Heat acclimation increases mitochondrial respiration capacity of C2C12 myotubes and protects against LPS-mediated energy deficit

This work investigated the effect of a 6-day heat acclimation (HA) protocol on myotube metabolic responses at baseline and in response to a subsequent lipopolysaccharide (LPS) challenge. C2C12 myotubes were incubated for 2 h/day at 40 °C for 6 days (HA) or maintained at 37 °C (C). Following 24-h recovery, myotubes were challenged with 500 ng/ml LPS for 2 h, then collected for analysis of protein markers of mitochondrial biogenesis and macronutrient storage. Functional significance of these changes was confirmed with mitochondrial respiration and glycolytic measurements on a Seahorse XF-96 analyzer. HA stimulated mitochondrial biogenesis and increased indicators of mitochondrial content [SIRT1 (+?62%); PGC-1α (+?57%); NRF-1 (+?40%); TFAM (+?141%); CS (+?25%); CytC (+?38%); all p?<?0.05]. Altered lipid biosynthesis enzymes [p-ACCa:ACC (+?59%; p?=?0.04) and FAS (??86%; p?<?0.01)] suggest fatty acid generation may have been downregulated, whereas increased GLUT4 (+?69%; p?<?0.01) and LDH-B (+?366%; p?<?0.01) suggest aerobic glycolytic capacity may have been improved. Mitochondrial biogenesis signaling in HA myotubes was suppressed by 500 ng/ml LPS (PGC-1α, NRF-1, TFAM; all p?> 0.05) but increased LDH-B (+?30%; p?=?0.02) and CPT-1 (+?55%; p?<?0.01) suggesting improved catabolic function. Basal respiration was increased in HA myotubes (+?8%; p?<?0.01) and HA myotubes maintained elevated basal respiration during LPS challenge (+?8%; p?<?0.01). LPS reduced peak respiration in C myotubes (??6%; p?<?0.01) but did not impair peak respiration in HA myotubes (p?>?0.05). Oxidative reliance was elevated in HA over that in control (+?25%; p?<?0.01) and in HA?+?LPS over C?+?LPS (+?30%; p?<?0.01). In summary, HA stimulated mitochondrial biogenesis in C2C12 myotubes. HA myotubes exhibited (1) elevated basal/peak mitochondrial respiration capacities; (2) greater oxidative reliance; and (3) protection against LPS-mediated respiration impairment. Collectively, these data suggest HA may improve aerobic metabolism in skeletal muscle and protect against LPS-mediated energy deficit.     

The Effects of Dietary Chromium(III) Picolinate on Growth Performance, Vital Signs, and Blood Measurements of Pigs During Immune Stress

This experiment used 24 pigs (26.0 kg) to investigate the effects of dietary chromium (Cr) on pigs challenged with lipopolysaccharide (LPS). Following 35 days of diet exposure, the immune stress treatments were: (1) phosphate-buffered saline (PBS) injection and no Cr, (2) LPS injection and no Cr, (3) LPS injection and Cr 1,000 ppb, and (4) LPS injection and Cr 2,000 ppb. At 0 h, PBS or LPS was injected intraperitoneally in each pig. During the first 12 h post-injection, pigs challenged with LPS lost 951 g, while the PBS group gained 170 g (p?<?0.001). Compared with the PBS group, LPS-challenged pigs consumed less feed (p?<?0.01) during the first 24 h. The LPS group had higher rectal temperature at 2 and 4 h and higher respiratory rate at 1.3 and 8.5 h than the PBS group (p?<?0.05). Plasma collected at 3 h had higher cortisol (p?<?0.001) and lower glucose (p?<?0.05) concentrations in the LPS group than the PBS group. However, supplemental Cr did not affect the response variables. Overall, the LPS challenge affects growth performance, vital signs, and plasma variables, but dietary Cr is unable to moderate stress-related effects associated with an LPS challenge.     

Skeletal muscle post-conditioning by diazoxide, anti-oxidative and anti-apoptotic mechanisms

Pretreatment with diazoxide, K_ATP channel opener, increases tissue tolerance against ischemia reperfusion (IR) injury. In clinical settings pretreatment is rarely an option therefore we evaluated the effect of post-ischemic treatment with diazoxide on skeletal muscle IR injury. Rats were treated with either saline, diazoxide (K_ATP opener; 40?mg/kg) or 5-hydroxydecanoate (5-HD; mitochondrial K_ATP inhibitor; 40?mg/kg) after skeletal muscle ischemia (3?h) and reperfusion (6, 24 or 48?h). Tissue contents of malondialdehyde (MDA), superoxide dismutase (SOD) and catalase (CAT) activities, Bax and Bcl-2 protein expression and muscle histology were determined. Apoptosis was examined (24 and 48?h) after ischemia. IR induced severe histological damage, increased MDA content and Bax expression (24 and 48?h; p?<?0.01) and decreased CAT and SOD activities (6 and 24?h, p?<?0.01 and 48?h, p?<?0.05), with no significant effect on Bcl-2 expression. Diazoxide reversed IR effects on MDA (6 and 24?h; p?<?0.05), SOD (6 and 24?h; p?<?0.01) and CAT (6 and 48?h, p?<?0.05 and 24?h p?<?0.01) and tissue damage. Diazoxide also decreased Bax (24 and 48?h; p?<?0.05) and increased Bcl-2 protein expression (24 and 48?h; p?<?0.01). Post-ischemic treatment with 5-HD had no significant effect on IR injury. Number of apoptotic nuclei in IR and 5-HD treated groups significantly increased (p?<?0.001) while diazoxide decreased apoptosis (p?<?0.01). The results suggested that post-ischemic treatment with diazoxide decrease oxidative stress in acute phase which modulates expression of apoptotic proteins in the late phase of reperfusion injury. Involvement of KATP channels in this effect require further evaluations.     

Reproductive axis response to repeated lipopolysaccharide administration in peripubertal female rats

Immune system disorders are often accompanied by alterations in the reproductive axis. Several reports have shown that administration of bacterial lipopolysaccharide (LPS) has central inflammatory effects and activates cytokine release in the hypothalamus where the luteinizing hormone releasing hormone (Gn-RH) neurons are located. The present study was designed to investigate the effect of repeated LPS administration on the neuroendocrine mechanisms of control of the reproductive axis in peripubertal female rats (30-day-old rats). With this aim, LPS (50 μg/kg weight) was administered to the animals during 25, 27 and 29 days of age and sacrificed on 30 day of life. Gn-RH, γ?amino butyric acid (GABA) and glutamic acid (GLU), two amino acids involved in the regulation of Gn-RH secretion, hypothalamic content were measured. LH and estradiol serum levels were also determined and the day of vaginal opening examined. The results showed a significant increase in Gn-RH and GLU content (p?<?0.0001), shared by a reduction of GABA one (p?<?0.0001). LH and estradiol serum levels were decreased (p?<?0.01, p?<?0.001) and delay in the day of vaginal opening was also observed in treated animals. Present results show that repeated LPS administration impaired reproductive function, modifying the neuroendocrine mechanisms of control of the axis in peripubertal female rats.     

Altered Trace Mineral Milieu Might Play An Aetiological Role in the Pathogenesis of Polycystic Ovary Syndrome

Insulin resistance is a very common associate of polycystic ovary syndrome (PCOS). Pathophysiology in relation with the essential elements including copper, magnesium, zinc, manganese, chromium, and calcium has been reported in women with insulin resistance. This prospective study was designed to explore whether the women with PCOS do exhibit altered serum element levels in association with/without insulin resistance. One hundred and thirty-two women with PCOS and forty-six control women were studied. Women with PCOS were further divided based on the presence of insulin resistance (insulin resistant: n?=?50; non-insulin resistant: n?=?82). In all women, basal levels of gonadotropins, prolactin, testosterone, insulin, glucose, and the six different elements were measured. Serum levels of testosterone (p?<?0.001), luteinizing hormone (p?<?0.05), and fasting insulin (p?<?0.004) were significantly higher in the PCOS population compared to controls as well as PCOS women without insulin resistance. Women with PCOS exhibited a significantly high calcium (p?<?0.04) and lower manganese levels (p?<?0.002) when compared to controls. However, the PCOS women with insulin resistance exhibited significantly lower serum levels of magnesium and chromium (p?<?0.04), in addition to higher levels of zinc and copper (p?<?0.04). The differences in calcium (p?<?0.03) and manganese levels (p?<?0.0001) became aggravated with the presence of insulin resistance when compared to control as well as PCOS women without insulin resistance. In PCOS-associated insulin resistance, circulating serum magnesium (r?=??0.31; p?<?0.03) and chromium (r?=??0.38; p?<?0.006) status significantly correlated with fasting insulin levels. We conclude that imbalanced element status may be a key foundation for insulin resistance in PCOS. The findings in this study should be investigated with further trials in order to obtain new insights into PCOS.     

Blood Metals Concentration in Type 1 and Type 2 Diabetics

Mechanisms for the onset of diabetes and the development of diabetic complications remain under extensive investigations. One of these mechanisms is abnormal homeostasis of metals, as either deficiency or excess of metals, can contribute to certain diabetic outcomes. Therefore, this paper will report the blood levels of chromium (Cr), copper (Cu), iron (Fe), manganese (Mn), mercury (Hg), nickel (Ni), lead (Pb), selenium (Se), and zinc (Zn) in subjects with type 1 diabetes (n?=?192, mean age 48.8 years, mean disease duration 20.6 years), type 2 diabetes (n?=?68, mean age 68.4 years, mean disease duration 10.2 years), and in control subjects (n?=?59, mean age 57.2 years), and discuss the results indicating their possible role in diabetes. The metal concentrations were measured by sector field inductively coupled plasma mass spectrometry after microwave-induced acid digestion of blood samples. The accuracy was checked using a blood-based certified reference material, and recoveries of all elements were in the range of 92–101 % of certified values. Type 1 diabetes was found to be associated with Cr (p?=?0.02), Mn (p?<?0.001), Ni (p?<?0.001), Pb (p?=?0.02), and Zn (p?<?0.001) deficiency, and type 2 diabetes with Cr (p?=?0.014), Mn (p?<?0.001), and Ni (p?<?0.001) deficiency. These deficiencies were appreciated also subdividing the understudied patients for gender and age groups. Furthermore, in type 1 diabetes, there was a positive correlation between Pb and age (p?<?0.001, ρ?=?0.400) and Pb and BMI (p?<?0.001, ρ?=?0.309), while a negative correlation between Fe and age (p?=?0.002, ρ?=??0.218). In type 2 diabetes, there was a negative correlation between Fe and age (p?=?0.017, ρ?=??0.294) and Fe and BMI (p?=?0.026, ρ?=??0.301). Thus, these elements may play a role in both forms of diabetes and combined mineral supplementations could have beneficial effects.     

210Po Activity and Concentrations of Selected Trace Elements (As, Cd, Cu, Hg, Pb, Zn) in the Muscle Tissue of Tunas Thunnus albacares and Katsuwonus pelamis from the Eastern Pacific Ocean

Daily mineral intake (DMI) of Cu and Zn, percentage weekly intake (PWI) of As, Cd, Hg, Pb, and doses of ²¹⁰Po were estimated by using their elemental concentration in muscle of two tuna species and the average tuna consumption in Mexico. Skipjack tuna Katsuwonus pelamis had significantly (p?<?0.05) higher levels of As (1.38???g?g^?1 dw) and Cu (1.85???g?g^?1 dw) than yellowfin tuna Thunnus albacares, whereas Pb concentrations (0.18???g?g^?1 dw) were significantly (p?<?0.05) higher in T. albacares. The sequence of elemental concentrations in both species was Zn?>?Cu?>?As?>?Hg?>?Pb?>?Cd. In T. albacares, concentrations of Cd and Pb in muscle tissue were positively correlated (p?<?0.05) with weight of specimens, while Cu was negatively correlated. DMI values were below 10?%. PWI figures (<2?%) are not potentially harmful to human health. ²¹⁰Po concentration in T. albacares and K. pelamis accounts for 13.5 to 89.7?% of the median individual annual dose (7.1???Sv) from consumption of marine fish and shellfish for the world population.     

Integrative ecological health assessments of an acid mine stream and in situ pilot tests for wastewater treatments

The impact of acid mine drainage (AMD) on a regional stream was evaluated using chemical analysis, biotic/ecological integrity (IBI), and habitat assessments along with the necropsy-based tissue analysis. In situ remediation tests were conducted for wastewater treatment using waste oyster shells. Monsoon rains caused the sloughing of AMD sediments, resulting in high acidity and turbidity. Friedman's two-way ANOVA showed that IBI values were significantly (p < 0.05) lower in the AMD-impacted sites than in the control and had an inverse relationship with pH. Tissue analysis revealed that all of the treatments, T1–T3, caused significant tissue damage (ANOVA; F = 11.949, p < 0.008), compared to the control. The in situ water treatment plant neutralized acid and removed 85–99% of Fe, Al, and Zn ions (χ² = 4.0–11.1, p < 0.05). Together, these approaches may be used as a key methodology for the integrative assessment and treatment of AMD-impacted water.     

Estimation of Copper and Iron Burden in Biological Samples of Various Stages of Hepatitis C and Liver Cirrhosis Patients

There is accumulative evidence that the metabolism of iron (Fe) and copper (Cu) is altered in human due to infections, indicating that both elements have roles in pathogenesis and progress of viral diseases. In the present study, the correlation of Cu and Fe was evaluate in biological samples (serum and scalp hair) of hepatitis C (hepatitis C virus (HCV)) patients of both genders at different stages. For comparative study, the scalp hair and serum samples of healthy individuals of same age group (30–50 years) and socioeconomic status were collected. The biological samples were analyzed for Fe and Cu by atomic absorption spectroscopy after microwave-assisted acid digestion. The validity and accuracy of methodology were checked by certified reference materials of same matrixes. The levels of Cu and Fe in biological samples were enhanced in hepatic disorder patients, including acute (after diagnosis test, anti-HCV sero-positive) hepatic fibrosis and liver cirrhosis as compared to healthy referents. The difference was significant (p?<?0.01) in the case of liver cirrhotic patients. It was observed that the data of Cu and Fe in referents and patients of both genders had normal distributions. The inter-elemental correlation (r) among Cu vs Fe in serum and scalp hair samples of referents and patients were not significant in both genders (p?>?0.1) except in the first stage of HCV (p?<?0.1). It was concluded that the increase of Cu and Fe content in human body seems to contribute to the development of cirrhosis in patients with viral hepatitis C.     

Association between circulating levels of heat-shock protein 27 and aggressive periodontitis

Heat-shock protein (Hsp) 27 is a major intracellular molecular chaperone and controller of intracellular responses to inflammatory signals. In the extracellular space, recombinant Hsp27 has been described to exert anti-inflammatory activities. The aim of this study was to assess the association between circulating levels of Hsp27 and different types of periodontitis. Pro- and anti-inflammatory cytokines and the stress proteins Hsp27 and Hsp60 with proposed anti- and pro-inflammatory properties, respectively, were measured by two-site ELISA in the serum of patients with aggressive periodontitis (AgP, n?=?30), chronic periodontitis (CP, n?=?29) and periodontally healthy controls (H, n?=?28). Furthermore, Hsp27 and Hsp60 levels were also measured longitudinally in 12 AgP patients at 6 time points up to 3 months after treatment. AgP patients had lower levels of Hsp27 compared to CP patients and healthy subjects (adjusted one-way ANOVA, p?<?0.001, followed by post hoc Tukey HSD comparisons), while no differences in levels of Hsp60 or cytokines between the three groups were detected. In CP patients and H subjects, the systemic Hsp27 levels correlated with Hsp60 (r?=?0.43, p?<?0.001; r?=?0.59, p?<?0.001, respectively) and with pro-inflammatory cytokines TNF-α (r?=?0.48, p?<?0.001; r?=?0.55, p?<?0.001, respectively) and IL-6 (r?=?0.44, p?<?0.01). However, no such correlations were detected in AgP cases. No consistent temporal patterns of changes of Hsp27 concentration were detected across AgP patients following periodontal treatment. This study provides the first evidence that Hsp27 may be differentially expressed and regulated in AgP patients as compared with CP patients and healthy individuals.     

Effects of High Zinc Levels on the Lipid Synthesis in Rat Hepatocytes

Zinc deficiency impairs the hepatic lipid metabolism. Previous studies were focused on the negative effects of zinc deficiency on the hepatic lipid metabolism. A few studies investigated the effects of high zinc levels on the lipid metabolism in hepatocytes. In this study, rat hepatocytes were cultured and treated with different and high concentrations of zinc to investigate the effects of high zinc levels on the lipid synthesis in hepatocytes in vitro. The levels of hepatocytes functional markers, including alkaline phosphatase, lactate dehydrogenase, and albumin, were significantly higher in the zinc treatment groups than in the control group (p?<?0.05, p?<?0.01). The mRNA and protein levels of sterol regulatory element-binding protein 1c (SREBP-1c) were significantly higher in the zinc treatment groups than in the control group (p?<?0.05, p?<?0.01). Furthermore, the mRNA expression levels of acetyl-CoA carboxylase 1 (ACC1) and fatty acid synthase (FAS) were significantly higher in the medium- and high-dose zinc treatment groups than in the control group (p?<?0.01). The mRNA levels of stearoyl-CoA desaturase-1 (SCD-1) were significantly higher in the high-dose group (p?<?0.01). These results indicate that high levels of zinc increase hepatocytes activity and SREBP-1c expression, which upregulate the expression of ACC1, FAS, and SCD-1, thereby improving the lipid metabolism in the hepatocytes.     

Stimulation and inhibition effects of algae-lytic products from Bacillus cereus strain L7 on Anabaena flos-aquae

Alga-bacterium relationships between a Bacillus cereus strain L7 and Anabaena flos-aquae were studied based on the effects of the algicidal substances on algal growth indicators such as enzyme activity and membrane lipid peroxidation. When exposed to algae-lytic products at a concentration of 0.05?mg?mL^?1, chlorophyll a (Chla), protein and phycobiliprotein contents increased significantly (p?<?0.05); superoxide dismutase (SOD), peroxidase (POD) and catalase (CAT) activities and malondialdehyde (MDA) concentrations increased slightly to stimulate the algae growth. When exposed to algae-lytic products at a concentration of 0.5?mg?mL^?1, algae growth and composition were inhibited. Chla, protein and phycobiliprotein concentrations decreased significantly (p?<?0.05 for protein, p?<?0.01 for Chla and phycobiliprotein). MDA concentrations increased significantly (p?<?0.05). POD and CAT activities increased by approximately six and three times, respectively, in 24?h compared with the control, then decreased to the initial level in 4?days. Algae-lytic products have not only inhibition but also stimulation effects on A. flos-aquae. Such effects are associated with antioxidative/oxidative reactions as indicated by the biomarkers SOD, POD, CAT, and MDA.     

Enhancement of purinergic signalling by excessive endogenous ATP in resiniferatoxin (RTX) neuropathy

ATP is a ligand of P2X family purinoceptors, and exogenous ATP administration evokes pain behaviors. To date, there is a lack of systematic studies to address relationships between endogenous ATP and neuropathic pain. In this report, we took advantage of a mouse model of resiniferatoxin (RTX)-induced neuropathic pain to address the role of endogenous ATP in neuropathic pain. After RTX administration, endogenous ATP markedly increased in dorsal root ganglia (DRGs) (p?<?0.01) and skin tissues (p?<?0.001). The excessive endogenous ATP was removed by apyrase, an ATP hydrolyzing enzyme, administration via either a lumbar puncture route (p?<?0.001) or an intraplantar injection (p?<?0.001), which led to the normalization of neuropathic pain. In addition, intraplantar treatment with apyrase caused mechanical analgesia. Linear analyses showed that the densities of P2X3(+) neurons (r?=??0.72, p?<?0.0001) and P2X3(+) dermal nerves (r?=??0.72, p?<?0.0001) were inversely correlated with mechanical thresholds. Moreover, the contents of endogenous ATP in skin tissues were linearly correlated with P2X3(+) dermal nerves (r?=?0.80, p?<?0.0001) and mechanical thresholds (r?=??0.80, p?<?0.0001). In summary, this study demonstrated that enhanced purinergic signalling due to an increase in endogenous ATP after RTX-induced nerve injury contributed to the development of neuropathic pain. The data in this report provide a new therapeutic strategy for pain control by targeting the endogenous ligand of purinergic signalling.     

24-Hour Pattern of Work-Related Injury Risk of French Firemen: Nocturnal Peak Time

The first aim of the study was to assess clock-time patterning of work-related injuries (WRIs) of firemen (FM) of Saône et Loire-71 (France) during the 4-yr span of 1 January 2004 to 31 December 2007. FM of this service are legally required to log every WRI and seek its evaluation by the medical service, whether the WRI was the result of worksite duties or exercise/sport activities at the station. WRI was defined specifically as a (nonexercise, nonsport, and nonemotional/stress) work-associated trauma, verified both by log book and medical records. For the corresponding years, the 24-h pattern of emergency calls (Calls) plus road traffic (Traffic) on the main roads of the service area was also assessed. Relative risk (R) of WRI was calculated as the quantity of WRIs/h divided by the quantity of Call responses/h?×?1000, which takes into account the number of at-risk FM/unit time, since each dispatched emergency vehicle is staffed with 4 FM. Comparably trained regular (RFM) and volunteer (VFM) FM experienced a total of 187 WRIs. The 24-h WRI curve patterns of RFM and VFM were correlated (r?=?0.4, p?<?.05), with no histogram difference (p?>?.05). Analysis of variance (ANOVA) validated comparable clock-time patterns in WRIs of RFM and VFM each year and each season (all p?<?.0001). Thus, time series of the RFM and VFM were pooled, revealing a statistical significant 24-h variation in WRIs (ANOVA, p?>?.0006; Cosinor analysis, p?<?.0001), with peak at 16:00?h and trough at 04:00?h. The 24-h pattern in Traffic, which mirrors that of human activity, with peak ～18:00?h and trough ～03:00?h, was also verified (ANOVA, p <?.0001; Cosinor, p?<?.0001). Calls (n?=?112,059) resulting in FM responses also exhibited statistically significant 24-h variation, with peak at ～20:00?h and trough at ～06:00?h. The 24-h pattern of R showed a nocturnal peak at 02:00?h (R?=?2.87?±?0.46; mean?±?SEM) and diurnal trough 14:00?h (R?=?1.30?±?0.05) (t test, p?<?.02); clock-time-related changes in R were further validated by ANOVA (p?=?.0001) and Cosinor (p?<?.0001), with acrophase (peak time, Ø) of 02:43?h?±?68?min (SD). The second aim of the study was to evaluate the relationship between the 24-h patterns of WRIs and lag-time (LT) response (used as a measure of work performance) of FM of the same service to urgent medical calls for out-of-hospital cardiac arrests. Highest R of WRI at 02:00?h corresponded closely to longest LT (raw data at ～02:00?h and Cosinor derived Ø of 02.54?h?±?71?min [SD]), thereby supporting the hypothesis of a common mechanism underlying the two 24-h profiles. A third aim was to determine the relevance of a new concept in work safety, “chronoprevention,” for future FM training programs. (Author correspondence: bergarein@yahoo.fr)     

24-hour Pattern in Lag Time of Response by Firemen to Calls for Urgent Medical Aid

The aim of the study was to assess the group 24-h pattern of lag time (LT) in response by regular and volunteer firemen (RFM and VFM) to calls for medical help (CFMH), specifically calls for out-of-hospital cardiac arrest (OHCA). LT, duration in min between a CFMH and departure of service vehicle equipped with a semiautomated defibrillator and generally staffed with four well-trained and ready-to-go FM, represents the integrated duration of several processes, each with separate reaction and decision-making times. The exact time of each CFHM (in min, h, day, month, yr) was recorded electronically, and the exact departure time from the station of the responding FM vehicle was recorded by an on-duty FM. Overall, CFMH made up 53?±?9% (SEM) of all emergencies calls for aid. To standardize the study methods, the reported findings are based on 568 CFMH specifically regarding OHCA that occurred during the 4-yr study span (January 2005 to December 2008). CFMH exhibited a 24-h pattern with a major peak at 10:00?h (mean?±?SEM: n?=?9.5?±?1.6) and major trough at 01:00?h (n?=?1.3?±?0.3; t test, p?<?.001). From year to year and season to season, a 24-h pattern was detected in the total of CFMH/h with two peaks (～10:00 and ～17:00h) and two troughs (～01:00 and ～15:00?h) (analysis of variance [ANOVA], p?<?.01; Cosinor, p?<?.05 to?<?.003), with neither season- nor year-related differences (χ², p?>?.05). In CFMH/h pooled time series, ANOVA-detected differences between the hourly means (p?<?.01), and Cosinor analysis validated a 24-h rhythm (p?<?.002). In raw data, the longest LT, indicative of poorest performance, occurred at 05:00?h (8.8?±?0.7?min) and the trough of LT, indicative of best performance, at 16:00?h (4.3?±?0.8?min (t test, p?<?.02). 24-h patterning in LT was validated both by ANOVA of hourly means (p?<?.0006) and Cosinor analysis (p?<?.05), with longest LT ～05:00?h and shortest LT ～16.00?h for data of the individual yearly time-series data. The 24-h LT rhythm was also validated in the pooled time series by Cosinor (p?<?.0001), with the 24-h mean?±?SEM?=?6?±?0.17?min and acrophase (peak) of 03:00?h?±?88?min (SD). Curve patterns of CFMH/h and LT/h differed widely. As a group phenomenon, the LT 24-h rhythm mimics the 24-h pattern of performance, as demonstrated by many laboratory and field investigations. The stability of the LT rhythm between years and seasons and its weak relationship with the CFMH 24-h pattern favors the hypothesis of an endogenous component or origin. The nighttime trough of performance is presumably linked to the elevated risk of work accidents in the same population of FM.     

Prognostic Value of Blood Zinc, Iron, and Copper Levels in Critically Ill Children with Pediatric Risk of Mortality Score III

We aimed to explore the association of blood Zn, Fe, and Cu concentrations and changes in the pediatric risk of mortality (PRISM) score in critically ill children, to predict prognosis. We included 31 children (22 boys and 9 girls, 1 month to 5 years old), who had been admitted to the intensive care unit of our hospital and who were critically ill according to PRISM score of III. Another 20 children (12 boys, 8 girls, 3 months to 5 years old) who were brought to the hospital for a health checkup were included as controls. We recorded clinical data, time in the intensive care unit, prognosis, and PRISM III score for critically ill children. Blood Cu, Zn, and Fe values were measured by inductively coupled plasma atomic emission spectrophotometry. Zn and Fe levels were significantly lower in patients than in controls (all p?<?0.05). Cu levels differed between patients and controls, but not significantly (p?>?0.05). In ill children, blood Zn and Fe concentrations were inversely correlated with PRISM III score (Zn: r?=??0.36; Fe: r?=??0.50, both p?<?0.05), with no significant correlation of blood Cu level and PRISM III score (r?=??0.13, p?>?0.05). Serious illness in children may lead to decreased Zn and Fe blood concentrations. Zn and Fe supplements may be beneficial for critically ill children.     

The evaluation of protective and mitigating effects of vitamin C against side effects induced by radioiodine therapy

The goal of this study was to evaluate the protective and mitigative effect of vitamin C on oxidative stress in differentiated thyroid cancer (DTC) patients ablated with radioiodine. 58 DTC patients selected for radioactive iodine therapy (RAIT) with 5550 MBq ¹³¹Iodine were divided into four groups. Group 1 (control group) consisted of patients who underwent RAIT routinely. Other patients received 1500 mg vitamin C daily 2 days after (group 2), 2 days before to 2 days after (group 3) and 2 days before RAIT (group 4). Serum oxidative stress markers including malondialdehyde (MDA), glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD) were measured immediately before and 2 days after RAIT. A significant increase in MDA after RAIT was observed in all groups (p?<?0.05). The concentrations of MDA were significantly higher in the control group compared to the intervention groups (p?<?0.05). A significant decrease in the control group (p?<?0.05) and increase in group 4 (p?<?0.05) were observed in GSH level after RAIT (p?<?0.05). Mean variation of GSH was significant between control group with groups 3 (p?<?0.01) and 4 (p?<?0.01). The results indicate that activity of SOD remained unchanged in all groups (p?>?0.05). A significant increase was observed in CAT activity after RAIT in all groups (p?<?0.05), which was higher in control group than intervention groups. In groups 3 (p?<?0.05) and 4 (p?<?0.05), this increase in CAT activity was significantly lower than the control group. RAIT causes serum oxidative stress, which can be ameliorated using vitamin C as an antioxidant. These results indicate that radioprotective effect of vitamin C is preferable to its mitigative effect.     

Thiamine deficiency induces oxidative stress in brain mitochondria of Mus musculus

The present investigation evaluates the changes in the levels of antioxidant enzymes, lipid peroxidation (LPO), and protein carbonyl content (PCC) in brain mitochondria following thiamine deficiency (TD). The study was carried out on Mus musculus allocated into three groups, namely control and thiamine-deficient group for 8 (TD 8) and 10 (TD 10) days. The LPO was measured in terms of reduced glutathione (GSH) and thiobarbituric acid reactive substance (TBARS). Antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were measured biochemically. A significant increase in the TBARS (p?<?0.0001) and PCC (p?<?0.001) levels in group II (TD 8) and group III (TD 10) animals was observed in comparison to controls. The GSH levels were found to be reduced in both the treated groups compared to the control. A significant reduction in the activities of SOD was also observed in group II (p?<?0.01) and group III (p?<?0.0001) animals in comparison to the control. Enzymatic activities of CAT (p?<?0.001) and GPx (p?<?0.05) were found to be significantly reduced in group III (TD 10) in comparison to the control. In conclusion, reduction in the activities of antioxidant enzymes as well as an increase in LPO and PCC following TD implies oxidative stress in brain mitochondria that may further leads to neurodegeneration.     

Hormonal, functional and genetic biomarkers in controlled ovarian stimulation: tools for matching patients and protocols

Background

The G protein-coupled estrogen receptor (GPER) is thought to be involved in non-genomic estrogen responses as well as processes such as cell proliferation and migration. In this study, we analyzed GPER expression patterns from endometriosis samples and normal endometrial tissue samples and compared these expression profiles to those of the classical sex hormone receptors.

Methods

A tissue microarray, which included 74 samples from different types of endometriosis (27 ovarian, 19 peritoneal and 28 deep-infiltrating) and 30 samples from normal endometrial tissue, was used to compare the expression levels of the GPER, estrogen receptor (ER)-alpha, ER-beta and progesterone receptor (PR). The immunoreactive score (IRS) was calculated separately for epithelium and stroma as the product of the staining intensity and the percentage of positive cells. The expression levels of the hormonal receptors were dichotomized into low (IRS?<?6) and high (IRS?>?=6) expression groups.

Results

The mean epithelial IRS (+/?standard deviation, range) of cytoplasmic GPER expression was 1.2 (+/?1.7, 0?C4) in normal endometrium and 5.1 (+/?3.5, 0?C12) in endometriosis (p?<?0.001), of nuclear GPER 6.4 (+/?2.6, 0?C12) and 6.8 (+/?2.9, 2?C12; p?=?0.71), of ER-alpha 10.6 (+/?2.4, 3?C12) and 9.8 (+/?3.0, 2?C12; p?=?0.26), of ER-beta 2.4 (+/?2.2; 0?C8) and 5.6 (+/?2.6; 0?C10; p?<?0.001), and of PR 11.5 (+/?1.7; 3?C12) and 8.1 (+/?4.5; 0?C12; p?<?0.001), respectively. The mean stromal IRS of nuclear GPER expression was 7.7 (+/?3.0; 2?C12) in endometrium and 10.8 (+/?1.7; 6?C12) in endometriosis (p?<?0.001), of ER-alpha 8.7 (+/?3.1; 2?C12) and 10.6 (+/?2.4; 2?C12; p?=?0.001), of ER-beta 1.8 (+/?2.0; 0?C8) and 5.4 (+/?2.5; 0?C10; p?<?0.001), and of PR 11.7 (+/?0.9; 8?C12) and 10.9 (+/?2.0; 3?C12; p?=?0.044), respectively. Cytoplasmic GPER expression was not detectable in the stroma of endometrium and endometriosis. The observed frequency of high epithelial cytoplasmic GPER expression levels was 50% (n?=?30/60) in the endometriosis and none (0/30) in the normal endometrium samples (p?<?0.001). High epithelial cytoplasmic GPER expression levels were more frequent in endometriomas (14/20, 70%; p?=?0.01), as compared to peritoneal (9/18, 50%) or deep-infiltrating endometriotic lesions (7/22, 31.8%). The frequency of high stromal nuclear GPER expression levels was 100% (n?=?74/74) in endometriosis and 76.7% (n?=?23/30) in normal endometrium (p?<?0.001). The frequency of high epithelial nuclear GPER expression levels did not differ between endometriosis and normal endometrium.

Conclusions

The present data indicate a unique GPER expression pattern in endometriosis, especially in endometriomas as compared to the normal endometrium. The overexpression of GPER in endometriotic lesions suggests a potential role for GPER in the hormonal regulation of endometriosis, which should be taken into consideration for future hormonal treatment strategies.