy. We report a rapid increase in LDL-C and LDL particle size by week 2 of treatment that was sustained during and after treatment in HIV/HCV-coinfected subjects. No change in serum LDL-C was observed at day 3 of treatment, in spite of a marked reduction in serum HCV viral load, suggesting LDL-C increases do not directly reflect HCV clearance as measured in peripheral blood. After effective DAA therapy for HCV, an increase in LDL should be anticipated in HIV/HCV-coinfected subjects. PMID:26559180

Serum osteoprotegerin is increased and predicts survival in idiopathic pulmonary arterial hypertension

PubMed Central

Condliffe, Robin; Pickworth, Josephine A.; Hopkinson, Kay; Walker, Sara J.; Hameed, Abdul G.; Suntharaligam, Jay; Soon, Elaine; Treacy, Carmen; Pepke-Zaba, Joanna; Francis, Sheila E.; Crossman, David C.; Newman, Christopher M. H.; Elliot, Charles A.; Morton, Allison C.; Morrell, Nicholas W.; Kiely, David G.; Lawrie, Allan

2012-01-01

We previously reported that osteoprotegerin (OPG) is regulated by pathways associated with pulmonary arterial hypertension (PAH), and is present at elevated levels within pulmonary vascular lesions and sera from patients with idiopathic PAH (IPAH). Since OPG is a naturally secreted protein, we investigated the relationship between serum OPG and disease severity and outcome in patients with IPAH and animal models. OPG mRNA expression was measured in pulmonary artery smooth muscle cells (PASMC) from pulmonary arteries of patients with and without IPAH. Serum concentrations of OPG were measured in a retrospective and prospective group of patients. OPG levels were compared with phenotypic data and other putative PAH biomarkers. Prognostic significance was assessed and levels compared with healthy controls. Correlation of OPG and pulmonary vascular remodeling was also performed in rodent models of PAH. OPG mRNA was significantly increased 2-fold in PASMC isolated from explanted PAH lungs compared with control. Serum OPG concentrations were markedly elevated in IPAH compared with controls. In Cohort 1 OPG levels significantly correlated with mean right atrial pressure and cardiac index, while in Cohort 2 significant correlations existed between age-adjusted OPG levels and gas transfer. In both cohorts an OPG concentration above a ROC-derived threshold of 4728 pg/ml predicted poorer survival. In two rodent models, OPG correlated with the degree of pulmonary vascular remodeling. OPG levels are significantly elevated in patients with idiopathic PAH and are of prognostic significance. The role of OPG as a potential biomarker and therapeutic target merits further investigation. PMID:22558516

Drug residues in serum of dogs receiving anticancer chemotherapy.

PubMed

Knobloch, A; Mohring, S A I; Eberle, N; Nolte, I; Hamscher, G; Simon, D

2010-01-01

The presence of drug residues in blood samples can represent an occupational hazard. However, studies on cytotoxic drug residues in serum of dogs are lacking in veterinary oncology. To evaluate possible occupational hazards associated with handling of blood samples from dogs receiving oncolytic drugs 7 days after treatment. Twenty-seven client-owned dogs treated for lymphoma or mast cell tumors with vincristine, vinblastine, cyclophosphamide, or doxorubicin. Prospective, observational study. Serum samples were either taken 7 days after administration of vincristine, cyclophosphamide, doxorubicin (lymphoma), and vinblastine (mast cell tumor), or 1-2 days after the last concurrent oral administration of cyclophosphamide (mast cell tumor). Additionally, serum was collected within 5 minutes of treatment. Measurement of drug residues in serum was performed by liquid chromatography tandem mass spectrometry (LC/MS/MS). In 33 samples collected within 5 minute of treatment, the median serum concentrations were vincristine: 37 microg/L (range: 11-87 microg/L), vinblastine: 13 microg/L (range: 13-35 microg/L), cyclophosphamide: 2,484 microg/L (range: 1,209-2,778 microg/L), doxorubicin: 404 microg/L (range: 234-528 microg/L). In 81 serum samples collected 7 days after treatment vinblastine (7 microg/L) was detected in 1 sample, and cyclophosphamide (7 and 9 microg/L) in 2 samples collected 1-2 days after oral administration of cyclophosphamide. Medications were not detected in any of the other samples. Handling of blood samples from dogs receiving oncolytic chemotherapy 7 days after treatment with vincristine, vinblastine, cyclophosphamide, and doxorubicin should not present a health hazard.

Induction of testicular damage by daily methamphetamine administration in rats.

PubMed

Lin, Ji-Fan; Lin, Yi-Hsuan; Liao, Po-Cheng; Lin, Yi-Chia; Tsai, Te-Fu; Chou, Kuang-Yu; Chen, Hung-En; Tsai, Shiow-Chwen; Hwang, Thomas I-Sheng

2014-02-28

Methamphetamine (METH)-induced brain damage and apoptosis within the central nervous system are well documented. This study was conducted to investigate the toxic effects of daily METH administration on the testes in a rat model. Male Sprague-Dawley rats (5 weeks old, ~100 g, n = 64) were divided into two groups and treated with vehicle (saline, control) or METH (10 mg/kg) for 15, 30, 60 and 90 days. The results showed that daily administration of METH decreased the body, testicular and epididymis weights as well as the serum levels of total testosterone. The increased apoptotic index (Bad/Bcl2 expression ratio) and levels of cleaved caspase-3 indicated that apoptosis had occurred in the testes of the METH-treated rats. The oxidative stress levels increased as the reduced and oxidized glutathione (GSH/GSSG) ratio decreased. The overall sperm counts decreased at 15 and 90 days, where- as morphologically abnormal sperm counts increased at 30, 60 and 90 days in the METH-treated rats. This study demonstrates that daily exposure to METH significantly reduced the number and quality of sperm in rats. The underlying pathophysiological mechanisms likely include the reduction of serum testosterone levels and the increase of oxidative stress and apoptosis in the rat testes.

HBsAg carrier status and the association between gestational diabetes with increased serum ferritin concentration in Chinese women.

PubMed

Lao, Terence T; Tse, Ka-Yu; Chan, Louis Y; Tam, Kar-Fai; Ho, Lai-Fong

2003-11-01

To determine whether the high prevalence of hepatitis B surface antigen (HBsAg) carriage in our population can explain the previous observation of an association between increased maternal serum ferritin concentration and gestational diabetes in Hong Kong Chinese women. A retrospective study was performed on 767 nonanemic women with singleton pregnancy who had iron status assessed at 28-30 weeks. The result of the routine antenatal HBsAg screening was retrieved from patient records. The HBsAg-positive and -negative groups were compared for maternal characteristics, prevalence of gestational diabetes in the third trimester, prevalence of high serum ferritin and iron concentrations, and transferrin saturation, which is defined as a value in the highest quartile established by the measurements obtained from the HBsAg-negative group. The incidences of oral glucose tolerance test and gestational diabetes were significantly increased in the HBsAg-positive group. The HBsAg-positive women with gestational diabetes had significantly increased prevalence of high serum ferritin compared with the HBsAg-negative women, irrespective of the latter's gestational diabetes status. Multiple logistic regression analysis confirmed the independent association between HBsAg carrier status with gestational diabetes (relative risk 3.51, 95% CI 1.83-6.73) but excluded high ferritin as an independent factor. Our results indicate that maternal HBsAg carriage could explain in part the association between increased serum ferritin concentration with gestational diabetes in Hong Kong Chinese women, and that HBsAg carrier status is an independent risk factor for gestational diabetes.

Serum from pregnant women with gestational diabetes mellitus increases the expression of FABP4 mRNA in primary subcutaneous human pre-adipocytes

PubMed Central

Li, Lan; Lee, Se Jin; Kook, Song Yi; Ahn, Tae Gyu; Lee, Ji Yeon

2017-01-01

Objective Gestational diabetes mellitus (GDM) is defined as glucose intolerance first detected during pregnancy. It can result in pregnancy complications such as birth injury, stillbirth. Fatty acid-binding protein 4 (FABP4), found in adipose tissue, is associated with insulin resistance, and type 2 diabetes. The aim of this study was to investigate whether FABP4 in the placenta and decidua of pregnant women with GDM is higher than that in normal pregnant women, and whether serum from pregnant women with GDM may cause adipocytes to secrete more FABP4 than does serum from a normal pregnant group. Methods We obtained placentas, deciduas, and serum from 12 pregnant women with GDM and 12 normal pregnant women and performed enzyme-linked immunosorbent assay, real time quantitative-polymerase chain reaction. We cultured human pre-adipocytes for 17 days with GDM and non-GDM serum and performed western blot, real time quantitative-polymerase chain reaction, and oil red O staining. Results Expression of FABP4 in serum, placenta and decidua of pregnant women with GDM was significantly higher than that in normal pregnant women. Serum from pregnant women with GDM increased the expression of FABP4 mRNA and decreased the expression of adiponectin mRNA in human pre-adipocytes significantly. Adipocyte cultured in GDM serum showed significantly greater lipid accumulation than those cultured in normal serum. Conclusion Our results suggest that FABP4 is higher in placenta and decidua from pregnant women with GDM. Increased circulating FABP4 in maternal serum from pregnant women with GDM may originate from adipocytes and the placenta. Circulating FABP4 can induce increased insulin resistance and decreased insulin sensitivity. PMID:28534013

Serum from pregnant women with gestational diabetes mellitus increases the expression of FABP4 mRNA in primary subcutaneous human pre-adipocytes.

PubMed

Li, Lan; Lee, Se Jin; Kook, Song Yi; Ahn, Tae Gyu; Lee, Ji Yeon; Hwang, Jong Yun

2017-05-01

Gestational diabetes mellitus (GDM) is defined as glucose intolerance first detected during pregnancy. It can result in pregnancy complications such as birth injury, stillbirth. Fatty acid-binding protein 4 (FABP4), found in adipose tissue, is associated with insulin resistance, and type 2 diabetes. The aim of this study was to investigate whether FABP4 in the placenta and decidua of pregnant women with GDM is higher than that in normal pregnant women, and whether serum from pregnant women with GDM may cause adipocytes to secrete more FABP4 than does serum from a normal pregnant group. We obtained placentas, deciduas, and serum from 12 pregnant women with GDM and 12 normal pregnant women and performed enzyme-linked immunosorbent assay, real time quantitative-polymerase chain reaction. We cultured human pre-adipocytes for 17 days with GDM and non-GDM serum and performed western blot, real time quantitative-polymerase chain reaction, and oil red O staining. Expression of FABP4 in serum, placenta and decidua of pregnant women with GDM was significantly higher than that in normal pregnant women. Serum from pregnant women with GDM increased the expression of FABP4 mRNA and decreased the expression of adiponectin mRNA in human pre-adipocytes significantly. Adipocyte cultured in GDM serum showed significantly greater lipid accumulation than those cultured in normal serum. Our results suggest that FABP4 is higher in placenta and decidua from pregnant women with GDM. Increased circulating FABP4 in maternal serum from pregnant women with GDM may originate from adipocytes and the placenta. Circulating FABP4 can induce increased insulin resistance and decreased insulin sensitivity.

Oxidative Stress is Increased in Serum from Mexican Patients with Relapsing-Remitting Multiple Sclerosis

PubMed Central

Ortiz, Genaro Gabriel; Macías-Islas, Miguel Ángel; Pacheco-Moisés, Fermín P.; Cruz-Ramos, José A.; Sustersik, Silvia; Barba, Elías Alejandro; Aguayo, Adriana

2009-01-01

Objective: To determine the oxidative stress markers in serum from patients with relapsing-remitting multiple sclerosis. Methods: Blood samples from healthy controls and 22 patients 15 women (7 aged from 20 to 30 and 8 were > 40 years old) and 7 men (5 aged from 20 to 30 and 2 were > 40 years old) fulfilling the McDonald Criteria and classified as having Relapsing-Remitting Multiple Sclerosis accordingly with Lublin were collected for oxidative stress markers quantification. Results: Nitric oxide metabolites (nitrates/nitrites), lipid peroxidation products (malondialdehyde plus 4-hidroxialkenals), and glutathione peroxidase activity were significantly increased in serum of subjects with relapsing-remitting multiple sclerosis in comparison with that of healthy controls. These data support the hypothesis that multiple sclerosis is a component closely linked to oxidative stress. PMID:19242067

Serum podocalyxin is significantly increased in early-onset preeclampsia and may represent a novel marker of maternal endothelial cell dysfunction.

PubMed

Chen, Qi; Wang, Yao; Li, Ying; Zhao, Min; Nie, Guiying

2017-11-01

Podocalyxin is a glomerular podocyte protein and increased in urine of preeclampsia. However, podocalyxin is also expressed in endothelial cells of other organs. Here we investigated whether podocalyxin is detectable in pregnant serum and whether the levels are altered in preeclampsia. Podocalyxin was determined by ELISA in sera collected from normal pregnancy across gestation (n = 44) and from preeclamptic pregnancies at diagnosis (n = 34) with gestation-age-matched controls (n = 68). Immunohistochemistry examined podocalyxin in placentas and in 32 human tissues on a tissue array. Human umbilical vein endothelial cells (HUVECs) were treated with interleukin (IL)-6 and podocalyxin was analysed by ELISA and western blotting. Podocalyxin was detected in serum of normal pregnancy, with levels increasing progressively with advancing gestation. Podocalyxin serum levels were significantly elevated in preeclampsia, especially the early-onset subtype. Within the placenta, blood vessels but not trophoblasts expressed podocalyxin, and preeclampsia didn't differ from controls. Endothelial cells in all 32 human organs examined, as well as HUVECs, expressed podocalyxin. Its levels increased in the conditioned media but decreased in the lysates when HUVECs were treated with IL-6. Podocalyxin likely derived from maternal endothelial cells is present in pregnant serum and significantly increased in early-onset preeclampsia. Podocalyxin release was stimulated by IL-6 in HUVECs.

Acute and subchronic administration of anandamide or oleamide increases REM sleep in rats.

PubMed

Herrera-Solís, Andrea; Vásquez, Khalil Guzmán; Prospéro-García, Oscar

2010-03-01

Anandamide and oleamide, induce sleep when administered acutely, via the CB1 receptor. Their subchronic administration must be tested to demonstrate the absence of tolerance to this effect, and that the sudden withdrawal of these endocannabinoids (eCBs) does not affect sleep negatively. The sleep-waking cycle of rats was evaluated for 24h, under the effect of an acute or subchronic administration of eCBs, and during sudden eCBs withdrawal. AM251, a CB1 receptor antagonist (CB1Ra) was utilized to block eCBs effects. Our results indicated that both acute and subchronic administration of eCBs increase REMS. During eCBs withdrawal, rats lack the expression of an abstinence-like syndrome. AM251 was efficacious to prevent REMS increase caused by both acute and subchronic administration of these eCBs, suggesting that this effect is mediated by the CB1 receptor. Our data further support a role of the eCBs in REMS regulation. (c) 2009 Elsevier Inc. All rights reserved.

Effect of 6-8 weeks of oral ursodeoxycholic acid administration on serum concentrations of fasting and postprandial bile acids and biochemical analytes in healthy dogs.

PubMed

Deitz, Krysta L; Makielski, Kelly M; Williams, Jackie M; Lin, Hui; Morrison, Jo Ann

2015-09-01

Ursodeoxycholic acid (UDCA) is commonly used for the treatment of hepatobiliary disease. UDCA is a bile acid that can be detected in the bile acid assay. Its effect on biochemical analytes is unknown. The aim of this study was to determine the effect of 6-8 weeks of UDCA administration on fasting and postprandial concentrations of serum bile acids (SBA), cholesterol, triglycerides, bilirubin, and liver enzyme activities in healthy dogs. Twenty healthy dogs received UDCA for 6-8 weeks. CBC, biochemistry profile, urinalysis, fasting and postprandial SBA, and hepatobiliary ultrasound examination were performed prior to starting UDCA (timepoint 0) and after 6-8 weeks of therapy, while animals were still receiving UDCA (timepoint 1). Timepoint 0 and timepoint 1 values were compared with a paired t-test. SBA were remeasured 72 hours after UDCA discontinuation. Only mean fasting SBA at timepoint 1 increased significantly (P = .03) from timepoint 0 (2.26 μmol/L at time 0 and 3.81 μmol/L at time 1) but were not elevated above the normal reference interval (0-9 μmol/L). Two dogs had timepoint 1 fasting SBA above the reference interval (10 and 11.7 μmol/L). One dog had timepoint 1 postprandial SBA above the reference interval at 20.1 μmol/L (reference interval 0-17 μmol/L). Repeat SBA 72 hours after UDCA discontinuation were normal. Long-term administration of UDCA to healthy dogs may increase fasting SBA above pretreatment values (typically within the reference interval). Long-term administration of UDCA to healthy dogs does not alter liver enzyme activities, and bilirubin, cholesterol, or triglyceride concentrations. © 2015 American Society for Veterinary Clinical Pathology.

Cuprophane but not synthetic membrane induces increases in serum tumor necrosis factor-alpha levels during hemodialysis.

PubMed

Canivet, E; Lavaud, S; Wong, T; Guenounou, M; Willemin, J C; Potron, G; Chanard, J

1994-01-01

Cytokine synthesis and secretion by blood mononuclear cells is a well-documented phenomenon in hemodialyzed patients. The present study was conducted in 17 chronically hemodialyzed patients to test the relative effect of uremic toxicity, membrane biocompatibility, dialysate composition, and the risk of endotoxinemia on the serum level of tumor necrosis factor-alpha (TNF-alpha). The only significant parameter that influenced circulating TNF-alpha was the chemical characteristics of the dialyzer membrane. Tumor necrosis factor-alpha levels significantly increased during the session with cuprophane, whereas they decreased with AN69. The TNF-alpha increase was documented whatever the dialysate buffer and the presence or absence (negative Limulus amoebocyte lysate test) of endotoxin in the dialysate. In the subgroup of patients treated with a contaminated dialysate and AN69, none had clinical symptoms and the central body temperature remained constant throughout the session. In these patients, serum TNF-alpha levels did not change after priming the dialyzer with sterile saline. In conclusion, the serum TNF-alpha level during hemodialysis appears to be modulated by biocompatibility, permeability, and binding properties of dialysis membrane rather than dialysate composition. Endotoxin in the dialysate did not result in positive TNF-alpha balance no matter what its possible priming effect on mononucleated blood cells.

Association between increased serum thyrotropin concentration and the oldest old: what do we know?

PubMed Central

Duarte, Glaucia Cruzes; Cendoroglo, Maysa Seabra; Araújo, Lara Miguel Quirino; Almada, Clineu de Mello

2015-01-01

To assess studies that evaluate the relation between serum thyrotropin concentration, very old subjects, and their events. We searched the PubMed, SciELO, and LILACS databases for articles published between 2004 and 2012. Our search was restricted to studies involving humans aged 65 years or older, and written in English, Spanish, or Portuguese. Studies that evaluated the association between elevated serum thyrotropin concentration among elderly subjects with subclinical hypothyroidism were chosen since at least in part they included a subpopulation of individuals aged 80 years and above. Thirteen studies were selected. No significant increase in risk of cardiovascular events, coronary heart disease, or total mortality was observed. Elevated thyrotropin concentration was associated with longevity. More randomized controlled trials are required to better define the potential benefits of elevated thyrotropin concentration in this oldest old population, hormone replacement, and longevity. PMID:25807244

77 FR 5027 - Food and Drug Administration Transparency Initiative: Exploratory Program To Increase Access to...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-01

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2009-N-0247] Food and Drug Administration Transparency Initiative: Exploratory Program To Increase Access to the... responsible for a broad range of compliance and enforcement activities. Increasing the transparency of these...

A lack of association between hyperserotonemia and the increased frequency of serum anti-myelin basic protein auto-antibodies in autistic children.

PubMed

Mostafa, Gehan Ahmed; Al-Ayadhi, Laila Yousef

2011-06-22

One of the most consistent biological findings in autism is the elevated blood serotonin levels. Immune abnormalities, including autoimmunity with production of brain specific auto-antibodies, are also commonly observed in this disorder. Hyperserotonemia may be one of the contributing factors to autoimmunity in some patients with autism through the reduction of T-helper (Th) 1-type cytokines. We are the first to investigate the possible role of hyperserotonemia in the induction of autoimmunity, as indicated by serum anti-myelin-basic protein (anti-MBP) auto-antibodies, in autism. Serum levels of serotonin and anti-MBP auto-antibodies were measured, by ELISA, in 50 autistic patients, aged between 5 and 12 years, and 30 healthy-matched children. Autistic children had significantly higher serum levels of serotonin and anti-MBP auto-antibodies than healthy children (P < 0.001 and P < 0.001, respectively). Increased serum levels of serotonin and anti-MBP auto-antibodies were found in 92% and 80%, respectively of autistic patients. Patients with severe autism had significantly higher serum serotonin levels than children with mild to moderate autism (P < 0.001). Serum serotonin levels had no significant correlations with serum levels of anti-MBP auto-antibodies in autistic patients (P = 0.39). Hyperserotonemia may not be one of the contributing factors to the increased frequency of serum anti-MBP auto-antibodies in some autistic children. These data should be treated with caution until further investigations are performed. However, inclusion of serum serotonin levels as a correlate may be useful in other future immune studies in autism to help unravel the long-standing mystery of hyperserotonemia and its possible role in the pathophysiology of this disorder.

Elevated Serum PSA is Associated With Human Herpesvirus 8 Infection and Increased Circulating Cytokine Levels in Men From Tobago.

PubMed

Henning, Jill D; Karamchandani, Jaideep M; Bonachea, Luis A; Bunker, Clareann H; Patrick, Alan L; Jenkins, Frank J

2017-05-01

Serum-prostate specific antigen (PSA) levels have been used for many years as a biomarker for prostate cancer. This usage is under scrutiny due to the fact that elevated PSA levels can be caused by other conditions such as benign prostatic hyperplasia and infections of or injury to the prostate. As a result, the identification of specific pathogens capable of increasing serum levels of PSA is important. A potential candidate responsible for elevated PSA is human herpesvirus 8 (HHV-8). We have reported previously that HHV-8 is capable of infecting and establishing a latent infection in the prostate. In this current study we test the hypothesis that HHV-8 infection is associated with elevated PSA levels. Circulating cytokine levels between men with elevated PSA and controls are also compared. HHV-8 serostatus was determined among men with elevated serum PSA (≥4 ng/ml; n = 168, no prostate cancer on biopsy) and age-matched controls (PSA <4 ng/ml; n = 234), Circulating cytokine levels were determined among a subset of each group (116 with elevated PSA and 85 controls). Men with an elevated serum PSA were significantly more likely to be HHV-8 seropositive (42.9%) than the age-matched cancer-free men (22.2%; OR 2.51; 95%CI 1.48-4.29, P = 00001). Comparison of circulating cytokine levels between men with elevated serum PSA and controls indicated that elevated serum PSA is associated with a pro-inflammatory response with a mixed Th1/Th2 response while HHV-8 infection was associated with significantly higher levels of IL12p70, IL-10, and IL-13 indicating a Th2 immune response. We found a significant association between HHV-8 infection and increased levels of serum PSA. In an age of patient-centered medicine, men with an elevated serum PSA should be considered for HHV-8 serology testing to determine if HHV-8 is responsible for the elevated PSA. Prostate 77: 617-624, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Effect of Administration of Nandrolone Decanoate upon Aldosterone Concentration and Serum Na+/K+ Levels in Albino Mice.

PubMed

Chowdhury, Parmita; Mahanta, Rita

2017-01-01

This article is a study of adverse effects associated with the abuse of recreational drugs such as anabolic androgenic steroids. Nandrolone decanoate is one such drug often abused by athletes and bodybuilders seeking enhanced physical strength or appearance. The use of such steroids has increased dramatically over the years. The present study was conducted to investigate the impact of nandrolone decanoate when consumed at an abused dose, upon serum aldosterone concentration in albino mice. Sodium and potassium ion concentrations were also monitored with the same experimental dosage. 0.1ml of 25 mg Nandrolone decanoate was administered to the animals twice a week for a period of 90 days. Blood samples for obtaining the serum from both normal and treated group of animals were collected at an interval of 15 days upto the 90th day. The present investigation revealed a significant increase (p<0.01) in the serum aldosterone and sodium ion concentrations in the treated group of animals compared to that in the normal group. Potassium ion concentration in the treated group did not exhibit a significant alteration when compared with the untreated animals. From the above observation, nandrolone decanoate abuse could be suggested as one of the causes of aldosterone and electrolyte imbalance in the body that could possibly be a serious risk factor for cardiovascular related disorders. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Severe hypophosphataemia after intravenous iron administration.

PubMed

Blazevic, A; Hunze, J; Boots, J M M

2014-01-01

Currently, in many centres, intravenous administration of iron is becoming increasingly popular because of higher efficacy and decreased side effects, mainly gastrointestinal, compared with oral iron therapy. Studies of intravenous ferric carboxymaltose administration in the postpartum setting and in patients with non-dialysis-dependent chronic kidney disease revealed a decrease in serum phosphate levels that was generally asymptomatic and transient. Here, we report four cases of severe and symptomatic hypophosphataemia after intravenous iron administration. All patients received this as therapy for iron deficiency anaemia due to heavy menstrual bleeding. In most cases, a pre-existent disorder in the phosphate homeostasis existed, such as a secondary (cases 3 and 4) or tertiary hyperparathyroidism (case 1). However, in the second case there were no risk factors for a dysregulation of the phosphate homeostasis. Based on these findings, we conclude that severe and symptomatic hypophosphatemia can occur as a side effect of intravenous iron administration and can persist for months after administration. Especially patients with low phosphate levels prior to therapy due to concomitant disorders in phosphate homeostasis (e.g. hyperparathyroidism, vitamin D deficiency) are at risk.

Interleukin-17 SNPs and serum levels increase ulcerative colitis risk: a meta-analysis.

PubMed

Li, Juan; Tian, Hao; Jiang, Hui-Jun; Han, Bin

2014-11-14

To investigate the associations of interleukin-17 (IL-17) genetic polymorphisms and serum levels with ulcerative colitis (UC) risk. Relevant articles were identified through a search of the following electronic databases, excluding language restriction: (1) the Cochrane Library Database (Issue 12, 2013); (2) Web of Science (1945-2013); (3) PubMed (1966-2013); (4) CINAHL (1982-2013); (5) EMBASE (1980-2013); and (6) the Chinese Biomedical Database (1982-2013). Meta-analysis was conducted using STATA 12.0 software. Crude odds ratios and standardized mean differences (SMDs) with corresponding 95% confidence intervals (CIs) were calculated. All of the included studies met all of the following five criteria: (1) the study design must be a clinical cohort or a case-control study; (2) the study must relate to the relationship between IL-17A/F genetic polymorphisms or serum IL-17 levels and the risk of UC; (3) all patients must meet the diagnostic criteria for UC; (4) the study must provide sufficient information about single nucleotide polymorphism frequencies or serum IL-17 levels; and (5) the genotype distribution of healthy controls must conform to the Hardy-Weinberg equilibrium (HWE). The Newcastle-Ottawa Scale (NOS) criteria were used to assess the methodological quality of the studies. The NOS criteria included three aspects: (1) subject selection: 0-4; (2) comparability of subjects: 0-2; and (3) clinical outcome: 0-3. NOS scores ranged from 0 to 9, with a score ≥ 7 indicating good quality. Of the initial 177 articles, only 16 case-control studies met all of the inclusion criteria. A total of 1614 UC patients and 2863 healthy controls were included in this study. Fourteen studies were performed on Asian populations, and two studies on Caucasian populations. Results of the meta-analysis revealed that IL-17A and IL-17F genetic polymorphisms potentially increased UC risk under both allele and dominant models (P < 0.001 for all). The results also showed that UC

Interleukin-17 SNPs and serum levels increase ulcerative colitis risk: A meta-analysis

PubMed Central

Li, Juan; Tian, Hao; Jiang, Hui-Jun; Han, Bin

2014-01-01

AIM: To investigate the associations of interleukin-17 (IL-17) genetic polymorphisms and serum levels with ulcerative colitis (UC) risk. METHODS: Relevant articles were identified through a search of the following electronic databases, excluding language restriction: (1) the Cochrane Library Database (Issue 12, 2013); (2) Web of Science (1945-2013); (3) PubMed (1966-2013); (4) CINAHL (1982-2013); (5) EMBASE (1980-2013); and (6) the Chinese Biomedical Database (1982-2013). Meta-analysis was conducted using STATA 12.0 software. Crude odds ratios and standardized mean differences (SMDs) with corresponding 95% confidence intervals (CIs) were calculated. All of the included studies met all of the following five criteria: (1) the study design must be a clinical cohort or a case-control study; (2) the study must relate to the relationship between IL-17A/F genetic polymorphisms or serum IL-17 levels and the risk of UC; (3) all patients must meet the diagnostic criteria for UC; (4) the study must provide sufficient information about single nucleotide polymorphism frequencies or serum IL-17 levels; and (5) the genotype distribution of healthy controls must conform to the Hardy-Weinberg equilibrium (HWE). The Newcastle-Ottawa Scale (NOS) criteria were used to assess the methodological quality of the studies. The NOS criteria included three aspects: (1) subject selection: 0-4; (2) comparability of subjects: 0-2; and (3) clinical outcome: 0-3. NOS scores ranged from 0 to 9, with a score ≥ 7 indicating good quality. RESULTS: Of the initial 177 articles, only 16 case-control studies met all of the inclusion criteria. A total of 1614 UC patients and 2863 healthy controls were included in this study. Fourteen studies were performed on Asian populations, and two studies on Caucasian populations. Results of the meta-analysis revealed that IL-17A and IL-17F genetic polymorphisms potentially increased UC risk under both allele and dominant models (P < 0.001 for all). The results also

Assessing the efficacy of perioperative carprofen administration in dogs undergoing surgical repair of a ruptured cranial cruciate ligament.

PubMed

Reese, C J; Trotter, E J; Short, C E; Erb, H N; Barlow, L L

2000-01-01

Twenty-one otherwise healthy dogs that presented for surgical repair of a ruptured cranial cruciate ligament were blindly and randomly given either carprofen (2.2 mg/kg body weight, orally) or a placebo beginning 12 hours preoperatively and continuing every 12 hours for a total of three doses. The patients were assessed for postoperative pain using a subjective pain score and given oxymorphone (0.1 mg/kg body weight, intramuscularly) every four hours if the pain score was 2 or greater. Blood samples were also collected to determine serum cortisol levels. There was a significant increase in serum cortisol levels in the immediate postoperative period in both the placebo group and the carprofen group (p less than 0.05). There was no significant difference in the percentage of increase in serum cortisol levels between the two groups. No correlation was evident between the serum cortisol levels and the corresponding pain scores in either group. This subjective method of assessing postoperative pain was not accurate and should not be relied upon for determination of postoperative analgesic administration. Perioperative oral administration of carprofen did not appear to be effective in controlling postoperative pain in these patients.

Body fat and insulin resistance independently predict increased serum C-reactive protein in hyperandrogenic women with polycystic ovary syndrome.

PubMed

Tosi, Flavia; Dorizzi, Romolo; Castello, Roberto; Maffeis, Claudio; Spiazzi, Giovanna; Zoppini, Giacomo; Muggeo, Michele; Moghetti, Paolo

2009-11-01

Increased serum C-reactive protein (CRP), an independent predictor of coronary heart disease, was reported in women with polycystic ovary syndrome (PCOS). It remains unclear whether this finding is due to the association between PCOS and either insulin resistance, obesity, or androgen excess, which are all common features of this condition. The aims of this study were to assess whether increased serum CRP is a specific feature of PCOS and to investigate the mechanisms underlying this association. Serum high-sensitivity CRP (hs-CRP) was measured in 86 hyperandrogenic women (age 21.6+/-4.2 years, body mass index (BMI) 23.6+/-3.5 kg/m2), 50 with PCOS and 36 with idiopathic hyperandrogenism (HA). Thirty-five BMI-matched healthy women were also studied as controls. In these subjects, endocrine and metabolic profiles were assessed. In all hyperandrogenic subjects and 14 controls, insulin sensitivity was measured by the glucose clamp technique. Body fat was measured by bioelectrical impedance. Hs-CRP concentrations were higher in PCOS women (3.43+/-2.01 mg/l) than in HA subjects and healthy women (2.43+/-1.04, P<0.005; and 2.75+/-0.86 mg/l, P<0.05 respectively versus PCOS). In multiple regression analyses, increased serum hs-CRP was independently predicted by higher body fat and lower insulin sensitivity. However, in lean women, serum-free testosterone was an additional, negative, predictive variable. PCOS is accompanied by a low-grade chronic inflammation. Body fat appears the main determining factor of this finding, which is only partly explained by insulin resistance. At least in lean women, androgen excess per se seems to play an additional, possibly protective, role in this association.

Increased serum IL-6, TNF-alpha and IL-10 levels in patients with bullous pemphigoid: relationships with disease activity.

PubMed

D'Auria, L; Mussi, A; Bonifati, C; Mastroianni, A; Giacalone, B; Ameglio, F

1999-01-01

The present report analyzes the serum levels of three cytokines, interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10) in 15 patients with bullous pemphigoid (BP) (compared with 20 healthy controls) to evaluate a possible involvement of these biological modulators in the clinical expression of this disease. BP is a rare bullous disease of autoimmune origin with evidence of inflammatory processes that cause skin lesions with local increase of various pro-inflammatory mediators. Determination of cytokine concentrations were obtained employing commercially available ELISA kits. The sera of BP patients showed increased levels of these three cytokines (P < 0.01). When the number of skin lesions (blisters and/or erosion) of each patient, employed as a marker of disease activity, was correlated with the serum levels of IL-6 and TNF-alpha, significant correlations were found (IL-6: P < 0.01 and TNF-alpha: P < 0.01, respectively), suggesting a possible role of these mediators in the development of BP blisters. The serum levels of IL-6 also correlated (P = 0.01 with those of serum C reactive protein (CRP), an acute-phase protein induced by IL-6 in hepatocytes. In addition, serum TNF-alpha and sE-selectin (an adhesion molecule previously reported to be increased by this cytokine) levels were also correlated (P < 0.05). On the basis of these data, it may be indicated that at least IL-6 and TNF-alpha are associated with the clinical expression of BP and that the endothelial activation (possibly induced by the TNF-alpha activity), seems to be an important phase of this dermatosis.

Serum 11 beta-hydroxyandrostenedione as an indicator of the source of excess androgen production in women with polycystic ovaries.

PubMed

Polson, D W; Reed, M J; Franks, S; Scanlon, M J; James, V H

1988-05-01

Serum 11 beta-hydroxyandrostenedione levels (11-OHA) were measured in normal women and women with polycystic ovaries (PCO) to assess their value in localizing the source of excessive androgen production in women with PCO. Serum 11-OHA was undetectable (less than 1.5 nmol/L) in an adrenalectomized woman, a woman with 11-hydroxylase deficiency, and a woman receiving chronic dexamethasone therapy, confirming the specificity of the antiserum used in this study. Serum 11-OHA concentrations were similar in normal women [mean, 5.0 +/- 2.3 (+/- SD) nmol/L] and women with PCO (5.0 +/- 2.1 nmol/L); serum androstenedione concentrations were increased in women with PCO. Thus, the ratio of androstenedione to 11-OHA was significantly higher (P less than 0.001) in women with PCO (2.0 +/- 0.7) than in normal women (1.1 +/- 0.5). Serum 11-OHA levels after adrenal suppression or stimulation were similar in women with PCO who had an ovulatory response and those who failed to ovulate after clomiphene administration. Administration of dexamethasone (1 mg) and injection of ACTH (250 micrograms) were associated with marked suppression and subsequent stimulation of serum 11-OHA levels in both normal women and women with PCO, and the responses were similar in the two groups. Also, the hour to hour and diurnal variations in serum 11-OHA were similar to those of androstenedione and cortisol during a 24-h period, indicating the adrenal origin of 11-OHA. Our finding of similar serum 11-OHA levels in the presence of increased serum androstenedione levels in women with PCO supports the concept that the ovary is the major source of excess androgen production in women with PCO.

Effectiveness of serum megakaryocyte potentiating factor in evaluating the effects of chrysotile and its heated products on respiratory organs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Takata, Ayako; Yamauchi, Hiroshi, E-mail: hyama@kitasato-u.ac.jp; Toya, Tadao

Chrysotile (CH), the most common form of asbestos, is rendered less toxic by heating it at 1000 {sup o}C and converting it to forsterite (FO-1000). However, further safety tests are needed to evaluate human health risk of these materials. It has been reported that serum concentrations of megakaryocyte potentiating factor N-ERC/mesothelin become elevated in patients with mesotheliomas caused by asbestos exposure. In this study, a single 2 mg dose of CH or FO-1000 was intratracheally administered to rats. Within 180 days after the administrations, serum N-ERC/mesothelin concentrations, levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in lung tissues and pathological changes in respiratory organsmore » were determined. In the CH group, a significant increase in serum N-ERC/mesothelin concentrations was observed immediately after intratracheal administration, and the elevation lasted for 30 days. In lung tissues, positive staining for 8-OHdG in bronchioles, alveolar epithelium, inflammatory cells, and granulomas was evidence of a marked DNA oxidative damage. Furthermore, measurements of 8-OHdG in lung tissues based on the HPLC-ECD method suggested that serum N-ERC/mesothelin concentrations tended to increase when there are significant DNA damages in lung tissues. In contrast, in the FO-1000 group, a marked rise in serum N-ERC/mesothelin concentrations occurred only in the early phase (1-7 days) after intratracheal administration. Similarly, FO-1000 induced elevation of 8-OHdG in lung tissues was transient and modest compared with those of the CH-treated animals. In both the CH and FO-1000 groups, we observed significant correlations between serum N-ERC/mesothelin concentrations and lung 8-OHdG concentrations (r = 0.559, p = 0.001 for the CH group; r = 0.516, p = 0.01 for the FO-1000 group). In summary, we demonstrated the possibility of using serum N-ERC/mesothelin concentrations as a useful biomarker for early phase exposure to either CH or FO-1000.« less

Increased serum chemerin concentrations in patients with polycystic ovary syndrome: Relationship between insulin resistance and ovarian volume.

PubMed

Huang, Rong; Yue, Jiang; Sun, Yun; Zheng, Jun; Tao, Tao; Li, Shengxian; Liu, Wei

2015-10-23

Chemerin has been linked to adiposity, and insulin resistance (IR) which are the common characteristics of polycystic ovary syndrome (PCOS). Chemerin also shows inhibitory action on follicular steroidogenesis. We investigated the associations between chemerin and IR or polycystic ovary morphology in patients with PCOS. A total of 148 women with newly diagnosed PCOS using Rotterdam criteria and 88 healthy individuals were enrolled. The recruited patients with PCOS were further stratified by tertiles of serum chemerin concentrations as follows: Group 1 (< 24.79 ng/ml), Group 2 (24.79-30.27 ng/ml), and Group 3 (> 30.27 ng/ml). Compared to controls, women with PCOS in each tertile had higher serum chemerin concentrations. By linear regression analysis, homeostasis model assessment-insulin resistance and ovarian volume showed significant associations with chemerin after adjusting for confounding factors (β = 0.257, P = 0.028; β = 0.276, P = 0.005, respectively). The odds ratios (ORs) for ovarian volume excess gradually increased across increasing tertiles of chemerin in the adjusted model [Group 1: reference; Group 2: OR 1.602; 95% confidence interval (CI): 1.170–2.194; Group 3: OR 1.857; 95% CI: 1.335-2.583]. Patients with PCOS showed increased serum chemerin concentrations as compared to healthy women. Individuals with higher chemerin tended to have higher risk for ovarian volume excess in patients with PCOS, regardless of adiposity.

Increased Serum Interleukin-10 but not Interleukin-4 Level in Children with Mycoplasma pneumoniae Pneumonia.

PubMed

Medjo, Biljana; Atanaskovic-Markovic, Marina; Nikolic, Dimitrije; Radic, Snezana; Lazarevic, Ivana; Cirkovic, Ivana; Djukic, Slobodanka

2017-08-01

Mycoplasma pneumoniae (MP) is a common cause of community-acquired pneumonia in children, and it has been associated with wheezing. The aim of this study was to examine the serum level of interleukin (IL)-4 and IL-10 in children with Mycoplasma pneumoniae pneumonia (MPP) and to analyse them in relation to the presence of wheezing. The study included 166 children with radiologically confirmed pneumonia. MP infection was confirmed by enzyme-linked immunosorbent assay (ELISA) serum MP-IgM and MP-IgG test and throat swab MP DNA with real-time polymerase chain reaction. Serum levels of IL-4 and IL-10 were measured using ELISA. There was no significant difference in serum level of IL-4 between children with MPP and those with non-MPP. Among children with MPP, we found similar level of IL-4 regardless of the personal and family history of allergy and asthma or the presence of wheezing. A significantly higher level of IL-10 was found in children with MPP than in children with non-MPP (32.92±18.582 vs. 27.01±14.100 pg/ml, p =0.022). Furthermore, wheezing children with MPP had a significantly higher level of IL-10 than children with MPP without wheezing (43.75±26.644 vs. 27.50±10.211 pg/ml, p=0.027). Our results show significantly increased serum level of IL-10 in children with MPP, which was significantly higher in children with wheezing. These findings may suggest a role of IL-10 in the pathogenesis of MPP and in the occurrence of wheezing during acute MP infection. © The Author [2017]. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Increased analgesia administration in emergency medicine after implementation of revised guidelines.

PubMed

Van Woerden, Geesje; Van Den Brand, Crispijn L; Den Hartog, Cornelis F; Idenburg, Floris J; Grootendorst, Diana C; Van Der Linden, M Christien

2016-12-01

The most common complaint of patients attending the emergency department (ED) is pain, caused by different diseases. Yet the treatment of pain at the ED is suboptimal, and oligoanalgesia remains common. The objective of this study is to determine whether the administration of analgesia at the ED increases by implementation of revised guidelines in pain management. We conducted a prospective pre-post intervention cohort study with implementation of a revised guideline for pain management at our ED, in which nurses are allowed to administer analgesia (including low-dosage piritramid (opioid) intravenous) without doctor intervention. Numeric Rating Scales (NRS) were measured, and administration of medication (main outcome) was documented. We included every adult patient presenting with pain (NRS 4-10) at the ED. A total of 2107 patients (1089 pre-implementation phase and 1018 post-implementation phase) were included in our study. During pre-implementation, 25.4 % of the patients with NRS between 4 and 10 received analgesia. After implementation, 32.0 % of these patients received analgesia (p < 0.001). After implementation of the revised guidelines in pain management at the ED, the administration of pain medication increased significantly. Nevertheless, the percentage of patients in pain receiving analgesia remain low (32 % after implementation).

Additional consumption of one egg per day increases serum lutein plus zeaxanthin concentration and lowers oxidized low-density lipoprotein in moderately hypercholesterolemic males.

PubMed

Kishimoto, Yoshimi; Taguchi, Chie; Saita, Emi; Suzuki-Sugihara, Norie; Nishiyama, Hiroshi; Wang, Wei; Masuda, Yasunobu; Kondo, Kazuo

2017-09-01

The egg is a nutrient-dense food and contains antioxidative carotenoids, lutein and zeaxanthin, but its impact on serum cholesterol levels has been a matter of concern, especially for individuals who have high serum cholesterol levels. We conducted this study to determine whether and how the daily additional consumption of one egg affects serum lipid profiles and parameters of LDL oxidation in moderately hypercholesterolemic males. Nineteen male Japanese adults (total cholesterol [TC]>5.2mmol/L) participated, consuming one soft boiled egg per day for 4weeks in addition to their habitual diet. Despite the significant increase in their intake of dietary cholesterol during the intervention period, the subjects' serum concentrations of TC and low-density lipoprotein cholesterol (LDL-C) did not increase. Their serum malondialdehyde modified low-density lipoprotein (MDA-LDL) concentrations were significantly decreased and their LDL oxidation lag times, reflecting the resistance of free-radical-induced LDL lipid peroxidation (ex vivo), was prolonged after 2 and 4weeks. At weeks 2 and 4, the subjects' serum lutein+zeaxanthin concentrations were significantly higher than their baseline values and showed both an inverse relation with MDA-LDL and a positive relationship with the LDL oxidation lag time. These data showed that in moderately hypercholesterolemic males, the additional consumption of one egg per day for 4weeks did not have adverse effects on serum TC or LDL-C, and it might reduce the susceptibility of LDL to oxidation through an increase in the serum lutein and zeaxanthin concentrations. Copyright © 2017 Elsevier Ltd. All rights reserved.

Age and body composition influence TSH concentrations after administration of rhTSH.

PubMed

Holthausen, F F; von Müller, F; Happel, C; Kranert, W T; Grünwald, F

2015-01-01

Previous studies listed body surface area (BSA), lean body mass (LBM), and age as modifying factors on the TSH concentrations after administration of recombinant human thyrotropin (rhTSH). The purpose of this study was to identify the main modifying factors on serum TSH levels and to compare the stimulation via single rhTSH injection after a short thyroid hormone withdrawal (THW) with that of the standard stimulating protocol. 106 patients with differentiated thyroid cancer (DTC) undergoing radioiodine therapy (RIT) after rhTSH administration were obtained through chart review. Two groups were evaluated: Group I was treated with a single rhTSH administration after two weeks of T3 therapy followed by one week of THW. Group II was stimulated according to the international standard protocol via rhTSH injections for two consecutive days. Serum TSH concentrations were documented prior to rhTSH administration (day 1 TSH), one day after (day 3 TSH) and 3-6 days after (mean 4.2 days, day 6 TSH) the last rhTSH injection. The following data was collected: age, gender, weight, height, BMI, LBM, BSA, residual thyroid tissue, CRP, creatinine, GFR, liver enzymes, alkaline phosphatase, cholesterol, and triglycerides. Group I: Age combined with anthropometric factors like BMI (TSH increase and day 6 TSH), BSA (TSH decrease), and gender (day 6 TSH) are the main modifying factors on serum TSH concentrations after rhTSH administration. Group II: Age and lean body mass (LBM) showed a significant impact on day 3 TSH, TSH increase (day 3-day 1), and TSH decrease (day 6-day 3). Day 6 TSH was found to be influenced by GFR (group II). Age and anthropometric parameters have significant independent influence on TSH concentrations after rhTSH injection in both groups. Anthropometric parameters (BSA, LBM) and demographic parameters (female gender) show strong influence on TSH concentrations. Further research should be conducted to examine the influence of body compartments on TSH levels

A lack of association between hyperserotonemia and the increased frequency of serum anti-myelin basic protein auto-antibodies in autistic children

PubMed Central

2011-01-01

Background One of the most consistent biological findings in autism is the elevated blood serotonin levels. Immune abnormalities, including autoimmunity with production of brain specific auto-antibodies, are also commonly observed in this disorder. Hyperserotonemia may be one of the contributing factors to autoimmunity in some patients with autism through the reduction of T-helper (Th) 1-type cytokines. We are the first to investigate the possible role of hyperserotonemia in the induction of autoimmunity, as indicated by serum anti-myelin-basic protein (anti-MBP) auto-antibodies, in autism. Methods Serum levels of serotonin and anti-MBP auto-antibodies were measured, by ELISA, in 50 autistic patients, aged between 5 and 12 years, and 30 healthy-matched children. Results Autistic children had significantly higher serum levels of serotonin and anti-MBP auto-antibodies than healthy children (P < 0.001 and P < 0.001, respectively). Increased serum levels of serotonin and anti-MBP auto-antibodies were found in 92% and 80%, respectively of autistic patients. Patients with severe autism had significantly higher serum serotonin levels than children with mild to moderate autism (P < 0.001). Serum serotonin levels had no significant correlations with serum levels of anti-MBP auto-antibodies in autistic patients (P = 0.39). Conclusions Hyperserotonemia may not be one of the contributing factors to the increased frequency of serum anti-MBP auto-antibodies in some autistic children. These data should be treated with caution until further investigations are performed. However, inclusion of serum serotonin levels as a correlate may be useful in other future immune studies in autism to help unravel the long-standing mystery of hyperserotonemia and its possible role in the pathophysiology of this disorder. PMID:21696608

Choline or CDP-choline alters serum lipid responses to endotoxin in dogs and rats: involvement of the peripheral nicotinic acetylcholine receptors.

PubMed

Ilcol, Yesim Ozarda; Yilmaz, Zeki; Cansev, Mehmet; Ulus, Ismail H

2009-09-01

We showed previously that choline administration protects dogs from endotoxin-induced multiple organ injury and platelet dysfunctions. Because sepsis/endotoxemia is associated with alterations in lipid metabolism, we have investigated whether choline or cytidine-5'-diphosphate choline, a choline donor, alters serum lipid responses to endotoxin in dogs and rats. In response to endotoxin, serum concentrations of triglycerides, choline-containing phospholipids, total cholesterol, and high-density lipoprotein cholesterol increased in a dose- and time-related manner. Administration of choline (20 mg/kg i.v. in dogs or 90 mg/kg i.p. in rats) or cytidine-5'-diphosphate choline (70 mg/kg i.v. in dogs) 5 min before and 4 and 8 h after endotoxin blocked or attenuated the increases in serum triglycerides, total cholesterol, and nonesterified fatty acids. Endotoxin-induced elevations in serum phospholipid levels did not change in rats and were enhanced in dogs by choline. In rats, serum lipid response to endotoxin was accompanied by severalfold elevations in serum levels of hepatorenal injury markers; their elevations were also blocked by choline. Pretreatment with hexamethonium blocked choline's effects on serum lipids and hepatorenal injury markers. Pretreatment with atropine blocked endotoxin-induced elevations in serum lipid and hepatorenal injury markers, but failed to alter choline's actions on these parameters. Choline treatment improved survival rate of rats in lethal endotoxin shock. In conclusion, these data show that choline treatment alters serum lipid responses to endotoxin and prevents hepatorenal injury during endotoxemia through a nicotinic acetylcholine receptor-mediated mechanism. Hence, choline and choline-containing compounds may have a therapeutic potential in the treatment of endotoxemia/sepsis.

Effect of increasing maximal aerobic exercise on serum muscles enzymes in professional field hockey players.

PubMed

Hazar, Muhsin; Otag, Aynur; Otag, Ilhan; Sezen, Mehmet; Sever, Ozan

2014-11-04

Exercise results in oxidative enzyme increase and micro-injuries in skeletal muscles. The aim of this study was to investigate the effect of maximal aerobic exercise on serum muscle enzymes in professional field hockey players. This study aims to determine the effect of increasing maximal aerobic exercise on creatine kinase (CK), creatine kinase-MB (CK-MB), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) serum levels. 31 young professional field hockey players (13 female and 18 male players) volunteered for this study. All participants underwent the shuttle run test. Blood samples were taken from each participant before the shuttle run test. Post test blood samples were taken immediately after exercise and one hour after respectively. Pre and post test CK, CK-MB, AST and ALT values were measured by means of auto analyzer using original kits. The acute post test measure of the CK level increased in male (p=0.002) and female (p=0.00) sportsmen. CK-MB values obtained one hour after the exercise was lower than those before the exercise in males (p=0.02). In females (p=0.017) and males (p=0.05) AST activity significantly increased immediately after exercise and decreased to resting activity 1 h recovery. ALT significantly increased immediately after exercise in female (p=0.03) and male (p=0.00) athletes and after 1 h recovery ALT activities decreased below resting values. The timing and severity of exercise used in our study increased CK values, decreased CK-MB values and AST, ALT values increased in female and male field hockey players.

Effects of prenatal lipopolysaccharide exposure on reproductive activities and serum concentrations of pituitary-gonadal hormones in mice offspring.

PubMed

Solati, Jalal; Hajikhani, Ramin; Rashidieh, Behnam; Jalilian, Mahshid Fatipour

2012-04-01

Maternal infection during pregnancy is a risk factor for some behavioral problems with neurodevelopmental origin. This study aimed to evaluate the effects of exposure of pregnant mice to the bacterial lipopolysaccharide (LPS) on sexual behaviour and serum level of pituitary-gonadal hormones of offspring in adulthood. In this Expremental study, pregnant NMRI mice (n=7/group) were treated with intra-peritoneal administration of LPS (1, 5 and 10 µg/kg) at day 10 of gestation. Induction of the pro-inflammatory cytokines, Tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β) and interleukin-6 (IL-6) were measured in maternal serum 2 hours following the maternal LPS challenge. Behavior in the adult male offspring reproductive activity was investigated using receptive female mice. Concentrations of testosterone, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in adult offspring serum were measured using the enzyme-linked immunosorbent assay (ELISA) method (at postnatal day 60, n=10/group). One-way ANOVA showed that LPS administration induces a significant increase in TNF-α, IL-1β and IL-6 levels of maternal serum. Prenatal LPS exposure reduces sexual behavior and serum concentration of LH and testosterone in adult male offspring. The overall results suggest that prenatal exposure to LPS increases pro- inflammatory cytokine levels, affects development of neuroendocrine systems and results in the inhibition of reproductive behaviors and reactivity of hypothalamic-pituitary-gonadal (HPG) axis in adult male offspring.

Isolation of human anti-serum albumin Fab antibodies with an extended serum-half life.

PubMed

Kang, Hyeon-Ju; Kim, Hye-Jin; Cha, Sang-Hoon

2016-01-01

The serum albumin (SA) has been exploited to generate long-acting biotherapeutics by taking advantage of the FcRn-mediated recycling mechanism in a direct or an indirect way. Since Fab fragments have been proven to be clinically safe for human usage, we assumed that human anti-SA Fab antibodies could have a great potential as a carrier molecule to extend the serum half-life of therapeutic proteins. We, herein, had attempted to isolate anti-SA Fab antibodies from HuDVFab-8L antibody library via a phage display technology, and identified eight discrete human Fab antibodies. One of the Fab antibodies, SL335, showed the strongest binding reactivity to human SA with nM range of affinity at both pH 6 and pH 7.4, and cross-reacted to SAs from various species including rat, mouse, canine and monkey. The in vivo pharmacokinetic assay using a rat model indicated that SL335 has approximately 10 fold longer serum half-life and 26 to 44-fold increase in AUC0 → ∞ compared to the negative control Fab molecule in both intravenous and subcutaneous administrations. Knowing that Fabs have proven to be safe in clinics for a long time, SL335 seems to have a great potential in generating long-acting protein drugs by tagging effector molecules with either chemical conjugation or genetic fusion. Copyright © 2015 Elsevier B.V. All rights reserved.

Serum glycerophosphate levels are increased in Japanese men with type 2 diabetes.

PubMed

Daimon, Makoto; Soga, Tomoyoshi; Hozawa, Atsushi; Oizumi, Toshihide; Kaino, Wataru; Takase, Kaoru; Karasawa, Shigeru; Jimbu, Yumi; Wada, Kiriko; Kameda, Wataru; Susa, Shinji; Kayama, Takamasa; Saito, Kaori; Tomita, Masaru; Kato, Takeo

2012-01-01

To identify metabolites showing changes in serum levels among Japanese male with diabetes. We performed metabolite profiling by coupling capillary electrophoresis with electrospray ionization time-of-flight mass spectrometry using fasting serum samples from Japanese male subjects with diabetes (n=17), impaired glucose tolerance (IGT; n=5) and normal glucose tolerance (NGT; n=14). Other than the expected differences in characteristics related to abnormal glucose metabolism, the percent body fat was significantly different among subjects with diabetes, IGT and NGT (27.3±6.2, 22.2±4.5 and 19.2±6.0%, respectively, p=0.0022). Therefore, percent body fat was considered as a possible confounding factor in subsequent analyses. Of 560 metabolites detected using our platform, the levels of 74 metabolites were quantified in all of the serum samples. Significant differences between diabetes and NGT were observed for 24 metabolites. The top-ranked metabolite was glycerol-3-phophate (glycerophosphate), which was significantly higher in subjects with diabetes than in those with NGT, even after Bonferroni correction for multiple testing (11.7±3.6 vs. 6.4±1.9 µM, respectively; corrected p=0.0222). Stepwise multiple regression analyses revealed that serum glycerophosphate levels were significantly correlated with 2-h plasma glucose after a 75-g oral glucose tolerance test (r=0.553, p=0.0005), independently of other characteristics, including FPG and HbA1c. Serum glycerophosphate levels were found to be elevated in Japanese men with diabetes, and correlated with 2-h PG, independent of FPG and HbA1c. Namely, serum glycerophosphate level at fasting condition can be a marker for predicting glucose intolerance. These results warrant further studies to evaluate the relevance of glycerophosphate in the pathophysiology of diabetes.

Feeding hydroalcoholic extract powder of Lepidium meyenii (maca) increases serum testosterone concentration and enhances steroidogenic ability of Leydig cells in male rats.

PubMed

Ohta, Y; Yoshida, K; Kamiya, S; Kawate, N; Takahashi, M; Inaba, T; Hatoya, S; Morii, H; Takahashi, K; Ito, M; Ogawa, H; Tamada, H

2016-04-01

Although Lepidium meyenii (maca), a plant growing in Peru's central Andes, has been traditionally used for enhancing fertility and reproductive performance in domestic animals and human beings, effects of maca on reproductive organs are still unclear. This study examined whether feeding the hydroalcoholic extract powder of maca for 6 weeks affects weight of the reproductive organs, serum concentrations of testosterone and luteinising hormone (LH), number and cytoplasmic area of immunohistochemically stained Leydig cells, and steroidogenesis of cultured Leydig cells in 8-week-old male rats. Feeding the extract powder increased weight of seminal vesicles, serum testosterone level and cytoplasmic area of Leydig cells when compared with controls. Weight of prostate gland, serum LH concentration and number of Leydig cells were not affected by the maca treatment. The testosterone production by Leydig cells significantly increased when cultured with 22R-hydroxycholesterol or pregnenolone and tended to increase when cultured with hCG by feeding the extract powder. The results show that feeding the hydroalcoholic extract powder of maca for 6 weeks increases serum testosterone concentration associated with seminal vesicle stimulation in male rats, and this increase in testosterone level may be related to the enhanced ability of testosterone production by Leydig cells especially in the metabolic process following cholesterol. © 2015 Blackwell Verlag GmbH.

Serum nesfatin-1 levels in overt and subclinical hyperthyroidism.

PubMed

Gungunes, A; Ozbek, M; Ginis, Z; Sahin, M; Demirci, T; Cakir Ozkaya, E; Karbek, B; Sayki Arslan, M; Ozturk Unsal, I; Tutal Akkaya, E; Ucan, B; Gultuna Ozguclu, S; Cakal, E; Topaloglu, O; Delibasi, T

2014-09-01

Nesfatin-1 was recently discovered anorexigenic peptide in the brain which is derived from nucleobindin-2. Central and peripheral administration of nesfatin-1, inhibits food intake, dose-dependently. Hyperthyroid patients have increased appetite and food intake with a craving for carbohydrate-rich food, at the beginning of disease, but the physiological mechanisms underlying this behavior is not known exactly. In this study, we investigated whether nesfatin-1 is involved in the regulation of appetite and body weight in hyperthyroidism, or not. A total of 70 patients with subclinical (35) and overt hyperthyroidism (35) compared with 35 control patients. Serum nesfatin-1 level was measured from all samples by commercial ELISA kit. Serum nesfatin-1 levels were similar between three groups (P=0.293). After adjusting for age and body mass index, nesfatin-1 levels in control group was not different from subclinical and overt hyperthyroid group, respectively (P=0.567 and P=0.519). These data showed that serum nesfatin-1 levels do not significant change in overt and subclinical hyperthyroidism.

Extension Master Gardener Intranet: Automating Administration, Motivating Volunteers, Increasing Efficiency, and Facilitating Impact Reporting

ERIC Educational Resources Information Center

Bradley, Lucy K.; Cook, Jonneen; Cook, Chris

2011-01-01

North Carolina State University has incorporated many aspects of volunteer program administration and reporting into an on-line solution that integrates impact reporting into daily program management. The Extension Master Gardener Intranet automates many of the administrative tasks associated with volunteer management, increasing efficiency, and…

Oral Administration of Cilostazol Increases Ocular Blood Flow in Patients with Diabetic Retinopathy.

PubMed

Hwang, Duck Jin; Shin, Joo Young; Yu, Hyeong Gon

2017-04-01

To investigate the effect of cilostazol on ocular hemodynamics and to determine whether the administration of cilostazol increases the ocular blood flow in patients with diabetic retinopathy. This prospective observational study investigated the effect of orally administered cilostazol on diabetic retinopathy. Before and after administration for 1 week, pulsatile ocular blood flow (POBF) and retrobulbar hemodynamics were measured using a POBF analyzer and transcranial Doppler imaging, respectively. Visual acuity, intraocular pressure, and blood pressure were also evaluated before and after treatment. Twenty-five eyes of 25 patients were included in this study. POBF increased significantly (16.8 ± 4.6 µL/sec vs. 19.6 ± 6.2 µL/sec, p < 0.001) after administration of cilostazol, while no significant change was identified in visual acuity, intraocular pressure, and blood pressure. Mean flow velocity in the ophthalmic artery as measured with transcranial Doppler imaging also increased significantly after medication (23.5 ± 5.6 cm/sec vs. 26.0 ± 6.9 cm/sec, p = 0.001). The change in POBF directly correlated with the change in mean flow velocity (r = 0.419, p = 0.007). Cilostazol was effective in increasing ocular blood flow in patients with diabetic retinopathy, possibly by modulating retrobulbar circulation.

Increased serum concentrations of Nɛ-carboxymethyllysine are related to the presence and the severity of rheumatoid arthritis.

PubMed

Knani, Ines; Bouzidi, Hassan; Zrour, Saoussen; Bergaoui, Naceur; Hammami, Mohamed; Kerkeni, Mohsen

2018-07-01

Background There are limited data regarding the contribution of advanced glycation end products in the presence of rheumatoid arthritis. We investigated whether serum N ɛ -carboxymethyllysine and pentosidine were related to the presence and the severity of rheumatoid arthritis. Methods Eighty patients with rheumatoid arthritis and 30 control subjects were included in a cross-sectional study. The severity of rheumatoid arthritis was assessed using the disease activity score for 28 joints. Serum N ɛ -carboxymethyllysine and pentosidine were measured by enzyme-linked immunosorbent assay. Results Serum N ɛ -carboxymethyllysine and pentosidine concentrations were significantly higher in patients with rheumatoid arthritis vs. control subjects ( P < 0.001). Serum N ɛ -carboxymethyllysine and pentosidine concentrations were significantly higher in rheumatoid arthritis patients with high disease activity vs. rheumatoid arthritis patients with moderate disease activity ( P < 0.001, P = 0.019, respectively). A multiple logistic regression analysis demonstrated that N ɛ -carboxymethyllysine was independently associated with the presence of rheumatoid arthritis (OR = 1.21, 95% CI: 1.05-1.39, P = 0.006). Furthermore, in a multivariate stepwise regression analysis, N ɛ -carboxymethyllysine was independently correlated with disease activity score for 28 joints (standardized β = 0.43, P = 0.001). Conclusion Serum N ɛ -carboxymethyllysine and pentosidine were increased during rheumatoid arthritis, and N ɛ -carboxymethyllysine was independently associated with the presence and the severity of rheumatoid arthritis.

Effect of different periods of chronic heat stress with or without vitamin C supplementation on bone and selected serum parameters of broiler chickens.

PubMed

Mosleh, Najmeh; Shomali, Tahoora; Nematollahi, Fahimeh; Ghahramani, Zahra; Ahrari Khafi, Mohammad Saeid; Namazi, Fatemeh

2018-04-01

This study evaluates the effect of different periods of chronic heat stress (CHS) on selected bone and serum parameters of broiler chickens with or without vitamin C administration. Ninety 23-day-old chickens were randomly allocated into seven groups: (1) control, (2) short-term CHS (5 days), (3) short-term CHS + vitamin C (12 g/100 l drinking water of a 50% product), (4) medium-term CHS (10 days), (5) medium-term CHS + vitamin C, (6) long-term CHS (20 days) and (7) long-term CHS + vitamin C. In heat-stressed groups the temperature was increased to 39 ± 1°C for 8 h/day. At the end of the experiment, blood samples were collected and shank, keel and tibia bones were removed. CHS was not associated with a drastic change in serum Ca and corticosterone, or bone characteristics (both cortical and trabecular bones in radiographical and histological evaluation), or birds' performance. Oxidative stress was present especially with short-term CHS. CHS, especially for short or medium periods, showed a tendency to increase serum vitamin C and administration of this vitamin did not make a significant change in its serum levels although it ameliorated oxidative stress. In conclusion, it seems that CHS is not associated with an appreciable change in broiler performance, bone characteristics, or selected serum parameters; and simultaneous vitamin C administration at the dosage of 12 g/100 l in drinking water has no beneficial effect apart from reducing oxidative stress especially in short-term chronically heat-stressed birds.

Supplementation with mixed tocopherols increases serum and blood cell gamma-tocopherol but does not alter biomarkers of platelet activation in subjects with type 2 diabetes.

PubMed

Clarke, Michael W; Ward, Natalie C; Wu, Jason H Y; Hodgson, Jonathan M; Puddey, Ian B; Croft, Kevin D

2006-01-01

Some studies have shown potential benefit of vitamin E on platelet function, but several clinical trials failed to show improved cardiovascular outcome with alpha-tocopherol supplementation. Gamma-tocopherol, a major dietary form of vitamin E, may have protective properties different from those of alpha-tocopherol. We compared the effects of supplementation with alpha-tocopherol (500 mg) and a gamma-tocopherol-rich compound (500 mg, containing 60% gamma-tocopherol) on serum and cellular tocopherol concentrations, urinary tocopherol metabolite excretion, and in vivo platelet activation in subjects with type 2 diabetes. Fifty-eight subjects were randomly assigned to receive either 500 mg alpha-tocopherol/d, 500 mg mixed tocopherols/d, or matching placebo. Serum, erythrocyte, and platelet tocopherol and urinary metabolite concentrations were measured at baseline and after the 6-wk intervention. Soluble CD40 ligand, urinary 11-dehydro-thromboxane B2, serum thromboxane B2, soluble P-selectin, and von Willebrand factor were measured as biomarkers of in vivo platelet activation. Serum alpha-tocopherol increased with both tocopherol treatments. Serum and cellular gamma-tocopherol increased 4-fold (P < 0.001) in the mixed tocopherol group, whereas red blood cell gamma-tocopherol decreased significantly after alpha-tocopherol supplementation. Excretion of alpha-carboxyethyl-hydroxychroman increased significantly after supplementation with alpha-tocopherol and mixed tocopherols. Excretion of gamma-carboxyethyl-hydroxychroman increased significantly after supplementation with mixed tocopherols and after that with alpha-tocopherol, which may reflect the displacement of gamma-tocopherol by alpha-tocopherol due to incorporation of the latter into lipoproteins in the liver. Neither treatment had any significant effect on markers of platelet activation. Supplementation with alpha-tocopherol decreased red blood cell gamma-tocopherol, whereas mixed tocopherols increased both serum

Brain-derived neurotrophic factor is increased in serum and skin levels of patients with chronic spontaneous urticaria.

PubMed

Rössing, K; Novak, N; Mommert, S; Pfab, F; Gehring, M; Wedi, B; Kapp, A; Raap, U

2011-10-01

Chronic spontaneous urticaria is triggered by many direct and indirect aggravating factors including autoreactive/autoimmune mechanisms, infections, non-allergic and pseudoallergic intolerance reactions. However, the role of neuroimmune mechanisms in chronic spontaneous urticaria so far is unclear. Thus, we wanted to address the regulation of the neurotrophin brain-derived neurotrophic factor (BDNF) in serum and inflammatory skin of patients with chronic spontaneous urticaria in comparison to subjects with healthy skin. Fifty adult patients with chronic spontaneous urticaria and 23 skin-healthy subjects were studied. Chronic spontaneous urticaria was defined as recurrent weals for more than 6 weeks. Autologous serum skin test was performed in all patients with chronic spontaneous urticaria and BDNF serum levels were analysed by enzyme immunoassay in all subjects. Furthermore, skin biopsies were taken from weals of eight patients with chronic spontaneous urticaria as well as from healthy skin of eight controls to evaluate the expression of BDNF and its receptors including tyrosine kinase (trk) B and pan-neurotrophin receptor p75(NTR) by immunohistochemistry. BDNF serum levels were detectable in all subjects studied. However, BDNF levels were significantly higher in patients with chronic spontaneous urticaria compared to non-atopic skin-healthy controls (P<0.001). Furthermore, epidermal and dermal expression of BDNF and epidermal expression of p75(NTR) was significantly higher in patients with chronic spontaneous urticaria compared with controls (P<0.05-0.001). There was no difference with regard to the expression of trkB between chronic spontaneous urticaria and controls and no difference in BDNF serum levels between autologous serum skin test-positive (n=23) and -negative (n=27) patients with chronic spontaneous urticaria. This study shows that BDNF is increased in serum and diseased skin of patients with chronic spontaneous urticaria, suggesting a role for

Neuropeptide Y administration into the third ventricle does not increase sucrose or ethanol self-administration but does affect the cortical EEG and increases food intake.

PubMed

Katner, S N; Slawecki, C J; Ehlers, C L

2002-03-01

Several studies have provided indirect evidence that neuropeptide Y (NPY) may play a role in the regulation of ethanol consumption. However, the direct effects of central NPY administration on ethanol drinking are unclear. This study examined the effects of NPY on ethanol, sucrose, and food consumption as well as its concomitant effects on the cortical EEG. Wistar rats were implanted with cortical recording electrodes and a cannula in the third ventricle after using a sucrose substitution procedure to establish ethanol self-administration. NPY (0-15 microg/3.0 microl) was infused into the third ventricle prior to drinking sessions, when 10% ethanol (10E), 2% sucrose (2S), 0.5% sucrose (0.5S), or food were available. Behavior and cortical EEG were monitored during the sessions. NPY had no effect on the intake of 10E, 2S, or 0.5S, but NPY (15 microg/3.0 microl) significantly increased food intake. Under baseline drinking conditions, EEG power in the 6-8 Hz range was significantly greater when 2S was consumed compared to 10E. NPY decreased power in the 8-16 Hz range, decreased peak frequency in the 6-8 Hz range, and increased peak frequency in the 32-50 Hz range when 10E or 2S was available. These data suggest that NPY administration into the third ventricle preferentially regulates feeding compared to ethanol or sucrose drinking. In addition, since NPY significantly altered the cortical EEG in the absence of effects on ethanol and sucrose consumption, these data may indicate that NPY's cortical EEG effects are more related to its sedative or anxiolytic properties, rather than any effect on consumption.

Protective effects of Mangifera indica L extract (Vimang), and its major component mangiferin, on iron-induced oxidative damage to rat serum and liver.

PubMed

Pardo-Andreu, Gilberto L; Barrios, Mariela Forrellat; Curti, Carlos; Hernández, Ivones; Merino, Nelson; Lemus, Yeny; Martínez, Ioanna; Riaño, Annia; Delgado, René

2008-01-01

In vivo preventive effects of a Mangifera indica L extract (Vimang) or its major component mangiferin on iron overload injury have been studied in rats given respectively, 50, 100, 250 mg kg(-1) body weight of Vimang, or 40 mg kg(-1) body weight of mangiferin, for 7 days prior to, and for 7 days following the administration of toxic amounts of iron-dextran. Both Vimang or mangiferin treatment prevented iron overload in serum as well as liver oxidative stress, decreased serum and liver lipid peroxidation, serum GPx activity, and increased serum and liver GSH, serum SOD and the animals overall antioxidant condition. Serum iron concentration was decreased although at higher doses, Vimang tended to increase it; percent tranferrin saturation, liver weight/body mass ratios, liver iron content was decreased. Treatment increased serum iron-binding capacity and decreased serum levels of aspartate-amine transferase (ASAT) and alanine-amine transferase (ALAT), as well as the number of abnormal Kupffer cells in iron-loaded livers. It is suggested that besides acting as antioxidants, Vimang extract or its mangiferin component decrease liver iron by increasing its excretion. Complementing earlier in vitro results from our group, it appears possible to support the hypothesis that Vimang and mangiferin present therapeutically useful effects in iron overload related diseases.

Variable Suppression of Serum Thyroxine in Female Mice of Different Inbred Strains by Triiodothyronine Administered in Drinking Water

PubMed Central

Hamidi, Sepehr; Aliesky, Holly; Chen, Chun-Rong; Rapoport, Basil

2010-01-01

Background Recombinant-inbred mouse strains differ in their susceptibility to Graves'-like hyperthyroidism induced by immunization with adenovirus expressing the human thyrotropin (TSH) receptor. Because one genetic component contributing to this susceptibility is altered thyroid sensitivity to TSH receptor agonist stimulation, we wished to quantify thyroid responsiveness to TSH. For such studies, it is necessary to suppress endogenous TSH by administering L-3,5,3′-triiodothyronine (L-T3), with the subsequent decrease in serum thyroxine (T4) reflecting endogenous TSH suppression. Our two objectives were to assess in different inbred strains of mice (i) the extent of serum T4 suppression after L-T3 administration and (ii) the magnitude of serum T4 increase induced by TSH. Methods Mice were tail-bled to establish baseline-serum T4 before L-T3 administration. We initially employed a protocol of L-T3-supplemented drinking water for 7 days. In subsequent experiments, we injected L-T3 intraperitoneally (i.p.) daily for 3 days. Mice were then injected i.p. with bovine TSH (10 mU) and euthanized 5 hours later. Serum T4 was assayed before L-T3 administration, and before and after TSH injection. In some experiments, serum T3 and estradiol were measured in pooled sera. Results Oral L-T3 (3 or 5 μg/mL) suppressed serum T4 levels by 26%–64% in female BALB/c mice but >95% in males. T4 suppression in female B6 mice ranged from 0% to 90%. In C3H mice, L-T3 at 3 μg/mL was ineffective but 5 μg/mL achieved >80% serum T4 reduction. Unlike inbred mice, in outbred CF1 mice the same protocol was more effective: 83% in females and 100% suppression in males. The degree of T4 suppression was unrelated to baseline T4, T3, or estradiol, but was related to mouse weight and postmortem T3, with greater suppression in larger mice (outbred CF1 animals and inbred males). Among females with serum T4 suppression >80%, the increase in serum T4 after TSH injection was greater for BALB

Increased serum advanced glycation end-products is a distinct finding in lean women with polycystic ovary syndrome (PCOS).

PubMed

Diamanti-Kandarakis, Evanthia; Katsikis, Ilias; Piperi, Christina; Kandaraki, Eleni; Piouka, Athanasia; Papavassiliou, Athanasios G; Panidis, Dimitrios

2008-10-01

Nonenzymatic advanced glycation and oxidation end-products, advanced glycation end-products (AGEs), impart a potent impact on vessels and other tissues in diabetic state and in euglycaemic conditions with increased oxidative stress. Insulin resistant (IR) polycystic ovary syndrome (PCOS) women, have elevated serum AGEs, increased receptor (RAGE) expression, and increased deposition with differential localization in the polycystic ovarian tissue (theca and granulosa) compared to normal. To determine whether the raised AGE levels in noninsulin resistant women with PCOS is a distinct finding compared with those presenting the isolated components of the syndrome and among PCOS subphenotypes. Noninsulin resistant women were selected in order to show that serum AGEs are elevated in PCOS independently of the presence of IR. Clinical trial. One hundred and ninety-three age- and BMI-matched young lean noninsulin resistant women were studied. Among them, 100 women were diagnosed with PCOS according to Rotterdam criteria, and divided to subphenotypes (hyperandrogenaemia with or without PCO morphology and with or without anovulation). Sixty-eight women with the isolated components of the PCOS phenotype were also studied along with 25 healthy women. Serum AGE levels, metabolic, hormonal profiles and intravaginal ultrasound were determined in all subjects. The studied population did not differ in BMI, fasting insulin concentration, waist : hip and glucose : insulin ratios. PCOS women exhibited statistically higher AGEs levels (7.96 +/- 1.87 U/ml, P < 0.001) compared with those with isolated hyperandrogenaemia (5.61 +/- 0.61 U/ml), anovulation (5.53 +/- 1.06 U/ml), US-PCO morphology (5.26 +/- 0.25 U/ml) and controls (5.86 +/- 0.89 U/ml). In PCOS, serum AGEs are distinctly elevated compared with women having the isolated characteristics of the syndrome. No difference was observed between PCOS subphenotypes. As chronic inflammation and increased oxidant stress have been

Oral chronic ethanol administration to rodents by agar gel diet.

PubMed

Bykov, I; Palmén, M; Piirainen, L; Lindros, K O

2004-01-01

Chronic ethanol administration to rodents requires specially designed equipment and is labor intensive. Here we report a new procedure. A commercial liquid diet preparation was made into a gel by addition of 0.5% agar. The gel, containing 5.3% ethanol, was offered in Falcon tubes equipped with a feeding opening. The gel consumption by C57/Bl mice resulted in high blood ethanol levels (average 43 mM). After 6 weeks, marked liver steatosis and significantly increased serum alanine aminotransferase levels had developed. Administration of ethanol in a nutritionally adequate gel provides a simple method for studies on chronic ethanol effects in rodents.

Low serum 25-hydroxyvitamin D is associated with increased risk of stress fracture during Royal Marine recruit training.

PubMed

Davey, T; Lanham-New, S A; Shaw, A M; Hale, B; Cobley, R; Berry, J L; Roch, M; Allsopp, A J; Fallowfield, J L

2016-01-01

The aim of this study was to investigate vitamin D status and stress fracture risk during Royal Marine military training. Poor vitamin D status was associated with an increased risk of stress fracture. Vitamin D supplementation may help to reduce stress fracture risk in male military recruits with low vitamin D status. Stress fracture is a common overuse injury in military recruits, including Royal Marine (RM) training in the UK. RM training is recognised as one of the most arduous basic training programmes in the world. Associations have been reported between serum 25-hydroxyvitamin D (25(OH)D) and risk of stress fracture, but the threshold of 25(OH)D for this effect remains unclear. We aimed to determine if serum 25(OH)D concentrations were associated with stress fracture risk during RM training. We prospectively followed 1082 RM recruits (males aged 16-32 years) through the 32-week RM training programme. Troops started training between September and July. Height, body weight and aerobic fitness were assessed at week 1. Venous blood samples were drawn at weeks 1, 15 and 32. Serum samples were analysed for 25(OH)D and parathyroid hormone (PTH). Seventy-eight recruits (7.2 %) suffered a total of 92 stress fractures. Recruits with a baseline serum 25(OH)D concentration below 50 nmol L(-1) had a higher incidence of stress fracture than recruits with 25(OH)D concentration above this threshold (χ(2) (1) = 3.564, p = 0.042; odds ratio 1.6 (95 % confidence interval (CI) 1.0-2.6)). Baseline serum 25(OH)D varied from 47.0 ± 23.7 nmol L(-1) in February, to 97.3 ± 24.6 nmol L(-1) in July (overall mean 69.2 ± 29.2 nmol L(-1), n = 1016). There were weak inverse correlations between serum 25(OH)D and PTH concentrations at week 15 (r = -0.209, p < 0.001) and week 32 (r = -0.214, p < 0.001), but not at baseline. Baseline serum 25(OH)D concentration below 50 nmol L(-1) was associated with an increased risk of stress fracture. Further

Dose-response effects of oral guanidinoacetic acid on serum creatine, homocysteine and B vitamins levels.

PubMed

Ostojic, Sergej M; Stojanovic, Marko; Drid, Patrik; Hoffman, Jay R

2014-12-01

Guanidinoacetic acid (GAA) is an intermediate in the biosynthesis of creatine (Cr), yet its use in human nutrition is limited due to a lack of a clear understanding of its' dose-response effect. Thus, the purpose of this study was to investigate the effect of three different dosages of GAA (1.2, 2.4 and 4.8 g/day) administered for 6 weeks on serum and urinary variables related to GAA metabolism. Forty-eight healthy volunteers participated in the randomized, placebo-controlled, double-blind, repeated-measure study. At baseline, after 1, 2, 4 and 6 weeks, participants provided both fasting blood samples and 24-h urine. GAA intervention significantly increased serum and urinary GAA, Cr and creatinine as compared to placebo (P < 0.05). Differences were found for serum GAA and Cr responses between the three GAA dosages, with high-dose GAA resulting in a greater increase (P < 0.05) in the plasma concentration of both variables as compared to other GAA dosages. In GAA groups, fasting plasma total homocysteine (T-Hcy) increased by 3.5 μmol/L on average at post-administration, yet no dose-response differences were found between trials. Serum B vitamins were not affected by either placebo or GAA intervention (P > 0.05). Results indicate that low-to-high dosages of exogenous GAA can increase serum concentrations of Cr and T-Hcy while not depleting the B vitamins pool available for remethylation of homocysteine. ClinicalTrials.gov, identification number NCT01133899.

Repeated Administration of Cigarette Smoke Condensate Increases Glutamate Levels and Behavioral Sensitization

PubMed Central

Ryu, In Soo; Kim, Jieun; Seo, Su Yeon; Yang, Ju Hwan; Oh, Jeong Hwan; Lee, Dong Kun; Cho, Hyun-Wook; Lee, Kyuhong; Yoon, Seong Shoon; Seo, Joung-Wook; Shim, Insop; Choe, Eun Sang

2018-01-01

Nicotine, a nicotinic acetylcholine receptor agonist, produces the reinforcing effects of tobacco dependence by potentiating dopaminergic and glutamatergic neurotransmission. Non-nicotine alkaloids in tobacco also contribute to dependence by activating the cholinergic system. However, glutamatergic neurotransmission in the dorsal striatum associated with behavioral changes in response to cigarette smoking has not been investigated. In this study, the authors investigated alterations in glutamate levels in the rat dorsal striatum related to behavioral alterations after repeated administration of cigarette smoke condensate (CSC) using the real-time glutamate biosensing and an open-field behavioral assessment. Repeated administration of CSC including 0.4 mg nicotine (1.0 mL/kg/day, subcutaneous) for 14 days significantly increased extracellular glutamate concentrations more than repeated nicotine administration. In parallel with the hyperactivation of glutamate levels, repeated administration of CSC-evoked prolonged hypersensitization of psychomotor activity, including locomotor and rearing activities. These findings suggest that the CSC-induced psychomotor activities are closely associated with the elevation of glutamate concentrations in the rat dorsal striatum. PMID:29615877

Very high serum ferritin levels are associated with increased mortality and critical care in pediatric patients.

PubMed

Bennett, Tellen D; Hayward, Kristen N; Farris, Reid W D; Ringold, Sarah; Wallace, Carol A; Brogan, Thomas V

2011-11-01

To determine whether an elevated serum ferritin level is independently associated with mortality and receipt of critical care in pediatric patients. Retrospective cohort study, open population. Seattle Children's Hospital, Seattle, WA, from September 2, 2003, to February 15, 2008. All patients tested for serum ferritin level from September 2, 2003, to August 16, 2007, with a level ≥1000 ng/mL. None. MAIN ANALYSIS: Cox regression. The predictor of interest was the patient-specific peak serum ferritin level, dichotomized a priori at 3000 ng/mL. The outcomes were mortality and intensive care unit admission. A total of 171 patients met the inclusion criteria. The observation time without death or intensive care unit admission ranged from 184 to 1621 days. The hazard ratio of death with peak ferritin of >3000 ng/mL was 4.32 (95% confidence interval 2.21-8.47, p < .001) compared to peak ferritin of 1000-3000 ng/mL. The hazard ratio of intensive care unit admission with peak ferritin of >3000 ng/mL was 2.49 (95% confidence interval 1.53-4.05, p < .001) compared to peak ferritin of 1000-3000 ng/mL. Both estimates were adjusted for bone marrow transplant, solid organ transplant, hemoglobinopathy, and existing rheumatologic disease. In this pediatric population, with serum ferritin levels of >3000 ng/mL, there was increased risk for both receipt of critical care and subsequent death.

Serum adiponectin is increased in advancing liver fibrosis and declines with reduction in fibrosis in chronic hepatitis B.

PubMed

Hui, Chee-Kin; Zhang, Hai-Ying; Lee, Nikki P; Chan, Weng; Yueng, Yui-Hung; Leung, Kar-Wai; Lu, Lei; Leung, Nancy; Lo, Chung-Mau; Fan, Sheung-Tat; Luk, John M; Xu, Aimin; Lam, Karen S; Kwong, Yok-Lam; Lau, George K K

2007-08-01

Despite the possible role of adiponectin in the pathogenesis of liver cirrhosis, few data have been collected from patients in different stages of liver fibrosis. We studied the role of adiponectin in 2 chronic hepatitis B (CHB)-patient cohorts. Serum adiponectin was quantified by enzyme-linked immunosorbent assay. One-hundred liver biopsy specimens from CHB patients with different stages of fibrosis and 38 paired liver biopsies from hepatitis B e antigen-positive patients randomized to lamivudine (n=15), pegylated interferon alfa-2a (n=15) or pegylated interferon alfa-2a plus lamivudine (n=8) therapy for 48 weeks were assessed. Serum adiponectin was detected at levels ranging over fourfold magnitude with advancing fibrosis stage and correlated positively with fibrosis stage [r=0.45, p<0.001]. CHB patients with stage 0-1 fibrosis had higher composition of high molecular weight (HMW) form of adiponectin when compared with CHB patients with liver cirrhosis [mean+/-SEM 51.2+/-2.1% vs. 40.9+/-1.7%, respectively, p=0.001]. After antiviral therapy, patients with fibrosis reduction had marked decline in serum adiponectin level and increase in HMW form of adiponectin [mean+/-SEM 43.5+/-1.2% vs. 37.0+/-3.0%, respectively, p=0.04]. Serum adiponectin may have a role in fibrosis progression in CHB infection. A marked decline in serum adiponectin after antiviral therapy is associated with fibrosis reduction.

Serum NT-proCNP levels increased after initiation of GH treatment in patients with achondroplasia/hypochondroplasia.

PubMed

Kubota, Takuo; Wang, Wei; Miura, Kohji; Nakayama, Hirofumi; Yamamoto, Keiko; Fujiwara, Makoto; Ohata, Yasuhisa; Tachibana, Makiko; Kitaoka, Taichi; Takakuwa, Satoshi; Miyoshi, Yoko; Namba, Noriyuki; Ozono, Keiichi

2016-06-01

Serum amino-terminal propeptide of C-type natriuretic peptide (NT-proCNP) levels have been proposed as a biomarker of linear growth in healthy children. The usefulness of NT-proCNP in patients with achondroplasia (ACH)/hypochondroplasia (HCH) remains to be elucidated. The objective was to study whether serum NT-proCNP level is a good biomarker for growth in ACH/HCH and other patients of short stature. This was a longitudinal cohort study. Sixteen children with ACH (aged 0·4-4·3 years), six children with HCH (2·7-6·3 years), 23 children with idiopathic short stature (ISS) (2·2-9·0 years), eight short children with GH deficiency (GHD) (2·9-6·8 years) and five short children born small for gestational age (SGA) (2·0-6·6 years). Patients with ACH/HCH received GH treatment for 1 year. Serum NT-proCNP levels and height were measured. NT-proCNP levels positively correlated with height velocity in these short children (P < 0·05, r = 0·27). NT-proCNP levels inversely correlated with age in children with ISS alone (P < 0·01, r = -0·55). Serum NT-proCNP levels in patients with ACH/HCH were increased 3 months following the initiation of GH treatment (P < 0·05). Height SDS gain during GH treatment for 1 year was positively correlated with the changes in NT-proCNP levels after the initiation of GH (P < 0·01, r = 0·72). Serum NT-proCNP levels may be a good biomarker to indicate the effect of GH treatment on growth in patients with ACH/HCH at least in the first year and height velocity in short stature patients. © 2016 John Wiley & Sons Ltd.

Steady-state serum salicylate levels in hospitalized patients with rheumatoid arthritis. Comparison of two dosage schedules of choline magnesium trisalicylate.

PubMed

Cassell, S; Furst, D; Dromgoole, S; Paulus, H

1979-04-01

When the total daily drug dose was individualized to produce a steady-state serum salicylate concentration between 20 and 35 mg/dl, clinically acceptable fluctuations of serum concentrations occurred during both twice daily and three times daily administration. In 6 rheumatoid arthritis patients receiving choline magnesium trisalicylate, mean steady-state serum levels were the same, and the ranges of hourly mean concentrations during 8 and 12 hour dosage intervals were 19 to 27 mg/dl and 17 to 30 mg/dl, respectively. Changing the dosing interval from 8 to 12 hours required a 50% increase in the fractional doses, but resulted in an increase of only 3 mg/dl in mean peak concentration and a ddecrease of 1 mg/dl in mean minimum concentration.

Increased serum levels of interleukin-17 and transforming growth factor-β in patients with Graves’ disease

NASA Astrophysics Data System (ADS)

Elvira, D.; Nasrul, E.; Sofyan, Y.; Decroli, E.; Darwin, E.

2018-03-01

Graves’ disease (GD) is an organ-specific autoimmune disease, characterized by excessive autoantibody levels due to tolerance breakdown of thyroid-specific autoantigens. To determine the role of interleukin-17 (IL-17) and transforming growth factor-ß (TGF-β) in GD, we assessed their serum levels in patients with GD and healthy controls. Thirty patients with hyperthyroidism, goiter, and positive thyroid-stimulating hormone receptor antibody diagnosed as GD, according to the clinical diagnostic criteria for autoimmune thyroid disease. Blood samples were also from 30 healthy individuals matched for age and sex as a control. Serum levels of IL-17 and TGF-ß were by using ELISA. IL-17 and TGF-ß levels (14.43 ± 2.15 pg/mL and 10.44 ± 3.19 pg/mL, respectively) were significantly higher in patients with GD than in controls (7.07 ± 1.45 pg/mL and 4.95 ± 1.35 pg/mL, respectively). However, no correlation between IL-17 and TGF-β level in patients with GD. The elevated serum level of IL-17 and TGF-β in patients with GD reflects Th-2 predominance, which causes increasing of these pro-inflammatory cytokines.

Increased pentosidine, an advanced glycation end product, in serum and synovial fluid from patients with knee osteoarthritis and its relation with cartilage oligomeric matrix protein

PubMed Central

Senolt, L; Braun, M; Olejarova, M; Forejtova, S; Gatterova, J; Pavelka, K

2005-01-01

Background: Pentosidine, an advanced glycation end product, increasingly accumulates in articular cartilage with age, and contributes to the pathogenesis of osteoarthritis (OA). Increased pentosidine concentrations are associated with inflammatory disorders—for example, rheumatoid arthritis. Objective: To compare pentosidine serum concentrations in patients with knee OA and in healthy volunteers and to determine a relationship between pentosidine and cartilage oligomeric matrix protein (COMP)—a marker of articular cartilage destruction. Methods: Paired serum and synovial fluid samples were obtained by arthrocentesis from 38 patients with knee OA and from 38 healthy volunteers. Pentosidine concentration was measured by reverse phase high performance liquid chromatography with fluorescent detection and COMP was determined by sandwich ELISA. Results: Significantly increased serum pentosidine (p<0.01) and COMP (p<0.05) levels were detected in the patients with OA compared with the control group. Serum pentosidine correlated significantly with synovial fluid pentosidine (p<0.001). Pentosidine in synovial fluid (p<0.05) and in serum (p<0.05) correlated significantly with synovial fluid COMP. Pentosidine and COMP concentrations did not correlate significantly with the radiological stage of the disease. Conclusion: Increased pentosidine serum concentration in patients with OA and its correlation with the cartilage destruction marker COMP in synovial fluid suggests that pentosidine may be important in OA pathology and is a new potential OA marker. PMID:15897309

Lower Serum Irisin Levels Are Associated with Increased Vascular Calcification in Hemodialysis Patients.

PubMed

He, Lian; He, Wan-Yu; A, La-Ta; Yang, Wen-Ling; Zhang, Ai-Hua

2018-01-01

Vascular calcification, which involves an active cellular transformation of vascular smooth muscle cells into bone forming cells, is prevalent and predicts mortality in dialysis patients. Its mechanisms are complex and unclear. We presume that irisin, a newly identified myokine also may play roles in vascular calcification in hemodialysis patients. This study aims to evaluate serum irisin levels and establish their relation to vascular calcification and other parameters in hemodialysis patients. A total of 150 patients on maintenance hemodialysis treatment and 38 age- and sex-matched healthy controls were enrolled in this cross-sectional study. Serum irisin concentrations were measured by ELISA. Vascular calcification was evaluated by abdominal aortic calcification scores. Serum irisin concentrations were significantly lower in hemodialysis patients than in controls [52.8 (22.0, 100.0) vs. 460.8 (434.8, 483.4) ng/ml, P<0.01]. In addition, irisin was negatively correlated with the parathyroid hormone level (P=0.01). The HD patients with vascular calcification showed significantly lower serum irisin concentrations [39.0 (21.7, 86.2) vs.79.0 (39.5, 130.2) ng/mL, P<0.01]. Compared with the group without vascular calcification multivariate logistic regression analyses revealed that serum irisin, HD vintage and age were significant independent determinant factors for vascular calcification in HD patients. Our results are the first to provide a clinical evidence of the association between serum irisin and vascular calcification in HD patients. Lower irisin levels, long-term hemodialysis and old ages are independent risk factors in HD patients. © 2018 The Author(s). Published by S. Karger AG, Basel.

Increased Kappa/Lambda Hybrid Antibody in Serum Is a Novel Biomarker Related to Disease Activity and Inflammation in Rheumatoid Arthritis.

PubMed

Yi, Lang; Hao, Mingju; Lu, Tian; Lin, Guigao; Chen, Lida; Gao, Ming; Fan, Gaowei; Zhang, Dong; Wang, Guojing; Yang, Xin; Li, Yulong; Zhang, Kuo; Zhang, Rui; Han, Yanxi; Wang, Lunan; Li, Jinming

2016-01-01

The κ/λ hybrid antibodies in normal human serum were reported recently, but their clinical relevance has not yet been explored. Rheumatoid arthritis (RA) is one of the major joint diseases, and the early diagnosis and treatment of RA remain a challenge. Here, we developed a double-sandwich enzyme-linked immunosorbent assay system to quantify relative serum κ/λ hybrid antibody levels in RA patients, osteoarthritis (OA) patients, and healthy controls (HC) in order to assess their potential use as a serological biomarker of early disease and clinical activity and to preliminarily investigate their immunomodulatory roles in RA. Surprisingly, we found that κ/λ hybrid antibody was markedly increased in both early and established RA. Serum κ/λ hybrid antibody levels were significantly correlated with clinical indexes and inflammatory markers in RA. Further analysis showed a positive correlation between κ/λ hybrid antibody levels and the 28-joint disease activity score (DAS28). In conclusion, serum κ/λ hybrid antibodies in RA were identified for the first time. High levels of κ/λ hybrid antibody may be a useful tool in distinguishing early RA from OA and HC. We suggest κ/λ hybrid antibody as a marker for disease activity. The increased κ/λ hybrid antibodies were associated with inflammatory conditions in RA.

Increased Kappa/Lambda Hybrid Antibody in Serum Is a Novel Biomarker Related to Disease Activity and Inflammation in Rheumatoid Arthritis

PubMed Central

Yi, Lang; Hao, Mingju; Lu, Tian; Lin, Guigao; Chen, Lida; Gao, Ming; Fan, Gaowei; Zhang, Dong; Wang, Guojing; Yang, Xin; Li, Yulong; Zhang, Kuo; Zhang, Rui; Han, Yanxi; Wang, Lunan; Li, Jinming

2016-01-01

The κ/λ hybrid antibodies in normal human serum were reported recently, but their clinical relevance has not yet been explored. Rheumatoid arthritis (RA) is one of the major joint diseases, and the early diagnosis and treatment of RA remain a challenge. Here, we developed a double-sandwich enzyme-linked immunosorbent assay system to quantify relative serum κ/λ hybrid antibody levels in RA patients, osteoarthritis (OA) patients, and healthy controls (HC) in order to assess their potential use as a serological biomarker of early disease and clinical activity and to preliminarily investigate their immunomodulatory roles in RA. Surprisingly, we found that κ/λ hybrid antibody was markedly increased in both early and established RA. Serum κ/λ hybrid antibody levels were significantly correlated with clinical indexes and inflammatory markers in RA. Further analysis showed a positive correlation between κ/λ hybrid antibody levels and the 28-joint disease activity score (DAS28). In conclusion, serum κ/λ hybrid antibodies in RA were identified for the first time. High levels of κ/λ hybrid antibody may be a useful tool in distinguishing early RA from OA and HC. We suggest κ/λ hybrid antibody as a marker for disease activity. The increased κ/λ hybrid antibodies were associated with inflammatory conditions in RA. PMID:27143816

Association of Low Serum Concentration of Bilirubin with Increased Risk of Coronary Artery Disease

DTIC Science & Technology

1994-01-01

g AD-A276 272... 08/17/93 Association of Low Serum Concentration of Bilirubin IN-House with Increased Risk of Coronary Artery Disease PE 62202F...as possible risk factors for angiographicaiiy documenLed coronary artery disease (CAD). The studies involved a "training" set of 619 men for whom...complete data on all risk factors considered were available, and a "test" set of 258 men for whom some risk factor data were not available. In both study

Thyroid stimulation with recombinant human thyrotropin in healthy cats, cats with non-thyroidal illness and in cats with low serum thyroxin and azotaemia after treatment of hyperthyroidism.

PubMed

van Hoek, Ingrid M; Vandermeulen, Eva; Peremans, Kathelijne; Daminet, Sylvie

2010-02-01

This study investigated the recombinant human thyrotropin (rhTSH) stimulation test in healthy cats (group 1), cats with non-thyroidal illness (group 2) and cats with low serum total T(4) (TT(4)) and azotaemia after (131)I treatment (group 3). Serum TT(4) responses and thyroidal pertechnetate uptake after administration of 25 microg rhTSH IV were assessed. Baseline serum TT(4) was significantly lower in group 3 compared with group 1, but not between other group pairs. Serum TT(4) increased significantly in groups 1 and 2 but not in group 3 after rhTSH administration. Post-rhTSH serum TT(4) concentrations differed significantly between groups 1 and 3 and groups 2 and 3, but not between groups 1 and 2. Thyroid/salivary gland uptake ratio (T/S uptake ratio) differed only significantly between groups 1 and 3. Stimulation with rhTSH is valuable to differentiate euthyroidism from iatrogenic hypothyroidism in cats. Copyright 2009 ESFM and AAFP. Published by Elsevier Ltd. All rights reserved.

Increased serum and testicular androgen levels in F1 rats with lifetime exposure to soy isoflavones.

PubMed

McVey, Mark J; Cooke, Gerard M; Curran, Ivan H A

2004-07-01

The consequences of dietary soy isoflavones on serum and testicular androgen levels were examined in F1 male rats from a multigeneration study investigating the effects of diets varying in isoflavone content. Rats were fed either a soy-free casein based diet (AIN93G) or a diet in which alcohol-washed soy protein replaced casein as the protein source and to which increasing amounts of Novasoy, a commercially available isoflavone supplement were added. Analysis of these diets showed that the isoflavone content in each diet was 0 (diet 1; casein based control), 31.7 (diet 2; alcohol-washed soy-based diet control), 36.1 (diet 3), 74.5 (diet 4), 235.6 (diet 5) and 1046.6 (diet 6) mg total isoflavones/kg pelleted diet. The levels of isoflavones in diet 1 would represent a daily intake level of 0 mg isoflavones, diets 2 and 3 estimate a low soy-containing human diet (e.g. North American), diet 4 would correspond to Asian diets (e.g. Japanese) or adult humans taking isoflavone supplements, diet 5 approximates the isoflavone intake by babies fed soy based infant formula and diet 6 approximates fivefold the intake levels by babies or 10-fold the intake levels of adults consuming high isoflavone containing diets. Serum testosterone (T) from F1 male rats sacrificed on postnatal days (PND) 28, 70, 120, 240 and 360 were low at PND 28 (0.4 ng/ml), increased approximately five to sixfold at PND 70 (2.5-3.0 ng/ml) and thereafter declined to a steady state level of approximately 1 ng/ml by PND 120. However, rats on diets 5 and 6 demonstrated altered serum testosterone profiles such that at days 120, testosterone levels remained significantly elevated at approximately 3 ng/ml (P < 0.05). Serum dihydrotestosterone levels exhibited similar profiles and the levels in PND 120 rats on diet 5 or 6 were also significantly elevated (two to threefold, P < 0.05). The intra-testicular testosterone concentration in rats on diet 5 was also elevated at PND 120 compared with diet 1 (P < 0

Predictors of serum 25(Oh)D increase following bimonthly supplementation with 100,000IU vitamin D in healthy, men aged 25-65 years.

PubMed

Tepper, Sigal; Shahar, Danit R; Geva, Diklah; Ish-Shalom, Sofia

2014-10-01

Vitamin D replenishment therapy typically entails standard dosages, but related increases in serum 25(OH)D levels vary between individuals. This study was aimed to identify factors that affect the efficacy of vitamin D supplementation. 79 healthy men aged 25-65 with 25(OH)D<20ng/ml participated in a vitamin D supplementation study. All participants received 100,000IU vitamin D bimonthly, e.g., 1666IU/day. Personal and demographic information, physical activity and sun-exposure questionnaires were completed by the participants. Weight, height, and waist circumference were recorded. Serum calcium, creatinine, 25(OH)D, PTH, lipid profile, and liver-enzyme levels were assessed. All measurements were repeated after 6 and 12 months. The difference between baseline serum 25(OH)D and 12-month measurements was calculated (delta). Linear regression was performed to identify predictors for increases in 25(OH)D levels. Mean serum 25(OH)D level increases according to BMI were 12.6±5.29ng/ml for BMI≤25, 10.12±4.95ng/ml for 2530, which differed significantly from the other BMI categories (p=0.003). In a regression model to predict 25(OH)D increase, BMI was the main predictor (p<0.001), explaining 21.6% of the variance in serum 25(OH)D (inverse association). Age, sun-exposure, serum cholesterol, physical-activity, baseline 25(OH)D levels and seasonality were insignificant. The full model explained 27.9% of the variance in serum 25(OH)D. This study's main findings are that BMI affect vitamin D response in healthy men. Quantitative supplementation adjustments may be warranted in obese men, for whom the dose may need to be doubled. This article is part of a special issue entitled '16th Vitamin D Workshop'. Copyright © 2013 Elsevier Ltd. All rights reserved.

Effect of short-term propofol administration on pancreatic enzymes and lipid biochemistry in children between 1 month and 36 months.

PubMed

Chauhan, Munish; Garg, Ashish; Bharadwaj, Avnish

2013-04-01

Use of propofol in pediatric age group has been marred by reports of its adverse effects like hypertriglyceridemia and acute pancreatitis, although a causal relation has not yet been established. This prospective, clinical trial was carried out to evaluate the effects of short-term propofol administration on serum lipid profile and serum pancreatic enzymes in children of ASA physical status I and II aged between 1 month and 36 months. Anesthesia was induced with Propofol (1%) in the dose of 3 mg·kg(-1) intravenously and was maintained by propofol infusion (0.5%) at the rate of 12 mg·kg(-1·) h(-1) for the first 20 min and at 8 mg·kg(-1·) h(-1) thereafter. The mean dose of propofol administered was 12.02 ± 2.75 mg·kg(-1) (fat load of 120.2 ± 27.5 mg·kg(-1) ). Lipid profile, serum amylase, and lipase were measured before induction of anesthesia, at 90 min, 4 h, and finally 24 h after induction. Serum lipase levels (P < 0.05), serum triglyceride levels (P < 0.05), and serum very low-density lipoproteins VLDL levels (P < 0.05) were raised significantly after propofol administration from baseline although remained within normal limits. Serum cholesterol levels and serum low-density lipoproteins LDL levels showed a statistically significant fall over 24 h. No significant changes in serum pancreatic amylase levels were seen (P > 0.05). None of the patients developed any clinical features of pancreatitis in the postoperative period. We conclude that despite a small, transient increase in serum triglycerides and pancreatic enzymes, short-term propofol administration in recommended dosages in children of ASA status I and II aged between 1 month and 36 months does not produce any clinically significant effect on serum lipids and pancreatic enzymes. © 2012 Blackwell Publishing Ltd.

Nephrotoxicity in rabbits after long-term nandrolone decanoate administration.

PubMed

Tsitsimpikou, Christina; Vasilaki, Fotini; Tsarouhas, Konstantinos; Fragkiadaki, Persefoni; Tzardi, Maria; Goutzourelas, Nikolaos; Nepka, Charitini; Kalogeraki, Alexandra; Heretis, Ioannis; Epitropaki, Zoi; Kouretas, Dimitrios; Tsatsakis, Aristidis M

2016-09-30

Among the various side effects of supra-physiological dose of anabolic androgenic steroids that are described, renal toxicity remains the least evaluated. The present study provides evidence that long-term administration of nandrolone decanoate could lead to alterations of renal function and structure in the experimental rabbit model. A pronounced increase in serum urea, creatinine, SGOT and SGPT is observed in the treated animals, with intramuscular administration being more detrimental. Histopathological evaluation of kidneys indicated hyperaemia, fibrosis and focal inflammation. Furthermore, the significantly increased telomerase activity found in the kidneys of the intramuscularly treated animals could possibly represent a counteracting survival mechanism. Oxidative stress markers that were influenced the most were TBARS, indicating lipid peroxidation, and GSH. An interesting finding in our study though, was that while intramuscular administration showed the highest biochemical derangement, oxidative stress markers provided mixed results between intramuscularly and subcutaneously treated rabbits. In conclusion, nephrotoxicity of nandrolone decanoate remains a multi-factorial, partly irreversible effect that involves augmented tissue oxidative status. Copyright © 2016. Published by Elsevier Ireland Ltd.

Chronic Administration of a Combination of Six Herbs Inhibits the Progression of Hyperglycemia and Decreases Serum Lipids and Aspartate Amino Transferase Activity in Diabetic Rats

PubMed Central

Shafiee-Nick, Reza; Vafaee Bagheri, Farzaneh; Rakhshandeh, Hassan

2012-01-01

The effects of a polyherbal compound, containing six plants (Allium sativum, Cinnamomum zeylanicum, Nigella sativa, Punica granatum, Salvia officinalis and Teucrium polium) were tested on biochemical parameters in streptozotocin-induced diabetic rats. Streptozotocin caused an approximately 3-fold increase in fasting blood sugar level after 2 days. The diabetic control rats showed further increase in blood glucose after 30 days (384 ± 25 mg/dl in day 30 versus 280 ± 12 mg/dl in day 2, P < 0.001). Administration of the compound blocked the increase of blood glucose (272 ± 7 and 269 ± 48 mg/dl at day 2 and day 30, respectively). Also, there was significant difference in the level of triglyceride (60 ± 9 versus 158 ± 37 mg/dl, P < 0.01), total cholesterol (55 ± 2 versus 97 ± 11 mg/dl, P < 0.01) and aspartate amino transferase activity (75 ± 12 versus 129 ± 18 U/L, P < 0.05) between treated rats and diabetic control group. In conclusion, the MSEC inhibited the progression of hyperglycemia and decreased serum lipids and hepatic enzyme activity in diabetic rats. Therefore, it has the potential to be used as a natural product for the management of diabetes. PMID:23304131

Subcutaneous Administration of Tramadol after Elective Surgery Is as Effective as Intravenous Administration in Relieving Acute Pain and Inflammation in Dogs

PubMed Central

Buhari, Salisu; Hashim, Kalthum; Yong Meng, Goh; Mustapha, Noordin Mohamed; Gan, Siew Hua

2012-01-01

Subcutaneous (SC) administration of tramadol was compared with intravenous (IV) administration to evaluate analgesia following canine ovariohysterectomy (OHE). Healthy female dogs (n = 12) between 1 and 3 years of age (1.95 ± 0.65 years), weighing between 10.5 and 17.1 kg (13.12 ± 1.95 kg), were used. Pain was assessed at baseline before surgery and then hourly for 8 hr after surgery. Tramadol was administered both SC and IV at a dose of 3 mg/kg and provided significant postoperative analgesia, as indicated by analgesiometry, β-endorphin levels, and interleukin 6 (IL-6) levels. The respiratory rates and rectal temperatures remained normal and were not significantly different between or within the groups. A significant increase in heart rate was observed at 4 hr for dogs in both groups relative to the baseline, but there was no significant difference in heart rates between the groups at any time point. A significant decrease in mechanical pain threshold was observed within each group after surgery, but both groups responded similarly, suggesting that SC administration of tramadol is as effective as IV administration. Increased serum levels of both IL-6 and β-endorphin 3 hr postoperatively further indicate that both routes of administration achieve similar pain control. Thus, the relative analgesic efficacy of SC tramadol is comparable to that of IV administration and can be used to achieve similar effects for postsurgical pain management in dogs undergoing OHE. PMID:22778699

Prolonged neurophysiologic effects of levetiracetam after oral administration in humans.

PubMed

Epstein, Charles M; Girard-Siqueira, Lhys; Ehrenberg, Joshua Andrew

2008-07-01

To determine whether neurophysiological effects of levetiracetam (LEV) outlast its serum half-life of approximately 7 h. Demonstration of prolonged effects would help to explain the efficacy of LEV at conventional dosing intervals that are longer than the serum half-life. Following an oral dose of LEV 3 g in 12 normal volunteers, we compared transcranial magnetic stimulation (TMS) measures of motor threshold (MT) and recruitment with LEV serum levels and subjective ratings of toxicity over 48 h. Subjects used a two-dimensional visual-analog scale to estimate the time course of any side effects. LEV serum levels and subjective toxicity both peaked around 1 h after oral administration. MT elevation was delayed in comparison to peak serum levels and subjective toxicity. MT was maximally elevated at 6-9 h, and recruitment maximally reduced at 0.6-9 h. Changes in both measures had recovered by approximately 50% at 24 h. Despite the time difference between toxicity and TMS changes, toxicity estimates correlated with the maximum increase in MT. There is a substantial time lag between LEV serum levels and TMS measures of neuronal effects, and a similar temporal dissociation between subjective toxicity and maximum TMS change. The time course of neurophysiological effects, as measured by TMS, may help to explain the sustained clinical efficacy of LEV despite a short peripheral half-life.

Tranilast reduces serum IL-6 and IL-13 and protects against thioacetamide-induced acute liver injury and hepatic encephalopathy.

PubMed

Abdelaziz, Rania R; Elkashef, Wagdi F; Said, Eman

2015-07-01

Hepatic encephalopathy is a serious neuropsychiatric disorder usually affecting either acute or chronic hepatic failure patients. Hepatic encephalopathy was replicated in a validated rat model to assess the potential protective efficacy of tranilast against experimentally induced hepatic encephalopathy. Thioacetamide injection significantly impaired hepatic synthetic, metabolic and excretory functions with significant increase in serum NO, IL-6 and IL-13 levels and negative shift in the oxidant/antioxidant balance. Most importantly, there was a significant increase in serum ammonia levels with significant astrocytes' swelling and vacuolization; hallmarks of hepatic encephalopathy. Tranilast administration (300 mg/kg, orally) for 15 days significantly improved hepatic functions, restored oxidant/antioxidant balance, reduced serum NO, IL-6 and IL-13 levels. Meanwhile, serum ammonia significantly declined with significant reduction in astrocytes' swelling and vacuolization. Several mechanisms can be implicated in the observed hepato- and neuroprotective potentials of tranilast, such as its anti-inflammatory potential, its antioxidant potential as well as its immunomodulatory properties. Copyright © 2015 Elsevier B.V. All rights reserved.

The detection of capsaicin and dihydrocapsaicin in horse serum following long-term local administration.

PubMed

Zak, A; Siwinska, N; Slowikowska, M; Borowicz, H; Szpot, P; Zawadzki, M; Niedzwiedz, A

2018-06-19

Capsaicin and dihydrocapsaicin are alkaloids with analgesic effects in humans and animals. When used locally, both of them minimalise pain sensation by defunctionalising nerve endings. According to the Federation Equestrian International Prohibited Substances List, these are substance banned in horse competitions. The aim of the study was to determine the detection time of capsaicin in both plasma and serum after long-term use of a gel recommended for commercial use and applied as intended. The objective of the study was to select the best material for the detection of capsaicin as a doping substance in horses. Nine healthy mature horses were administered 0.1% capsaicin topically in the form of a commercial analgesic gel (15 g of the gel per limb) to the front limbs every 24 hours for five days with a polar fleece bandage. Blood serum and plasma were collected prior to gel application and in the 12th, 18th, 24th, 36th, 42nd, 48th, 60th, 84th, 108th, 132nd, 156th hour after the gel application. Qualitative and quantitative analysis was performed using ultra-high performance liquid chromatography coupled with a triple quadrupole mass spectrometry (UHPLC-QqQ-MS/MS). The concentration of capsaicin in the serum samples did not exceed the lower limit of quantification. Capsaicin was not detected in the plasma samples during the entire study period. Dihydrocapsaicin was not detected in blood serum or plasma. The presented results suggest that capsaicin is not detected in horse serum in the 24-hour-periodfollowing its last application according to the dosage regimen used by owners and veterinarians for therapy rather than doping, based on a five day gel application and a polar bandage.

Increased serum ferritin levels are independently related to incidence of prediabetes in adult populations.

PubMed

Meng, G; Yang, H; Bao, X; Zhang, Q; Liu, L; Wu, H; Du, H; Xia, Y; Shi, H; Guo, X; Liu, X; Li, C; Su, Q; Gu, Y; Fang, L; Yu, F; Sun, S; Wang, X; Zhou, M; Jia, Q; Guo, Q; Song, K; Huang, G; Wang, G; Wu, Y; Niu, K

2017-04-01

To comprehensively and exhaustively assess the relationship between serum ferritin levels and incidence of prediabetes in a prospective study. This prospective cohort study (n=7380) with a mean follow-up of 3.07 years (range: 1-7, 95% CI: 3.03-3.12) was conducted in Tianjin, China. Blood fasting glucose, oral glucose tolerance test, serum ferritin levels and other potentially confounding factors were measured at baseline and at each year of follow-up. Adjusted Cox proportional hazards regression models were used to assess the gender-specific relationship between baseline and mean serum ferritin quintiles and prediabetes. The incidence of prediabetes was 85 per 1000 person-years among men and 44 per 1000 person-years among women during follow-up (from 2007 to 2014). After adjusting for potential confounders, hazard ratios (95% CI) for prediabetes across baseline ferritin quintiles were: for men, 1.00, 1.13 (0.90-1.40), 1.20 (0.97-1.48), 1.41 (1.14-1.73) and 1.73 (1.41-2.11); and for women, 1.00, 1.01 (0.74-1.38), 0.68 (0.48-0.96), 0.84 (0.61-1.15) and 1.07 (0.80-1.45), respectively. Similar results were also observed for mean ferritin levels. Both baseline and mean serum ferritin levels were significantly and linearly related to prediabetes in men, whereas U-shaped relationships were observed between baseline and mean serum ferritin and prediabetes in women. The relationship between prediabetes risk and mean serum ferritin levels may be more stable than one with baseline serum ferritin levels. Copyright © 2016. Published by Elsevier Masson SAS.

Maternal serum soluble CD30 is increased in pregnancies complicated with acute Pyelonephritis

PubMed Central

Kusanovic, Juan Pedro; Romero, Roberto; Espinoza, Jimmy; Gotsch, Francesca; Edwin, Samuel; Chaiworapongsa, Tinnakorn; Mittal, Pooja; Soto, Eleazar; Erez, Offer; Mazaki-Tovi, Shali; Than, Nandor Gabor; Friel, Lara; Yoon, Bo Hyun; Mazor, Moshe; Hassan, Sonia

2007-01-01

Objectives Normal pregnancy is characterized by activation of the innate immunity and suppression of the adaptive limb of the immune response. However, pregnant women are more susceptible to the effects of infection and microbial products than non-pregnant women. CD30 is a member of the tumor necrosis factor receptor superfamily and is preferentially expressed by activated T cells producing Th2-type cytokines. Its soluble form (sCD30) is proposed to be an index of Th2 immune response. High serum concentrations of sCD30 have been found in the acute phase of viral infections, such as HIV-1 and hepatitis B. There is, however, conflicting evidence about serum sCD30 concentration in patients with bacterial infections. The objective of this study was to determine whether there are changes in the serum concentration of sCD30 in pregnant women with pyelonephritis. Methods This cross-sectional study included normal pregnant women (N=89) and pregnant women with pyelonephritis (N=41). Maternal serum concentration of sCD30 was measured by a specific and sensitive enzyme-linked immunoassay. Non-parametric tests were used for comparisons. A p value <0.05 was considered statistically significant. Results (1) Pregnant women with pyelonephritis had a significantly higher median serum concentration of sCD30 than those with a normal pregnancy (median: 44.3 U/ml, range: 16–352.5 vs. median: 29.7 U/ml, range: 12.2–313.2, respectively; p<0.001); and (2) No significant differences were found in the median maternal serum concentration of sCD30 between pregnant women with pyelonephritis who had a positive blood culture compared to those with a negative blood culture (median:47.7 U/mL, range: 17.1–118.8 vs. median: 42.6 U/mL, range: 16–352.5, respectively; p=0.86). Conclusions Acute pyelonephritis during pregnancy is associated with a higher maternal serum concentration of sCD30 than normal pregnancy. This finding is novel, and suggests that pregnant women with pyelonephritis may

Maternal serum soluble CD30 is increased in pregnancies complicated with acute pyelonephritis.

PubMed

Kusanovic, Juan Pedro; Romero, Roberto; Esoinoza, Jimmy; Gotsch, Francesca; Edwin, Samuel; Chaiworapongsa, Tinnakorn; Mittal, Pooja; Soto, Eleazar; Erez, Offer; Mazaki-Tovi, Shali; Than, Nandor Gabor; Friel, Lara A; Yoon, Bo Hyun; Mazor, Moshe; Hassan, Sonia S

2007-11-01

Normal pregnancy is characterized by activation of the innate immunity and suppression of the adaptive limb of the immune response. However, pregnant women are more susceptible to the effects of infection and microbial products than non-pregnant women. CD30 is a member of the tumor necrosis factor receptor superfamily and is preferentially expressed by activated T cells producing Th2-type cytokines. Its soluble form (sCD30) is proposed to be an index of Th2 immune response. High serum concentrations of sCD30 have been found in the acute phase of viral infections, such as HIV-1 and hepatitis B. There is, however, conflicting evidence about serum sCD30 concentration in patients with bacterial infections. The objective of this study was to determine whether there are changes in the serum concentration of sCD30 in pregnant women with pyelonephritis. This cross-sectional study included normal pregnant women (N = 89) and pregnant women with pyelonephritis (N = 41). Maternal serum concentration of sCD30 was measured by a specific and sensitive enzyme-linked immunoassay. Non-parametric tests were used for comparisons. A p value <0.05 was considered statistically significant. (1) Pregnant women with pyelonephritis had a significantly higher median serum concentration of sCD30 than those with a normal pregnancy (median 44.3 U/mL, range 16-352.5 vs. median 29.7 U/mL, range 12.2-313.2, respectively; p < 0.001), and (2) No significant differences were found in the median maternal serum concentration of sCD30 between pregnant women with pyelonephritis who had a positive blood culture compared to those with a negative blood culture (median 47.7 U/mL, range 17.1-118.8 vs. median 42.6 U/mL, range 16-352.5, respectively; p = 0.86). Acute pyelonephritis during pregnancy is associated with a higher maternal serum concentration of sCD30 than normal pregnancy. This finding is novel and suggests that pregnant women with pyelonephritis may have a complex immune state in which there is

Association of Increased Serum Ferritin With Impaired Muscle Strength/Quality in Hemodialysis Patients.

PubMed

Nakagawa, Chie; Inaba, Masaaki; Ishimura, Eiji; Yamakawa, Tomoyuki; Shoji, Shigeichi; Okuno, Senji

2016-07-01

We reported previously that muscle quality and muscle strength provide clinically relevant predictors for better survival in hemodialysis patients. Iron overload might impair muscle function by its accumulation in muscle in such patients. Serum ferritin, a marker for body iron store, was examined for its association with handgrip strength (HGS) and muscle quality which was defined as the ratio of HGS to arm lean mass measured with dual-energy X-ray absorptiometry. In 300 Japanese hemodialysis patients, age, hemodialysis duration, body mass index, and serum albumin were 58.0 ±12.0 (mean ± standard deviation) years, 4.2 (1.8-10.4) (median [25th-75th percentile]) years, 20.4 ± 2.8 kg/m(2), 4.0 ± 0.3 g/dL, respectively. Hemoglobin and hematocrit were 8.9 ± 1.2 g/dL, and 28.8 ± 3.9%, respectively, whereas transferrin saturation and serum ferritin were 29.8 ± 11.0% and 100 (54-172) ng/mL, respectively. Serum ferritin significantly correlated in a positive manner with the total dose of iron orally administered during the previous 6 months (r = 0.185, P = .0013). HGS and muscle quality were 23.1 ± 10.4 kg and 11.6 ± 3.8 kg/kg, respectively. In multivariate analysis to elucidate the factors associated with HGS and muscle quality in 300 hemodialysis patients, which included transferrin saturation and log serum ferritin, in addition to age, gender, hemodialysis duration, the presence/absence of diabetes, body mass index as independent variables, log serum ferritin emerged as a significant and independent factor which associated in a negative fashion with HGS (β = -0.091, P = .0395) and tendency toward negative association with muscle quality (β = -0.100, P = .0754). In summary, the present study demonstrated the significant association of serum ferritin with HGS and muscle quality in hemodialysis patients and thus suggested that we should be careful of iron overload to avoid its possible harmful effect on muscle in such patients. Copyright © 2016 National Kidney

Serum insulin-like growth factor-I (IGF-I) levels during long-term IGF-I treatment of children and adults with primary GH resistance (Laron syndrome).

PubMed

Laron, Z; Klinger, B; Silbergeld, A

1999-01-01

Serum IGF-I levels were measured in 14 patients (9 children and 5 adults) with Laron syndrome (LS) during long-term treatment by IGF-I. Recombinant IGF-I (FK-780, Fujisawa Pharmaceutical Co. Ltd., Japan) was administered once daily subcutaneously before breakfast for 3-5 years to the children and for 9 months to the adults. The initial daily dose was 150 micrograms/kg for children and 120 micrograms/kg for adults. Before initiation of treatment the mean overnight fasting levels of serum IGF-I in the children was 3.2 +/- 0.8 nmol/l (mean +/- SEM), rising to 10 +/- 1.7 nmol/l during long-term treatment even on a dose of 120 micrograms/kg/day. The serum IGF-I levels 4 hours after injection rose from 31.2 +/- 3.5 to 48 +/- 2 nmol/l. In the adult patients, the initial basal IGF-I was 4.1 +/- 0.7 nmol/l, rising to 16.1 +/- 3.84 nmol/l after 8-9 months treatment. Serum IGF-I levels at 4 hours after injection rose in the adult patients from 24.1 +/- 5.8 up to 66.8 +/- 15.4 nmol/l. A progressively increasing half-life during long term exogenous administration of IGF-I to patients with Laron syndrome was demonstrated by following serum IGF-I dynamics after injection. Based on the fact that no antibodies to IGF-I were detected and on findings in previous studies, it is speculated that the increasing serum IGF-I levels during long-term IGF-I treatment are caused by an increase in serum IGFBP-3 induced by chronic IGF-I administration. It is concluded that treatment with IGF-I necessitates regular monitoring of serum IGF-I levels; in patients in whom the age adjusted maximal levels are exceeded, a reduction of the daily IGF-I dose is indicated to avoid undesirable effects.

Synergistic Increase of Serum BDNF in Alzheimer Patients Treated with Cerebrolysin and Donepezil: Association with Cognitive Improvement in ApoE4 Cases

PubMed Central

Alvarez, Irene; Iglesias, Olalla; Crespo, Ignacio; Figueroa, Jesus; Aleixandre, Manuel; Linares, Carlos; Granizo, Elias; Garcia-Fantini, Manuel; Marey, Jose; Masliah, Eliezer; Winter, Stefan; Muresanu, Dafin; Moessler, Herbert

2016-01-01

Background: Low circulating brain derived neurotrophic factor may promote cognitive deterioration, but the effects of neurotrophic and combination drug therapies on serum brain derived neurotrophic factor were not previously investigated in Alzheimer’s disease. Methods: We evaluated the effects of Cerebrolysin, donepezil, and the combined therapy on brain derived neurotrophic factor serum levels at week 16 (end of Cerebrolysin treatment) and week 28 (endpoint) in mild-to-moderate Alzheimer’s disease patients. Results: Cerebrolysin, but not donepezil, increased serum brain derived neurotrophic factor at week 16, while the combination therapy enhanced it at both week 16 and study endpoint. Brain derived neurotrophic factor responses were significantly higher in the combination therapy group than in donepezil and Cerebrolysin groups at week 16 and week 28, respectively. Brain derived neurotrophic factor increases were greater in apolipoprotein E epsilon-4 allele carriers, and higher brain derived neurotrophic factor levels were associated with better cognitive improvements in apolipoprotein E epsilon-4 allele patients treated with Cerebrolysin and the combined therapy. Conclusion: Our results indicate a synergistic action of Cerebrolysin and donepezil to increase serum brain derived neurotrophic factor and delaying cognitive decline, particularly in Alzheimer’s disease cases with apolipoprotein E epsilon-4 allele. PMID:27207906

Daily morphine administration increases impulsivity in rats responding under a 5‐choice serial reaction time task

PubMed Central

Maguire, DR; Henson, C

2016-01-01

Background and Purpose Repeated administration of a μ opioid receptor agonist can enhance some forms of impulsivity, such as delay discounting. However, it is unclear whether repeated administration alters motor impulsivity. Experimental Approach We examined the effects of acute administration of morphine and amphetamine prior to and during daily morphine administration in rats responding under a five‐choice serial reaction time task. Rats (n = 5) were trained to detect a brief flash of light presented randomly in one of five response holes; responding in the target hole delivered food, whereas responding in the wrong hole or responding prior to illumination of the target stimulus (premature response) initiated a timeout. Premature responding served as an index of motor impulsivity. Key Results Administered acutely, morphine (0.1–10 mg·kg−1, i.p.) increased omissions and modestly, although not significantly, premature responding without affecting response accuracy; amphetamine (0.1–1.78 mg·kg−1, i.p.) increased premature responding without changing omissions or response accuracy. After 3 weeks of 10 mg·kg−1·day−1 morphine, tolerance developed to its effects on omissions whereas premature responding increased approximately fourfold, compared with baseline. Effects of amphetamine were not significantly affected by daily morphine administration. Conclusions and Implications These data suggest that repeated administration of morphine increased effects of morphine on motor impulsivity, although tolerance developed to other effects, such as omissions. To the extent that impulsivity is a risk factor for drug abuse, repeated administration of μ opioid receptor agonists, for recreational or therapeutic purposes, might increase impulsivity and thus the risk for drug abuse. PMID:26776751

Chronic Cladribine Administration Increases Amyloid Beta Peptide Generation and Plaque Burden in Mice

PubMed Central

Hayes, Crystal D.; Dey, Debleena; Palavicini, Juan Pablo; Wang, Hongjie; Araki, Wataru; Lakshmana, Madepalli K.

2012-01-01

Background The clinical uses of 2-chloro-2′-deoxyadenosine (2-CDA) or cladribine which was initially prescribed to patients with hematological and lymphoid cancers is now extended to treat patients with multiple sclerosis (MS). Previous data has shown that 2-CDA has high affinity to the brain and readily passes through the blood brain barrier reaching CSF concentrations 25% of that found in plasma. However, whether long-term administration of 2-CDA can lead to any adverse effects in patients or animal models is not yet clearly known. Methodology Here we show that exposure of 2-CDA to CHO cells stably expressing wild-type APP751 increased generation and secretion of amyloid β peptide (Aβ) in to the conditioned medium. Interestingly, increased Aβ levels were noticed even at non-toxic concentrations of 2-CDA. Remarkably, chronic treatment of APdE9 mice, a model of Alzheimer's disease with 2-CDA for 60 days increased amyloid plaque burden by more than 1-fold. Increased Aβ generation appears to result from increased turnover of APP as revealed by cycloheximide-chase experiments. Additionally, surface labeling of APP with biotin and immunoprecipitation of surface labeled proteins with anti-biotin antibody also indicated increased APP at the cell surface in 2-CDA treated cells compared to controls. Increased turnover of APP by 2-CDA in turn might be a consequence of decreased protein levels of PIN 1, which is known to regulate cis-trans isomerization and phosphorylation of APP. Most importantly, like many other oncology drugs, 2-CDA administration led to significant delay in acquiring a reward-based learning task in a T maze paradigm. Conclusions Taken together, these data provide compelling evidence for the first time that chronic 2-CDA administration can increase amyloidogenic processing of APP leading to robustly increased plaque burden which may be responsible for the observed deficits in learning skills. Thus chronic treatment of mice with 2-CDA can have

Increased bioavailability of tacrolimus after rectal administration in rats.

PubMed

Sakai, Masayuki; Hobara, Norio; Hokama, Nobuo; Kameya, Hiromasa; Ohshiro, Susumu; Sakanashi, Matao; Saitoh, Hiroshi

2004-09-01

The oral bioavailability of tacrolimus is low and varies considerably in humans due to first-pass metabolism by cytochrome P450 (CYP) 3A4 and the active efflux mediated by P-glycoprotein. This study was undertaken to elucidate the usefulness of rectal administration of tacrolimus as an alternative route to improve its bioavailability. Tacrolimus powder was suspended in a suppository base (witepsol H-15) and the tacrolimus suppository was inserted into the anus of the rats. For comparison, tacrolimus was suspended in 0.5% sodium methylcellulose solution and administered orally to rats. The dose of tacrolimus was fixed to 2 mg/kg. Blood samples were collected periodically up to 24 h after dosing, and tacrolimus concentrations were assayed by microparticle enzyme immunoassay. The whole blood concentrations of tacrolimus after rectal administration were much greater than those after oral administration. The C(max) and AUC(0-24 h) values after rectal administration were 3.9- and 6.9-fold greater than those after oral administration, respectively. These results clearly suggest a possibility that rectal administration of tacrolimus is capable of improving its bioavailability and cutting the costs of tacrolimus treatment.

Association of vascular endothelial growth factor (VEGF) gene polymorphism and increased serum VEGF concentration with pancreatic adenocarcinoma.

PubMed

Sivaprasad, Siddapuram; Govardhan, Bale; Harithakrishna, Ramanujam; Venkat Rao, Guduru; Pradeep, Rebala; Kunal, Bharadhwaj; Ramakrishna, Nalla; Anuradha, Shekaran; Reddy, Duvvuru Nageshwar

2013-01-01

BACKGROUND &AIM: Pancreatic cancer is related to high mortality rate. The vascular endothelial growth factor (VEGF) has a strong influence in tumor-related angiogenesis having association with the grade of angiogenesis and the prognosis of different solid tumors including pancreatic cancer. The present study was aimed to analyze the genotype and haplotype distribution of VEGF gene single nucleotide polymorphisms (SNPs), -460T/C, +405G/C, +936C/T, in patients with pancreatic adenocarcinoma from South India, and the effect of these SNPs on serum VEGF level. Total 80 patients with pancreatic adenocarcinoma and 87 controls were recruited. The genotype of VEGF gene polymorphisms was determined in both patients and controls using polymerase chain reaction-restriction fragment length polymorphism method. The serum VEGF protein was estimated by standard enzyme-linked immunosorbent assay. The genotype, +405G/G of VEGF gene showed a significant association with the patients with pancreatic adenocarcinoma (P = 0.012, Odds ratio: 2.133), whereas no significant difference was found in the genotype distribution of SNPs, -460C/T and +936C/T between patient and control groups (P > 0.05). Serum VEGF level was found to be significantly high in patients (1315.10 pg/Ml, SD ± 230.79) when compared to controls (591.35 pg/mL, SD ± 92.48) (P < 0.0001), which showed a strong genotype-phenotype correlation between genotype +405G/G and serum VEGF level. Further, the haplotype C-G-T showed a strong association with the disease, and no specific haplotype was associated with increased serum VEGF level. The polymorphism, +405G/C but not -460T/C and +936C/T, of VEGF gene is strongly associated with pancreatic adenocarcinoma, and this SNP has significant influence on serum VEGF level. Copyright © 2013 IAP and EPC. Published by Elsevier B.V. All rights reserved.

The effect of serum on the secretion of radiolabeled mucous macromolecules into the lumen of the cat trachea

DOE Office of Scientific and Technical Information (OSTI.GOV)

Peatfield, A.C.; Hall, R.L.; Richardson, P.S.

1982-02-01

We studied the effect of placing serum within a segment of trachea on secretion into its lumen in the cat. A segment of cervical trachea was isolated from the rest of the airway in situ. Secretions were radiolabeled biosynthetically by the administration of two radiolabeled precursors: (35S)sodium sulphate and (3H)glucose. Autologous serum placed in the segment at a dilution of 1 in 8 increased the output of radiolabeled macromolecules: (35S) by 80% and (3H) by 159% (p less than 0.001). At a dilution of 1 in 24, serum still increased the output of both isotopes. At dilutions of 1 inmore » 48 and 1 in 80 the increases were significant for (35S) but not for (3H). Heating the serum to 90 degrees C diminished its effects. Fractionating the serum by dialysis and gel filtration showed that the components of molecular weight less than about 13,000 daltons had no effect on secretion, whereas three higher molecular weight fractions all increased secretion. Two alien proteins (horseradish peroxidase and bovine serum albumin) stimulated secretion but a large molecular weight carbohydrate (carboxymethyl cellulose) did not. Atropine and propranolol, at doses that greatly reduced the effect of parasympathetic and sympathetic nerve activity, did not diminish the effects of serum, which therefore appeared to be independent of nerve activity. Gel filtration of the secretions elicited by serum showed that the predominant component was excluded even by Sepharose CL-2B and thus had a high molecular weight. We conclude that there are several components of serum that promote the secretion of mucus glycoproteins into the cat trachea. The relevance of these findings to diseases of human airways is considered.« less

Absorption of clonazepam after intranasal and buccal administration.

PubMed Central

Schols-Hendriks, M W; Lohman, J J; Janknegt, R; Korten, J J; Merkus, F W; Hooymans, P M

1995-01-01

Serum concentrations of clonazepam after intranasal, buccal and intravenous administration were compared in a cross-over study in seven healthy male volunteers. Each subject received a 1.0 mg dose of clonazepam intranasally and buccally and 0.5 mg intravenously. A Cmax of 6.3 +/- 1.0 ng ml-1 (mean; +/- s.d.) was measured 17.5 min (median) (range 15-20 min) after intranasal administration. A second peak (4.6 +/- 1.3 ng ml-1) caused by oral absorption was seen after 1.7 h (range 0.7-3.0 h). After buccal administration a Cmax of 6.0 +/- 3.0 ng ml-1 was measured after 50 min (range 30-90 min) with a second peak of 6.5 +/- 2.5 ng ml-1 after 3.0 h (range 2.0-4.0 h). Two minutes after i.v. injection of 0.5 mg clonazepam the serum concentration was 27 +/- 18 ng ml-1. It is concluded that intranasal clonazepam is an alternative to buccal administration. However, the Cmax of clonazepam after intranasal administration is not high enough to recommend the intranasal route as an alternative to intravenous injection. PMID:7640154

Cocaine Self-Administration Produces a Persistent Increase in Dopamine D2High Receptors

PubMed Central

Briand, Lisa A.; Flagel, Shelly B.; Seeman, Philip; Robinson, Terry E.

2008-01-01

Cocaine addicts are reported to have decreased numbers of striatal dopamine D2 receptors. However, in rodents, repeated cocaine administration consistently produces hypersensitivity to the psychomotor activating effects of both indirect dopamine agonists, such as cocaine itself, and importantly, to direct-acting D2 receptor agonists. The current study reports a possible resolution to this long-standing paradox. The dopamine D2 receptor exists in both a low and a high affinity state, and dopamine exerts its effects via the more functionally relevant high-affinity D2 receptor (D2High). We report here that cocaine self-administration experience produces a large (approximately 150%) increase in the proportion of D2High receptors in the striatum with no change in the total number of D2 receptors, and this effect is evident both 3 and 30 days after the discontinuation of cocaine self-administration. Changes in D2High receptors would not be evident with the probes used in human (and non-human primate) imaging studies. We suggest, therefore, that cocaine addicts and animals previously treated with cocaine may be hyper-responsive to dopaminergic drugs in part because an increase in D2High receptors results in dopamine supersensitivity. This may also help explain why stimuli that increase dopamine neurotransmission, including drugs themselves, are so effective in producing relapse in individuals with a history of exposure to cocaine. PMID:18284941

SGLT2 inhibitor lowers serum uric acid through alteration of uric acid transport activity in renal tubule by increased glycosuria

PubMed Central

Chino, Yukihiro; Samukawa, Yoshishige; Sakai, Soichi; Nakai, Yasuhiro; Yamaguchi, Jun-ichi; Nakanishi, Takeo; Tamai, Ikumi

2014-01-01

Sodium glucose cotransporter 2 (SGLT2) inhibitors have been reported to lower the serum uric acid (SUA) level. To elucidate the mechanism responsible for this reduction, SUA and the urinary excretion rate of uric acid (UEUA) were analysed after the oral administration of luseogliflozin, a SGLT2 inhibitor, to healthy subjects. After dosing, SUA decreased, and a negative correlation was observed between the SUA level and the UEUA, suggesting that SUA decreased as a result of the increase in the UEUA. The increase in UEUA was correlated with an increase in urinary d-glucose excretion, but not with the plasma luseogliflozin concentration. Additionally, in vitro transport experiments showed that luseogliflozin had no direct effect on the transporters involved in renal UA reabsorption. To explain that the increase in UEUA is likely due to glycosuria, the study focused on the facilitative glucose transporter 9 isoform 2 (GLUT9ΔN, SLC2A9b), which is expressed at the apical membrane of the kidney tubular cells and transports both UA and d-glucose. It was observed that the efflux of [14C]UA in Xenopus oocytes expressing the GLUT9 isoform 2 was trans-stimulated by 10 mm d-glucose, a high concentration of glucose that existed under SGLT2 inhibition. On the other hand, the uptake of [14C]UA by oocytes was cis-inhibited by 100 mm d-glucose, a concentration assumed to exist in collecting ducts. In conclusion, it was demonstrated that the UEUA could potentially be increased by luseogliflozin-induced glycosuria, with alterations of UA transport activity because of urinary glucose. PMID:25044127

Effect of increasing dietary antioxidants on concentrations of vitamin E and total alkenals in serum of dogs and cats.

PubMed

Jewell, D E; Toll, P W; Wedekind, K J; Zicker, S C

2000-01-01

Oxidative damage to DNA, proteins, and lipids has been implicated as a contributor to aging and various chronic diseases. The presence of total alkenals (malondialdehyde and 4-hydroxyalkenals) in blood or tissues is an indicator of lipid peroxidation, which may be a result of in vivo oxidative reactions. Vitamin E functions as a chain-breaking antioxidant that prevents propagation of free radical damage in biologic membranes. This 6-week dose-titration study was conducted to assess the effect of selected dietary vitamin E levels on byproducts of in vivo oxidative reactions in dogs and cats. Forty healthy adult dogs and 40 healthy adult cats were assigned to four equal groups per species in a complete random block design. A control group for both dogs and cats was fed dry food containing 153 and 98 IU vitamin E/kg of food (as fed), respectively. Canine and feline treatment groups were fed the same basal dry food with vitamin E added at three different concentrations. The total analyzed dietary vitamin E levels for the canine treatment groups were 293, 445, and 598 IU vitamin E/kg of food, as fed. The total analyzed dietary vitamin E levels for the feline treatment groups were 248, 384, and 540 IU vitamin E/kg of food, as fed. Increasing levels of dietary vitamin E in dog and cat foods caused significant increases in serum vitamin E levels compared with baseline values. Although all treatments increased concentrations of vitamin E in serum, all were not effective at decreasing serum alkenal levels. The thresholds for significant reduction of serum alkenal concentrations in dogs and cats were 445 and 540 IU vitamin E/kg of food, respectively, on an as-fed basis. The results of this study show that normal dogs and cats experience oxidative damage and that increased dietary levels of antioxidants may decrease in vivo measures of oxidative damage.

Cobicistat Significantly Increases Tacrolimus Serum Concentrations in a Renal Transplant Recipient with Human Immunodeficiency Virus Infection.

PubMed

Han, Zhe; Kane, Brenna M; Petty, Lindsay A; Josephson, Michelle A; Sutor, Jozefa; Pursell, Kenneth J

2016-06-01

Cobicistat is a pharmacokinetic booster in several fixed-dose combination products for treatment of human immunodeficiency virus (HIV) infection. As a potent inhibitor of cytochrome P450 (CYP) 3A enzymes, significant drug-drug interactions are expected between cobicistat and medications that are metabolized primarily through the CYP3A pathway, including calcineurin inhibitors (e.g., tacrolimus and cyclosporine). We describe a case of tacrolimus toxicity due to supratherapeutic tacrolimus concentrations when Stribild (elvitegravir, cobicistat, emtricitabine, and tenofovir disoproxil fumarate) was initiated for newly diagnosed HIV infection in a 50-year-old renal transplant recipient who was previously receiving a stable tacrolimus regimen. Drug-drug interaction via CYP3A inhibition was acknowledged, and weekly labs were ordered to allow for close monitoring of renal function and tacrolimus serum concentrations as recommended by Stribild prescribing information. The patient reported headache, insomnia, stomachache, and decreased urine output within 1 week of starting Stribild and was found to have acute kidney injury (serum creatinine [S cr ]concentration increasing from 1.5-2.3 mg/dl) and a serum tacrolimus concentration of 111.2 ng/ml at 1 week follow-up (goal trough level 4-6 ng/ml). Both tacrolimus and Stribild were withheld. In 15 days, the patient's tacrolimus serum concentration returned to goal. In the interim, he required twice/week clinic visits for laboratory assessments and an emergency department visit for management of hyperkalemia (potassium 6.5 mEq/L). Triumeq (abacavir, dolutegravir, and lamivudine) was started about 4 weeks later after S cr returned to baseline, and his tacrolimus serum trough concentrations subsequently remained stable. To our knowledge, this is the first case report describing the extent, significance, and onset of cobicistat and tacrolimus drug-drug interaction in clinical practice. As more fixed-dose combination products

Polychlorinated Biphenyl Congeners that Increase the Glucuronidation and Biliary Excretion of Thyroxine Are Distinct from the Congeners that Enhance the Serum Disappearance of Thyroxine

PubMed Central

Martin, L. A.; Wilson, D. T.; Reuhl, K. R.; Gallo, M. A.

2012-01-01

Polychlorinated biphenyl (PCB) congeners differentially reduce serum thyroxine (T4) in rats, but little is known about their ability to affect biliary excretion of T4. Thus, male Sprague-Dawley rats were orally administered Aroclor-1254, Aroclor-1242 (32 mg/kg per day), PCB-95, PCB-99, PCB-118 (16 mg/kg per day), PCB-126 (40 μg/kg per day), 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (3.9 μg/kg per day), or corn oil for 7 days. Twenty-four hours after the last dose, [125I]T4 was administered intravenously, and blood, bile, and urine samples were collected for quantifying [125I]T4 and in bile [125I]T4 metabolites. Serum T4 concentrations were reduced by all treatments, but dramatic reductions occurred in response to Aroclor-1254, PCB-99 [phenobarbital (PB)-type congener], and PCB-118 (mixed-type congener). None of the treatments increased urinary excretion of [125I]T4. Aroclor-1254, PCB-118, TCDD, and PCB-126 (TCDD-type congener) increased biliary excretion of T4-glucuronide by 850, 756, 710, and 573%, respectively, corresponding to marked induction of hepatic UDP-glucuronosyltransferase (UGT) activity toward T4. PCB-95 and PCB-99 did not induce UGT activity; therefore, the increased biliary excretion of T4-glucuronide was related to the affinity of congeners for the aryl hydrocarbon receptor. The disappearance of [125I]T4 from serum was rapid (within 15-min) and was increased by Aroclor-1254, PCB-99 and PCB-118. Thus, reductions in serum T4 in response to PCBs did not always correspond with UGT activity toward T4 or with increased biliary excretion of T4-glucuronide. The rapid disappearance of [125I]T4 from the serum of rats treated with PB-like PCBs suggests that increased tissue uptake of T4 is an additional mechanism by which PCBs may reduce serum T4. PMID:22187485

Pro: Higher serum bicarbonate in dialysis patients is protective.

PubMed

Misra, Madhukar

2016-08-01

Chronic metabolic acidosis is common in dialysis patients. Bicarbonate administration via the dialysate helps maintain the acid-base balance in these patients. Serum bicarbonate level in dialysis patients is determined by several factors that include dietary protein intake, nutritional status and dialysis prescription, etc. Additionally, a meaningful interpretation of serum bicarbonate in dialysis patients requires an understanding of complexities involving its measurement. Both very low as well very high levels of serum bicarbonate have been associated with adverse outcomes in observational studies. However, recent observational data, when adjusted for the confounding effects of nutritional status, do not associate higher predialysis serum bicarbonate with adverse consequences. At this time, there are no prospective studies available that have examined the association of serum bicarbonate with hard outcomes in dialysis patients. The ideal level of serum bicarbonate in dialysis patients is therefore unknown. This article examines the available data with regard to the benefits of higher predialysis serum bicarbonate. © The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Autoantibody signatures as biomarkers to distinguish prostate cancer from benign prostatic hyperplasia in patients with increased serum prostate specific antigen.

PubMed

O'Rourke, Dennis J; DiJohnson, Daniel A; Caiazzo, Robert J; Nelson, James C; Ure, David; O'Leary, Michael P; Richie, Jerome P; Liu, Brian C-S

2012-03-22

Serum prostate specific antigen (PSA) concentrations lack the specificity to differentiate prostate cancer from benign prostate hyperplasia (BPH), resulting in unnecessary biopsies. We identified 5 autoantibody signatures to specific cancer targets which might be able to differentiate prostate cancer from BPH in patients with increased serum PSA. To identify autoantibody signatures as biomarkers, a native antigen reverse capture microarray platform was used. Briefly, well-characterized monoclonal antibodies were arrayed onto nanoparticle slides to capture native antigens from prostate cancer cells. Prostate cancer patient serum samples (n=41) and BPH patient samples (collected starting at the time of initial diagnosis) with a mean follow-up of 6.56 y without the diagnosis of cancer (n=39) were obtained. One hundred micrograms of IgGs were purified and labeled with a Cy3 dye and incubated on the arrays. The arrays were scanned for fluorescence and the intensity was quantified. Receiver operating characteristic curves were produced and the area under the curve (AUC) was determined. Using our microarray platform, we identified autoantibody signatures capable of distinguishing between prostate cancer and BPH. The top 5 autoantibody signatures were TARDBP, TLN1, PARK7, LEDGF/PSIP1, and CALD1. Combining these signatures resulted in an AUC of 0.95 (sensitivity of 95% at 80% specificity) compared to AUC of 0.5 for serum concentration PSA (sensitivity of 12.2% at 80% specificity). Our preliminary results showed that we were able to identify specific autoantibody signatures that can differentiate prostate cancer from BPH, and may result in the reduction of unnecessary biopsies in patients with increased serum PSA. Copyright © 2011 Elsevier B.V. All rights reserved.

Successful pregnancy and live birth from a hypogonadotropic hypogonadism woman with low serum estradiol concentrations despite numerous oocyte maturations: a case report.

PubMed

Matsumoto, Kaori; Imakawa, Kazuhiko; Hayashi, Chuyu

2017-09-20

The increase in serum estradiol (E 2 ) concentrations during the follicular phase becomes the index of oocyte maturation in vivo. When ovarian stimulation is performed to hypogonadotropic hypogonadism (HH) patients with only follicle stimulating hormone (FSH), proper increase in serum E 2 concentrations is not observed. Even if oocytes are obtained, which usually have low fertilization rate. In this report, we would like to present an unique case, in which under low E 2 concentrations and without luteinizing hormone (LH) administration, numerous mature oocytes could be obtained and a healthy baby delivered. During controlled ovarian stimulation (COS) with only recombinant follicular stimulating hormone (rFSH) administrations, a 26-year-old Japanese woman with hypothalamic amenorrhea (i.e., hypogonadotropic hypogonadism) developed numerous follicles despite low serum E 2 , 701 pg/ml, and high progesterone (P 4 ) concentrations, 2.11 ng/ml, on the day of induced ovulation. However, 33 cumulus-oocyte complexes (COCs) were successfully obtained; following the embryo culture, four early embryos and six blastocysts were cryopreserved. This patient received hormone replacement therapy (HRT), during which one of six cryopreserved blastocysts was thawed and transferred into the uterine lumen. The patient became pregnant from the first transfer, went through her pregnancy without any complications, and delivered a healthy male baby in the 39th week. Low E 2 concentrations in follicular fluids (FFs) are suggestive that aromatase and/or 17β-hydroxysteroid dehydrogenase (17β-HSD) could be low. Serum E 2 concentrations may not be the most important index for oocyte maturation during COS, and suggested that oocyte maturation was in progress even under low serum E 2 and high P 4 conditions. Even if serum E 2 concentrations did not properly increase, numerous mature oocytes could be obtained, resulting in the birth of a healthy baby.

Increased production of 4 kDa amyloid beta peptide in serum deprived human primary neuron cultures: possible involvement of apoptosis.

PubMed

LeBlanc, A

1995-12-01

The etiology of the amyloid beta peptide in sporadic Alzheimer's disease (AD) is not known. Amyloid beta peptide (A beta), a proteolytic product of the amyloid precursor protein (APP), is deposited in the senile plaques and cerebrovascular tissues of individuals with either sporadic or familial AD (FAD). Increased A beta production from mutant APPs in FAD fosters the hypothesis that overexpression of A beta plays a primary role in the pathogenesis of AD. The absence of APP mutations in sporadic AD which displays identical pathological features than FAD such as synapse and neuronal loss, senile plaques and neurofibrillary tangles, suggests other causes for overexpression and/or deposition of A beta. To investigate the effect of neuronal death on APP metabolism and A beta secretion, human primary neuron cultures were induced to undergo apoptosis by serum deprivation. Serum deprived neurons display shrunken and rounded morphology, contain condensed chromatine and fragmented DNA, which are characteristic of apoptosis. In serum deprived neurons, metabolism of APP through the nonamyloidogenic secretory pathway is decreased to 20% from 40% in control cultures whereas 4kDa A beta is increased three- to fourfold. The results suggest that human neurons undergoing apoptosis generate excess A beta and indicates a possible mechanism for increased A beta in the absence of APP mutations.

Oral administration of Lactobacillus plantarum CJLP133 and CJLP243 alleviates birch pollen-induced allergic rhinitis in mice.

PubMed

Choi, S-P; Oh, H-N; Choi, C-Y; Ahn, H; Yun, H S; Chung, Y M; Kim, B; Lee, S J; Chun, T

2018-03-01

In this study, we evaluated the therapeutic efficacy of selected probiotics in a mouse model of birch pollen (BP)-induced allergic rhinitis. Oral administration of Lactobacillus plantarum CJLP133 and CJLP243 ameliorated the symptoms of BP-induced allergic rhinitis by reducing airway hyperresponsiveness, and both the histological scores and the number of infiltrated cells in the nasal cavities and lungs. Compared with those from vehicle-treated mice, bronchoalveolar lavage fluid and draining lymph node samples from CJLP133 and CJLP243-administrated mice showed diminished numbers of immune cells, increased secretion of a Th1-type cytokine (IFN-γ) and decreased production of Th2-type cytokines (IL-4, IL-5 and IL-13). Consistent with these results, levels of IL-4, IL-5, IL-13, serum IgE and BP-specific serum IgG1 were decreased, whereas secretion of IFN-γ and BP-specific serum IgG2a was augmented upon administration of CJLP133 and CJLP243 in mice. Oral administration of L. plantarum CJLP133 and CJLP243 alleviates symptoms of BP-induced allergic rhinitis in mice by recovering Th1/Th2 balance via enhancement of the Th1-type immune response. Lactobacillus plantarum CJLP133 and CJLP243 have therapeutic effects on BP-induced allergic rhinitis in an animal model. © 2017 The Society for Applied Microbiology.

Low serum magnesium levels are associated with increased risk of fractures: a long-term prospective cohort study.

PubMed

Kunutsor, Setor Kwadzo; Whitehouse, Michael Richard; Blom, Ashley William; Laukkanen, Jari Antero

2017-07-01

Magnesium, which is an essential trace element that plays a key role in several cellular processes, is a major component of bone; however, its relationship with risk of major bone fractures is uncertain. We aimed to investigate the association of baseline serum magnesium concentrations with risk of incident fractures. We analyzed data on 2245 men aged 42-61 years in the Kuopio Ischemic Heart Disease prospective cohort study, with the assessment of serum magnesium measurements and dietary intakes made at baseline. Hazard ratios [95% confidence intervals (CI)] for incident total (femoral, humeral, and forearm) and femoral fractures were assessed. During a median follow-up of 25.6 years, 123 total fractures were recorded. Serum magnesium was non-linearly associated with risk of total fractures. In age-adjusted Cox regression analysis, the hazard ratio (HR) (95% CIs) for total fractures in a comparison of the bottom quartile versus top quartile of magnesium concentrations was 2.10 (1.30-3.41), which persisted on adjustment for several established risk factors 1.99 (1.23-3.24). The association remained consistent on further adjustment for renal function, socioeconomic status, total energy intake, and several trace elements 1.80 (1.10-2.94). The corresponding adjusted HRs for femoral fractures were 2.56 (1.38-4.76), 2.43 (1.30-4.53) and 2.13 (1.13-3.99) respectively. There was no evidence of an association of dietary magnesium intake with risk of any fractures. In middle-aged Caucasian men, low serum magnesium is strongly and independently associated with an increased risk of fractures. Further research is needed to assess the potential relevance of serum magnesium in the prevention of fractures.

The increased concentration of macrophage migration inhibitory factor in serum and cerebrospinal fluid of patients with tick-borne encephalitis.

PubMed

Grygorczuk, Sambor; Parczewski, Miłosz; Świerzbińska, Renata; Czupryna, Piotr; Moniuszko, Anna; Dunaj, Justyna; Kondrusik, Maciej; Pancewicz, Sławomir

2017-06-24

Host factors determining the clinical presentation of tick-borne encephalitis (TBE) are not fully elucidated. The peripheral inflammatory response to TBE virus is hypothesized to facilitate its entry into central nervous system by disrupting the blood-brain barrier with the involvement of a signaling route including Toll-like receptor 3 (TLR3) and pro-inflammatory cytokines macrophage migration inhibitory factor (MIF), tumor necrosis factor-α (TNFα), and interleukin-1 beta (IL-1β). Concentrations of MIF, TNFα, and IL-1β were measured with commercial ELISA in serum and cerebrospinal fluid (CSF) from 36 hospitalized TBE patients, 7 patients with non-TBE meningitis, and 6 controls. The CSF albumin quotient (AQ) was used as a marker of blood-brain barrier permeability. Single nucleotide polymorphisms rs3775291, rs5743305 (associated with TLR3 expression), and rs755622 (associated with MIF expression) were assessed in blood samples from 108 TBE patients and 72 non-TBE controls. The data were analyzed with non-parametric tests, and p < 0.05 was considered significant. The median serum and CSF concentrations of MIF and IL-1β were significantly increased in TBE group compared to controls. MIF concentration in serum tended to correlate with AQ in TBE, but not in non-TBE meningitis. The serum concentration of TNFα was increased in TBE patients bearing a high-expression TLR3 rs5743305 TT genotype, which also associated with the increased risk of TBE. The low-expression rs3775291 TLR3 genotype TT associated with a prolonged increase of CSF protein concentration. The high-expression MIF rs755622 genotype CC tended to correlate with an increased risk of TBE, and within TBE group, it was associated with a mild presentation. The results point to the signaling route involving TLR3, MIF, and TNFα being active in TBE virus infection and contributing to the risk of an overt neuroinvasive disease. The same factors may play a protective role intrathecally contributing to the

Hepatic injury due to combined choline-deprivation and thioacetamide administration: an experimental approach to liver diseases.

PubMed

Al-Humadi, Hussam; Theocharis, Stamatios; Dontas, Ismene; Stolakis, Vasileios; Zarros, Apostolos; Kyriakaki, Argyro; Al-Saigh, Rafal; Liapi, Charis

2012-12-01

The induction of prolonged choline-deprivation (CD) in rats receiving thioacetamide (TAA) is an experimental approach of mild hepatotoxicity that could resemble commonly presented cases in clinical practice (in which states of malnutrition and/or alcoholism are complicated by the development of other liver-associated diseases). The present study aimed to investigate the time-dependent effects of a 30-, a 60- and a 90-day dietary CD and/or TAA administration on the adult rat liver histopathology and the serum markers of hepatic functional integrity. Rats were divided into four main groups: (a) control, (b) CD, (c) TAA and (d) CD + TAA. Dietary CD was provoked through the administration of choline-deficient diet, while TAA administration was performed ad libitum through the drinking water (300 mg/l of drinking water). Histological examination of the CD + TAA liver sections revealed micro- and macro-vesicular steatosis with degeneration and primary fibrosis at day 30, to extensive steatosis and fibrosis at day 90. Steatosis was mostly of the macrovesicular type, involving all zones of the lobule, while inflammatory infiltrate consisted of foci of acute and chronic inflammatory cells randomly distributed in the lobule. These changes were accompanied by gradually increasing mitotic activity, as well as by a constantly high alpha-smooth muscle actin immunohistochemical staining. The determination of hepatocellular injury markers such as the serum enzyme levels' of alanine aminotransferase and aspartate aminotransferase demonstrated a decrease at day 30 (they returned to control levels at days 60 and 90). However, the determination of those serum enzymes used for the assessment of cholestatic liver injury (gamma-glutamyltransferase, alkaline phosphatase) revealed a constant (time-independent) statistically-significant increase versus control values. Long-term combined dietary CD and TAA administration could be a more realistic experimental approach to human liver diseases

Technical note. The serum concentration of the advanced glycation end-product N epsilon-(carboxymethyl)lysine is increased in uremia.

PubMed

Degenhardt, T P; Grass, L; Reddy, S; Thorpe, S R; Diamandis, E P; Baynes, J W

1997-10-01

Advanced glycation end products (AGEs) such as pentosidine and N epsilon-(carboxymethyl)lysine (CML) have been traditionally quantified by HPLC or gas chromatography--mass spectrometry (GC/MS). Enzyme-linked immunosorbent assays (ELISA) have been introduced as a convenient alternative to simplify the detection and measurement of AGEs in proteins and tissues, but some of these studies are limited by the lack of information on the structure of the epitopes recognized by antibodies to AGE-proteins. In this work we demonstrate that an antibody used in a previous study, reporting increased levels of AGEs in patients with diabetes or on continuous ambulatory peritoneal dialysis (CAPD) and hemodialysis (HD), recognizes CML as its major epitope. We also show that there is a significant correlation between the concentration of AGEs in serum measured by ELISA and a GC/MS assay for CML in serum proteins. Both analyses yielded comparable results, with patients on CAPD and HD having about threefold higher AGE- or CML-concentrations in their serum. Our data suggest that ELISA assays for CML should be useful for the clinical measurement of AGEs in serum proteins.

Increased brain and plasma oxytocin after nasal and peripheral administration in rats and mice.

PubMed

Neumann, Inga D; Maloumby, Rodrigue; Beiderbeck, Daniela I; Lukas, Michael; Landgraf, Rainer

2013-10-01

The possibility to improve socio-emotional behaviors in humans by intranasal administration of synthetic oxytocin (OXT) attracts increasing attention, but its uptake into the brain has never been demonstrated so far. Here we used simultaneous microdialysis in both the dorsal hippocampus and amygdala of rats and mice in combination with concomitant blood sampling from the jugular vein to study the dynamics of the neuropeptide in brain extracellular fluid and plasma after its nasal administration. OXT was found to be increased in microdialysates from both the hippocampus and amygdala with peak levels occurring 30-60min after nasal administration. Despite a similar temporal profile of OXT concentrations in plasma, peripheral OXT is unlikely to contribute to dialysate OXT as calculated from in vitro recovery data, indicating a central route of transport. Moreover, intraperitoneal administration of synthetic OXT in identical amounts caused rapid peak levels in brain dialysates and plasma during the first 30min after treatment and a subsequent return toward baseline. While the precise route(s) of central transport remain to be elucidated, our data provide the first evidence that nasally applied OXT indeed reaches behaviorally relevant brain areas, and this uptake is paralleled by changes in plasma OXT. Copyright © 2013 Elsevier Ltd. All rights reserved.

Increase in serum noradrenaline concentration by short dives with bradycardia in Indo-Pacific bottlenose dolphin Tursiops aduncus.

PubMed

Suzuki, Miwa; Tomoshige, Mika; Ito, Miki; Koga, Sotaro; Yanagisawa, Makio; Bungo, Takashi; Makiguchi, Yuya

2017-07-01

In cetaceans, diving behavior immediately induces a change in blood circulation to favor flow to the brain and heart; this is achieved by intense vasoconstriction of the blood vessels that serve other organs. This blood circulation response is allied to a decrease in heart rate in order to optimize oxygen usage during diving. Vasoconstrictors are present in all mammals and stimulate the contraction of the smooth muscle in the walls of blood vessels. The most important of these vasoconstrictors are the hormones adrenaline (A), noradrenaline (NA), and angiotensin II (ANG II). At present, the contribution of these hormones to vasoconstriction during diving in cetaceans is unclear. To elucidate their possible roles, changes in serum levels of A, NA and ANG II were monitored together with heart rate in the Indo-Pacific bottlenose dolphin Tursiops aduncus during 90 and 180s dives. Both brief diving periods induced an increase in serum NA concentration and a decrease in heart rate; however, no changes were detected in serum levels of A or ANG II. These data indicate that NA may play a role in diving-induced vasoconstriction. Copyright © 2017 Elsevier Inc. All rights reserved.

Low serum IGF-1 and increased cytokine levels in tracheal aspirate samples are associated with bronchopulmonary dysplasia.

PubMed

Yılmaz, Cansu; Köksal, Nilgün; Özkan, Hilal; Dorum, Bayram Ali; Bağcı, Onur

2017-01-01

Yılmaz C, Köksal N, Özkan H, Dorum BA, Bağcı O. Low serum IGF-1 and increased cytokine levels in tracheal aspirate samples are associated with bronchopulmonary dysplasia. Turk J Pediatr 2017; 59: 122-129. Despite developments in the perinatal and neonatal care, bronchopulmonary dysplasia (BPD) is still the most frequently seen long-term complication in preterm infants. The aim of this prospective study is to investigate the association between the development of BPD and serial measurements of IGF-1 levels and their relationship with levels of IGF-1 and cytokine in tracheal aspirate fluids. A total of 40 premature infants, born at a gestational age of ≤ 32 weeks, were enrolled in the study. On postnatal day-1, 3, 7, 21 and 28 serum IGF-1 levels and IGF-1 levels, IL-6, IL-8, IL-10 and TNF-alpha levels in tracheal aspirate fluid samples of intubated cases were examined. Mean gestational age of 40 patients included in the study was 29.41 ± 2.23 weeks, and their mean birth weight was 1,256.85 ± 311.48 g. BPD was detected in 35% of cases. Mean gestational week and birth weight of the cases that developed BPD were 30 ± 3 weeks and 1,150 ± 295 g, respectively. Serum IGF-1 levels on postnatal day-1, 3, 7, 21 and 28 in cases who developed BPD were significantly lower when compared with those without BPD (p < 0.01). Levels of IL-6, IL-8, IL-10, and TNF-alpha in tracheal aspirate samples were significantly higher in cases with BPD compared to those without BPD (p < 0.05). IGF-1 levels in tracheal aspirate fluid samples did not differ significantly based on the presence of BPD (p > 0.05). Severity of BPD was associated with decreased serum IGF-1 levels and increased cytokine levels in tracheal aspirate samples.

Effect of sildenafil citrate (Viagra®) on trace element concentration in serum and brain of rats.

PubMed

Fayed, Abdel-Hasseb A; Gad, Shereen B

2011-12-01

As a vasodilator with good hemodynamic effects, sildenafil has been successfully used in the treatment of patients with pulmonary hypertension and cardiovascular diseases. By selectively inhibiting phosphodiestrase type 5 (PDE-5) and thus effectively reducing the breakdown of c GMP, sildenafil administration can markedly improve the erectile dysfunction. Sildenafil also elevates localized cerebral blood flow in rat brain. The objective of the present study was to investigate the effect of sildenafil on the level of trace elements (Zinc (Zn), copper (Cu), iron (Fe), selenium (Se), cobalt (Co), and chromium (Cr)) in blood and brain of rats. Sixteen male albino rats weighing 180-200 g were divided into two groups (8 rats/group). Sildenafil (Viagra, Pfizer Inc.) was dissolved in saline and administered at a dose of 10mg/kg i.p. (0.5 ml volume) to rats in the treated group every 72 h for 12 injections. Rats in the control group were administered the same volume of saline as in treated group. All rats were sacrificed 24h after the last injection. Blood samples were collected and serum was separated and stored at -20°C. Brains were dissected and stored frozen until analysis. Trace elements concentrations were determined by flame emission atomic absorption spectrophotometer. Results showed that sildenafil injection significantly (P<0.05) increased serum and brain Se and Cu concentrations. Moreover, sildenafil increased the Cr concentration in the brain tissue. It was concluded that sildenafil citrate administration increased serum Se and Cu as well as, increased brain Se, Cu, and Cr concentrations in rats. Copyright © 2011 Elsevier GmbH. All rights reserved.

ACTION OF SERUM ON FIBROBLASTS IN VITRO

PubMed Central

Carrel, Alexis; Ebeling, Albert H.

1923-01-01

It may be concluded that, under the conditions of the experiments: 1. The duration of life of fibroblasts is not altered by the presence of 7 per cent serum in a medium composed of fibrin and Tyrode solution, but is slightly decreased when the concentration of the serum reaches 25 per cent. 2. Fibroblasts cultivated in serum or in Tyrode solution are only in a condition of survival; they do not build up new protoplasm from the serum proteins and their mass does not increase. 3. When embryonic tissue juice is added to the medium, the tissues increase in mass. But the rate of growth is the same in media containing 0 per cent and 10 per cent serum. In 25 per cent serum, however, the rate of growth slightly decreases. Even in the presence of embryonic tissue juice, serum does not increase the rate of growth of connective tissue. 4. The nitrogenous compounds contained in serum are not used as food material by fibroblasts growing in vitro. PMID:19868757

Pharmacokinetic and behavioural profile of THC, CBD, and THC+CBD combination after pulmonary, oral, and subcutaneous administration in rats and confirmation of conversion in vivo of CBD to THC.

PubMed

Hložek, Tomáš; Uttl, Libor; Kadeřábek, Lukáš; Balíková, Marie; Lhotková, Eva; Horsley, Rachel R; Nováková, Pavlína; Šíchová, Klára; Štefková, Kristýna; Tylš, Filip; Kuchař, Martin; Páleníček, Tomáš

2017-12-01

Metabolic and behavioural effects of, and interactions between Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are influenced by dose and administration route. Therefore we investigated, in Wistar rats, effects of pulmonary, oral and subcutaneous (sc.) THC, CBD and THC+CBD. Concentrations of THC, its metabolites 11-OH-THC and THC-COOH, and CBD in serum and brain were determined over 24h, locomotor activity (open field) and sensorimotor gating (prepulse inhibition, PPI) were also evaluated. In line with recent knowledge we expected metabolic and behavioural interactions between THC and CBD. While cannabinoid serum and brain levels rapidly peaked and diminished after pulmonary administration, sc. and oral administration produced long-lasting levels of cannabinoids with oral reaching the highest brain levels. Except pulmonary administration, CBD inhibited THC metabolism resulting in higher serum/brain levels of THC. Importantly, following sc. and oral CBD alone treatments, THC was also detected in serum and brain. S.c. cannabinoids caused hypolocomotion, oral treatments containing THC almost complete immobility. In contrast, oral CBD produced mild hyperlocomotion. CBD disrupted, and THC tended to disrupt PPI, however their combination did not. In conclusion, oral administration yielded the most pronounced behavioural effects which corresponded to the highest brain levels of cannabinoids. Even though CBD potently inhibited THC metabolism after oral and sc. administration, unexpectedly it had minimal impact on THC-induced behaviour. Of central importance was the novel finding that THC can be detected in serum and brain after administration of CBD alone which, if confirmed in humans and given the increasing medical use of CBD-only products, might have important legal and forensic ramifications. Copyright © 2017 Elsevier B.V. and ECNP. All rights reserved.

High-Dose Intramuscular Vitamin D Provides Long-Lasting Moderate Increases in Serum 25-Hydroxvitamin D Levels and Shorter-Term Changes in Plasma Calcium.

PubMed

Gorman, Shelley; Zafirau, Mark Zafir; Lim, Ee Mun; Clarke, Michael W; Dhamrait, Gursimran; Fleury, Naomi; Walsh, John P; Kaufmann, Martin; Jones, Glenville; Lucas, Robyn M

2017-09-01

The best management of vitamin D deficiency, defined as a 25-hydroxyvitamin D [(25(OH)D] level <50 nM, is unclear. Intramuscular (IM) injection of a large bolus of vitamin D (≥100 000 IU) is used, but its safety is uncertain. In 10 adults given an IM injection of 600 000IU vitamin D3, we measured at baseline and at 1, 2, 3, and 4 weeks postinjection the serum levels of vitamin D3, 25(OH)D3, 25(OH)D2, total 25(OH)D, 3-epi-25(OH)D3, and 24,25-dihydroxyvitamin D3 [24,25(OH)2D3] using a standardized LC with tandem MS (MS/MS) assay; serum levels of 25(OH)D using the Abbott ARCHITECT i2000 immunoassay; and markers of bone metabolism. Bone markers and 25(OH)D (immunoassay) were remeasured at 24 weeks. All participants had baseline total 25(OH)D levels >50 nM. Serum 25(OH)D levels increased at 3, 4, and 24 weeks postinjection, peaking at 4 weeks [mean ± SEM of 126 ± 7.9 nM (immunoassay) and 100 ± 5.5 nM (LC-MS/MS)] but generally remained <125 nM, the upper limit recommended by the U.S. Institute of Medicine. Serum 24,25(OH)2D3 levels increased at 3 and 4 weeks postinjection. Serum ionized calcium levels were higher than baseline at 1, 3, and 4 weeks postinjection but remained within the clinically normal range. Other biochemical parameters, including other vitamin D metabolites, plasma alkaline phosphatase, and parathyroid hormone levels, were unchanged. IM injection of a large bolus of vitamin D effectively increases serum 25(OH)D levels without evidence of metabolic abnormality.

Advanced gestational age increases serum carbohydrate-deficient transferrin levels in abstinent pregnant women.

PubMed

Bakhireva, Ludmila N; Cano, Sandra; Rayburn, William F; Savich, Renate D; Leeman, Lawrence; Anton, Raymond F; Savage, Daniel D

2012-01-01

Carbohydrate-deficient transferrin (%CDT) is a well-established and highly specific biomarker for sustained heavy consumption of alcohol. However, in pregnant women, the specificity of this biomarker might be affected by advanced gestational age, even after accounting for increased transferrin concentrations in pregnancy. The goal of this prospective study was to assess the variability in %CDT during pregnancy among alcohol-abstaining patients. Patients were recruited during one of the first prenatal care visits and followed-up to term. Abstinence was confirmed by maternal self-report and by alcohol biomarkers. Biomarkers assessed in the mother included serum gamma-glutamyltranspeptidase, urine ethyl glucuronide and ethyl sulfate, and whole blood phosphatidylethanol (PEth). In addition, PEth was measured in a dry blood spot card obtained from a newborn. For %CDT analysis, serum samples were collected at baseline and at term and analyzed by an internationally validated high-performance liquid chromatography and spectrophotometric detection method. At recruitment (mean gestational age 22.6 ± 7.3 weeks), the mean %CDT concentration was 1.49 ± 0.30%, while at term, it increased to 1.67 ± 0.28% (P = 0.001). Using a conventional cutoff concentration %CDT >1.7%, 22.9 and 45.7% of the sample would be classified as 'positive' for this biomarker at recruitment and at term, respectively (P = 0.011 ). These results suggest that a conventional cutoff of 1.7% might be too low for pregnant women and would generate false-positive results. We propose that %CDT >2.0% be used as a cutoff concentration indicative of alcohol exposure in pregnant women. The sensitivity of %CDT at this cutoff for heavy drinking during pregnancy needs to be assessed further.

Heat increases MDMA-enhanced NAcc 5-HT and body temperature, but not MDMA self-administration.

PubMed

Feduccia, Allison A; Kongovi, Nundhun; Duvauchelle, Christine L

2010-12-01

There is a concern that hot environments enhance adverse effects of 3,4-methylenedioxymethamphetamine (MDMA or "Ecstasy"). In this study, long-term (4-weeks) daily MDMA self-administration sessions and an MDMA Challenge test were conducted with rats under normal and high thermal conditions (23° or 32°C). During MDMA self-administration sessions, activity and body temperature were increased by heat or MDMA experience, while MDMA self-administration rates increased with experience, but were comparable between thermal conditions. At the MDMA Challenge test (3.0 mg/kg, i.v.), in vivo microdialysis showed that nucleus accumbens serotonin (NAcc 5-HT) and dopamine (DA) responses were significantly increased in both thermal conditions. In the heated environment, MDMA-stimulated 5-HT responses and core temperature (but not DA) were significantly greater than at room temperature. Though the heated environment did not acutely boost MDMA intake, exaggerated NAcc 5-HT responses to MDMA may result in 5-HT depletion; a condition associated with Ecstasy use escalation and neural dysfunctions altering mood and cognition. Copyright © 2010 Elsevier B.V. All rights reserved.

Heat increases MDMA-enhanced NAcc 5-HT and body temperature, but not MDMA self-administration

PubMed Central

Feduccia, Allison A.; Kongovi, Nundhun

2011-01-01

There is concern that hot environments enhance adverse effects of 3,4-methylenedioxymethamphetamine (MDMA or “Ecstasy”). In this study, long-term (4-wks) daily MDMA self-administration sessions and an MDMA challenge test were conducted with rats under normal and high thermal conditions (23° or 32° C). During MDMA self-administration sessions, activity and body temperature were increased by heat or MDMA experience, while MDMA self-administration rates increased with experience, but were comparable between thermal conditions. At the MDMA challenge test (3.0 mg/kg, i.v.), in vivo microdialysis showed nucleus accumbens serotonin (NAcc 5-HT) and dopamine (DA) responses were significantly increased in both thermal conditions. In the heated environment, MDMA-stimulated 5-HT responses and core temperature (but not DA) were significantly greater than at room temperature. Though the heated environment did not acutely boost MDMA intake, exaggerated NAcc 5-HT responses to MDMA may result in 5-HT depletion; a condition associated with Ecstasy use escalation and neural dysfunctions altering mood and cognition. PMID:20888192

Report: Management Alert - Salary Increases for Certain Administratively Determined Positions

EPA Pesticide Factsheets

Report #18-N-0154, April 16, 2018. The purpose of this alert is to notify the EPA of certain factual info while our audit of the Office of the Administrator's (present and prior administrations) use of administratively determined positions continues.

Transient increase in alcohol self-administration following a period of chronic exposure to corticosterone

PubMed Central

Besheer, Joyce; Fisher, Kristen R.; Lindsay, Tessa G.; Cannady, Reginald

2013-01-01

Stressful life events and chronic stressors have been associated with escalations in alcohol drinking. Stress exposure leads to the secretion of glucocorticoids (cortisol in the human; corticosterone (CORT) in the rodent). To model a period of heightened elevations in CORT, the present work assessed the effects of chronic exposure to the stress hormone CORT on alcohol self-administration. Male Long Evans rats were trained to self-administer a sweetened alcohol solution (2% sucrose/15% alcohol) resulting in moderate levels of daily alcohol intake (0.5–0.7 g/kg). Following stable baseline operant self-administration, rats received CORT in the drinking water for 7 days. A transient increase in alcohol self-administration was observed on the first self-administration session following CORT exposure, and behavior returned to control levels by the second session. Control experiments determined that this increase in alcohol self-administration was specific to alcohol, unrelated to general motor activation, and functionally dissociated from decreased CORT levels at the time of testing. These results indicate that repeated exposure to heightened levels of stress hormone (e.g., as may be experienced during stressful episodes) has the potential to lead to exacerbated alcohol intake in low to moderate drinkers. Given that maladaptive drinking patterns, such as escalated alcohol drinking following stressful episodes, have the potential to put an individual at risk for future drinking disorders, utilization of this model will be important for examination of neuroadaptations that occur as a consequence of CORT exposure in order to better understand escalated drinking following stressful episodes in nondependent individuals. PMID:23643750

Effect of combined administration of ginger (Zingiber officinale Roscoe) and atorvastatin on the liver of rats.

PubMed

Heeba, Gehan H; Abd-Elghany, Manal I

2010-12-01

Ginger is known to possess hypolipidemic, antioxidant and hepatoprotective properties. Combination therapy often takes advantage of complementary effects of different agents. This study investigated the combined effect of ginger extract (GE) and atorvastatin on lipid profile and on atorvastatin-induced hepatic injury. Rats were randomized into: control; GE (400 mg/kg); atorvastatin (20 mg/kg) alone or with GE or vitamin E, and atorvastatin (80 mg/kg) alone or with GE or vitamin E. Administration of 80 mg/kg atorvastatin for 4 weeks had major hepatotoxic effect whereas the lower dose (20 mg/kg) seems to cause mild liver injury. Besides lowering serum total cholesterol and hepatic superoxide dismutase (SOD) and catalase (CAT), atorvastatin significantly increased serum aminotransferases, hepatic malondialdehyde (MDA) and nitric oxide (NO). Concurrent administration of GE and atorvastatin had the opposite effect. Histopathological study revealed that GE reduced liver lesions induced by atorvastatin. The results indicate that the ability of ginger to lower serum cholesterol and to decrease aminotransferases, MDA and NO is clinically important, because its chronic administration will neither lead to side-effects nor to hepatic changes as occurs with high atorvastatin doses. Therefore, combination regimens containing GE and low dose of statins could be advantageous in treating hypercholesterolemic patients which are susceptible to liver function abnormalities. Copyright © 2010 Elsevier GmbH. All rights reserved.

Administration of melatonin protects against acetylsalicylic acid-induced impairment of male reproductive function in mice

PubMed Central

Emami, Niloufar Hedayati; Lafout, Farzaneh Mahmoudi; Mohammadghasemi, Fahimeh

2018-01-01

Objective(s): Melatonin, an important hormone secreted by the epiphysis, is a powerful anti-oxidant with a high potential to neutralize medical toxins. The goal of this study was to demonstrate the beneficial effect of melatonin on epididymal sperm and reproductive parameters in mice treated with acetylsalicylic acid (ASA). Materials and Methods: Male adult mice were divided into four treatment groups: control, ASA, melatonin, and ASA+melatonin. Mice were administered ASA (50 mg/kg, orally) and/or melatonin (10 mg/kg, intraperitoneally), or vehicle control, for 14 days. Sperm count, sperm motility, and sperm morphology were evaluated to assess fertility. A colorimetric assay was used to measure serum total antioxidant capacity (TAC). A sperm chromatin dispersion (SCD) test was used to assess sperm chromatin integrity. Sex hormone levels were measured by ELISA. Results: Compared to the control group, ASA treatment resulted in a significant decrease in sperm parameters (P<0.05), as well as a decrease in the integrity of sperm chromatin (P<0.01). ASA treatment also reduced serum testosterone and TAC levels (P<0.05). Co-administration of melatonin with ASA significantly improved epididymal sperm parameters and increased serum testosterone and TAC levels compared to the ASA-treated group. LH level was not different in the combined treatment group compared to control or ASA treatment. Conclusion: Short-term administration of ASA (50 mg/kg) has adverse effects on male reproductive function in mice. Co-administration of melatonin protects against ASA-induced impairment of male reproductive function by preventing the reduction in serum TAC and testosterone levels seen with ASA treatment alone. PMID:29456808

Heparin-induced increase in serum levels of aminotranferases. A controlled clinical trial.

PubMed

Nielsen, H K; Husted, S E; Koopmann, H D; Fasting, H; Simonsen, O; Andersen, K; Husegaard, H C; Petersen, T K

1984-01-01

Sixty-four patients over the age of 40 years, undergoing elective surgery of at least one hour's duration, were randomized to treatment with either a thromboembolic deterrent ( TED ) stocking (Kendall Co.) or subcutaneous low-dose heparin 5 000 IU every 12 hours. Serum levels of alanine aminotransferase (S-ALAT), aspartate aminotransferase (S-ASAT), gamma-glutamyl transpeptidase (S-gamma-GT) and alkaline phosphatase (S-ALP) were measured. S-ALAT increased significantly on the 5th and 10th postoperative day, from 27 +/- 2 (x +/- SE) to 40 +/- 4 (p less than 0.01) and 55 +/- 7 U/l (p less than 0.001), respectively, in the heparin group and was significantly higher in the heparin than in the TED group both on the 5th (p less than 0.01) and 10th (p less than 0.05) postoperative day. S-ASAT and S-gamma-GT increased significantly during heparin treatment, but did not differ significantly from the values of the TED group. No change in S-ALP was registered in either group. It is concluded that prophylactic treatment with low-dose heparin induces a significant increase in S-aminotransferase levels, especially in S-ALAT. The phenomenon has profound differential diagnostic implications in conditions such as pulmonary embolism and acute myocardial infarction.

Inhibition of autoimmune diabetes in NOD mice with serum from streptococcal preparation (OK-432)-injected mice.

PubMed Central

Seino, H; Satoh, J; Shintani, S; Takahashi, K; Zhu, X P; Masuda, T; Nobunaga, T; Saito, M; Terano, Y; Toyota, T

1991-01-01

We have recently reported that systemic and chronic administration of recombinant tumour necrosis factor alpha (TNF-alpha), as well as streptococcal preparation (OK-432), inhibits development of insulin-dependent diabetes mellitus (IDDM) in NOD mice and BB rats, models of IDDM. In this study we examined whether serum containing endogenous TNF induced by OK-432 injection could inhibit IDDM in NOD mice. Treatment twice a week from 4 weeks of age with OK-432-injected mouse serum, which contained endogenous TNF (75U), but not IL-1, IL-2 and interferon-gamma (IFN-gamma) activity, reduced the intensity of insulitis and significantly inhibited the cumulative incidence of diabetes by 28 weeks of age in NOD mice, as compared with the incidence in non-treated mice (P less than 0.01) and in mice treated with control serum (P less than 0.02). This inhibitory effect of the serum was diminished, although not significantly, by neutralization of serum TNF activity with anti-mouse TNF antibody. In the mice treated with the serum from OK-432-injected mice, Thy-1.2+ or CD8+ spleen cells decreased (P less than 0.01) and surface-Ig+ (S-Ig+) cells increased (P less than 0.05), whereas the proliferative response of spleen cells to concanavalin A (P less than 0.01) and lipopolysaccharide (P less than 0.05) increased. The results indicate that the inhibition by OK-432 treatment of IDDM in NOD mice was partially mediated by serum factors including endogenous TNF. PMID:1747949

Asystole and increased serum myoglobin levels associated with 'packing blackout' in a competitive breath-hold diver.

PubMed

Andersson, Johan P A; Linér, Mats H; Jönsson, Henrik

2009-11-01

Many competitive breath-hold divers use 'glossopharyngeal insufflation', also called 'lung packing', to overfill their lungs above normal total lung capacity. This increases intrathoracic pressure, decreases venous return, compromises cardiac pumping, and reduces arterial blood pressure, possibly resulting in a syncope breath-hold divers call 'packing blackout'. We report a case with a breath-hold diver who inadvertently experienced a packing blackout. During the incident, an electrocardiogram (ECG) and blood pressure were recorded, and blood samples for determinations of biomarkers of cardiac muscle perturbation (creatine kinase-MB isoenzyme (CK-MB), cardiac troponin-T (TnT), and myoglobin) were collected. The ECG revealed short periods of asystole during the period of 'packing blackout', simultaneous with pronounced reductions in systolic, diastolic, and pulse pressures. Serum myoglobin concentration was elevated 40 and 150 min after the incident, whereas there were no changes in CK-MB or TnT. The ultimate cause of syncope in this diver probably was a decrease in cerebral perfusion following glossopharyngeal insufflation. The asystolic periods recorded in this diver could possibly indicate that susceptible individuals may be put at risk of a serious cardiac incident if the lungs are excessively overinflated by glossopharyngeal insufflation. This concern is further substantiated by the observed increase in serum myoglobin concentration after the event.

Bacoside A and bromelain relieve dichlorvos induced changes in oxidative responses in mice serum.

PubMed

Agarwal, Sonam; Chaudhary, Bharti; Bist, Renu

2016-07-25

Reactive oxygen species (ROS) may be involved in the pathogenesis of serum induced by dichlorvos. Therefore, the rationale of present research was to evaluate the ameliorative efficacy of bacoside A and bromelain on oxidative stress biomarkers in serum of dichlorvos intoxicated mice. Also the level of serum antioxidants viz. catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) and reduced glutathione (GSH) were measured. For experiments, mice were allocated into six groups. First group received saline as a vehicle; second group was administered with dichlorvos (40 mg/kg b.w.); third group was administered with bromelain (70 mg/kg b.w.), fourth group received dose of bacoside A (5 mg/kg b.w.), fifth group was given concomitant exposure of bacoside A and bromelain both and mice of sixth group were exposed to bacoside A, bromelain and dichlorvos for 21 days consecutively. Oxidative stress biomarkers thiobarbituric acid reactive substances (TBARS) and protein carbonyl content (PCC) and antioxidants (CAT, SOD, GPx and GSH) level of serum was determined to elucidate the protective potential of bacoside A and bromelain against dichlorvos intoxication. Significantly increased TBARS and PCC level in second group suggests that dichlorvos enhances the production of free radicals in serum of mice (p < 0.05). Antioxidants treatment significantly decreased the levels of TBARS and PCC (p < 0.05). Dichlorvos administration causes a significant reduction in the level of CAT, SOD, GPx and GSH (p < 0.05) which was restored significantly by co-administration of bromelain and bacoside A in dichlorvos exposed mice (p < 0.05). The bacoside A and bromelain are attributed with antioxidant properties. Finding of research conclude that concomitant exposure of bacoside A and bromelain was much effective in combating oxidative stress induced by dichlorvos. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Increased serum ferritin levels in patients with Crimean-Congo hemorrhagic fever: can it be a new severity criterion?

PubMed

Barut, Sener; Dincer, Fatma; Sahin, Idris; Ozyurt, Huseyin; Akkus, Mehmet; Erkorkmaz, Unal

2010-01-01

Serum ferritin is one of the markers indicating hemophagocytosis that may have a role in the pathogenesis of Crimean-Congo hemorrhagic fever (CCHF). This study was designed to determine any correlation between serum ferritin and routine diagnostic laboratory markers of CCHF, and to investigate the relationship between serum ferritin levels and disease severity. Sixty-six patients with CCHF admitted to the hospital during the spring and summer months of 2006 and 2007 were included in the study. Serum ferritin levels were measured in sera obtained during the initial days of hospitalization. Data from 53 patients showing decreasing platelet counts over the first three days were used for further analysis and these patients were divided into two groups according to disease severity: group A included severe cases with lowest platelet counts < or =20x10(9)/l and group B included mild cases with lowest platelet counts >20x10(9)/l. Forty patients (60.6%) were male (mean age 43+/-17 years). Three patients died, thus the fatality rate was 4.5%. Fifty-one patients (77.3%) had abnormal serum ferritin levels, with levels above 500 ng/ml in 62.1%. There was a significant negative correlation between ferritin levels and concordant platelet counts (p<0.001; r=-0.416) and ferritin was also found to be positively correlated with aspartate aminotransferase (p<0.001; r=0.625), alanine aminotransferase (p<0.001; r=0.479), and lactate dehydrogenase (p<0.001; r=0.684). Group A had higher ferritin levels than group B (p < 0.001). Receiver operating characteristic analysis revealed that a ferritin level of > or =1862ng/ml had a sensitivity of 87.5% and a specificity of 83.8% in differentiating severe cases from mild ones. Increased serum ferritin levels may suggest a significant role of hemophagocytosis in the pathogenesis of CCHF and may be a useful marker for diagnosis, disease activity, and prognosis. Copyright 2009 International Society for Infectious Diseases. Published by Elsevier Ltd

Protective effect of Tuscan black cabbage sprout extract against serum lipid increase and perturbations of liver antioxidant and detoxifying enzymes in rats fed a high-fat diet.

PubMed

Melega, S; Canistro, D; De Nicola, G R; Lazzeri, L; Sapone, A; Paolini, M

2013-09-28

A diet rich in fat is considered a primary risk factor for CVD, cancer and failures in metabolism and endocrine functions. Hyperlipidaemia generates oxidative stress and weakens antioxidant defences as well as metabolic detoxification systems. Brassicaceae are vegetables rich in glucosinolates and isothiocyanates, affecting enzymatic antioxidant as well as phase II enzymes and conceivably counteracting high-fat diet (HFD)-associated pathologies. The protective role of Tuscan black cabbage (a variety of kale) sprout extract (TBCSE) intake against HFD alterations was here studied. The effects on rat hepatic antioxidant as well as detoxifying enzymes, and serum lipid- and body weightlowering properties of TBCSE, were investigated. Feeding the animals with a HFD for 21 d increased body as well as liver weights, and induced hyperlipidaemia, as confirmed by a higher serum lipid profile v. control diet. Daily intragastric administration of TBCSE to HFD-fed rats lowered serum total cholesterol, TAG and NEFA. Body and liver weight gains were also reduced. Antioxidant (catalase, NAD(P)H:quinone reductase, oxidised glutathione reductase and superoxide dismutase) and phase II (glutathione S-transferase and uridine diphosphate glucuronosyl transferase) enzymes were down-regulated by the HFD, while the extract restored normal levels in most groups. Generation of toxic intermediates, and membrane fatty acid composition changes by the HFD, might account for the altered hepatic antioxidant and detoxifying enzyme functions. The recovering effects of TBCSE could be attributed to high flavonoid, phenolic and organosulphur compound content, which possess free-radical-scavenging properties, enhance the antioxidant status and stimulate lipid catabolism. TBCSE intake emerges to be an effective alimentary strategy to counteract the perturbations associated with a diet rich in fat.

Clinical significance of serum cortisol levels following surgery for congenital heart disease.

PubMed

Teagarden, Alicia M; Mastropietro, Christopher W

2017-03-01

Use of hydrocortisone to treat refractory haemodynamic instability in patients recovering from surgery for congenital heart disease is common practice at many centres. We aimed to determine whether there is a relationship between total serum cortisol concentrations and haemodynamic response to this therapy. Material and methods We retrospectively reviewed patients <21 years who underwent cardiac surgery from 2011 to 2013, received hydrocortisone within 72 hours postoperatively, and had total serum cortisol measurements contemporaneous with its administration. Favourable responders were defined as patients in whom, at 24 hours after hydrocortisone initiation, either (1) systolic blood pressure was increased or unchanged and vasoactive-inotrope score was decreased or (2) systolic blood pressure increased by ⩾10% of baseline and vasoactive-inotrope score was unchanged. Variables were compared using t-tests or Mann-Whitney U tests as appropriate. In total, 24 patients were reviewed, with a median age of 1.4 months and range of 0.1-232 months. Among them, 14 (58%) patients responded favourably to hydrocortisone. At 24 hours, the median change in vasoactive-inotrope score was -18% in favourable responders and +31% in those who did not respond favourably, p=0.001. The mean pre-hydrocortisone total serum cortisol in favourable responders was 17.4±10.9 µg/dl compared with 46.1±44.7 µg/dl in those who did not respond favourably, p=0.03. Total serum cortisol obtained before initiation of hydrocortisone was significantly lower in patients who responded favourably to this therapy. Total serum cortisol may therefore be helpful in identifying children recovering from cardiac surgery who may or may not haemodynamically improve with hydrocortisone.

High ambient temperature increases intravenous methamphetamine self-administration on fixed and progressive ratio schedules in rats.

PubMed

Cornish, Jennifer L; Clemens, Kelly J; Thompson, Murray R; Callaghan, Paul D; Dawson, Bronwyn; McGregor, Iain S

2008-01-01

Methamphetamine is a drug that is often consumed at dance parties or nightclubs where the ambient temperature is high. The present study determined whether such high ambient temperatures alter intravenous methamphetamine self-administration in the rat. Male Hooded Wistar rats were trained to self-administer intravenous methamphetamine (0.1 mg/kg/infusion) under a fixed ratio 1 (FR1) or progressive ratio (PR) schedule of reinforcement at an ambient temperature of 23 +/- 1 degrees C. They were then given their daily self-administration session at a raised ambient temperature of 30 +/- 1 degrees C. Methamphetamine self-administration was increased at 30 degrees C under both FR1 and PR reinforcement schedules, with the latter effect indicating that heat enhances the motivation to obtain methamphetamine. High temperatures did not alter self-administration of the D1 receptor agonist SKF 82958 in methamphetamine-experienced rats suggesting some specificity in the methamphetamine effect. When rats were given access to drink isotonic saline solution during methamphetamine self-administration sessions they drank much more solution at 30 degrees C than 23 degrees C. However, availability of isotonic saline to drink did not alter the heat-induced facilitation of methamphetamine self-administration (PR schedule) indicating that the heat effect does not simply reflect increased motivation for intravenous fluids. Hyperthermia was evident in rats self-administering methamphetamine at high ambient temperatures and fluid consumption did not prevent this effect. Heat did not affect blood levels of methamphetamine, or its principal metabolite amphetamine indicating that the facilitatory effect of heat did not reflect altered methamphetamine pharmacokinetics. Overall, these results show that high ambient temperatures increase the reinforcing efficacy of methamphetamine and encourage higher levels of drug intake.

Increased serum brain-derived neurotrophic factor (BDNF) is predictive of cocaine relapse outcomes: A prospective study

PubMed Central

D’Sa, Carrol; Fox, Helen C.; Hong, Adam K.; Dileone, Ralph J.; Sinha, Rajita

2011-01-01

Background Cocaine dependence is associated with high relapse rates but few biological markers associated with relapse outcomes have been identified. Extending preclinical research showing a role for central Brain Derived Neurotrophic Factor (BDNF) in cocaine seeking, we examined whether serum BDNF is altered in abstinent, early recovering, cocaine-dependent individuals and if it is predictive of subsequent relapse risk. Methods Serum samples were collected across three consecutive mornings from 35 treatment-engaged, 3 week abstinent cocaine-dependent inpatients (17M/18F) and 34 demographically matched hospitalized healthy control participants (17M/17F). Cocaine dependent individuals were prospectively followed on days 14, 30 and 90 post-treatment discharge to assess cocaine relapse outcomes. Time to cocaine relapse, number of days of cocaine use (frequency), and amount of cocaine use (quantity) were the main outcome measures. Results High correlations in serum BDNF across days indicated reliable and stable serum BDNF measurements. Significantly higher mean serum BDNF levels were observed for the cocaine-dependent patients compared to healthy control participants (p<.001). Higher serum BDNF levels predicted shorter subsequent time to cocaine relapse (hazard ratio: HR: 1.09, p<.05), greater number of days (p<.05) and higher total amounts of cocaine used (p = .05). Conclusions High serum BDNF levels in recovering cocaine-dependent individuals are predictive of future cocaine relapse outcomes and may represent a clinically relevant marker of relapse risk. These data suggest that serum BDNF levels may provide an indication of relapse risk during early recovery from cocaine dependence. PMID:21741029

Increasing synthetic serum substitute (SSS) concentrations in P1 glucose/phosphate-free medium improves implantation rate: a comparative study.

PubMed

Ben-Yosef, D; Yovel, I; Schwartz, T; Azem, F; Lessing, J B; Amit, A

2001-11-01

To assess the comparative efficacy of IVF medium (MediCult, with 5.2 mM glucose) and a glucose/phosphate-free medium, P1 (Irvine Scientific), and to investigate the influence of increasing the serum supplementation (synthetic serum substitute; SSS; Irvine Scientific) to P1 on embryo development and implantation. Patients were randomly assigned to IVF medium (Group 1, cycles n = 172) or P1 supplemented with 10% SSS (Group 2, cycles n = 229) according to the medium scheduled for use on the day of oocyte retrieval. Another 555 IVF consequent cycles (Group 3) were performed using increased SSS concentrations (20%) in P1 medium. In this large series of IVF cycles, we herein demonstrate that significantly higher pregnancy and implantation rates were found when embryos were cultured in glucose/phosphate-free medium P1 supplemented with 20% SSS compared to supplementation with the lower SSS concentration and with IVF medium.

Oral Administration of Probiotics Increases Paneth Cells and Intestinal Antimicrobial Activity.

PubMed

Cazorla, Silvia I; Maldonado-Galdeano, Carolina; Weill, Ricardo; De Paula, Juan; Perdigón, Gabriela D V

2018-01-01

The huge amount of intestinal bacteria represents a continuing threat to the intestinal barrier. To meet this challenge, gut epithelial cells produce antimicrobial peptides (AMP) that act at the forefront of innate immunity. We explore whether this antimicrobial activity and Paneth cells, the main intestinal cell responsible of AMP production, are influenced by probiotics administration, to avoid the imbalance of intestinal microbiota and preserve intestinal barrier. Administration of Lactobacillus casei CRL 431 (Lc 431) and L. paracasei CNCM I-1518 (Lp 1518) to 42 days old mice, increases the number of Paneth cells on small intestine, and the antimicrobial activity against the pathogens Staphylococcus aureus and Salmonella Typhimurium in the intestinal fluids. Specifically, strong damage of the bacterial cell with leakage of cytoplasmic content, and cellular fragmentation were observed in S. Typhimurium and S. aureus . Even more important, probiotics increase the antimicrobial activity of the intestinal fluids at the different ages, from weaning (21 days old) to old age (180 days old). Intestinal antimicrobial activity stimulated by oral probiotics, do not influence significantly the composition of total anaerobic bacteria, lactobacilli and enterobacteria in the large intestine, at any age analyzed. This result, together with the antimicrobial activity observed against the same probiotic bacteria; endorse the regular consumption of probiotics without adverse effect on the intestinal homeostasis in healthy individuals. We demonstrate that oral probiotics increase intestinal antimicrobial activity and Paneth cells in order to strengthen epithelial barrier against pathogens. This effect would be another important mechanism by which probiotics protect the host mainly against infectious diseases.

Enhanced AMPA Receptor Activity Increases Operant Alcohol Self-administration and Cue-Induced Reinstatement

PubMed Central

Cannady, Reginald; Fisher, Kristen R.; Durant, Brandon; Besheer, Joyce; Hodge, Clyde W.

2012-01-01

Long-term alcohol exposure produces neuroadaptations that contribute to the progression of alcohol abuse disorders. Chronic alcohol consumption results in strengthened excitatory neurotransmission and increased AMPA receptor signaling in animal models. However, the mechanistic role of enhanced AMPA receptor activity in alcohol reinforcement and alcohol-seeking behavior remains unclear. This study examined the role of enhanced AMPA receptor function using the selective positive allosteric modulator, aniracetam, in modulating operant alcohol self-administration and cue-induced reinstatement. Male alcohol-preferring (P-) rats, trained to self-administer alcohol (15%, v/v) versus water were pretreated with aniracetam to assess effects on maintenance of alcohol self-administration. To determine reinforcer specificity, P-rats were trained to self-administer sucrose (0.8%, w/v) versus water, and effects of aniracetam were tested. The role of aniracetam in modulating relapse of alcohol-seeking was assessed using a response-contingent cue-induced reinstatement procedure in P-rats trained to self-administer 15% alcohol. Aniracetam pretreatment significantly increased alcohol-reinforced responses relative to vehicle treatment. This increase was not attributed to aniracetam-induced hyperactivity as aniracetam pretreatment did not alter locomotor activity. AMPA receptor involvement was confirmed because DNQX (AMPA receptor antagonist) blocked the aniracetam-induced increase in alcohol self-administration. Aniracetam did not alter sucrose-reinforced responses in sucrose-trained P-rats, suggesting that enhanced AMPA receptor activity is selective in modulating the reinforcing function of alcohol. Finally, aniracetam pretreatment potentiated cue-induced reinstatement of alcohol-seeking behavior versus vehicle treated-P-rats. These data suggest that enhanced glutamate activity at AMPA receptors may be key in facilitating alcohol consumption and seeking behavior which could

Enhanced AMPA receptor activity increases operant alcohol self-administration and cue-induced reinstatement.

PubMed

Cannady, Reginald; Fisher, Kristen R; Durant, Brandon; Besheer, Joyce; Hodge, Clyde W

2013-01-01

Long-term alcohol exposure produces neuroadaptations that contribute to the progression of alcohol abuse disorders. Chronic alcohol consumption results in strengthened excitatory neurotransmission and increased α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptors (AMPA) receptor signaling in animal models. However, the mechanistic role of enhanced AMPA receptor activity in alcohol-reinforcement and alcohol-seeking behavior remains unclear. This study examined the role of enhanced AMPA receptor function using the selective positive allosteric modulator, aniracetam, in modulating operant alcohol self-administration and cue-induced reinstatement. Male alcohol-preferring (P-) rats, trained to self-administer alcohol (15%, v/v) versus water were pre-treated with aniracetam to assess effects on maintenance of alcohol self-administration. To determine reinforcer specificity, P-rats were trained to self-administer sucrose (0.8%, w/v) versus water, and effects of aniracetam were tested. The role of aniracetam in modulating relapse of alcohol-seeking was assessed using a response contingent cue-induced reinstatement procedure in P-rats trained to self-administer 15% alcohol. Aniracetam pre-treatment significantly increased alcohol-reinforced responses relative to vehicle treatment. This increase was not attributed to aniracetam-induced hyperactivity as aniracetam pre-treatment did not alter locomotor activity. AMPA receptor involvement was confirmed because 6,7-dinitroquinoxaline-2,3-dione (AMPA receptor antagonist) blocked the aniracetam-induced increase in alcohol self-administration. Aniracetam did not alter sucrose-reinforced responses in sucrose-trained P-rats, suggesting that enhanced AMPA receptor activity is selective in modulating the reinforcing function of alcohol. Finally, aniracetam pre-treatment potentiated cue-induced reinstatement of alcohol-seeking behavior versus vehicle-treated P-rats. These data suggest that enhanced glutamate activity at AMPA

Increased serum IL-6 level time-dependently regulates hyperalgesia and spinal mu opioid receptor expression during CFA-induced arthritis

PubMed Central

Tekieh, E.; Zaringhalam, Jalal; Manaheji, H.; Maghsoudi, N.; Alani, B.; Zardooz, H.

2011-01-01

Interleukin (IL)-6 is known to cause pro- and anti-inflammatory effects during different stages of inflammation. Recent therapeutic investigations have focused on treatment of various inflammatory disorders with anti-cytokine substances. As a result, the aim of this study was to further elucidate the influence of IL-6 in hyperalgesia and edema during different stages of Complete Freund's Adjuvant (CFA)-induced arthritis (AA) in male Wistar rats. AA was induced by a single subcutaneous injection of CFA into the rats' hindpaw. Anti-IL-6 was administered either daily or weekly during the 21 days of study. Spinal mu opioid receptor (mOR) expression was detected by Western blotting. Daily and weekly treatment with an anti-IL-6 antibody significantly decreased paw edema in the AA group compared to the AA control group. Additionally, daily and weekly anti-IL-6 administration significantly reduced hyperalgesia on day 7 in the AA group compared to the AA control group; however, there were significant increases in hyperalgesia in the antibody-treated group on days 14 and 21 compared to the AA control group. IL-6 antibody-induced increases in hyperalgesia on the 14th and 21st days after CFA injection correlated with a time-dependent, significant reduction in spinal mOR expression during anti-IL-6 treatment. Our study confirmed the important time-dependent relationship between serum IL-6 levels and hyperalgesia during AA. These results suggest that the stages of inflammation in AA must be considered for anti-hyperalgesic and anti-inflammatory interventions via anti-IL-6 antibody treatment. PMID:27857662

Increased serum IL-6 level time-dependently regulates hyperalgesia and spinal mu opioid receptor expression during CFA-induced arthritis.

PubMed

Tekieh, E; Zaringhalam, Jalal; Manaheji, H; Maghsoudi, N; Alani, B; Zardooz, H

2011-01-01

Interleukin (IL)-6 is known to cause pro- and anti-inflammatory effects during different stages of inflammation. Recent therapeutic investigations have focused on treatment of various inflammatory disorders with anti-cytokine substances. As a result, the aim of this study was to further elucidate the influence of IL-6 in hyperalgesia and edema during different stages of Complete Freund's Adjuvant (CFA)-induced arthritis (AA) in male Wistar rats. AA was induced by a single subcutaneous injection of CFA into the rats' hindpaw. Anti-IL-6 was administered either daily or weekly during the 21 days of study. Spinal mu opioid receptor (mOR) expression was detected by Western blotting. Daily and weekly treatment with an anti-IL-6 antibody significantly decreased paw edema in the AA group compared to the AA control group. Additionally, daily and weekly anti-IL-6 administration significantly reduced hyperalgesia on day 7 in the AA group compared to the AA control group; however, there were significant increases in hyperalgesia in the antibody-treated group on days 14 and 21 compared to the AA control group. IL-6 antibody-induced increases in hyperalgesia on the 14 th and 21 st days after CFA injection correlated with a time-dependent, significant reduction in spinal mOR expression during anti-IL-6 treatment. Our study confirmed the important time-dependent relationship between serum IL-6 levels and hyperalgesia during AA. These results suggest that the stages of inflammation in AA must be considered for anti-hyperalgesic and anti-inflammatory interventions via anti-IL-6 antibody treatment.

Liver congestion in heart failure contributes to inappropriately increased serum hepcidin despite anemia.

PubMed

Ohno, Yukako; Hanawa, Haruo; Jiao, Shuang; Hayashi, Yuka; Yoshida, Kaori; Suzuki, Tomoyasu; Kashimura, Takeshi; Obata, Hiroaki; Tanaka, Komei; Watanabe, Tohru; Minamino, Tohru

2015-01-01

Hepcidin is a key regulator of mammalian iron metabolism and mainly produced by the liver. Hepcidin excess causes iron deficiency and anemia by inhibiting iron absorption from the intestine and iron release from macrophage stores. Anemia is frequently complicated with heart failure. In heart failure patients, the most frequent histologic appearance of liver is congestion. However, it remains unclear whether liver congestion associated with heart failure influences hepcidin production, thereby contributing to anemia and functional iron deficiency. In this study, we investigated this relationship in clinical and basic studies. In clinical studies of consecutive heart failure patients (n = 320), anemia was a common comorbidity (41%). In heart failure patients without active infection and ongoing cancer (n = 30), log-serum hepcidin concentration of patients with liver congestion was higher than those without liver congestion (p = 0.0316). Moreover, in heart failure patients with liver congestion (n = 19), the anemia was associated with the higher serum hepcidin concentrations, which is a type of anemia characterized by induction of hepcidin. Subsequently, we produced a rat model of heart failure with liver congestion by injecting monocrotaline that causes pulmonary hypertension. The monocrotaline-treated rats displayed liver congestion with increase of hepcidin expression at 4 weeks after monocrotaline injection, followed by anemia and functional iron deficiency observed at 5 weeks. We conclude that liver congestion induces hepcidin production, which may result in anemia and functional iron deficiency in some patients with heart failure.

Experimental hyperthyroidism decreases gene expression and serum levels of adipokines in obesity.

PubMed

Luvizotto, Renata de Azevedo Melo; do Nascimento, André Ferreira; de Síbio, Maria Teresa; Olímpio, Regiane Marques Castro; Conde, Sandro José; Lima-Leopoldo, Ana Paula; Leopoldo, André Soares; Cicogna, Antonio Carlos; Nogueira, Célia Regina

2012-01-01

To analyze the influence of hyperthyroidism on the gene expression and serum concentration of leptin, resistin, and adiponectin in obese animals. Male Wistar rats were randomly divided into two groups: control (C)-fed with commercial chow ad libitum-and obese (OB)-fed with a hypercaloric diet. After group characterization, the OB rats continued receiving a hypercaloric diet and were randomized into two groups: obese animals (OB) and obese with 25 μg triiodothyronine (T(3))/100 BW (OT). The T(3) dose was administered every day for the last 2 weeks of the study. After 30 weeks the animals were euthanized. Samples of blood and adipose tissue were collected for biochemical and hormonal analyses as well as gene expression of leptin, resistin, and adiponectin. T(3) treatment was effective, increasing fT(3) levels and decreasing fT(4) and TSH serum concentration. Administration of T(3) promotes weight loss, decreases all fat deposits, and diminishes serum levels of leptin, resistin, and adiponectin by reducing their gene expression. Our results suggest that T(3) modulate serum and gene expression levels of leptin, resistin, and adiponectin in experimental model of obesity, providing new insights regarding the relationship between T(3) and adipokines in obesity.

Experimental Hyperthyroidism Decreases Gene Expression and Serum Levels of Adipokines in Obesity

PubMed Central

Luvizotto, Renata de Azevedo Melo; do Nascimento, André Ferreira; de Síbio, Maria Teresa; Olímpio, Regiane Marques Castro; Conde, Sandro José; Lima-Leopoldo, Ana Paula; Leopoldo, André Soares; Cicogna, Antonio Carlos; Nogueira, Célia Regina

2012-01-01

Aims. To analyze the influence of hyperthyroidism on the gene expression and serum concentration of leptin, resistin, and adiponectin in obese animals. Main Methods. Male Wistar rats were randomly divided into two groups: control (C)—fed with commercial chow ad libitum—and obese (OB)—fed with a hypercaloric diet. After group characterization, the OB rats continued receiving a hypercaloric diet and were randomized into two groups: obese animals (OB) and obese with 25 μg triiodothyronine (T3)/100 BW (OT). The T3 dose was administered every day for the last 2 weeks of the study. After 30 weeks the animals were euthanized. Samples of blood and adipose tissue were collected for biochemical and hormonal analyses as well as gene expression of leptin, resistin, and adiponectin. Results. T3 treatment was effective, increasing fT3 levels and decreasing fT4 and TSH serum concentration. Administration of T3 promotes weight loss, decreases all fat deposits, and diminishes serum levels of leptin, resistin, and adiponectin by reducing their gene expression. Conclusions. Our results suggest that T3 modulate serum and gene expression levels of leptin, resistin, and adiponectin in experimental model of obesity, providing new insights regarding the relationship between T3 and adipokines in obesity. PMID:22645452

Low serum insulin-like growth factor-I (IGF-I) level is associated with increased risk of vascular dementia.

PubMed

Quinlan, Patrick; Horvath, Alexandra; Nordlund, Arto; Wallin, Anders; Svensson, Johan

2017-12-01

Insulin-like growth factor-I (IGF-I) is important for the adult brain, but little is known of the role of IGF-I in Alzheimeŕs disease (AD) or vascular dementia (VaD). A prospective study of 342 patients with subjective or objective mild cognitive impairment recruited at a single memory clinic. We determined whether serum IGF-I concentrations at baseline were associated with the risk of all-cause dementia, AD, or VaD. Patients developing mixed forms of AD and VaD were defined as suffering from VaD. The statistical analyses included Cox proportional hazards regression analysis. During the follow-up (mean 3.6 years), 95 (28%) of the patients developed all-cause dementia [AD, n=37 (11%) and VaD, n=42 (12%)]. Low as well as high serum IGF-I (quartile 1 or 4 vs. quartiles 2-3) did not associate with all-cause dementia [crude hazard ratio (HR) 1.30, 95% confidence interval (CI): 0.81-2.08 and crude HR 1.05, 95% CI: 0.63-1.75, respectively] or AD (crude HR 0.79, 95% CI: 0.35-1.79 and crude HR 0.94, 95% CI: 0.43-2.06, respectively]. In contrast, low serum IGF-I concentrations were associated with increased risk of VaD (quartile 1 vs. quartiles 2-3, crude HR 2.22, 95% CI: 1.13-4.36). The latter association remained significant also after adjustment for multiple covariates. In a memory clinic population, low serum IGF-I was a risk marker for subsequent VaD whereas low IGF-I did not associate with the risk of AD. High serum IGF-I was not related to the risk of conversion to dementia. Copyright © 2017 Elsevier Ltd. All rights reserved.

Increased serum procalcitonin levels in pregnant patients with asymptomatic bacteriuria.

PubMed

Bilir, Filiz; Akdemir, Nermin; Ozden, Selcuk; Cevrioglu, A Serhan; Bilir, Cemil

2013-09-05

Among the pregnancy urinary tract infections, asymptomatic bacteriuria (ASB) is the most common one. Untreated ASB can progress to pyelonephritis in 30-50% of the patients and can also result in prematurity in 27% of the pregnancy so it needs immediate diagnosis and treatment. In this study, we wanted to evaluate procalcitonin levels, compared to other inflammatory in pregnant women with ASB. The study was designed between the period of January 2012 and February 2013 at Sakarya University School of Medicine, Department of Gynecology and Obstetrics. The study population included 30 pregnant patients with asymptomatic bacteriuria and 39 healthy pregnant controls. Mean age was 28 (SD, 5.5) of the study population; mean maternal weight was 70 (SD, 8) kilogram. There were no statically significant differences between the groups according to the routine biochemical parameters, but gestational age was significantly lower in the ASB group compared to the controls (20.4 vs 28.6, respectively; p < 0.001). Serum procalcitonin levels were negative in all of the controls. In ASB group, 9 (30%) patients had procalcitonin levels greater than >0.05 ng/ml and 21(70%) patients had negative procalcitonin levels (Chi-squrae, p < 0.001). The sensitivity and specificity of procalcitonin assay for ASB was calculated as 30% and 100%, respectively. The positive predictive value was 100% and the negative predictive value was 65%. The most frequent microorganisms in the urine culture were Escherichia coli (26 patients, 87%), Proteus mirabilis (3 patients, 10%) and Klebsiella (1 patient, 3%) in the ASB group. We experienced four (44%) recurrences among nine positive procalcitonin in ASB patients after completion of treatment of the first ASB diagnosis. Procalcitonin levels were significantly higher in ASB group than the control group and serum procalcitonin levels were higher in pregnant women with recurrent ASB. This finding is an important result revealed that high procalcitonin level can

EFFECTS OF PREDNISOLONE AND TRIAMCINOLONE ON CORTICOSTEROID LEVELS IN PAROTID FLUID, SERUM, AND URINE.

DTIC Science & Technology

A simultaneous determination was made of 17-OHCS in serum, urine, and parotid fluid, by the Porter-Silber reaction, after the oral administration of...prednisolone, triamcinolone, or placebo to 240 normal human subjects. The data clearly demonstrate the homology of serum and parotid fluid 17-OHCS

Expulsion of Nippostrongylus brasiliensis from rats protected with serum. I. The efficacy of sera from singly and multiply infected donors related to time of administration and volume of serum injected.

PubMed Central

Miller, H R

1980-01-01

Several of the parameters related to the efficacy of passive protection against Nippostrongylus brasiliensis were studied in female hybrid (PVG/c x DA)F1 and outbred Wistar rats. The time after infection at which immune serum was given did, to some extent, alter the degree of protection conferred. There was substantial protection 8 days after challenge in rats given hyperimmune serum (HIS) either as daily injections 4-7 days post-infection or as a single dose on day 4. Eight separate experiments in which HIS was injected 4 days after challenge with 1000 l3 resulted in expulsion of 96 +/- 2% of the worm burdens by day 8. In a further six experiments, following infection with 2000 l3 and using the same protocol, 85 +/- 3% of the worm burden was expelled by day 8. A lag of 2 days between serum transfer and commencement of worm expulsion was consistently observed and, within the space of a further 2-4 days, more than 95% of the parasites were expelled. Transplanted 'normal' and 'damaged' adult worms were also susceptible to the passive transfer of HIS. Sera recovered from rats immunized with two or three challenges (hyperimmune sera) were more protective than sera from rats given one challenge. Serum from rats challenged for the first time 6 days previously conferred significant protection against a 1000 l3 infection and sera recovered 8 and 10-12 days post-infection with 4000 l3 protected recipients with increasing effectiveness. Thoracic duct lymph collected on the tenth day of infection with 4000 l3 was also protective. The response to both primary infection and hyperimmune serum was dose-dependent. The consistently good protection achieved in the present study when compared with the variable success of previous experiments (reviewed by Ogilvie & Jones, 1971) may be a function of the strain and sex of the rats used, together with modifications of the immunization protocols. The relevance of these findings to mucosal defences against N. brasiliensis is discussed

The effect of the parenteral administration of a rabbit anti-(mouse)-IgD serum on the immune response of mice to sheep erythrocytes.

PubMed Central

Dresser, D W; Parkhouse, R M

1978-01-01

Experiments have been carried out to find out if the administration of an anti-IgD serum to mice interferes in anyway with their immune response to sheep red blood cells. This was done to test a hypothesis that a biological role for IgD might be as a critical cellular receptor for antigen. Our results show that the injection of anti-IgD two days before antigen results in suppression of primary responses and priming (the antigen dependent generation of memory cells) but has no suppressive effect on a secondary response. On this indirect evidence we conclude that it is likely that IgD is present on antigen-sensitive percursor cells but not on memory cells. PMID:367957

Subject-specific increases in serum S-100B distinguish sports-related concussion from sports-related exertion.

PubMed

Kiechle, Karin; Bazarian, Jeffrey J; Merchant-Borna, Kian; Stoecklein, Veit; Rozen, Eric; Blyth, Brian; Huang, Jason H; Dayawansa, Samantha; Kanz, Karl; Biberthaler, Peter

2014-01-01

The on-field diagnosis of sports-related concussion (SRC) is complicated by the lack of an accurate and objective marker of brain injury. To compare subject-specific changes in the astroglial protein, S100B, before and after SRC among collegiate and semi-professional contact sport athletes, and compare these changes to differences in S100B before and after non-contact exertion. Longitudinal cohort study. From 2009-2011, we performed a prospective study of athletes from Munich, Germany, and Rochester, New York, USA. Serum S100B was measured in all SRC athletes at pre-season baseline, within 3 hours of injury, and at days 2, 3 and 7 post-SRC. Among a subset of athletes, S100B was measured after non-contact exertion but before injury. All samples were collected identically and analyzed using an automated electrochemiluminescent assay to quantify serum S100B levels. Forty-six athletes (30 Munich, 16 Rochester) underwent baseline testing. Thirty underwent additional post-exertion S100B testing. Twenty-two athletes (16 Rochester, 6 Munich) sustained a SRC, and 17 had S100B testing within 3 hours post-injury. The mean 3-hour post-SRC S100B was significantly higher than pre-season baseline (0.099±0.008 µg/L vs. 0.058±0.006 µg/L, p = 0.0002). Mean post-exertion S100B was not significantly different than the preseason baseline. S100B levels at post-injury days 2, 3 and 7 were significantly lower than the 3-hour level, and not different than baseline. Both the absolute change and proportional increase in S100B 3-hour post-injury were accurate discriminators of SRC from non-contact exertion without SRC (AUC 0.772 and 0.904, respectively). A 3-hour post-concussion S100B >0.122 µg/L and a proportional S100B increase of >45.9% over baseline were both 96.7% specific for SRC. Relative and absolute increases in serum S100B can accurately distinguish SRC from sports-related exertion, and may be a useful adjunct to the diagnosis of SRC.

Chronic administration of dietary grape seed extract increases colonic expression of gut tight junction protein occludin and reduces fecal calprotectin: a secondary analysis of healthy Wistar Furth rats.

PubMed

Goodrich, Katheryn M; Fundaro, Gabrielle; Griffin, Laura E; Grant, Ar'quette; Hulver, Matthew W; Ponder, Monica A; Neilson, Andrew P

2012-10-01

Animal studies have demonstrated the potential of grape seed extract (GSE) to prevent metabolic syndrome, obesity, and type 2 diabetes. Recently, metabolic endotoxemia induced by bacterial endotoxins produced in the colon has emerged as a possible factor in the etiology of metabolic syndrome. Improving colonic barrier function may control endotoxemia by reducing endotoxin uptake. However, the impact of GSE on colonic barrier integrity and endotoxin uptake has not been evaluated. We performed a secondary analysis of samples collected from a chronic GSE feeding study with pharmacokinetic end points to examine potential modulation of biomarkers of colonic integrity and endotoxin uptake. We hypothesized that a secondary analysis would indicate that chronic GSE administration increases colonic expression of intestinal tight junction proteins and reduces circulating endotoxin levels, even in the absence of an obesity-promoting stimulus. Wistar Furth rats were administered drinking water containing 0.1% GSE for 21 days. Grape seed extract significantly increased the expression of gut junction protein occludin in the proximal colon and reduced fecal levels of the neutrophil protein calprotectin, compared with control. Grape seed extract did not significantly reduce serum or fecal endotoxin levels compared with control, although the variability in serum levels was widely increased by GSE. These data suggest that the improvement of gut barrier integrity and potential modulation of endotoxemia warrant investigation as a possible mechanism by which GSE prevents metabolic syndrome and associated diseases. Further investigation of this mechanism in high-fat feeding metabolic syndrome and obesity models is therefore justified. Copyright © 2012 Elsevier Inc. All rights reserved.

Relationship among serum taurine, serum adipokines, and body composition during 8-week human body weight control program.

PubMed

You, Jeong Soon; Park, Ji Yeon; Zhao, Xu; Jeong, Jin Seok; Choi, Mi Ja; Chang, Kyung Ja

2013-01-01

Human adipose tissue is not only a storage organ but also an active endocrine organ to release adipokines. This study was conducted to investigate the relationship among serum taurine and adipokine levels, and body composition during 8-week human body weight control program in obese female college students. The program consisted of diet therapy, exercise, and behavior modification. After the program, body weight, body fat mass, percent body fat, and body mass index (BMI) were significantly decreased. Serum triglyceride (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) levels were significantly decreased. Also serum adiponectin level was significantly increased and serum leptin level was significantly decreased. There were no differences in serum taurine and homocysteine levels. The change of serum adiponectin level was positively correlated with change of body fat mass and percent body fat. These results may suggest that body fat loss by human body weight control program is associated with an increase in serum adiponectin in obese female college students. Therefore, further study such as taurine intervention study is needed to know more exact correlation between dietary taurine intake and serum adipokines or body composition.

Increased EPA levels in serum phospholipids of humans after four weeks daily ingestion of one portion chicken fed linseed and rapeseed oil

PubMed Central

2012-01-01

Since the amounts of arachidonic acid (AA) and EPA in food may have implications for human health, we investigated whether a small change in chicken feed influenced the blood lipid concentration in humans ingesting the chicken. Forty-six young healthy volunteers (age 20–29) were randomly allocated into two groups in a double-blind dietary intervention trial, involving ingestion of about 160 g chicken meat per day for 4 weeks. The ingested meat was either from chickens given a feed concentrate resembling the commercial chicken feed, containing 4% soybean oil (SO), or the meat was from chickens given a feed where the soybean oil had been replaced by 2% rapeseed oil plus 2% linseed oil (RLO). Serum total cholesterol, LDL and HDL cholesterol, triacylglycerols, serum phospholipid fatty acid concentration, blood pressure, body weight and C-reactive protein were determined at baseline and post-intervention. In subjects consuming chicken meat from the RLO group there was a significantly (p < 0.001) increased concentration of EPA in serum phospholipids, and a reduced ratio between AA and EPA. The participants that had a low% of EPA + DHA in serum phospholipids (less than 4.6%), all increased their% of EPA + DHA after the four week intervention period when consuming the RLO chicken. No significant response differences in cholesterol, triacylglycerol, C-reactive protein, body weight or blood pressure were observed between the groups. This trial demonstrates that a simple change in chicken feed can have beneficial effects on amount of EPA and the AA/EPA ratio in human serum phospholipids. PMID:22913248

Increased EPA levels in serum phospholipids of humans after four weeks daily ingestion of one portion chicken fed linseed and rapeseed oil.

PubMed

Haug, Anna; Nyquist, Nicole F; Mosti, Therese J; Andersen, Malin; Høstmark, Arne T

2012-08-22

Since the amounts of arachidonic acid (AA) and EPA in food may have implications for human health, we investigated whether a small change in chicken feed influenced the blood lipid concentration in humans ingesting the chicken. Forty-six young healthy volunteers (age 20-29) were randomly allocated into two groups in a double-blind dietary intervention trial, involving ingestion of about 160 g chicken meat per day for 4 weeks. The ingested meat was either from chickens given a feed concentrate resembling the commercial chicken feed, containing 4% soybean oil (SO), or the meat was from chickens given a feed where the soybean oil had been replaced by 2% rapeseed oil plus 2% linseed oil (RLO).Serum total cholesterol, LDL and HDL cholesterol, triacylglycerols, serum phospholipid fatty acid concentration, blood pressure, body weight and C-reactive protein were determined at baseline and post-intervention. In subjects consuming chicken meat from the RLO group there was a significantly (p < 0.001) increased concentration of EPA in serum phospholipids, and a reduced ratio between AA and EPA. The participants that had a low% of EPA + DHA in serum phospholipids (less than 4.6%), all increased their% of EPA + DHA after the four week intervention period when consuming the RLO chicken. No significant response differences in cholesterol, triacylglycerol, C-reactive protein, body weight or blood pressure were observed between the groups. This trial demonstrates that a simple change in chicken feed can have beneficial effects on amount of EPA and the AA/EPA ratio in human serum phospholipids.

Long-term effects of intermittent equine parathyroid hormone fragment (ePTH-1-37) administration on bone metabolism in healthy horses.

PubMed

Weisrock, Katharina U; Winkelsett, Sarah; Martin-Rosset, William; Forssmann, Wolf-Georg; Parvizi, Nahid; Coenen, Manfred; Vervuert, Ingrid

2011-11-01

Intermittent administration of parathyroid hormone (PTH) is an anabolic therapy for osteoporotic conditions in humans. This study evaluated the effects of equine PTH fragment (ePTH-1-37) administration on bone metabolism in 12 healthy horses. Six horses each were treated once daily for 120days with subcutaneous injections of 0.5μg/kg ePTH-1-37 or placebo. Blood was collected to determine ionized calcium (Ca(++)), total Ca (Ca(T)), inorganic phosphorus, serum equine osteocalcin (eOC), carboxy-terminal telopeptide of type I collagen (ICTP), bone-specific alkaline phosphatase, and carboxy-terminal cross-linked telopeptide of type I collagen. Bone mineral density (BMD) was determined with dual X-ray absorptiometry of the metacarpus and calcaneus. Significantly higher blood Ca(++) and plasma Ca(T) concentrations were measured 5h after ePTH-1-37 administration compared to placebo. Higher serum eOC concentrations were found for ePTH-1-37 treatment at days 90 (P<0.05) and 120 (P=0.05). Significantly higher serum ICTP levels were observed with ePTH-1-37 treatment at days 60 and 90. For both study groups, BMD increased significantly in the calcaneus. Long-term use of ePTH-1-37 seemed to have no negative effects on bone metabolism in healthy horses. The absence of undesirable side effects is the premise to ensure safety for further clinical investigations in horses with increased bone resorption processes. Copyright © 2011 Elsevier Ltd. All rights reserved.

Serum studies in man after administration of vitamin A acetate and vitamin A alcohol

PubMed Central

Fitzgerald, Oliver; Fennelly, James J.; Hingerty, Daniel J.

1962-01-01

Vitamin A acetate and vitamin A alcohol, triolein I131, oleic acid I131, and fat balance tests have been assessed in studies on cases of coeliac disease, pancreatic insufficiency, and some disorders of the small intestinal wall. In coeliac disease a very low serum carotene and flat vitamin A absorption curves have been noted. The contrast between vitamin A acetate and alcohol curves has been clearly shown in cases of pancreatic disorder showing maldigestion. The correlation between vitamin A and triolein I131 absorption (0·89) is closer than that between vitamin A and fat balance. In assessing intestinal absorption serum carotene figures are of value only if very low figures are found. PMID:13893355

Effect of kisspeptin-10, LH and hCG on serum testosterone concentrations in stallions, donkeys and mules.

PubMed

Akhtar, Rana Waseem; Shah, Syed Aftab Hussain; Qureshi, Irfan Zia

2017-10-15

This study was conducted to determine the response of serum testosterone (T) in male equines (stallions, donkeys and mules) after administering intravenous doses of kisspeptin-10 (KP-10), human chorionic gonadotropin (hCG) and luteinizing hormone (LH) and saline as a control. The animals were divided into four groups of three each: Group I, 3 ml of 0.95% saline; Group II, 50 μg KP-10; Group III, 2500 IU hCG and group IV, 400 μg LH. The administration of KP-10 and hCG to stallions resulted in a significant increase in serum T concentration at 240 min; whereas it was significantly higher at 30, 60, 120, and 240 min with LH treatment as compared to pre-dose concentrations. Both KP-10 and hCG significantly elevated the T concentrations in donkeys at 120 and 240 min, respectively; whereas it was significantly higher at 60, 120, and 240 min with LH treatment as compared to pre-dose concentration. Both KP-10 and LH elevated T in donkeys at 240 min as compared to the control and hCG concentrations. After 120 and 240 min, T concentrations in mules were higher (p < 0.05) with administration of KP-10, hCG and LH as compared to the control. In conclusion, the administration of KP-10, hCG and LH elevate the serum T concentration in normal male equines. It is suggested that KP-10 may be useful in situations where an increase in T is desired. Further work is required to determine the effect of KP-10 on T in male equids with reproductive abnormalities before it can be used in clinical situations. Copyright © 2017 Elsevier Inc. All rights reserved.

Differential uptake of salicylate in serum, cerebrospinal fluid, and perilymph.

PubMed

Jastreboff, P J; Hansen, R; Sasaki, P G; Sasaki, C T

1986-10-01

After intraperitoneal administration of salicylate in anesthetized rats and guinea pigs, we found that salicylate levels in perilymph (PL) are closely related to both drug levels in cerebrospinal fluid (CSF) and in serum, with higher levels systematically observed in PL than in CSF. Further analysis suggests that salicylate is not passively transported into PL across CSF but, rather, is transported from blood directly to PL. The time course of salicylate uptake in rats reveals maximum levels at 1 1/2 hours (serum) and two to four hours (CSF and PL). On the other hand, salicylate uptake into serum and CSF of guinea pigs exhibits a longer time course, with maximum levels reached at four hours (serum) and five hours (CSF). These data, not previously available, are basic to our understanding of salicylate-related auditory effects.

Repeated chlorpromazine administration increases a behavioural response of rats to 5-hydroxytryptamine receptor stimulation.

PubMed Central

Green, A R

1977-01-01

1 The hyperactivity syndrome produced in rats by administration of tranylcypromine (20 mg/kg i.p.) followed 30 min later by L-tryptophan (50 mg/kg i.p.) is generally considered to be due to increased 5-hydroxytryptamine (5-HT) functional activity. It is inhibited by chlorpromazine (30 mg/kg i.p.) injected 60 min before the tranylcypromine. However, chlorpromazine injection for 4 days either at a dose of 30 mg/kg once daily or 5 mg/kg twice daily results in an enhanced hyperactivity response to tranylcypromine and L-tryptophan administration 24 h after the final dose of chlorpromazine. 2 One injection of chlorpromazine (30 mg/kg) did not produce enhancement 24 h later and the inhibition of the tranylcypromine/L-tryptophan hyperactivity observed after acute chlorpromazine injection was seen if the rats were given tranylcypromine and L-tryptophan 1 h after the fourth chlorpromazine (30 mg/kg) dose. 3 Chlorpromazine (30 mg/kg) once daily or 5 mg/kg twice daily for 4 days resulted in rats displaying enhanced behavioral responses to the suggested 5-HT agonist 5-methoxy N,N-dimethyltryptamine (2 mg/kg) on day 5. 4 Chlorpromazine (30 mg/kg) once daily for 4 days produces a slight increase in brain 5-hydroxytryptamine (5-HT) concentration on day 5, but no difference in the rate of brain 5-HT synthesis or the rate of 5-HT accumulation after tranylcypromine and L-tryptophan administration. 5. There is some evidence that chlorpromazine blocks 5-HT receptors. It has also been observed that several other neuroleptic drugs do not produce enhanced 5-HT responses after repeated administration. It is suggested therefore that the enhanced behavioural response to 5-HT receptor stimulation following repeated chlorpromazine administration may be because this drug blocks 5-HT receptors. PMID:264797

Validation of an immunoassay for canine thyroid-stimulating hormone and changes in serum concentration following induction of hypothyroidism in dogs.

PubMed

Williams, D A; Scott-Moncrieff, C; Bruner, J; Sustarsic, D; Panosian-Sahakian, N; Unver, E; el Shami, A S

1996-11-15

To validate a new immunoradiometric assay for canine thyroid-stimulating hormone (cTSH) and to document changes in serum cTSH concentration during induction of hypothyroidism in dogs. Six healthy adult male Beagles. Sensitivity, specificity, precision, and accuracy of the cTSH assay were evaluated in vitro. Hypothyroidism was induced in dogs by i.v. administration of sodium iodide I 131 solution. Subsequently, L-thyroxine was administered orally to normalize serum thyroxine concentrations. The cTSH assay appeared to be specific and was sufficiently sensitive to detect cTSH in the serum of these dogs prior to induction of hypothyroidism. There was a 35-fold increase in mean serum cTSH concentration following induction of hypothyroidism, and 35 days after initiation of thyroid replacement therapy, mean serum cTSH concentration was not significantly greater than mean baseline value. Assay of serum cTSH is likely to prove helpful in the differential diagnosis of primary, secondary, and tertiary hypothyroidism in dogs, and in monitoring response to thyroid hormone replacement treatment.

The Contingency of Cocaine Administration Accounts for Structural and Functional Medial Prefrontal Deficits and Increased Adrenocortical Activation

PubMed Central

Anderson, Rachel M.; Cosme, Caitlin V.; Glanz, Ryan M.; Miller, Mary C.; Romig-Martin, Sara A.; LaLumiere, Ryan T.

2015-01-01

The prelimbic region (PL) of the medial prefrontal cortex (mPFC) is implicated in the relapse of drug-seeking behavior. Optimal mPFC functioning relies on synaptic connections involving dendritic spines in pyramidal neurons, whereas prefrontal dysfunction resulting from elevated glucocorticoids, stress, aging, and mental illness are each linked to decreased apical dendritic branching and spine density in pyramidal neurons in these cortical fields. The fact that cocaine use induces activation of the stress-responsive hypothalamo-pituitary-adrenal axis raises the possibility that cocaine-related impairments in mPFC functioning may be manifested by similar changes in neuronal architecture in mPFC. Nevertheless, previous studies have generally identified increases, rather than decreases, in structural plasticity in mPFC after cocaine self-administration. Here, we use 3D imaging and analysis of dendritic spine morphometry to show that chronic cocaine self-administration leads to mild decreases of apical dendritic branching, prominent dendritic spine attrition in PL pyramidal neurons, and working memory deficits. Importantly, these impairments were largely accounted for in groups of rats that self-administered cocaine compared with yoked-cocaine- and saline-matched counterparts. Follow-up experiments failed to demonstrate any effects of either experimenter-administered cocaine or food self-administration on structural alterations in PL neurons. Finally, we verified that the cocaine self-administration group was distinguished by more protracted increases in adrenocortical activity compared with yoked-cocaine- and saline-matched controls. These studies suggest a mechanism whereby increased adrenocortical activity resulting from chronic cocaine self-administration may contribute to regressive prefrontal structural and functional plasticity. SIGNIFICANCE STATEMENT Stress, aging, and mental illness are each linked to decreased prefrontal plasticity. Here, we show that chronic

Alteration in metabolism and toxicity of acetaminophen upon repeated administration in rats.

PubMed

Kim, Sun J; Lee, Min Y; Kwon, Do Y; Kim, Sung Y; Kim, Young C

2009-10-01

Our previous studies showed that administration of a subtoxic dose of acetaminophen (APAP) to female rats increased generation of carbon monoxide from dichloromethane, a metabolic reaction catalyzed mainly by cytochrome P450 (CYP) 2E1. In this study we examined the changes in metabolism and toxicity of APAP upon repeated administration. An intraperitoneal dose of APAP (500 mg/kg) alone did not increase aspartate aminotransferase, alanine aminotransferase, or sorbitol dehydrogenase activity in serum, but was significantly hepatotoxic when the rats had been pretreated with an identical dose of APAP 18 h earlier. The concentrations and disappearance of APAP and its metabolites in plasma were monitored for 8 h after the treatment. APAP pretreatment reduced the elevation of APAP-sulfate, but increased APAP-cysteine concentrations in plasma. APAP or APAP-glucuronide concentrations were not altered. Administration of a single dose of APAP 18 h before sacrifice increased microsomal CYP activities measured with p-nitrophenol, p-nitroanisole, and aminopyrine as probes. Expression of CYP2E1, CYP3A, and CYP1A proteins in the liver was also elevated significantly. The results suggest that administration of APAP at a subtoxic dose may result in an induction of hepatic CYP enzymes, thereby altering metabolism and toxicological consequences of various chemical substances that are substrates for the same enzyme system.

Abnormal serum pancreatic enzymes, but not pancreatitis, are associated with an increased risk of malignancy in patients with intraductal papillary mucinous neoplasms.

PubMed

Roch, Alexandra M; Parikh, Janak A; Al-Haddad, Mohammad A; DeWitt, John M; Ceppa, Eugene P; House, Michael G; Nakeeb, Attila; Schmidt, C Max

2014-10-01

Pancreatitis is associated with intraductal papillary mucinous neoplasm (IPMN). This association is in part due to inflammation from pancreatic ductal obstruction. Although the correlation between pancreatitis and the malignant potential of IPMN is unclear, the 2012 International Consensus Guidelines (ICG) consider pancreatitis a "worrisome feature." We hypothesized that serum pancreatic enzymes, markers of inflammation, are a better predictor of malignancy than pancreatitis in patients with IPMN. Between 1992 and 2012, 364 patients underwent resection for IPMN at a single university hospital. In the past decade, serum amylase and lipase were collected prospectively as an inflammatory marker in 203 patients with IPMN at initial surveillance and "cyst clinic" visits. The latest serum pancreatic enzyme values within 3 months preoperatively were studied. Pancreatitis was defined according to the 2012 revision of the Atlanta Consensus. Of the 203 eligible patients, there were 76 with pancreatitis. Pancreatitis was not associated with an increased rate of malignancy (P = .51) or invasiveness (P = .08). Serum pancreatic enzymes categorically outside of normal range (high or low) were also not associated with malignancy or invasiveness. In contrast, as a continuous variable, the higher the serum pancreatic enzymes were, the greater the rate of invasive IPMN. Of the 127 remaining patients without pancreatitis, serum pancreatic enzymes outside of normal range (low and high) were each associated with a greater rate of malignancy (P < .0001 and P = .0009, respectively). Serum pancreatic enzyme levels above normal range (high) were associated with a greater rate of invasiveness (P = .02). In patients with IPMN without a history of pancreatitis, serum pancreatic enzymes outside of the normal range are associated with a greater risk of malignancy. In patients with a history of pancreatitis, there is a positive correlation between the levels of serum pancreatic enzymes

Reduced folate and serum vitamin metabolites in patients with rectal carcinoma: an open-label feasibility study of pemetrexed with folic acid and vitamin B12 supplementation

PubMed Central

Odin, Elisabeth A.; Carlsson, Göran U.; Kurlberg, Göran K.; Björkqvist, Hillevi G.; Tångefjord, Maria T.; Gustavsson, Bengt G.

2016-01-01

The objectives of this single-center, open-label, phase II study were to evaluate (a) the feasibility and safety of neoadjuvant administration of pemetrexed with oral folic acid and vitamin B12 (FA/B12) in newly diagnosed patients with resectable rectal cancer and (b) intracellular and systemic vitamin metabolism. Patients were treated with three cycles of pemetrexed (500 mg/m2, every 3 weeks) and FA/B12 before surgery. The reduced folates tetrahydrofolate, 5-methyltetrahydrofolate, and 5,10-methylenetetrahydrofolate were evaluated from biopsies in tumor tissue and in adjacent mucosa. Serum levels of homocysteine, cystathionine, and methylmalonic acid were also measured. All 37 patients received three cycles of pemetrexed; 89.2% completed their planned dosage within a 9-week feasibility time frame. Neither dose reductions nor study drug-related serious adverse events were reported. Reduced folate levels were significantly higher in tumor tissue compared with adjacent mucosa at baseline. After FA/B12 administration, tissue levels of reduced folates increased significantly and remained high during treatment in both tumor and mucosa until surgery. Serum levels of cystathionine increased significantly compared with baseline after FA/B12 administration, but then decreased, fluctuating cyclically during pemetrexed therapy. Homocysteine and methylmalonic acid levels decreased significantly after FA/B12 administration, and remained below baseline levels during the study. These results indicate that administration of three neoadjuvant cycles of single-agent pemetrexed, every 3 weeks, with FA/B12 in patients with resectable rectal cancer is feasible and tolerable. Tissue and serum vitamin metabolism results demonstrate the influence of pemetrexed and FA/B12 on vitamin metabolism and warrant further study. PMID:26825869

Improving Communication Skills among High School Assistant Principals To Increase Administrative Team Effectiveness.

ERIC Educational Resources Information Center

Hosack, Mary Browne

This paper describes a practicum program that was developed to increase the effectiveness of the administrative team at one high school. A lack of communication skills had prevented the target group from working together as a team. Strategies included role-play activities, workshops, and communication skill-development meetings. A series of…

Head-out immersion in hot water increases serum BDNF in healthy males.

PubMed

Kojima, Daisuke; Nakamura, Takeshi; Banno, Motohiko; Umemoto, Yasunori; Kinoshita, Tokio; Ishida, Yuko; Tajima, Fumihiro

2017-11-20

Brain-derived neurotrophic factor (BDNF) is an important neurotrophin. The present study investigated the effects of head-out water immersion (HOI) on serum BDNF concentrations. Eight healthy men performed 20 min head-out water immersion at 42 °C (hot-HOI) and 35 °C (neutral-HOI). These experimental trials were administered in a randomised order separated by at least 7 days. Venous blood samples were withdrawn at rest, immediately after the 20-min HOI, as well as at 15 and 30 min after the end of the HOI. Serum BDNF and S100β, plasma cortisol, platelet and monocyte counts, and core body temperature (T cb ) were measured. T cb was higher at the end of the hot-HOI and 15 min after hot-HOI (p < 0.01), but recovered to pre-HOI level at 30 min after hot-HOI. No change in T cb was recorded during neutral-HOI. BDNF level was higher (p < 0.05) at the end of the hot-HOI and at 15 min after the end of hot-HOI, and returned to the baseline at 30 min after hot-HOI. S100β, platelet count and monocyte count remained stable throughout the study. Cortisol level was lower at the end of the hot-HOI and returned to pre-HOI level during the recovery period. BDNF and S100β, cortisol, and platelet and monocyte counts did not change throughout the neutral-HOI study. The present findings suggested that the increase in BDNF during 20-min hot-HOI was induced by hyperthermia through enhanced production, rather than by changes in permeability of the blood-brain barrier (BBB), platelet clotting mechanisms or secretion from monocytes.

Effects of febuxostat on serum urate level in Japanese hyperuricemia patients.

PubMed

Yamamoto, Tetsuya; Hidaka, Yuji; Inaba, Masaaki; Ishimura, Eiji; Ooyama, Hiroshi; Kakuda, Hirokazu; Moriwaki, Yuji; Higami, Kenshi; Ohtawara, Akira; Hosoya, Tatsuo; Nishikawa, Hazime; Taniguchi, Atsuo; Ueda, Takanori; Yamauchi, Takahiro; Fujimori, Shin; Mineo, Ikuo; Yamanaka, Hisashi

2015-09-01

We assessed the efficacy and adverse effects of febuxostat in male hyperuricemia patients. This was a 12-week, multicenter, open-label, uncontrolled study. The enrolled subjects were 89 hyperuricemic male patients (12 overexcretors, 56 normal excretors, and 21 underexcretors). The endpoint was percent change in serum urate level. The concentration of urate in serum before and 12 weeks after beginning administration of febuxostat in the overexcretors was 9.34 ± 1.48 and 5.59 ± 1.17 mg/dl, respectively, while those were 8.59 ± 1.24 and 5.41 ± 1.35 mg/dl, respectively, in the normal excretors, and 8.29 ± 1.01and 5.11 ± 1.71 mg/dl, respectively, in the underexcretors. After 12 weeks, the rate of change in serum urate after beginning administration of febuxostat was - 0.384 ± 0.186 in the overexcretors, - 0.368 ± 0.128 in the normal excretors, and - 0.365 ± 0.217 in the underexcretors, with no significant differences among them. A common adverse event related to febuxostat was gout flare. Febuxostat effectively reduced the concentration of urate in serum in hyperuricemic patients regardless of the level of uric acid excreted in urine without severe adverse effects.

INCREASED SERUM LEVELS OF UREA AND CREATININE ARE SURROGATE MARKERS FOR DISRUPTION OF RETINAL PHOTORECEPTOR EXTERNAL LIMITING MEMBRANE AND INNER SEGMENT ELLIPSOID ZONE IN TYPE 2 DIABETES MELLITUS.

PubMed

Saxena, Sandeep; Ruia, Surabhi; Prasad, Senthamizh; Jain, Astha; Mishra, Nibha; Natu, Shankar M; Meyer, Carsten H; Gilhotra, Jagjit S; Kruzliak, Peter; Akduman, Levent

2017-02-01

To evaluate the role of serum urea and creatinine as surrogate markers for disruption of retinal photoreceptor external limiting membrane (ELM) and inner segment ellipsoid zone (EZ) in Type 2 diabetic retinopathy (DR) using spectral-domain optical coherence tomography, for the first time. One hundred and seventeen consecutive cases of Type 2 diabetes mellitus (diabetes without retinopathy [No DR; n = 39], nonproliferative diabetic retinopathy [NPDR; n = 39], proliferative diabetic retinopathy [PDR; n = 39]) and 40 healthy control subjects were included. Serum levels of urea and creatinine were assessed using standard protocol. Spectral-domain optical coherence tomography was used to grade the disruption of ELM and EZ as follows: Grade 0, no disruption of ELM and EZ; Grade 1, ELM disrupted, EZ intact; Grade 2, ELM and EZ disrupted. Data were analyzed statistically. Increase in serum levels of urea (F = 22.93) and creatinine (F = 15.82) and increased grades of disruption of ELM and EZ (γ = 116.3) were observed with increased severity of DR (P < 0.001). Increase in serum levels of urea (F = 10.45) and creatinine (F = 6.89) was observed with increased grades of disruption of ELM and EZ (P = 0.001). Serum levels of urea and creatinine are surrogate markers for disruption of retinal photoreceptor ELM and EZ on spectral-domain optical coherence tomography in DR.

Increased Serum IGFBP-1 and Reduced Insulin Resistance After Roux-En-Y Gastric Bypass in Chinese Patients with Type 2 Diabetes: a 6-Month Follow-Up.

PubMed

Song, Zhigao; Dai, Xiaojian; Yu, Hao; Luo, Qing; Zhang, Hongbin; Wu, Liangping

2018-04-24

This study aimed to measure changes of insulin-like growth factor binding protein-1 (IGFBP-1) in patients with type 2 diabetes mellitus (T2D) following gastric bypass surgery. A total of 10 patients with T2D underwent laparoscopic Roux-en-Y gastric bypass (RYGB) surgery. Patient height, weight, waist circumference, and hip circumference were measured pre- and post-operatively at 6 months after surgery. Serum samples were collected at 6 months after surgery to determine fasting blood glucose, glycosylated Hb, fasting insulin, C-peptide, and 2-h postprandial blood glucose, insulin, and C-peptide. Serum was collected at 3 days and 6 months after surgery and IGFBP-1 level determined using ELISA. Serum samples were also collected from 30 healthy weight subjects and 27 overweight control subjects. Body weight, BMI, and waist circumference were significantly improved following RYGB surgery. Blood glucose, fasting blood glucose, 2-h postprandial blood glucose, and HbA1c were also significantly improved. Fasting C-peptide and 2-h postprandial C-peptide were non-significantly reduced. Serum IGFBP-1 significantly increased at 3 days and 6 months after RYGB surgery. Pre-operative serum IGFBP-1 was not significantly different from healthy weight subjects or overweight subjects. Increased serum level of IGF-binding proteins after RYGB in 6 months is increased post-surgery compared with overweight and healthy weight controls. IGFBP-1 may serve as part of new supplementary criteria for surgical selection and for defining the success of RYGB.

9 CFR 102.1 - Licenses issued by the Administrator.

Code of Federal Regulations, 2011 CFR

2011-01-01

... biological products under the Virus-Serum-Toxin Act shall hold an unexpired and unrevoked U.S. Veterinary Biologics Establishment License issued by the Administrator and a U.S. Veterinary Biological Product License...

9 CFR 102.1 - Licenses issued by the Administrator.

Code of Federal Regulations, 2010 CFR

2010-01-01

... biological products under the Virus-Serum-Toxin Act shall hold an unexpired and unrevoked U.S. Veterinary Biologics Establishment License issued by the Administrator and a U.S. Veterinary Biological Product License...

Lack of increase of serum adiponectin concentrations with a moderate weight loss during six months on a high-caloric diet in military service among a young male Finnish population.

PubMed

Mousavinasab, Firoozeh; Tähtinen, Tuula; Jokelainen, Jari; Koskela, Pentti; Vanhala, Mauno; Oikarinen, Jorma; Keinänen-Kiukaanniemi, Sirkka

2005-02-01

An increase of insulin resistance and a worsening of lipid profile during 6 mo of military service in young male Finnish population has previously been shown by us. The present study demonstrates unfavorable changes of serum adiponectin concentrations and their association with weight loss in these particular circumstances. Adiponectin in a range of 4.3-21.2 microg/mL was present in the serum samples and had a significant negative correlation with weight, body mass index, waist to hip ratio, and insulin. Fasting serum lipids and plasma insulin significantly increased and serum adiponectin levels significantly decreased during the military service. Even the subjects with a 5-10% decrease in body weight showed the same result. In cases with more than 10% weight reduction and a significant decrease of fasting insulin concentration, the total and low density lipoprotein cholesterol significantly increased and adiponectin concentration tended to decreased. Only in severely obese cases (BMI >/= 30 kg/m2) with more than 10% decrease in body mass index adiponectin levels tended to increase, although not statistically significantly. This study shows that serum adiponectin concentrations decreased during a 6 mo high-caloric diet in military service, and even a moderate weight reduction induced by high-energy expenditure in exercise during service did not increase its levels.

Moderate high fat diet increases sucrose self-administration in young rats.

PubMed

Figlewicz, Dianne P; Jay, Jennifer L; Acheson, Molly A; Magrisso, Irwin J; West, Constance H; Zavosh, Aryana; Benoit, Stephen C; Davis, Jon F

2013-02-01

We have previously reported that a moderately high fat diet increases motivation for sucrose in adult rats. In this study, we tested the motivational, neurochemical, and metabolic effects of the high fat diet in male rats transitioning through puberty, during 5-8 weeks of age. We observed that the high fat diet increased motivated responding for sucrose, which was independent of either metabolic changes or changes in catecholamine neurotransmitter metabolites in the nucleus accumbens. However, AGRP mRNA levels in the hypothalamus were significantly elevated. We demonstrated that increased activation of AGRP neurons is associated with motivated behavior, and that exogenous (third cerebroventricular) AGRP administration resulted in significantly increased motivation for sucrose. These observations suggest that increased expression and activity of AGRP in the medial hypothalamus may underlie the increased responding for sucrose caused by the high fat diet intervention. Finally, we compared motivation for sucrose in pubertal vs. adult rats and observed increased motivation for sucrose in the pubertal rats, which is consistent with previous reports that young animals and humans have an increased preference for sweet taste, compared with adults. Together, our studies suggest that background diet plays a strong modulatory role in motivation for sweet taste in adolescent animals. Published by Elsevier Ltd.

Moderate High Fat Diet Increases Sucrose Self-Administration In Young Rats

PubMed Central

Figlewicz, Dianne P.; Jay, Jennifer L.; Acheson, Molly A.; Magrisso, Irwin J.; West, Constance H.; Zavosh, Aryana; Benoit, Stephen C.; Davis, Jon F.

2012-01-01

We have previously reported that a moderately high fat diet increases motivation for sucrose in adult rats. In this study, we tested the motivational, neurochemical, and metabolic effects of the high fat diet in male rats transitioning through puberty, during 5-8 weeks of age. We observed that the high fat diet increased motivated responding for sucrose, which was independent of either metabolic changes or changes in catecholamine neurotransmitter metabolites in the nucleus accumbens. However, AGRP mRNA levels in the hypothalamus were significantly elevated. We demonstrated that increased activation of AGRP neurons is associated with motivated behavior, and that exogenous (third cerebroventricular) AGRP administration resulted in significantly increased motivation for sucrose. These observations suggest that increased expression and activity of AGRP in the medial hypothalamus may underlie the increased responding for sucrose caused by the high fat diet intervention. Finally, we compared motivation for sucrose in pubertal vs. adult rats and observed increased motivation for sucrose in the pubertal rats, which is consistent with previous reports that young animals and humans have an increased preference for sweet taste, compared with adults. Together, our studies suggest that background diet plays a strong modulatory role in motivation for sweet taste in adolescent animals. PMID:23023044

Administration of contrast media just before cisplatin-based chemotherapy increases cisplatin-induced nephrotoxicity.

PubMed

Sendur, M A N; Aksoy, S; Yaman, S; Arik, Z; Tugba Kos, F; Akinci, M B; Civelek, B; Yildirim Ozdemir, N; Uncu, D; Zengin, N

2013-01-01

There is a clinical need to predict the probability of cisplatin-induced nephrotoxicity (CIN) in order to make decisions about patient management and relevant preventive measures. The purpose of this study was to develop a risk prediction methodology of CIN. 197 consecutive cancer patients, whose serum creatinine was measured at least 48 h before every cycle of cisplatin-based chemotherapy, were included in the study. Demographic and clinical data were collected from the patient medical records. Renal function was evaluated at least 48 h before treatment (day 0) of each cycle, based on the Modification of Diet in Renal Disease (MDRD) formula. CIN was defined as a decrease of ≥ 25% in glomerular filtration rate (GFR) compared to baseline GFR values. The mean age of the study population was 54.5±9.6 years. Fifty-eight patients (29.4%) whose GFR had decreased by at least 25% compared to baseline values formed the CIN group, and the remaining 139 patients formed the non-CIN group. No significant differences were noted between the CIN and non-CIN groups in terms of age, gender, body mass index and smoking history. Metastatic disease was similar in both groups (p=0.86). History of hypertension (p=0.81), diabetes mellitus (p=0.72), and cardiovascular disease (p=0.58) were similar in the two groups. Chemotherapeutic agents used concurrently with cisplatin were similar in both groups. Significantly more radiologic examinations using contrast media were performed in the CIN group compared with the non-CIN group (p=0.01). In patients exposed to contrast media within a week before cisplatin administration, the risk of CIN was 2.56-fold higher (957 percent; CI 1.28-5.11) than in patients without such exposure (p=0.009). In patients with exposure to contrast media within a week before cisplatin administration, the risk of CIN was significantly higher than in patients without such an exposure. No additional risk factors for CIN were found in this retrospective observational

Increased serum procalcitonin levels in pregnant patients with asymptomatic bacteriuria

PubMed Central

2013-01-01

Background Among the pregnancy urinary tract infections, asymptomatic bacteriuria (ASB) is the most common one. Untreated ASB can progress to pyelonephritis in 30-50% of the patients and can also result in prematurity in 27% of the pregnancy so it needs immediate diagnosis and treatment. In this study, we wanted to evaluate procalcitonin levels, compared to other inflammatory in pregnant women with ASB. Methods The study was designed between the period of January 2012 and February 2013 at Sakarya University School of Medicine, Department of Gynecology and Obstetrics. The study population included 30 pregnant patients with asymptomatic bacteriuria and 39 healthy pregnant controls. Results Mean age was 28 (SD, 5.5) of the study population; mean maternal weight was 70 (SD, 8) kilogram. There were no statically significant differences between the groups according to the routine biochemical parameters, but gestational age was significantly lower in the ASB group compared to the controls (20.4 vs 28.6, respectively; p < 0.001). Serum procalcitonin levels were negative in all of the controls. In ASB group, 9 (30%) patients had procalcitonin levels greater than >0.05 ng/ml and 21(70%) patients had negative procalcitonin levels (Chi-squrae, p < 0.001). The sensitivity and specificity of procalcitonin assay for ASB was calculated as 30% and 100%, respectively. The positive predictive value was 100% and the negative predictive value was 65%. The most frequent microorganisms in the urine culture were Escherichia coli (26 patients, 87%), Proteus mirabilis (3 patients, 10%) and Klebsiella (1 patient, 3%) in the ASB group. We experienced four (44%) recurrences among nine positive procalcitonin in ASB patients after completion of treatment of the first ASB diagnosis. Discussion Procalcitonin levels were significantly higher in ASB group than the control group and serum procalcitonin levels were higher in pregnant women with recurrent ASB. This finding is an important

Effect of short-term zinc supplementation on zinc and selenium tissue distribution and serum antioxidant enzymes.

PubMed

Skalny, Andrey A; Tinkov, Alexey A; Medvedeva, Yulia S; Alchinova, Irina B; Karganov, Mikhail Y; Skalny, Anatoly V; Nikonorov, Alexandr A

2015-01-01

A significant association between Zn and Se homeostasis exists. At the same time, data on the influence of zinc supplementation on selenium distribution in organs and tissues seem to be absent. Therefore, the primary objective of the current study is to investigate the influence of zinc asparaginate supplementation on zinc and selenium distribution and serum superoxide dismutase (SOD) and glutathione peroxidase (GPx) activity in Wistar rats. 36 rats were used in the experiment. The duration of the experiment was 7 and 14 days in the first and second series, respectively. The rats in Group I were used as the control ones. Animals in Groups II and III daily obtained zinc asparaginate (ZnA) in the doses of 5 and 15 mg/kg weight, respectively. Zinc and selenium content in liver, kidneys, heart, muscle, serum and hair was assessed using inductively coupled plasma mass spectrometry. Serum SOD and GPx activity was analysed spectrophotometrically using Randox kits. Intragastric administration of zinc asparaginate significantly increased liver, kidney, and serum zinc content without affecting skeletal and cardiac muscle levels. Zinc supplementation also stimulated selenium retention in the rats' organs. Moreover, a significant positive correlation between zinc and selenium content was observed. Finally, zinc asparaginate treatment has been shown to modulate serum GPx but not SOD activity. The obtained data indicate that zinc-induced increase in GPx activity may be mediated through modulation of selenium status. However, future studies are required to estimate the exact mechanisms of zinc and selenium interplay.

Iron and Vitamin C Co-Supplementation Increased Serum Vitamin C Without Adverse Effect on Zinc Level in Iron Deficient Female Youth

PubMed Central

Khoshfetrat, Mohammad Reza; Mortazavi, Sima; Neyestani, Tirang; Mahmoodi, Mohammad Reza; Zerafati-Shoae, Nahid; Mohammadi-Nasrabadi, Fatemeh

2014-01-01

Background: Iron supplementation can decrease the absorption of zinc and influence other antioxidants levels such as vitamin C. This study aimed to investigate the effect of iron supplements alone and in combination with vitamin C on zinc and vitamin C status in iron deficient female students. Methods: In a double-blind randomized clinical trail, 60 iron deficient students were selected from 289 volunteers residing in dormitory. After matching, subjects were randomly assigned into two groups: Group I (50 mg elemental iron supplements) and Group II (50 mg elemental iron + 500 mg ascorbic acid). Serum ferritin, iron, serum zinc, and plasma vitamin C concentrations were measured by using enzyme-linked immunosorbent assay, spectrophotometer, atomic absorption spectrometer, and colorimeter, respectively after 6 and 12 weeks supplementation. Student's t-test and repeated measures analysis of variance were applied to analyze the data using SPSS software. Results: Serum zinc levels had no significant differences between 2 groups at the baseline; however, its concentration decreased from 80.9 ± 4.2-68.9 ± 2.7 μg/dl to 81.2 ± 4.5-66.1 ± 2.9 μg/dl (P < 0.001) in Groups I and II, respectively after 6 weeks of supplementation. Continuous supplementation increased serum zinc concentration to baseline levels (79.0 ± 2.9 μg/dl; P < 0.01) in Group I and 70.5 ± 3.1 μg/dl in Group II following 12 weeks of supplementation. Plasma vitamin C increased from 3 ± 0/1-3.3 ± 0.2 mg/dl to 2.7 ± 0. 1-4.2 ± 0.2 mg/dl (P < 0.01) in Groups I and II, respectively. At the end of study, plasma vitamin C significantly increased from 3.3 ± 0.3-4.7 ± 0.3 (P < 0.01) to 4.2 ± 0.2-7.1 ± 0.2 (P < 0.001) in Groups I and II, respectively. Conclusions: Iron supplementation with and without vitamin C led to reduction in serum Zn in iron-deficient female students after 6 weeks. However, the decreasing trend stops after repletion of iron stores and Zn levels returned to the approximately

Association between serum soluble CD30 and serum creatinine before and after renal transplantation.

PubMed

López-Hoyos, M; San Segundo, D; Benito, M J; Fernández-Fresnedo, G; Ruiz, J C; Rodrigo, E; Gómez-Alamillo, C; Benito, A; Arias, M

2008-11-01

There is increasing evidence that circulating levels of soluble CD30 (sCD30) may represent a biomarker for outcome in kidney transplantation. The aim of this study was to measure the pre- and posttransplantation serum levels of sCD30 in cadaveric kidney transplant recipients and correlate them with serum creatinine. Serum sCD30 was measured by a commercial enzyme-linked immunosorbent assay (ELISA) from prospective samples of 38 kidney allograft recipients serially transplanted at our center. Samples were collected at day 0 pretransplantation and at months 6, 12, 18, and 24 posttransplantation. We also studied sera from 29 patients with chronic kidney disease (CKD) at different stages of the K/DOQI guidelines, as a control group. Serum levels of sCD30 decreased significantly in samples posttransplantation compared with pretransplantation. The significant decrease after transplantation may be related to the improvement in renal function since we observed a significant correlation between serum levels of sCD30 and creatinine (sCr) at all times of the study. In addition, the patients with chronic renal failure showed a significant association between serum sCD30 and sCr (r = .454; P = .013). Our results did not suggest that the measurement of sCD30 may be used as a valuable biomarker in renal transplantation. Increased levels may be related to a decrease in its renal elimination.

Serum concentrations and effects of detomidine delivered orally to horses in three different mediums.

PubMed

Ramsay, Edward C; Geiser, Dennis; Carter, Wyndee; Tobin, Thomas

2002-10-01

To compare the effect of orally delivered detomidine on head posture when administered alone or in combination with two different food items, and to determine the serum concentrations of detomidine after oral delivery. Prospective randomized experimental study. Fifteen adult grade mares weighing 328-537 kg. The horses were randomly assigned to one of the three treatment groups (five horses each). The groups were given detomidine (0.06 mg kg -1 ): alone; mixed with 3 mL of an apple sauce and gum mixture; or mixed with 3 mL molasses. Head droop, measured before treatment and at 15, 30, 45, 60, 75, 90, and 105 minutes after treatment, was used to evaluate sedation. Yohimbine (0.1 mg kg -1 IV) was administered after the 90-minute evaluation. Blood samples were collected from the detomidine-alone group before treatment and at 15, 30, 45, 60, 75, and 90 minutes after treatment. Sera were analyzed for detomidine equivalent concentrations by an ELISA. Head droop percentages were compared using a repeated measures analysis of variance. Significant mean head droop developed in each treatment group by 30 minutes and persisted until reversal with yohimbine. After yohimbine administration, head positions returned to 87-91% of pre-treatment levels. There were no significant differences among the oral treatment groups at any time. Mean serum detomidine equivalents increased slowly until 45-minute post-administration, but never exceeded 30 ng mL -1 . Orally administered detomidine results in measurable serum drug concentrations using any of the delivery mediums investigated, and can be expected to produce profound head droop in horses approximately 45 minutes after administration. Copyright © 2002 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.

Plant sterol ester diet supplementation increases serum plant sterols and markers of cholesterol synthesis, but has no effect on total cholesterol levels.

PubMed

Weingärtner, Oliver; Bogeski, Ivan; Kummerow, Carsten; Schirmer, Stephan H; Husche, Constanze; Vanmierlo, Tim; Wagenpfeil, Gudrun; Hoth, Markus; Böhm, Michael; Lütjohann, Dieter; Laufs, Ulrich

2017-05-01

This double-blind, randomized, placebo-controlled, cross-over intervention-study was conducted in healthy volunteers to evaluate the effects of plant sterol ester supplemented margarine on cholesterol, non-cholesterol sterols and oxidative stress in serum and monocytes. Sixteen volunteers, average age 34 years, with no or mild hypercholesterolemia were subjected to a 4 week period of daily intake of 3g plant sterols per day supplied via a supplemented margarine on top of regular eating habits. After a wash-out period of one week, volunteers switched groups. Compared to placebo, a diet supplementation with plant sterols increased serum levels of plant sterols such as campesterol (+0.16±0.19mg/dL, p=0.005) and sitosterol (+0.27±0.18mg/dL, p<0.001) and increased markers of cholesterol synthesis such as desmosterol (+0.05±0.07mg/dL, p=0.006) as well as lathosterol (+0.11±0.16mg/dL, p=0.012). Cholesterol serum levels, however, were not changed significantly (+18.68±32.6mg/dL, p=0.052). These findings could not be verified in isolated circulating monocytes. Moreover, there was no effect on monocyte activation and no differences with regard to redox state after plant sterol supplemented diet. Therefore, in a population of healthy volunteers with no or mild hypercholesterolemia, consumption of plant sterol ester supplemented margarine results in increased concentrations of plant sterols and cholesterol synthesis markers without affecting total cholesterol in the serum, activation of circulating monocytes or redox state. Copyright © 2016 Elsevier Ltd. All rights reserved.

Atrazine Does Not Induce Pica Behavior at Doses that Increase Hypothalamic-Pituitary-Adrenal Axis Activation and Cause Conditioned Taste Avoidance.

EPA Science Inventory

Previous work has shown that a single oral administration of atrazine (ATR), a chlorotriazine herbicide, induces dose-dependent increases in plasma adrenocorticotropic hormone (ACTH), serum corticosterone (CORT) and progesterone. The mechanism for these effects is unknown. To tes...

Calcium dobesilate reduces endothelin-1 and high-sensitivity C-reactive protein serum levels in patients with diabetic retinopathy

PubMed Central

Javadzadeh, Alireza; Ghorbanihaghjo, Amir; Adl, Farzad Hami; Andalib, Dima; Khojasteh-Jafari, Hassan

2013-01-01

Purpose To determine the benefits of calcium dobesilate (CaD) administration on endothelial function and inflammatory status in patients with diabetic retinopathy through measurement of serum levels of endothelin-1 and high-sensitivity C-reactive protein (hsCRP). Methods In a double-blind, randomized clinical trial, 90 patients with either severe nonproliferative or proliferative diabetic retinopathy and with blood glucose level of 120–200 mg/dl were randomly allocated to treatment with either CaD tablets (500 mg daily) or placebo for 3 months. Visual acuity, intraocular pressure, and macular status were performed before the study. The serum levels of endothelin-1 and hsCRP were evaluated in both groups before and at the third month of the trial. Results The median serum level of hsCRP significantly differed between the groups 3 months following the CaD or placebo administration (2.2 mg/l in the CaD group versus 3.7 mg/l in the placebo group, p=0.01). The mean endothelin-1 serum level was 0.69±0.32 pg/ml in the CaD group and 0.86±0.30 pg/ml in the placebo group (p=0.01). Furthermore, in the CaD group, the serum levels of both endothelin-1 and hsCRP were significantly decreased 3 months after administration of CaD (p<0.001). Conclusions Administration of the CaD in the patients with diabetic retinopathy may reduce the serum levels of endothelin-1 and hsCRP. This might imply amelioration of the endothelial function and inflammatory status following CaD therapy in these patients. PMID:23335852

Increased plasma/serum levels of prolactin in multiple sclerosis: a meta-analysis.

PubMed

Wei, Wei; Liu, Lei; Cheng, Zhong-Le; Hu, Bo

2017-08-01

Prolactin (PRL) is a polypeptide hormone that is known to stimulate humoral and cell mediated immune responses. PRL levels have been investigated in several autoimmune diseases including multiple sclerosis (MS); however, these have yielded different and inconsistent results. This study aims to perform a more precise evaluation on the plasma/serum PRL levels in MS patients, and to explore the available influential factors. Research related to plasma/serum PRL levels in MS patients and healthy controls were gathered using PubMed, EMBASE and The Cochrane Library database (until Mar 31 2016). Pooled standard mean difference (SMD) with 95% confidence interval (CI) was calculated by fixed-effects or random-effect model analysis. Heterogeneity test was performed by the Q statistic and quantified using I 2 , and publication bias was evaluated using a funnel plot and Egger's linear regression test. 516 articles were obtained after searching databases, and 8 studies with 426 MS patients and 296 controls were finally included. Meta-analysis revealed that, compared with the control group, the MS group had significantly higher plasma/serum PRL levels, with the SMD of 0.55 and 95%CI (0.39, 0.72). Subgroup analyses showed that region, age and disease duration were associated with PRL level in MS patients. In summary, our meta-analysis revealed a significantly higher PRL level in MS patients than healthy controls, and it is influenced by region, age and disease duration.

Serum laminin in malaria.

PubMed Central

Wenisch, C; Graninger, W; Viravan, C; Looareesuwan, S; Parschalk, B; Wernsdorfer, W

1994-01-01

AIM--To determine serum laminin concentrations in patients with uncomplicated Plasmodium falciparum malaria. METHODS--An enzyme linked immunosorbent assay (ELISA) was used to determine serum laminin concentrations in 54 patients with acute uncomplicated P falciparum malaria during and after treatment, and in 17 control subjects in Bangkok, Thailand. RESULTS--Raised concentrations of soluble laminin were observed in patients (mean (SD) concentration 628 (225) ng/ml), compared with normal controls (490 (116) ng/ml), during the acute phase of the disease. During treatment, serum laminin concentrations decreased and returned to normal within three days. Serum laminin concentrations were correlated with parasite counts before treatment, and with the serum concentration of soluble intercellular adhesion molecule-1 (ICAM-1), soluble E-selectin, and soluble tumour necrosis factor receptor at 55 kilodaltons. CONCLUSIONS--These findings are compatible with an increased production or release of laminin in P falciparum malaria, which could indicate a role for the subendothelial basement membrane in the pathogenesis of the disease. PMID:7525659

Serum HSP70

PubMed Central

Dutta, Sudhir K.; Girotra, Mohit; Singla, Montish; Dutta, Anand; Stephen, F. Otis; Nair, Padmanabhan P.; Merchant, Nipun B.

2014-01-01

Objectives Heat shock protein 70 (HSP70) is overexpressed in human pancreatic cancer cell lines. To determine if serum HSP70 levels are elevated in patients with pancreatic cancer and can function as a biomarker for early detection of pancreatic cancer. Methods Study subjects were divided into 3 groups: histologically proven pancreatic cancer (PC; n = 23), chronic pancreatitis (CP; n = 12), and matched normal control subjects (C; n = 10). Serum HSP70 levels were determined using a novel immunoelectrophoresis method developed and validated by the authors. Significance of difference between the groups was analyzed with analysis of variance (ANOVA). Receiver operating characteristic (ROC) curve analysis was performed to discriminate patients with pancreatic cancer from normal controls. Results The mean ± SE serum HSP70 levels in the PC, CP, and C groups were 1.68 ± 0.083 ng/mL, 0.40 ± 0.057 ng/mL, and 0.04 ng/mL, respectively. Serum HSP70 levels in the PC group were significantly higher compared with either the CP or C groups (P < 0.01). The sensitivity and specificity of elevated serum HSP70 in the PC group was 74% and 90%, respectively. Conclusions Serum HSP70 levels are significantly increased in patients with pancreatic cancer and may be useful as an additional biomarker for the detection of pancreatic cancer. PMID:22158074

Increased Circulating Level of the Survival Factor GP88 (Progranulin) in the Serum of Breast Cancer Patients When Compared to Healthy Subjects

PubMed Central

Tkaczuk, Katherine Rak; Yue, Binbin; Zhan, Min; Tait, Nancy; Yarlagadda, Lavanya; Dai, Huifang; Serrero, Ginette

2011-01-01

Introduction: GP88 (PC-Cell Derived Growth Factor, progranulin) is a glycoprotein overexpressed in breast tumors and involved in their proliferation and survival. Since GP88 is secreted, an exploratory study was established to compare serum GP88 level between breast cancer patients (BC) and healthy volunteers (HV). Methods: An IRB approved prospective study enrolled 189 stage 1–4 BC patients and 18 HV. GP88 serum concentration was determined by immunoassay. Results: Serum GP88 level was 28.7 + 5.8 ng/ml in HV and increased to 40.7 + 16.0 ng/ml (P = 0.007) for stage 1–3 and 45.3 + 23.3 ng/ml (P = 0.0007) for stage 4 BC patients. There was no correlation between the GP88 level and BC characteristics such as age, race, tumor grade, ER, PR and HER-2 expression. Conclusion: These data suggest that serial testing of serum GP88 levels may have value as a circulating biomarker for detection, monitoring and follow up of BC. PMID:21792312

Constitutive Knockout of Kalirin-7 Leads to Increased Rates of Cocaine Self-Administration

PubMed Central

Kiraly, Drew D.; Nemirovsky, Natali E.; LaRese, Taylor P.; Tomek, Seven E.; Yahn, Stephanie L.; Olive, M. Foster; Eipper, Betty A.

2013-01-01

Kalirin-7 (Kal7) is a Rho-guanine nucleotide exchange factor that is localized in neuronal postsynaptic densities. Kal7 interacts with the NR2B subunit of the NMDA receptor and regulates aspects of dendritic spine dynamics both in vitro and in vivo. Chronic treatment with cocaine increases dendritic spine density in the nucleus accumbens (NAc) of rodents and primates. Kal7 mRNA and protein are upregulated in the NAc following cocaine treatment, and the presence of Kal7 is necessary for the normal proliferation of dendritic spines following cocaine use. Mice that constitutively lack Kal7 [Kalirin-7 knockout mice (Kal7KO)] demonstrate increased locomotor sensitization to cocaine and a decreased place preference for cocaine. Here, using an intravenous cocaine self-administration paradigm, Kal7KO mice exhibit increased administration of cocaine at lower doses as compared with wild-type (Wt) mice. Analyses of mRNA transcript levels from the NAc of mice that self-administered saline or cocaine reveal that larger splice variants of the Kalrn gene are increased by cocaine more dramatically in Kal7KO mice than in Wt mice. Additionally, transcripts encoding the NR2B subunit of the NMDA receptor increased in Wt mice that self-administered cocaine but were unchanged in similarly experienced Kal7KO mice. These findings suggest that Kal7 participates in the reinforcing effects of cocaine, and that Kal7 and cocaine interact to alter the expression of genes related to critical glutamatergic signaling pathways in the NAc. PMID:23894151

Comparison of effect of an increased dosage of vonoprazan versus vonoprazan plus lafutidine on gastric acid inhibition and serum gastrin.

PubMed

Suzuki, Takahiro; Kagami, Takuma; Uotani, Takahiro; Yamade, Mihoko; Hamaya, Yasushi; Iwaizumi, Moriya; Osawa, Satoshi; Sugimoto, Ken; Miyajima, Hiroaki; Furuta, Takahisa

2018-01-01

Vonoprazan, a novel potassium-competitive acid blocker, elicits potent acid inhibition and hypergastrinemia at a dose of 20 mg. Its recommended maintenance dose for gastro-esophageal reflux disease is 10 mg, which is sometimes insufficient for preventing nocturnal acid breakthrough (NAB). Concomitant use of a histamine 2 receptor antagonist (H 2 RA) is effective for NAB. However, further acid inhibition by addition of H2RA has concern of hypergastrinemia again. Lafutidine (H2RA) is known to stimulate somatostatin release. The aim of this study is to compare the levels of acid inhibition and serum gastrin attained by addition of lafutidine to vonoprazan 10 mg with levels after a dose increase of vonoprazan from 10 to 20 mg. Thirteen healthy volunteers underwent 24-h intragastric pH monitoring and serum gastrin measurements on day 7 of three different regimens: vonoprazan 10 mg, vonoprazan 10 mg plus lafutidine 10 mg, and vonoprazan 20 mg. Median pH 4 holding time ratios (range) by vonoprazan 10 mg, vonoprazan 10 mg plus lafutidine 10 mg, and vonoprazan 20 mg were 82% (47-88%), 88% (76-93%), and 99% (95-100%) while those at nighttime from 10 p.m. to 8 a.m. were 94% (29-100%), 100% (95-100%), and 100%, respectively. The incidences of NAB with vonoprazan 10 mg, vonoprazan plus lafutidine, and vonoprazan 20 mg were 38, 8, and 0%, respectively. Respective serum gastrin levels were 420 (173-508), 323 (196-521), and 504 (400-812) pg/ml. Addition of lafutidine 10 mg to vonoprazan 10 mg achieved sufficient acid inhibition, especially at nighttime, without further increase of serum gastrin levels.

Hyperplastic thymus with increased angiogenesis is correlated with elevated serum thyroglobulin level in differentiated thyroid cancer patients with TENIS syndrome

PubMed Central

Zhang, Guangjian; Gao, Rui; Wang, Yuanbo; Liu, Yan; Li, Juan; Jia, Xi; Liang, Yiqian; Yang, Aimin

2018-01-01

Aims To investigate the association between angiogenetic activity of hyperplastic thymus and serum thyroglobulin (Tg) level in differentiated thyroid carcinoma patients with thyroglobulin (Tg)-elevated Negative Iodine Scintigraphy (TENIS) Syndrome. Methods A cohort of 30 consecutive patients who underwent total thyroidectomy followed by radioiodine ablation and had TENIS syndrome received integrin αvβ3 targeted imaging with 99mTc-HYNIC-PEG4-E[PEG4-c(RGDfk)]2 (99mTc-3PRGD2). The correlation of angiogenetic activity of the thymus and the serum Tg levels was evaluated in patients with enlarged thymus. Results Enlarged thymus was detected in 9 out of the 30 TENIS patients and all hyperplastic thymus showed an increased accumulation of the tracer (median tumor/background ratio: 2.8). Five of them had only mediastinal uptake and surgical removal of the mediastinal mass in one provided histopathologic evidence of thymic tissue. The other four were not assigned further treatment and were free of disease in the follow-up, though their stimulated Tg levels consistently increased. Four out of the 9 patients showed 99mTc-3PRGD2 uptake outside the mediastinum were assigned surgery followed by radioiodine treatment. Their stimulated Tg levels decreased after iodine ablation, but not drop back to normal. A significant linear correlation was observed between serum Tg levels and the degree of angiogenesis in the hyperplastic thymus. Conclusions The angiogenetic activity in hyperplastic thymus was related with the consistently elevated serum Tg levels in TENIS syndrome patients. Based on the existing literature and current data, we propose further intervention for patients with RGD uptake outside thymus, while close follow-up for patients with only mediastinal uptake. PMID:29423055

Serum and Wound Vancomycin Levels After Intrawound Administration in Primary Total Joint Arthroplasty.

PubMed

Johnson, Jeremiah D; Nessler, Joseph M; Horazdovsky, Ryan D; Vang, Sandy; Thomas, Avis J; Marston, Scott B

2017-03-01

Periprosthetic joint infection is the most common cause of readmissions after total joint arthroplasty (TJA). Intrawound vancomycin powder (VP) has reduced infection rates in spine surgery; however, there are no data regarding VP in primary TJA. Thirty-four TJA patients received 2 g of VP intraoperatively to investigate VP's pharmacokinetics. Serum and wound concentrations were measured at multiple intervals over 24 hours after closure. All serum concentrations were subtherapeutic (<15μg/mL) and peaked 12 hours after closure (4.7μg/mL; standard deviation [SD], 3.2). Wound concentrations were 922 μg/mL (SD, 523) 3 hours after closure and 207 μg/mL (SD, 317) at 24 hours. VP had a half-life of 7.2 hours (95% confidence interval, 7.0-9.3) in TJA wounds. VP produced highly therapeutic intrawound concentrations while yielding low systemic levels in TJA. VP may serve as a safe adjunct in the prevention of periprosthetic joint infection. Copyright © 2015 Elsevier Inc. All rights reserved.

Post-transplant increased levels of serum sCD30 is a marker for prediction of kidney allograft loss in a 5-year prospective study.

PubMed

Delgado, Julio C; Pavlov, Igor Y; Shihab, Fuad S

2009-12-01

Levels of sCD30 represent a biomarker for early outcome in kidney transplantation. The purpose of this study was to determine the role of sCD30 levels for prediction of graft loss in the late post-transplant period. Sera were collected immediately pre-transplant and yearly thereafter for up to 5-year post-transplant in 37 primary renal transplant recipients. Levels of serum sCD30 were tested using a fluorescent microsphere assay. Levels of sCD30 significantly decreased after transplantation and remained normal in 34 patients without graft loss up to 5-year post-transplant. Elevated levels of serum sCD30 preceded the increase of serum creatinine in patients with subsequent graft loss. Elevated levels of serum sCD30 post-transplant might be a marker for predicting subsequent graft loss in the post-transplant period.

Pharmacokinetics of tilmicosin after oral administration in swine.

PubMed

Shen, Jianzhong; Li, Cun; Jiang, Haiyang; Zhang, Suxia; Guo, Ping; Ding, Shuangyang; Li, Xiaowei

2005-06-01

To determine the pharmacokinetics of tilmicosin after oral administration of a single dose of tilmicosin base in swine. 10 healthy swine. Tilmicosin base was administered via stomach tube at a single dose of 20 mg/kg (n = 5) or 40 mg/kg (5). Blood samples were obtained from a jugular vein immediately before and at 10, 20, and 30 minutes and 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 120 hours after administration of tilmicosin. Tilmicosin concentrations in serum were quantified by use of a high-performance liquid chromatography procedure with UV light. Data for tilmicosin concentrations versus time were analyzed by use of compartmental and noncompartmental methods. Tilmicosin concentrations in serum decreased in a biexponential manner after oral administration. Mean +/- SD values for absorption half-lives were 1.49 +/- 0.23 hours and 1.64 +/- 0.40 hours, distribution half-lives were 2.96 +/- 0.58 hours and 3.20 +/- 0.76 hours, elimination half-lives were 25.26 +/- 8.25 and 20.69 +/- 5.07 hours, peak concentrations were 1.19 +/- 0.30 microg/mL and 2.03 +/- 0.28 microg/mL, and time to peak concentrations was 3.12 +/- 0.50 hours and 3.48 +/- 0.77 hours after oral administration of tilmicosin base at a single dose of 20 or 40 mg/kg, respectively. In swine, tilmicosin was rapidly absorbed and slowly eliminated after oral administration of a single dose of tilmicosin base powder.

Parenteral nutrition in short bowel syndrome patients, regardless of its duration, increases serum proinflammatory cytokines.

PubMed

Bizari, Letícia; da Silva Santos, Andressa Feijó; Foss, Norma Tiraboschi; Marchini, Júlio Sérgio; Suen, Vivian Marques Miguel

2016-07-01

Short bowel syndrome is a severe malabsorption disorder, and prolonged parenteral nutrition is essential for survival in some cases. Among the undesirable effects of long-term parenteral nutrition is an increase in proinflammatory cytokines. The aim of the present study was to measure the serum levels of interleukin-6, interleukin-10, tumor necrosis factor alpha, and transforming growth factor beta, in patients with short bowel syndrome on cyclic parenteral nutrition and patients who had previously received but no longer require parenteral nutrition. The study was cross-sectional and observational. Three groups were studied as follows: Parenteral nutrition group, 9 patients with short bowel syndrome that receive cyclic parenteral nutrition; Oral nutrition group, 10 patients with the same syndrome who had been weaned off parenteral nutrition for at least 1 year prior to the study; Control group, 13 healthy adults, matched for age and sex to parenteral and oral groups. The following data were collected: age, tobacco use, drug therapies, dietary intake, body weight, height, blood collection. All interleukins were significantly higher in the parenteral group compared with the control group as follows: interleukin-6: 22 ± 19 vs 1.5 ± 1.4 pg/mL, P= .0002; transforming growth factor β: 854 ± 204 vs 607 ± 280 pg/mL, P= .04; interleukin-10: 8 ± 37 vs 0.6 ± 4, P= .03; tumor necrosis factor α: 20 ± 8 vs 8 ± 4 pg/mL, P< .0001. We concluded that parenteral nutrition in short bowel syndrome patients, regardless of its duration, increases serum proinflammatory cytokines. Copyright © 2016 Elsevier Inc. All rights reserved.

Increased serum levels of S100A8/A9 and S100A12 are associated with cardiovascular disease in patients with inactive systemic lupus erythematosus.

PubMed

Tydén, Helena; Lood, Christian; Gullstrand, Birgitta; Jönsen, Andreas; Nived, Ola; Sturfelt, Gunnar; Truedsson, Lennart; Ivars, Fredrik; Leanderson, Tomas; Bengtsson, Anders A

2013-11-01

Patients with SLE have an increased morbidity and mortality from cardiovascular disease (CVD). The reason for this is not entirely understood, but is believed to be partly related to the long-lasting inflammatory process seen in SLE. The aim of the present study was to investigate whether there is an association between CVD and serum levels of the proinflammatory proteins S100A8/A9 and S100A12 in SLE. Serum levels of S100A8/A9 and S100A12 were measured with ELISA in 237 SLE patients with clinically inactive disease and without infections, as well as in 100 healthy individuals. Cardiovascular manifestations were defined according to the SLICC/ACR Damage Index (SLICC/ACR-DI). Serum levels of S100A8/A9 were elevated in our inactive SLE patients as compared with healthy individuals (P < 0.0001), which was not seen for S100A12 (P = 0.12). SLE patients with a history of CVD had increased serum levels of both S100A8/A9 and S100A12 compared with patients with no CVD or venous thromboembolism (P = 0.003 and P = 0.006, respectively). The presence of organ damage according to SLICC/ACR-DI was associated with an increase in both S100A8/A9 and S100A12 serum levels (P = 0.001 and P = 0.006, respectively). Elevated serum levels of S100A8/A9 and S100A12 may be used as an indicator of severe disease and CVD in SLE, suggesting that SLE patients with elevated serum S100A8/A9 and S100A12 concentrations may benefit from more intense cardiovascular primary preventive strategies and possibly also from more intense and early immunosuppressive treatment.

Serum apolipoprotein E concentration and polymorphism influence serum lipid levels in Chinese Shandong Han population.

PubMed

Han, ShuYi; Xu, YiHui; Gao, MeiHua; Wang, YunShan; Wang, Jun; Liu, YanYan; Wang, Min; Zhang, XiaoQian

2016-12-01

Apolipoprotein E (ApoE), which has been shown to influence serum lipid parameters, can bind to multiple types of lipids and plays an important role in the metabolism and homeostasis of lipids and lipoproteins. A previous study showed that ApoE concentration significantly affects serum lipid levels independently of ApoE polymorphism. The serum lipid levels were also closely correlated with dietary habits, and Shandong cuisine is famous for its high salt and oil contents, which widely differ among the different areas in China. Therefore, studying the effect of ApoE polymorphism on ApoE concentration and serum lipid levels in Shandong province is very important.A total of 815 subjects including 285 men and 530 women were randomly selected and studied from Jinan, Shandong province. In order to evaluate the association of ApoE polymorphism and serum level on lipid profiles, the ApoE genotypes, as well as levels of fasting serum ApoE and other lipid parameters, were detected in all subjects.The frequency of the ApoE E3 allele was highest (83.1%), while those of E2 and E4 were 9.4% and 7.5%, respectively, which are similar to those in other Asian populations. ApoE2 allele carriers showed significantly increased ApoE levels but lower levels of serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and Apolipoprotein B (ApoB).We found that ApoE level is influenced by ApoE polymorphism in a gene-dependent manner. The ApoE polymorphism showed different influences on serum lipid parameters with increasing age and body mass index (BMI) in our Shandong Han population.

Serum apolipoprotein E concentration and polymorphism influence serum lipid levels in Chinese Shandong Han population

PubMed Central

Han, ShuYi; Xu, YiHui; Gao, MeiHua; Wang, YunShan; Wang, Jun; Liu, YanYan; Wang, Min; Zhang, XiaoQian

2016-01-01

Abstract Apolipoprotein E (ApoE), which has been shown to influence serum lipid parameters, can bind to multiple types of lipids and plays an important role in the metabolism and homeostasis of lipids and lipoproteins. A previous study showed that ApoE concentration significantly affects serum lipid levels independently of ApoE polymorphism. The serum lipid levels were also closely correlated with dietary habits, and Shandong cuisine is famous for its high salt and oil contents, which widely differ among the different areas in China. Therefore, studying the effect of ApoE polymorphism on ApoE concentration and serum lipid levels in Shandong province is very important. A total of 815 subjects including 285 men and 530 women were randomly selected and studied from Jinan, Shandong province. In order to evaluate the association of ApoE polymorphism and serum level on lipid profiles, the ApoE genotypes, as well as levels of fasting serum ApoE and other lipid parameters, were detected in all subjects. The frequency of the ApoE E3 allele was highest (83.1%), while those of E2 and E4 were 9.4% and 7.5%, respectively, which are similar to those in other Asian populations. ApoE2 allele carriers showed significantly increased ApoE levels but lower levels of serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and Apolipoprotein B (ApoB). We found that ApoE level is influenced by ApoE polymorphism in a gene-dependent manner. The ApoE polymorphism showed different influences on serum lipid parameters with increasing age and body mass index (BMI) in our Shandong Han population. PMID:27977609

[The effect of various methods of luteal phase supplementation on serum progesterone level].

PubMed

Jakiel, G; Bokiniec, M; Bakalczuk, S; Jakubczak, A; Mroczkowski, A

1998-12-01

Examined was the effect of luteal phase supplementation on serum progesterone level with the use of two methods: oral administration of 10 mg dydrogesterone twice daily since the detection of corpus luteum till the menstruation and intramuscular HCG administration in the dose 1500 IU every 4 days and 10 mg dydrogesterone twice daily in the same period. A randomized study, controlled by placebo. 56 infertile women, with luteal phase deficiency assessed on the basis of basal body temperature (decrease shortly after the peak the luteal phase shorter than 11 days) and ovulation determined sonographically. Progesterone was evaluated by an EIA method, on the 3rd, 7th and 11th day since the corpus luteum occurred. The peak of progesterone concentration was assessed in the midluteal phase (7th day) in both supplemented groups, significantly higher than in the placebo group, also in group with dydrogesterone and HCG it was higher than in group with dydrogesterone alone. Progesterone concentration decrease on the 11th day after the ovulation to the values comparable with the placebo group. It has been found that both methods increase serum progesterone level in the time of an assumed implantation but they do not affect the premenstrual period if conception is not achieved.

Prepartum supplementation of conjugated linoleic acids (CLA) increased milk energy output and decreased serum fatty acids and β-hydroxybutyrate in early lactation dairy cows

PubMed Central

Oliveira, Rafael Caputo; Pralle, Ryan S.; de Resende, Lucas C.; Nova, Carlos Henrique P. C.; Caprarulo, Valentina; Jendza, Joshua A.; Troescher, Arnulf

2018-01-01

Prepartum supplementation with conjugated linoleic acid (CLA) may influence lipolysis and hyperketonemia in dairy cows. The objective of this study was to examine the effect of prepartum CLA supplementation on lactation performance and serum fatty acids (FA) and β-hydroxybutyrate (BHB) in early lactation dairy cows, and secondarily on reproductive performance. Multiparous cows were enrolled in the study at 18 days prior to expected calving date, and randomly assigned 100 g/day of Lutrell Pure (BASF, Ludwigshafen, Germany; 75% FA), providing 10 g/day of each CLA isomer (trans-10 cis-12 and cis-9 trans-11 CLA) or equivalent amount of rumen inert fatty acids as control (78 g/day of Energy Booster 100; Milk Specialties Global, Eden Prairie, MN). Treatments were top dressed daily to individual cows from enrollment to calving and all cows were offered the same ration. Blood samples were collected on the first day of supplementation, 10 days prepartum, and 1, 7, 14, and 30 days postpartum. Hyperketonemia was defined as serum BHB ≥ 1.2 mM. Milk yield was recorded daily until 60 days postpartum and averaged weekly. Milk samples were obtained weekly for component analysis. Prepartum CLA supplementation tended to increase serum concentration of cis-9, trans-11 CLA and increased trans-10, cis-12 CLA prepartum. Cows supplemented with CLA had increased milk protein yield and tended to have increased milk fat yield and milk yield, which together resulted in greater energy content of milk. Cows supplemented with CLA had lower serum FA on day 1 and 7 postpartum and overall lower serum BHB postpartum, which resulted in decreased prevalence of hyperketonemia on day 14 postpartum. There were no differences in body condition score change, other health disorders, or reproductive outcomes by treatment. Together, these findings indicate that prepartum CLA supplementation may be a plausible strategy to positively influence postpartum performance. PMID:29772023

Higher serum triglyceride to high-density lipoprotein cholesterol ratio was associated with increased cardiovascular mortality in female patients on peritoneal dialysis.

PubMed

Wu, H; Xiong, L; Xu, Q; Wu, J; Huang, R; Guo, Q; Mao, H; Yu, X; Yang, X

2015-08-01

High serum triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio has been found to be an independent predictor for cardiovascular events in the general population. We aimed to evaluate whether a high TG/HDL-C ratio was associated with an increased risk of mortality in patients on continuous ambulatory peritoneal dialysis (CAPD). In this single-center retrospective cohort study, 1170 incident patients on peritoneal dialysis (PD) from 1 January 2007 to 31 December 2011 were recruited and followed up until 31 December 31 2013. The mean age was 47.4 ± 15.2 years, and 24.7% were diabetic. During a median of the 34.5-month follow-up period, 213 (18.2%) deaths occurred, 121 of which (56.8%) were caused by cardiovascular disease (CVD). The serum median TG/HDL-C ratio at baseline was 2.57 (range: 0.06-39.39). On multivariate Cox regression analysis, the highest quartile of the TG/HDL-C ratio (≥4.19) was associated with increased risk of all-cause mortality (hazard ratio (HR) 1.98, 95% confidence interval (CI), 1.17-3.36; P = 0.011) and CVD mortality (HR 2.28, 95% CI, 1.16-4.47; P = 0.017). For female patients, each one-unit higher baseline TG/HDL-C was associated with 13% (95% CI 1.06-1.22; P = 0.001) increased risk of CVD mortality, whereas such an association was not observed for male patients, (HR 1.00, 95% CI 0.92-1.08; P = 0.977). A higher serum TG/HDL-C ratio was associated with an increased risk of all-cause and CVD mortality in PD patients. Moreover, the increased risk of CVD mortality was significantly higher in female than male PD patients. Copyright © 2015 Elsevier B.V. All rights reserved.

Chronic administration of branched-chain amino acids impairs spatial memory and increases brain-derived neurotrophic factor in a rat model.

PubMed

Scaini, Giselli; Comim, Clarissa M; Oliveira, Giovanna M T; Pasquali, Matheus A B; Quevedo, João; Gelain, Daniel P; Moreira, José Cláudio F; Schuck, Patrícia F; Ferreira, Gustavo C; Bogo, Maurício R; Streck, Emilio L

2013-09-01

Maple syrup urine disease (MSUD) is a neurometabolic disorder that leads to the accumulation of branched-chain amino acids (BCAAs) and their α-keto branched-chain by-products. Because the neurotoxic mechanisms of MSUD are poorly understood, this study aimed to evaluate the effects of chronic administration of a BCAA pool (leucine, isoleucine and valine). This study examined the effects of BCAA administration on spatial memory and the levels of brain-derived neurotrophic factor (BNDF). We examined both pro-BDNF and bdnf mRNA expression levels after administration of BCAAs. Furthermore, this study examined whether antioxidant treatment prevented the alterations induced by BCAA administration. Our results demonstrated an increase in BDNF in the hippocampus and cerebral cortex, accompanied by memory impairment in spatial memory tasks. Additionally, chronic administration of BCAAs did not induce a detectable change in pro-BDNF levels. Treatment with N-acetylcysteine and deferoxamine prevented both the memory deficit and the increase in the BDNF levels induced by BCAA administration. In conclusion, these results suggest that when the brain is chronically exposed to high concentrations of BCAA (at millimolar concentrations) an increase in BDNF levels occurs. This increase in BDNF may be related to the impairment of spatial memory. In addition, we demonstrated that antioxidant treatment prevented the negative consequences related to BCAA administration, suggesting that oxidative stress might be involved in the pathophysiological mechanism(s) underlying the brain damage observed in MSUD.

A quality improvement project to increase self-administration of medicines in an acute hospital.

PubMed

Garfield, S; Bell, H; Nathan, C; Randall, S; Husson, F; Boucher, C; Taylor, A; Lloyd, J; Backhouse, A; Ritchie, L; Franklin, B D

2018-03-24

A patient survey found significantly fewer patients reported they had self-administered their medicines while in hospital (20% of 100 patients) than reported that they would like to (44% of 100). We aimed to make self-administration more easily available to patients who wanted it. We conducted a failure, modes and effects analysis, collected baseline data on four wards and carried out observations. Our initial assessment suggested that the main areas we should focus on were raising patient awareness of self-administration, changing the patient assessment process and creating a storage solution for medicines being self-administered. We developed new patient information leaflets and posters and a doctor's assessment form using Plan-Do-Study-Act cycles. We developed initial designs for a storage solution. We piloted the new materials on three wards; the fourth withdrew due to staff shortages. Following collection of baseline data, we continued to collect weekly data. We found that the proportion of patients who wished to self-administer who reported that they were able to do so, significantly increased from 41% (of 155 patients) to 66% (of 118 patients) during the study, despite a period when the hospital was over capacity. Raising and maintaining healthcare professionals' awareness of self-administration can greatly increase the proportion of patients who wish to self-administer who actually do so. Healthcare professionals prefer multi-disciplinary input into the assessment process.

Activation of the Ca2+-sensing receptor increases renal claudin-14 expression and urinary Ca2+ excretion

PubMed Central

Dimke, Henrik; Desai, Prajakta; Borovac, Jelena; Lau, Alyssa; Pan, Wanling; Alexander, R. Todd

2016-01-01

Kidney stones are a prevalent clinical condition imposing a large economic burden on the health-care system. Hypercalciuria remains the major risk factor for development of a Ca2+-containing stone. The kidney’s ability to alter Ca2+ excretion in response to changes in serum Ca2+ is in part mediated by the Ca2+-sensing receptor (CaSR). Recent studies revealed renal claudin-14 (Cldn14) expression localized to the thick ascending limb (TAL) and its expression to be regulated via the CaSR. We find that Cldn14 expression is increased by high dietary Ca2+ intake and by elevated serum Ca2+ levels induced by prolonged 1,25-dihydroxyvitamin D3 administration. Consistent with this, activation of the CaSR in vivo via administration of the calcimimetic cinacalcet hydrochloride led to a 40-fold increase in Cldn14 mRNA. Moreover, overexpression of Cldn14 in two separate cell culture models decreased paracellular Ca2+ flux by preferentially decreasing cation permeability, thereby increasing transepithelial resistance. These data support the existence of a mechanism whereby activation of the CaSR in the TAL increases Cldn14 expression, which in turn blocks the paracellular reabsorption of Ca2+. This molecular mechanism likely facilitates renal Ca2+ losses in response to elevated serum Ca2+. Moreover, dys-regulation of the newly described CaSR-Cldn14 axis likely contributes to the development of hypercalciuria and kidney stones. PMID:23283989

Daily Administration of Short-Acting Liothyronine Is Associated with Significant Triiodothyronine Excursions and Fails to Alter Thyroid-Responsive Parameters.

PubMed

Jonklaas, Jacqueline; Burman, Kenneth D

2016-06-01

Although most studies of levothyroxine-liothyronine combination therapy employ once-daily hormone administration, the kinetics of once-daily liothyronine have been studied infrequently. The aim of this study was to document both the peak and trough serum triiodothyronine (T3) levels that occur with once-daily liothyronine administration, along with changes in thyroid-responsive parameters. Participants with hypothyroidism were studied prospectively at an academic institution. Patients were switched from levothyroxine monotherapy to liothyronine monotherapy with 15 μg liothyronine for two weeks, and then continued liothyronine at doses of 30-45 μg for a further four weeks in an open-label, single-arm study. Weekly trough levels of T3 were documented. In addition, hourly T3 concentrations immediately following liothyronine tablet administration were documented for eight hours during the sixth week of therapy. Serum thyrotropin (TSH) and free thyroxine (fT4) concentrations were documented. Biochemical markers, markers of energy metabolism, anthropometric parameters, well-being, and hyperthyroid symptoms were also assessed. Mean serum TSH levels increased from 1.56 ± 0.81 mIU/L at baseline to 5.90 ± 5.74 mIU/L at two weeks and 3.84 ± 3.66 mIU/L at six weeks. Trough T3 levels decreased from 99.5 ± 22.9 to 91.9 ± 40.2 at two weeks and recovered to 96.1 ± 32.2 at six weeks. The peak T3 concentration after dosing of liothyronine during week 6 was 292.8 ± 152.3 ng/dL. fT4 levels fell once levothyroxine was discontinued and plateaued at 0.44 ng/dL at week 4. The sex hormone binding globulin (SHBG) concentration decreased at week 2 (p = 0.002). Hyperthyroid symptoms and SF36-PCS scores increased significantly at weeks 4-5 of liothyronine therapy (p = 0.04-0.005). Preference for liothyronine therapy increased from 6% to 39% over the study period. Once-daily dosing of liothyronine at doses of 30-45 μg did not return serum

Severity-Related Increase and Cognitive Correlates of Serum VEGF Levels in Alzheimer's Disease ApoE4 Carriers.

PubMed

Alvarez, X Anton; Alvarez, Irene; Aleixandre, Manuel; Linares, Carlos; Muresanu, Dafin; Winter, Stefan; Moessler, Herbert

2018-01-01

Vascular endothelial growth factor (VEGF) is an angioneurin involved in the regulation of vascular and neural functions relevant for the pathophysiology of Alzheimer's disease (AD), but the influence of AD severity and ApoE4 status on circulating VEGF and its relationship with cognition has not been investigated. We assessed serum VEGF levels and cognitive performance in AD, amnestic mild cognitive impairment (MCI), and control subjects. VEGF levels were higher in AD patients than in MCI cases and controls (p < 0.05) and showed a progressive increase with clinical severity in the whole study population (p < 0.01). Among AD patients, severity-related VEGF elevations were significant in ApoE4 carriers (p < 0.05), but not in non-carriers. Increased VEGF levels were associated with disease severity and showed mild correlations with cognitive impairment that were only consistent for the ADAS-cog+ items remembering test instructions (memory) and maze task (executive functions) in the group of AD patients (p < 0.05). On the other hand, higher VEGF values were related to better memory and language performance in ApoE4 carriers with moderately-severe AD. According to these results showing severity- and ApoE4-related differences in serum VEGF and its cognitive correlates, it is suggested that increases in VEGF levels might represent an endogenous response driven by pathological factors and could entail cognitive benefits in AD patients, particularly in ApoE4 carriers. Our findings support the notion that VEGF constitutes a relevant molecular target to be further explored in AD pathology and therapy.

Oral administration of antimicrobials increase antimicrobial resistance in E. coli from chicken--a systematic review.

PubMed

Simoneit, C; Burow, E; Tenhagen, B-A; Käsbohrer, A

2015-01-01

Antimicrobials play an important role in animal and human health care. It was the aim of this systematic review to assess the effects of oral administration of antimicrobials on the development of antimicrobial resistance (AMR) in Escherichia coli (E. coli) from chickens. Moreover, the effects of the administration of more than one antimicrobial and of different dosages were studied. Literature was searched in November 2012 from the electronic databases ISI Web of Science, PubMed, Scopus and a national literature database (DIMDI) as well as the database ProQuest LLC. The search was updated in March 2014. Original studies describing a treatment (A) and a control group of either non-treatment (C) or initial value (0) and determining AMR in E. coli at different sample points (SP) were included. The literature search resulted in 35 full text articles on the topic, seven (20%) of which contained sufficient information on the administered antimicrobial and the impact of treatment on AMR. Most papers described the use of more than one antimicrobial, several dosages, controls (non-treatment or pre-treatment) and measured AMR at different SPs leading to a total of 227 SPs on the impact of the use of antimicrobials on AMR in chickens. 74% of the SPs (168/227) described a higher AMR-rate in E. coli from treated animals than from controls. After the administration of a single antimicrobial, AMR increased at 72% of the SPs. Administration of more than one antimicrobial increased AMR at 82% of the SPs. Higher dosages were associated with similar or higher AMR rates. The limited number of studies for each antimicrobial agent and the high variability in the resistance effect call for more well designed studies on the impact of oral administration on AMR development and spread. Copyright © 2014 Elsevier B.V. All rights reserved.

Serum ceruloplasmin protein expression and activity increases in iron-deficient rats and is further enhanced by higher dietary copper intake

PubMed Central

Ranganathan, Perungavur N.; Lu, Yan; Jiang, Lingli; Kim, Changae

2011-01-01

Increases in serum and liver copper content are noted during iron deficiency in mammals, suggesting that copper-dependent processes participate during iron deprivation. One point of intersection between the 2 metals is the liver-derived, multicopper ferroxidase ceruloplasmin (Cp) that is important for iron release from certain tissues. The current study sought to explore Cp expression and activity during physiologic states in which hepatic copper loading occurs (eg, iron deficiency). Weanling rats were fed control or low iron diets containing low, normal, or high copper for ∼ 5 weeks, and parameters of iron homeostasis were measured. Liver copper increased in control and iron-deficient rats fed extra copper. Hepatic Cp mRNA levels did not change; however, serum Cp protein was higher during iron deprivation and with higher copper consumption. In-gel and spectrophotometric ferroxidase and amine oxidase assays demonstrated that Cp activity was enhanced when hepatic copper loading occurred. Interestingly, liver copper levels strongly correlated with Cp protein expression and activity. These observations support the possibility that liver copper loading increases metallation of the Cp protein, leading to increased production of the holo enzyme. Moreover, this phenomenon may play an important role in the compensatory response to maintain iron homeostasis during iron deficiency. PMID:21768302

Butter naturally enriched in cis-9, trans-11 CLA prevents hyperinsulinemia and increases both serum HDL cholesterol and triacylglycerol levels in rats.

PubMed

de Almeida, Mariana Macedo; Luquetti, Sheila Cristina Potente Dutra; Sabarense, Céphora Maria; do Amaral Corrêa, José Otávio; dos Reis, Larissa Gomes; Santos da Conceição, Ellen Paula; Lisboa, Patrícia Cristina; de Moura, Egberto Gaspar; Gameiro, Jacy; da Gama, Marco Antônio Sundfeld; Lopes, Fernando César Ferraz; Garcia, Raúl Marcel González

2014-12-22

Evidence from in vitro and animal studies indicates that conjugated linoleic acid (CLA) possesses anti-diabetic properties, which appear to be attributed to cis-9, trans-11 CLA, the major CLA isomer in ruminant fat. However, there is a shortage of studies addressing CLA from natural source. The present study aimed to evaluate the effects of butter naturally enriched in cis-9, trans-11 CLA on parameters related to glucose tolerance, insulin sensitivity and dyslipidemia in rats. Forty male Wistar rats were randomly assigned to the following dietary treatments (n=10/group), for 60 days: 1) Normal fat-Soybean oil (NF-So): diet containing 4.0% soybean oil (SO); 2) High Fat-Control Butter (HF-Cb): diet containing 21.7% control butter and 2.3% SO; 3) High Fat-CLA enriched Butter (HF-CLAb): diet containing 21.7% cis-9, trans-11 CLA-enriched butter and 2.3% SO; and 4) High fat-Soybean oil (HF-So): diet containing 24.0% SO. HF-Cb and HF-CLAb diets contained 0.075% and 0.235% of cis-9, trans-11 CLA, respectively. HF-CLAb-fed rats had lower serum insulin levels at fasting than those fed with the HF-Cb diet, while the PPARγ protein levels in adipose tissue was increased in HF-CLAb-fed rats compared to HF-Cb-fed rats. Furthermore, R-QUICK was lower in HF-Cb than in NF-So group, while no differences in R-QUICK were observed among NF-So, HF-CLAb and HF-So groups. Serum HDL cholesterol levels were higher in HF-CLAb-fed rats than in those fed NF-So, HF-Cb and HF-So diets, as well as higher in NF-So-fed rats than in HF-Cb and HF-So-fed rats. HF-CLAb, HF-Cb and HF-So diets reduced serum LDL cholesterol levels when compared to NF-So, whereas serum triacylglycerol levels were increased in HF-CLAb. Feeding rats on a high-fat diet containing butter naturally enriched in cis-9, trans-11 CLA prevented hyperinsulinemia and increased HDL cholesterol, which could be associated with higher levels of cis-9, trans-11 CLA, vaccenic acid, oleic acid and lower levels of short and medium

Dietary Almonds Increase Serum HDL Cholesterol in Coronary Artery Disease Patients in a Randomized Controlled Trial.

PubMed

Jamshed, Humaira; Sultan, Fateh Ali Tipoo; Iqbal, Romaina; Gilani, Anwar Hassan

2015-10-01

More than one-half of coronary artery disease (CAD) patients have low HDL cholesterol despite having well-managed LDL cholesterol. Almond supplementation has not been shown to elevate circulating HDL cholesterol concentrations in clinical trials, perhaps because the baseline HDL cholesterol of trial subjects was not low. This clinical trial was designed to test the effect of almond supplementation on low HDL cholesterol in CAD patients. A total of 150 CAD patients (50 per group), with serum LDL cholesterol ≤100 mg/dL and HDL cholesterol ≤40 mg/dL in men and ≤50 mg/dL in women, were recruited from the Aga Khan University Hospital. After recording vital signs and completing a dietary and physical activity questionnaire, patients were randomly assigned to 1 of the following 3 groups: the no-intervention group (NI), the Pakistani almonds group (PA), and the American almonds group (AA). The respective almond varieties (10 g/d) were given to patients with instructions to soak them overnight, remove the skin, and eat them before breakfast. Blood samples for lipid profiling, body weight, and blood pressure were collected, and assessment of dietary patterns was done at baseline, week 6, and week 12. Almonds significantly increased HDL cholesterol. At weeks 6 and 12, HDL cholesterol was 12-14% and 14-16% higher, respectively, in the PA and AA than their respective baselines. In line with previous reports, serum concentrations of total cholesterol, triglycerides, LDL cholesterol, and VLDL cholesterol; total-to-HDL and LDL-to-HDL cholesterol ratios, and the atherogenic index were reduced in both the PA and AA at weeks 6 and 12 compared with baseline (P < 0.05). Effects on serum lipids did not differ between the 2 almond groups. Dietary patterns, body weight, and blood pressure did not change in any of the 3 groups during the trial. A low dose of almonds (10 g/d) consumed before breakfast can increase HDL cholesterol, in addition to improving other markers of abnormal

Effect of L-ascorbic acid on nickel-induced alterations in serum lipid profiles and liver histopathology in rats.

PubMed

Das, Kusal K; Gupta, Amrita Das; Dhundasi, Salim A; Patil, Ashok M; Das, Swastika N; Ambekar, Jeevan G

2006-01-01

Nickel exposure greatly depletes intracellular ascorbate and alters ascorbate-cholesterol metabolism. We studied the effect of the simultaneous oral treatment with L-ascorbic acid (50 mg/100 g body weight (BW) and nickel sulfate (2.0 mg/100 g BW, i.p) on nickelinduced changes in serum lipid profiles and liver histopathology. Nickel-treated rats showed a significant increase in serum low-density lipoprotein-cholesterol, total cholesterol, triglycerides, and a significant decrease in serum high-density lipoprotein-cholesterol. In the liver, nickel sulfate caused a loss of normal architecture, fatty changes, extensive vacuolization in hepatocytes, eccentric nuclei, and Kupffer cell hypertrophy. Simultaneous administration of L-ascorbic acid with nickel sulfate improved both the lipid profile and liver impairments when compared with rats receiving nickel sulfate only. The results indicate that L-ascorbic acid is beneficial in preventing nickel-induced lipid alterations and hepatocellular damage.

Study on rectal administration of azithromycin by suppository for pediatric use.

PubMed

Maeda, Miyuki; Nakano, Yukitaka; Aoyama, Takahiko; Matsumoto, Yoshiaki; Fujito, Hiroshi

2016-04-01

Azithromycin (AZM) is widely used as a first-line treatment option for children with mycoplasma pneumonia. Although pharmacists perform medication counseling in the pediatric ward, children often experience vomiting as a result of oral AZM administration. Drugs that are administered rectally are generally considered to enter the circulation system without passing through the liver first. The aim of our study was to prepare an AZM suppository and investigate the pharmaceutical properties and well as pharmacokinetics of the rectal administration route in humans. Five healthy volunteers were enrolled in the study. All subjects provided written informed consent before participating in the study. Subjects were randomly assigned to either oral administration of oral AZM 500-mg tablet or rectal administration of 125-mg, 250-mg, or 500-mg AZM suppository. Blood samples for preparation of serum were collected predose as well as at 1, 2, 3, 4, 6, 12, and 24 hours following the first rectal dose. Serum concentrations of AZM were determined by high-performance liquid chromatography (HPLC) with electrochemical detection. The bioavailability of the AZM suppository through rectal administration was 20.3% compared to oral administration. We hypothesize that the surface area where AZM is absorbed also affects the absorption by rectal administration. Although further investigation is necessary to improve the absorption of AZM by the rectum and to ensure safety in children, the AZM suppository may be an effective preparation in cases where oral administration is not tolerated.