GH Group Research Articles

Effects of ADAR1 inducer / inhibitor on cognitive impairment and the expression of ADAR1 protein of social isolation mice

Objective To explore the effects of ADAR1 inducer and inhibitor on cognition and ADAR1 expression of isolated BALB/c mice. Methods Sixty healthy BALB/c mice were divided into 6 groups according to randomized design with 10 animals each group, the gregarious control group (GH), social isolation model group (SI), ADAR1 inducer treated gregarious group (GH+ IFN-γ), ADAR1inhibitor treated gregarious group (GH+ EHNA), ADAR1 inducer treated isolation group (SI+ IFN-γ) and ADAR1 inhibitor treated isolation group (SI+ EHNA). Mice in drug treatment groups were treated with ADAR1 inducer (5.0×104 U/kg, 20 ml/kg, ip) and inhibitor (10 mg/kg, 20 ml/kg, ip). Objection recognition test was used to measure cognition.Immunohistochenmistry was used to measure ADAR1 immunoreactivity and Western blot was used to measure ADAR1 protein expression. Results In the objection recognition test, the non-spatial discrimination index of mice in SI group (-0.16±0.09) was significantly lower than that of GH group (0.41±0.17, P<0.01), the non-spatial discrimination index of mice in SI+ IFN-γ group (0.20±0.09) and in SI+ EHNA group (-0.29±0.12) was higher (P<0.01) and lower (P<0.05) than that of the SI group respectively. The immunohistochemistry results showed that the ADAR1 immunoreactivity in hippocampus of mice in SI group (Hilus: (0.013±0.003), CA1: (0.021±0.005)) decreased significantly compared to those of GH group(Hilus: (0.021±0.002), (0.047±0.004); both P<0.05). And GH+ IFN-γgroup mice showed increased ADAR1 immunoreactivity obviously in Hilus (( 0.013±0.003) vs (0.023±0.004), P<0.01) and in CA1 ((0.021±0.005) vs (0.040±0.005), P<0.01) compared with that of SI group, ADAR1 inducer recovered the above abnornal ADAR1 immunoreactivity.Western blot results showed that the ADAR1 protein expression of mice in SI group (0.48±0.07) in hippocampus was significantly decreased (P<0.01) compared to that of GH group (1.00±0.00) .The level of ADAR1 protein in SI+ IFN-γgroup(0.82±0.04) increased compared with that of SI group. Conclusions Four weeks of social isolation can reduce the non-spatial cognitive ability of BALB/c mice and decrease the expression of ADAR1 in the hippocampus. The ADAR1 inducers and inhibitors can reverse and aggravate the cognitive impairment caused by social isolation respectively. The related mechanisms may be related to the expression of ADAR1. Key words: Social isolation; Cognitive function; BALB/c mice; Adenosine deaminase 1 acting on RNA

Calcium and Magnesium Urinary Excretion in Dairy Cows with Different Fee of Glucose Metabolization

Background: The post-partum period in dairy cows is accompanied by a low glucose metabolism in adipose tissue and skeletal muscle tissue, being glucose conducted to the milk production. In humans, low glucose metabolism is associated with metabolic syndromes, the high glucose levels reduce tubular reabsorption of Magnesium (Mg) and Calcium (Ca), leading to hypomagnesemia and hypocalcemia. These minerals are important to the dairy cow, as their decrease leads to diseases. The aim of this study was to evaluate the relationship between glucose metabolism rate with the urinary excretion of Ca and Mg in multiparous dairy cows during the post-partum period.Materials, Methods &amp; Results: Twenty dairy cows were used from a commercial farm southern Brazil, in the semi-extensive system. Glucose tolerance tests were performed (TTG) on day 9 relative to calving. The cows were categorized into three groups according to the glucose metabolism rate (area under the glucose curve, glucose half-life and glucose consumption rate): High Glucose Metabolization (GA); Intermediate Glucose Metabolizing (GI); and Low Glucose Metabolization (GL). Blood and urine samples were collected on days 0, + 3, + 6, + 9, +16 and +2 3 in relation to calving for to determine the levels of Ca, Mg, insulin (Ins), non-esterified fatty acids (NEFA) and Glu. In urine was evaluated the excretion of Ca and Mg. The cows were milked twice a day (at 3:00 a.m. and 3:00 p.m.) and the milk yield (kg/cow) was recorded daily and averages were generated every five days from day 15 to day 60 postpartum. The statistical analyses were performed with the MIXED procedure to assess the main effect of group, time (in days) and their interaction by using version 9.2 SAS software. The influence of the different rates of glucose metabolism on milk production was observed, the GB group had a production than GH group (30.88 ± 1.44 kg vs 23.96 ± 1.43 kg, P &lt; 0.01), but did not differ from GI. The GL group showed higher levels of Glu compared to GA (P &lt; 0.05). The plasma Ca levels were higher in GL (P &lt; 0.05) compared with GH. The NEFA, insulin, and excretion of minerals did not differ between groups (P &gt; 0.05).Discussion: The low glucose metabolism in humans causes an increase in the excretion of Ca and Mg urine, however, in the animals studied, these changes were not observed. This result can be attributed to the fact that insulin resistance is transitory in dairy cattle. The higher glucose levels in the GL group are related due to the lower capacity of glucose entry in the peripheral tissues (adipose and skeletal muscle), which reflected in the higher milk production observed this group. However, the higher calcium concentrations were not expected, since the release of insulin by β-pancreatic cells is dependent on calcium. Possibly, these higher calcium levels in GB, are related to higher milk production, requiring a greater amount of calcium for the production of casein, increasing bone mobilization, intestinal absorption. The energy metabolites, non-esterified fatty acids and insulin, did not differ between groups, suggesting that the animals did not present different metabolic conditions. We conclude that multiparous dairy cows with low glucose metabolism rate (GB) have higher levels of glucose after delivery and increased milk production. The metabolism rate of glucose did not influence the excretion of the Ca and Mg minerals.

Outcomes of poor responders following growth hormone co-treatment with IVF/ICSI mild stimulation protocol: a retrospective cohort study.

No research has studied the effect of GH co-treatment in mild stimulation protocol for poor responders. We therefore conducted this retrospective analysis to assess the outcome of IVF/ICSI cycles after the adjunct GH use to the mild stimulation protocol in poor responders. 132 poor responders who received mild stimulation protocol at Reproductive Medicine Center of Changzheng Hospital from January 2014 to December 2016 were included in this study. Good-quality embryo rate, clinical pregnancy rate, and live birth rate were compared between the GH group (n=61) and control group (n=71). IVF good-quality embryo rate (68.1 versus 51.5%; P=0.008*) and ICSI good-quality embryo rate (53.9 versus 36.7%; P=0.045*) was significantly higher in the GH group. Though the clinical outcomes did not reach a statistically significant difference between the two groups due to the limited sample size, there was a trend of higher rate in GH group in the aspect of clinical pregnancy rate (52.4 versus 47.1%; P=0.609) and live birth rate (35.7 versus 27.5%; P=0.392). The results suggested that the adjuvant GH treatment in mild stimulation protocol for poor responders could significantly improve good-quality embryo rate, and might therefore improve the clinical outcomes.

Association of insulin resistance and autonomic tone in patients with pregnancy-induced hypertension

ABSTRACTPregnancy-induced hypertension (PIH) remains the main cause of maternal and fatal mortality. Insulin resistance (IR) and autonomic nervous system (ANS) imbalance are two principal drivers of PIH development. Few previous researches investigated the association between IR and ANS imbalance in Chinese PIH patients. 120 pregnant women were enrolled in our study, sixty healthy pregnant women (control group), fourty one gestational hypertension (GH group) and nineteen preeclampsia patients (PE group). The homeostasis model assessment of IR (HOMA-IR) and markers of ANS (plasma biomarkers and heart rate variability (HRV) components) were collected. Body mass index (BMI), Ln(HOMA-IR), noradrenaline level, LnTP (total power), Ln SDNN (standard deviation of the normal-to-normal interval), LnLF (low frequency), LnLF/LnHF (low frequency/high frequency) were different in the GH and PE groups compared with the controls. Significant correlations were observed between Ln (HOMA-IR) and gestational duration (r = 0.237, P = 0.031), BMI（r = 0.314, P = 0.002), systolic blood pressure (r = 0.108, P = 0.016), noradrenaline (r = 0.451, P = 0.009), LnTP (r = −0.269, P = 0.015) and LnLF/HF (r = 0.183, P = 0.026) in those PIH patients. Furthermore, BMI, noradrenaline and LnTP were independent determinants of Ln(HOMA-IR) in PIH patients by multiple regression analysis. Our finding verified both IR and ANS imbalance were more severe in PIH patients than healthy pregnant women. Moreover, IR had a close association with ANS parameters in PIH patients, suggesting that they probably had contributory effects on the occurrence and development of PIH. We propose that these parameters could be added to the traditional indexes for individualized treatment of PIH patients in the future.

Longitudinal characterization of renal proximal tubular markers in normotensive and preeclamptic pregnancies.

Glomerular damage is common in preeclampsia (PE), but the extent and etiology of tubular injury are not well understood. The aim of this study was to evaluate tubular injury in patients with PE and to assess whether it predates clinical disease. We performed a prospective cohort study of 315 pregnant women who provided urine samples at the end of the second trimester and at delivery. This analysis included women who developed PE (n = 15), gestational hypertension (GH; n = 14), and normotensive controls (NC; n = 44). Urinary markers of tubular injury, α1-microglobulin (A1M), retinol-binding protein (RBP), kidney-injury molecule-1 (KIM1), complement C5b-9, tissue inhibitor metalloproteinase-2 (TIMP-2), and insulin-like growth factor binding protein-7 (IGFBP-7) were measured by enzyme-linked immunosorbent assay (ELISA) and reported in relation to urine creatinine concentration. Second-trimester concentrations of all markers were similar among groups. At delivery, A1M concentrations were higher in the PE group than in the GH and NC groups as an A1M/creatinine ratio >13 (66.7, 8.3, and 35%, respectively, P = 0.01). Concentrations of C5b-9 were higher in the PE group than in the GH and NC groups (medians 9.85, 0.05, and 0.28 ng/mg, respectively, P = 0.003). KIM1, RBP, TIMP-2, and IGFBP-7 concentrations did not differ among groups at delivery. In conclusion, proximal tubular dysfunction, as assessed by A1M and C5b-9, developed during the interval between the end of the second trimester and delivery in patients with PE. However, this was not matched by abnormalities in markers previously associated with tubular cell injury (KIM-1, IGFBP-7, and TIMP-2).

Proteolytic Mediators in Gestational Diabetes Mellitus and Gingivitis.

This study evaluates levels of matrix metalloproteinase (MMP)-8, MMP-9, and tissue inhibitor of MP-1 (TIMP-1) in biofluids of women with gestational diabetes mellitus (GDM) and systemically healthy counterparts with different statuses of periodontal health. Seventy-one women with GDM and gingivitis (Gg), 30 women with GDM and healthy periodontium (Gh), 28 systemically and periodontally healthy women (Hh), and 37 systemically healthy women with gingivitis (Hg) were evaluated. MMP-8, MMP-9, and TIMP-1 levels were determined in gingival crevicular fluid (GCF), saliva, and serum by immunofluorometric and enzyme-linked immunosorbent assays. Full-mouth clinical periodontal parameters were recorded. GCF and serum MMP-8 concentrations, serum MMP-9 concentrations, and serum MMP-8/MMP-1 and MMP-9/MMP-1 molar ratios were significantly higher in Gg compared with Hg group (P <0.05). Serum MMP-8 levels and salivary TIMP-1 levels were higher in Gh compared with Hg group (P <0.05) whereas salivary MMP-8/TIMP-1 molar ratio was lower in Gh compared with Hg group (P <0.05). Elevated concentrations of GCF MMP-8 and MMP-9 were found in Gg compared with Gh group (P <0.05). Significant correlations were found between local levels of biomarkers and clinical periodontal parameters in only GDM group. GDM may modulate both local and circulating levels of MMP-8 especially when associated with gingivitis.

Abstract 184: Intravenous Thrombolysis for Acute Ischemic Stroke in the “Golden Hour”: a Propensity-matched Analysis of SITS-EAST Registry

Background &amp; Purpose: There are scarce data regarding outcomes of AIS patients treated with IVT within 60 min from symptom onset (“golden hour”). We sought to compare outcomes between AIS patients treated within (OTT≤60 min) and outside (OTT: 61-270min) the “golden hour” [GH(+) &amp; GH (-)] using a propensity score matching approach. Methods: Patients were evaluated during a 12-year period in a large, international, prospective registry of IVT (SITS-EAST). They underwent serial NIHSS-score assessments at baseline, 2 hrs and 24 hrs following tPA-bolus. Clinical recovery (CR) at 2 and 24 hrs was defined as a reduction of ≥10 points in NIHSS-score compared with baseline, or a NIHSS-score of ≤3 at 2 and 24 hrs respectively. A relative reduction in NIHSS-score of ≥40% at 2 hrs was predictive of complete recanalization (CREC). sICH was defined using SITS-MOST criteria; 3-month favourable functional outcome (FFO) was defined as a mRS-score of 0-1. The two groups were matched for demographics, risk factors, baseline NIHSS, admission blood pressure and serum glucose. Results: Out of 19.077 tPA-treated AIS patients, 71 patients in GH(+) group [mean age 67±13 years; median NIHSS-score 12 points (IQR 10); median onset to treatment time (OTT) 55min, (IQR 10)] were matched to 6882 patients in GH(-) group (mean age 67±12 years; median NIHSS-score 11 points (IQR 9); median OTT 155min (IQR 55)]. The two groups did not differ in any of the matched characteristics (p&gt;0.1). GH(+) had significantly (p&lt;0.05) higher rates of 2hr (31% vs. 12%) and 24hr (41% vs. 27%) CR, CREC (39% vs. 21%) and 3-month FFO (47% vs. 34%). The rates of sICH (0% vs. 2%) and 3-month mortality (9% vs. 13%) were similar (p&gt;0.2) in the two groups. GH(+) was independently (p&lt;0.05) associated with 2hr CR (OR:5.5; 95%CI: 2.6-12.0), 24hr CR (OR:2.0; 95%CI: 1.1-3.6), CREC (OR:2.4; 95%CI: 1.4-4.3), and 3-month FFO (OR:2.3; 95%CI: 1.3-4.1) in multivariable logistic regression analyses adjusting for potential confounders. Conclusions: AIS patients treated with IVT within the GH have substantially higher odds of early CR and FFO. These findings highlight the potential of mobile stroke units to further improve AIS outcomes by increasing the rates of tPA delivery within the GH.

Potential diagnostic biomarkers for chronic kidney disease of unknown etiology (CKDu) in Sri Lanka: a pilot study

BackgroundIn Sri Lanka, there exists chronic kidney disease of both known (CKD) and unknown etiologies (CKDu). Identification of novel biomarkers that are customized to the specific causative factors would lead to early diagnosis and clearer prognosis of the diseases. This study aimed to find genetic biomarkers in blood to distinguish and identify CKDu from CKD as well as healthy populations from CKDu endemic and non-endemic areas of Sri Lanka.MethodsThe expression patterns of a selected panel of 12 potential genetic biomarkers were analyzed in blood using RT-qPCR. Fold changes of gene expressions in early and late stages of CKD and CKDu patients, and an apparently healthy population of a CKDu endemic area, Girandurukotte (GH) were calculated relative to apparently healthy volunteers from a CKDu non-endemic area, Kandy (KH) of Sri Lanka, using the comparative CT method.ResultsSignificant differences were observed between KH and early stage CKDu for both the insulin-like growth factor binding protein 1 (IGFBP1; p = 0.012) and kidney injury molecule-1 (KIM1; p = 0.003) genes, and KH and late stage CKD and CKDu for the glutathione-S-transferase mu 1 (GSTM1; p < 0.05) gene. IGFBP1 and KIM1 genes showed significant difference between the early and late stage CKDu (p < 0.01). The glutamate cysteine ligase catalytic subunit (GCLC) gene had significantly different expression between KH and all the other study groups (p < 0.01). The GH group was significantly different from the KH group for the oxidative stress related genes, G6PD, GCLC and GSTM1 (p < 0.01), and also the KIM1 gene (p = 0.003). IGFBP1, insulin-like growth factor binding protein 3 (IGFBP3), fibronectin 1 (FN1) and KIM1 showed significant correlations with serum creatinine, and IGFBP1, KIM1 and kallikrein 1 (KLK1) with eGFR (p < 0.05).ConclusionA panel consisting of IGFBP1, KIM1, GCLC and GSTM1 genes could be used in combination for early screening of CKDu, whereas these genes in addition with FN1, IGFBP3 and KLK1 could be used to monitor progression of CKDu. The regulation of these genes has to be studied on larger populations to validate their efficiency for further clinical use.

Breed composition does not influence the performance of Holstein-Gyr crossbred as oocyte donors for OPU/IVP.

Holstein-Gyr crossbred cattle are strategic for dairy systems in tropical countries, since they combine milk yield genetics with adaptability to tropical climate. However, Holstein (Bos taurus) and Gyr (Bos indicus) breeds present remarkable differences regarding reproductive physiology. Brazil stands out as the world’s largest user of embryo in vitro production (IVP) in bovine, and the use of this technique is increasing in dairy systems. As Holstein-Gyr crossbreds are important oocyte donors for IVP, the present work aimed at investigating whether increased Gyr or Holstein breed composition influences donor’s performance. Sixteen Holstein-Gyr crossbred females presenting increased (HG, 71.4 to 87.5% Holstein; n = 9) or decreased (GH, 40.2 to 46.6% Holstein; n = 7) Holstein composition were submitted to three ovum pick up (OPU) sessions. We observed similar (P = 0.2946) antral follicle count between HG and GH donors (24.8 ± 3.2 vs 29.4 ± 2.8 respectively; mean ± SEM). Groups also display similar morphological oocyte grading (Grade I: 0.1 ± 0.1 vs 0.1 ± 0.1 – P = 0.9680; Grade II: 0.9 ± 0.5 vs 1.9 ± 0.5 – P = 0.1942; Grade III, 4.0 ± 1.2 vs 7.2 ± 1.4 – P = 0.1047, HG vs GH respectively; mean ± SEM). Additionally, the proportion of viable oocyte was similar between HG and GH groups (27.8% vs 31.9%, respectively, P = 0.3500) and oocyte lipid area fraction (6.8% vs 9.5%, respectively; P = 0.1539). Our results indicate that the individual variation has more influence than breed composition of crossbred oocyte donors.

CXC chemokine CXCL12 tissue expression and circulating levels in peptic ulcer patients with Helicobacter pylori infection

Helicobacter pylori (H. pylori) infection is among the most prevalent human infections. CXCL12 is a well-known CXC chemokine involved in inflammation and play major roles in angiogenesis. There is currently very limited data on the role of CXCL12 in peptic ulcer disease. Hence, we aimed to explore whether CXCL12 is involved in the pathogenesis of peptic ulcer induced by H. pylori. In this study, we enrolled 102 H. pylori-infected patients, including 51 with active ulcer (GA) and 51 with healing ulcer (GH). We also recruited 50 healthy subjects as control, which did not show any sign or symptoms of chronic inflammatory diseases, infection, or immune-related disorders. Endoscopy was performed to determine the stage of the disease. ELISA was used for detection of H. pylori infection and CXCL12 measurement. We also employed western blotting to detect CXCL12 in ulcerative lesions of H. pylori. Demographic data were also collected by questionnaire. Our results demonstrated that CXCL12 serum levels in GA group (151.8±18.31pg/mL) were significantly higher than those in GH (36.89±6.78pg/mL) and control groups (33.77±9.12pg/mL) (P<0.0001). However, we did not observe a significant difference between GH and control groups. Moreover, overexpression of CXCL12 in gastric lesions of patients in GA group was confirmed by Western blot analysis. According to the result of the present study, it could be concluded that CXCL12 is involved in the pathogenesis and healing of H. pylori-induced peptic ulcer. CXCL12 serum levels may also be used to distinguish between GA and GH phases of the disease.

Genomic study of the mammary gland in bovines acclimated to a tropical environment

This study aims at examining the expression of genes on the mammary gland, corresponding to various levels of adaptation or acclimatization to environmental stress. The authors utilized 18 cows from three genetic groups, Holstein Brazil (HB), Gyr (GG) and Gyrolando (GH ), all in the same stage of lactation, and subjected them to the same management conditions. Venous and arterial blood were collected to determine the hormonal profile and blood chemistry. Mammary gland tissue was used for transcriptomic studies. Prolactin and GH plasmatic concentrations were higher in Holstein animals. There were no differences in IGF-1 concentrations among the experimental groups. T 3 concentrations were similar among the Holstein and Gyr groups. From the 4608 transcripts in the BLO-Bovine EST (Michigan State University, US) databank that were used in this experiment, 105 differentially expressed genes were identified in at least one of the groups. Among these, the authors highlighted 14 genes that were related to the structure of the mammary gland (CRDGF, CD97, GH, endoglin, LTF, INPP, PTP), to response to thermal stress (Crh_11, v-Fos, Cdc37) and to milk protein (RPL35, κ-casein, β-casein, α-s2-casein). Eight of these were validated through real-time polymerase chain reaction. The HB animals, in comparison with the GH and Gyr groups, presented up-regulated genes associated with epithelium cellular differentiation and proliferation, milk productivity and decreased heat stress tolerance. Gyr animals presented up-regulated transcripts associated with cellular defence, apoptosis processes and increased tolerance to heat stress. The GH group showed intermediary results compared with the other two groups. Keywords: Dairy cow, mammary gland, transcriptomic, thermic stress

Citalopram attenuates tau hyperphosphorylation of cortex and memory deficits in social isolation-reared rats

Objective To explore the effect of citalopram on tau phosphorylation and memory deficits induced by social isolation (SI) in adult rats. Methods Sixty Sprague-Dawley adult rats (8 months) were grouped or isolation reared for six-weeks. Following the initial two-week period of rearing, citalopram (10 mg/kg, i.p.) was administered for 4 weeks. Novel object recognition test, Western blot and ELISA were used to detect recognitive function, the levels of tau and GSK-3β protein, and melatonin level respectively. Results In the novel object recognition test, compared with the citalopram group(0.71±0.05) and housed group(0.73±0.13), discrimination ratio(0.48±0.15) in SI group was significant decreased (P<0.05). Tau hyperphosphorylation at Tau-1 ((0.88±0.11)), Ser396 (3.94±0.74) episodes were found and almost reversed by citalopram at Tau-1 (1.56±0.17), Ser396 (2.31±0.24) episodes in SI group. Compared with GH group, the total level of GSK-3β(1.12±0.09) was significantly increased, while the level of Ser9-phosphorylated GSK-3β (inactive form) (0.47±0.11) was significantly decreased in the SI group, both of which were reversed by citalopram (GSK-3β (0.87±0.08) and Ser9-phosphorylated GSK-3β (0.80±0.07)). The melatonin level was decreased in SI group ((359.54±18.80)pg/ml), and citalopram could partly restore the level of melatonin (418.15±18.72)pg/ml, P<0.05). Conclusion The results demonstrate that citalopram increases the level of melatonin which negatively regulates GSK-3β and attenuates tau hyperphosphorylation and memory deficits induced by SI in adult rats. Key words: Social isolation; tau protein; Citalopram; Alzheimer's disease; Melatonin

Puberty and Pubertal Growth in GH-treated SGA Children: Effects of 2 Years of GnRHa Versus No GnRHa.

Most studies on puberty in children born small for gestational age (SGA) report height and age at onset of puberty. GH-treated SGA children with an adult height (AH) expectation below -2.5 SDS at onset of puberty can benefit from an additional 2 years of GnRH analog (GnRHa) treatment. There are no data on puberty and growth after discontinuation of GnRHa treatment in GH-treated SGA children. This study aimed to investigate the effects on puberty and pubertal growth of 2 years GnRHa vs no GnRHa in GH-treated SGA children. This was a GH trial involving 76 prepubertal short SGA children (36 girls) treated with GH. Thirty-two children received additional GnRHa for 2 years. Pubertal stages were 3-monthly assessed according to Tanner. Age, bone age, and median height at pubertal onset were lower in girls and boys in the GH/GnRHa group compared with the GH group. In girls and boys treated with GH/GnRHa, pubertal duration after stop of GnRHa treatment was shorter than pubertal duration in those with GH only (40.9 vs 46.7 mo; P = .044; 50.8 vs 57.5 months; P = .006; respectively). Height gain from onset of puberty until AH, including height gain during 2 years of GnRHa treatment, was 25.4 cm in girls and 33.0 cm in boys, which was 6.6 cm more than girls and boys treated with GH only. AH was similar in children treated with GH/GnRHa compared with those with GH only. GH-treated SGA children who start puberty with an AH expectation below -2.5 SDS and are treated with 2 years of GnRHa have a shorter pubertal duration after discontinuation of GnRHa compared with pubertal duration in children treated with GH only. Height gain from onset of puberty until AH is, however, more due to adequate growth during 2 years of GnRHa treatment resulting in a similar AH as children treated with GH only.

Different Concentrations of Notoginsenoside Rg1 Attenuate Hypoxic and Hypercapnia Pulmonary Hypertension by Reducing the Expression of ERK in Rat PASMCs

Pulmonary arterial hypertension (PAH) is a serious disease which is characterized by increased vascular resistance and pressure. We have previously hypothesized that panax notoginseng saponins (PNS) might attenuate pulmonary vasoconstriction under hypoxia and hypercapnia condition. This study aims to investigate the effect of notoginsenoside R g1 , a main ingredient of PNS, with various concentrations (8, 40, 100 mg/L, respectively) on extracellular signal regulated kinase (ERK1/2) signaling pathway in pulmonary arterial smooth muscle cells (PASMCs). In addition, PASMCs were randomly divided into six groups: SD rat under normoxic condition as control group (N group), hypoxia hypercapnia group (H group), DMSO control group (HD group), R g1 -treatment groups (R gL R gM and R gH group). Western-blot and RT-PCR were used to test the expression of p-ERK protein and the expression of ERK1 mRNA and ERK2 mRNA. This study provided the evidence that the expression of p-ERK protein and the expression of ERK1 mRNA and ERK2 mRNA in HD group and H group were obviously higher than that in N group (P < 0.01), Whereas the level of ERK1/2 mRNA in R g1 -treatment groups was significantly lower than that in HD group and H group (P < 0.01), and the proper concentration of R g1 is 40 mg/L. These results suggested that notoginsenoside R g1 can attenuate pulmonary vasoconstriction which may lead to HHPV through reducing the expression of ERK1/2.

Low insulin resistance after surgery predicts poor GH suppression one year after complete resection for acromegaly: a retrospective study.

Remission of acromegaly is defined as a nadir in GH <1.0 ng/mL during a 75-g oral glucose tolerance test (75gOGTT) and insulin-like growth factor-1 (IGF-1) normalization. Recently, a lower cut-off value for GH nadir (<0.4 ng/mL) has been proposed. We retrospectively evaluated the prevalence and clinical characteristics of postoperative cases with normalized IGF-1 levels and a GH nadir of 0.4-1.0 ng/mL one year after complete resection of GH-secreting pituitary adenoma (GHoma). We included 110 cases of acromegaly with complete adenoma resection, no preoperative treatment, preoperative glycosylated hemoglobin <6.5%, preoperative basal plasma glucose <126 mg/dL, GH nadir <1.0 ng/mL during a 75gOGTT, and normalized IGF-1 at the first postoperative year evaluation, whereupon patients were divided into two groups: control (GH nadir <0.4 ng/mL) and high GH (GH nadir >0.4 ng/mL). Clinical parameters, including measures of insulin secretion and resistance, were compared between groups. The high GH group included 10 patients (9.1%) and had a lesser level of insulin resistance immediately following surgery and at the first postoperative year evaluation. On single regression analysis, insulin resistance immediately following surgery was predictive of and correlated with the GH nadir at the first postoperative year evaluation. The GH nadir at the first postoperative year evaluation may be insufficient in patients with normalized IGF-1 with low insulin resistance immediately following complete resection of GHoma. Careful evaluation is needed to assess remission in such patients.

Growth hormone (GH) dose-dependent IGF-I response relates to pubertal height gain.

BackgroundResponsiveness to GH treatment can be estimated by both growth and ∆IGF-I. The primary aim of the present study was to investigate if mimicking the physiological increase during puberty in GH secretion, by using a higher GH dose could lead to pubertal IGFs in short children with low GH secretion. The secondary aim was to explore the relationship between IGF-I, IGFBP-3 and the IGF-I/IGFBP-3 ratio and gain in height.MethodsA multicentre, randomized, clinical trial (TRN88-177) in 104 children (90 boys), who had received GH 33 μg/kg/day during at least 1 prepubertal year. They were followed from GH start to adult height (mean, 7.5 years; range, 4.6–10.7). At onset of puberty, children were randomized into three groups, to receive 67 μg/kg/day (GH67) given once (GH67x1; n = 30) or divided into two daily injection (GH33x2; n = 36), or to remain on a single 33 μg/kg/day dose (GH33x1; n = 38). The outcome measures were change and obtained mean on-treatment IGF-ISDS, IGFBP3SDS and IGF-I/IGFBP3 ratioSDS during prepuberty and puberty. These variables were assessed in relation to prepubertal, pubertal and total gain in heightSDS.ResultsMean prepubertal increases 1 year after GH start were: 2.1 IGF-ISDS, 0.6 IGFBP3SDS and 1.5 IGF-I/IGFBP3ratioSDS. A significant positive correlation was found between prepubertal ∆IGFs and both prepubertal and total gain in heightSDS. During puberty changes in IGFs were GH dose-dependent: mean pubertal level of IGF-ISDS was higher in GH67 vs GH33 (p = 0.031). First year pubertal ∆IGF-ISDS was significantly higher in the GH67vs GH33 group (0.5 vs −0.1, respectively, p = 0.007), as well as ∆IGF-ISDS to the pubertal mean level (0.2 vs −0.2, p = 0.028). In multivariate analyses, the prepubertal increase in ‘∆IGF-ISDS from GH start’ and the ‘GH dose-dependent pubertal ∆IGF-ISDS’ were the most important variables for explaining variation in prepubertal (21 %), pubertal (26 %) and total (28 %) gain in heightSDS.Trial registrationTRN 88–177, not applicable 1988.ConclusionThe dose-dependent change in IGFs was related to a dose-dependent pubertal gain in heightSDS. The attempt to mimic normal physiology by giving a higher GH dose during puberty was associated with both an increase in IGF-I and a dose-dependent gain in heightSDS.Electronic supplementary materialThe online version of this article (doi:10.1186/s12902-015-0080-8) contains supplementary material, which is available to authorized users.

Evaluating Indeterminate Interferon-γ-Release Assay Results in Patients With Chronic Inflammatory Diseases Receiving Immunosuppressive Therapy.

To analyze the rate of indeterminate interferon-γ-release assay (specifically the QuantiFeron-TB Gold In-Tube [QFT-GIT]) testing for Mycobacterium tuberculosis in patients with chronic inflammatory disease (CID) compared with the general hospital population (GH) and a healthy reference group of hospital employees (HR), and to analyze factors associated with an indeterminate test result. Adults with a QFT-GIT result within a large regional US health system were included. We compared the likelihood of having an indeterminate test across each patient group. Among patients with CID, we estimated the effect of glucocorticoids, biologic agents, and disease-modifying antirheumatic drug (DMARD) use on the likelihood of having an indeterminate test, controlling for age, sex, comorbidities, and prior health services use. Of the 55,108 patients who met the inclusion criteria, CID made up 5.2% (n = 2,864), GH 48.2%, and HR 46.6% of the study population. Indeterminate results were present in 5.3% of the CID group, 1.9% of the GH group, and 1.5% of the HR group. Compared with HR, patients with CID were 2.4 times as likely to have indeterminate test results (adjusted risk ratio [RR] 2.4, 95% confidence interval [95% CI] 1.9-2.9). In adjusted models restricted to patients with CID, glucocorticoid use significantly increased the likelihood of an indeterminate test (adjusted RR 1.4 [95% CI 1.02-2.0]) while DMARD use decreased this likelihood (adjusted RR 0.7 [95% CI 0.5-0.97]) when compared to patients not receiving medications. Patients with CID were more likely to have indeterminate QFT-GIT results when compared to HR subjects. Among patients with CID, only glucocorticoid use was associated with an increased likelihood of having an indeterminate test result.

Difficult behaviors in the emergency department: a cohort study of housed, homeless and alcohol dependent individuals.

BackgroundThis study contrasted annual rates of difficult behaviours in emergency departments among cohorts of individuals who were homeless and low-income housed and examined predictors of these events.MethodsInterviews in 1999 with men who were chronically homeless with drinking problems (CHDP) (n = 50), men from the general homeless population (GH) (n = 61), and men residing in low-income housing (LIH) (n = 58) were linked to catchment area emergency department records (n = 2817) from 1994 to 1999. Interview and hospital data were linked to measures of difficult behaviours.ResultsAmong the CHDP group, annual rates of visits with difficult behaviours were 5.46; this was 13.4 (95% CI 10.3–16.5) and 14.3 (95% CI 11.2–17.3) times higher than the GH and LIH groups. Difficult behaviour incidents included physical violence, verbal abuse, uncooperativeness, drug seeking, difficult histories and security involvement. Difficult behaviours made up 57.54% (95% CI 55.43–59.65%), 24% (95% CI 19–29%), and 20% (95% CI 16–24%) of CHDP, GH and LIH visits. Among GH and LIH groups, 87% to 95% were never involved in verbal abuse or violence. Intoxication increased all difficult behaviours while decreasing drug seeking and leaving without being seen. Verbal abuse and violence were less likely among those housed, with odds ratios of 0.24 (0.08, 0.72) and 0.32 (0.15, 0.69), respectively.ConclusionsViolence and difficult behaviours are much higher among chronically homeless men with drinking problems than general homeless and low-income housed populations. They are concentrated among subgroups of individuals. Intoxication is the strongest predictor of difficult behaviour incidents.

Annual Rates of Appearing Unconscious in the Emergency Department, Among Low Income Housed, Homeless and Alcohol Dependent Men

We examined the frequency and mental health factors associated with presenting unconscious in the emergency department among low-income and homeless men. Interviews of men who are chronically homeless with drinking problems (CHDP) (n = 50), in the general homeless population (GH) (n = 61) and in low-income housing (LIH) (n = 58) were linked to emergency department records over 5 years (n = 2817). Incidence rates and factors associated with unconsciousness presentation were examined with multivariate models. The CHDP group presented unconscious 0.716 times per year, four times more than the other groups. Among the CHDP, GH and LIH groups, 22 %, 10 % and 3 % of individuals presented unconscious at least once annually, with 60 %, 4 % and 15 % being found unconscious in a public place. Intoxication and head injury were predictive of unconscious presentation. Our results show that presenting unconscious in the emergency department is a significant problem for homeless men, many of whom are found in public places.

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Objectives We studied angiotensin-I levels in pregnant women with AH and healthy pregnant women. Methods 77 pregnant women with chronic hypertension (CH group), 32 pregnant women with gestational hypertension (GH group), 45 healthy pregnant women (C group) were examined at the Minsk Clinical Hospital N1. Once per pregnancy trimester angiotensin-I levels were determined with radioimmunoassay technique using multicrystalline “Bertold” gamma-counter, “Immunotech” reagents. Results Angiotensin-I levels in patients with AH left high along the pregnancy: CH group – I trimester 10.27 (7.07–14,18)mg/l, II trimester 9.06 (0.54–24.54) mg/l, III trimester – 11.81(9.86–17.86) mg/l; GH group – II trimester 12.37 (6.21–18.43) mg/l, III trimester – 11.81 (9.86–17.86) mg/l; C group – I trimester 9.93 (0.31–19,52) mg/l, II trimester – 0.36 (0.26–3.38) mg/l, III trimester – 0.25 (0.23–0.36) mg/l. In C group angiotensin-I levels decreased in II trimester comparing with I trimester (p = 0.039), levels left low in III trimester. Significant differences (p ⩽ 0,002) among angiotensin-I levels in CH, GH, C groups in II, III trimesters were observed. 95 percentile of angiotensin-I level was 5.23 mg/l for healthy pregnant women in II trimester. It was judged by fourfold table that the angiotensin-I normal levels upper interval was 5.23 mg/l in pregnant women in II trimester. This concentration meets 94% specificity, 62% optimal diagnostic sensitivity, 0.97 positive and 0.48 negative predictive value. In GH group angiotensin-I level in all 32 patients exceeds 5.23 mg/l. In CH group angiotensin-I level is lower than 5.23 mg/l in 16 women and exceeds this level in 61 women (80%). Conclusions Angiotensin-I level exceeds 5.23 mg/l during the gestation in 85% patients with AH (100% in GH group, 80% in CH group). In group C, in II,III trimesters angiotensin-I levels were significantly lower, than in other groups. Disclosures N. Tselikava: None.