Contribution of estrogen receptor subtypes,ERα, ERβ, and GPER1 in rapid estradiol‐mediated enhancement of hippocampal synaptic transmission in mice

Estradiol rapidly modulates hippocampal synaptic plasticity and synaptic transmission; however, the contribution of the various estrogen receptors to rapid changes in synaptic function is unclear. This study examined the effect of estrogen receptor selective agonists on hippocampal synaptic transmission in slices obtained from 3–5‐month‐old wild type (WT), estrogen receptor alpha (ERαKO), and beta (ERβKO) knockout female ovariectomized mice. Hippocampal slices were prepared 10–16 days following ovariectomy and extracellular excitatory postsynaptic field potentials were recorded from CA3‐CA1 synaptic contacts before and following application of 17β‐estradiol‐3‐benzoate (EB, 100 pM), the G‐protein estrogen receptor 1 (GPER1) agonist G1 (100 nM), the ERα selective agonist propyl pyrazole triol (PPT, 100 nM), or the ERβ selective agonist diarylpropionitrile (DPN, 1 µM). Across all groups, EB and G1 increased the synaptic response to a similar extent. Furthermore, prior G1 application occluded the EB‐mediated enhancement of the synaptic response and the GPER1 antagonist, G15 (100 nM), inhibited the enhancement of the synaptic response induced by EB application. We confirmed that the ERα and ERβ selective agonists (PPT and DPN) had effects on synaptic responses specific to animals that expressed the relevant receptor; however, PPT and DPN produced only a small increase in synaptic transmission relative to EB or the GPER1 agonist. We demonstrate that the increase in synaptic transmission is blocked by inhibition of extracellular signal‐regulated kinase (ERK) activity. Furthermore, EB was able to increase ERK activity regardless of genotype. These results suggest that ERK activation and enhancement of synaptic transmission by EB involves multiple estrogen receptor subtypes. © 2015 Wiley Periodicals, Inc.     

Frequency and Factors Associated with Small Intestinal Bacterial Overgrowth in Patients with Cirrhosis of the Liver and Extra Hepatic Portal Venous Obstruction

Spontaneous bacterial peritonitis (SBP), a common complication of cirrhosis of liver, might result from translocation of bacteria from the small bowel. However, there is scanty data on frequency of small intestinal bacterial overgrowth (SIBO) in patients with cirrhosis of the liver. There are no data on SIBO in patients with extra-hepatic portal venous obstruction (EHPVO) in the literature. A total of 174 patients with cirrhosis of the liver, 28 with EHPVO and 51 healthy controls were studied for SIBO using glucose hydrogen breath test (GHBT). Persistent rise in breath hydrogen 12 ppm above basal (at least two readings) was considered diagnostic of SIBO. Of 174 patients (age 47.2 ± 11.9 years, 80.5% male) with cirrhosis due to various causes, 67 (38.5%) were in Child’s class A, 70 (40.2%) class B and 37 (21.7%) class C. Of the 174 patients with cirrhosis, 42 (24.14%) had SIBO as compared to 1 of 51 (1.9%) healthy controls (P < 0.0001). Patients with EHPVO had similar frequency of SIBO compared to healthy controls [2/28 (7.14%) vs 1/51 (1.97%), P = ns]. Frequency of SIBO in Child’s A, B and C was comparable [13 (18.6%) vs 16 (23.9%) and 13 (35.1%), respectively; P = ns]. Presence of SIBO were not related to ascites, etiology of cirrhosis, and degree of liver dysfunction. SIBO is common in patients with cirrhosis of the liver. Patients with EHPVO do not have higher frequency of SIBO than healthy subjects. SIBO in cirrhosis is not related to the degree of derangement in liver function or of portal hypertension.     

Health Risk Behavior Among Justice Involved Male and Female Youth: Exploratory,Multi-Group Latent Class Analysis

Background: Youth involved in the juvenile justice system experience a disproportionate prevalence of serious mental health issues, substance abuse, and are at an increased risk of engaging in risky sexual practices. Gender differences exist, with girls at a markedly greater risk of acquiring a sexually transmitted disease. Objectives: The present study seeks to determine if there are subgroups of male and female youth who differ in their health risk behavior. If so, do any male or female subgroups at different levels of health risk differ in regard to their sociodemographic and psychological factors, and finally, what are intervention/service delivery implications of these differences. Methods: Youth were participants in an innovative health service at a centralized intake facility located in a large southeastern U.S. city. Latent class analysis and multinomial logistic regression is utilized to examine the heterogeneity of health risk behaviors across gender groups in a sample of 777 newly arrested youth. Results: Results indicate a three class solution provided the optimal fit with the data for each gender group: a Lower Health Risk group, a Higher Health Risk group, and a Highest Health Risk group. Multinomial logistic regression analysis identified significant sociodemographic and depression effects among both male and female youth. Conclusions/Importance: Youth characterized by risky sexually behavior, elevated depression, and drug involvement should be the focus of integrated intervention services. This study documents the critical need for front end, juvenile justice intake facilities to provide behavioral and public health screening, with treatment follow-up, on newly arrested youth.     

Auditory evoked responses during different phases of menstrual cycle

The electrophysiological correlates of changes in sensory function during menstrual cycle has already been studied and attributed to the hormonal influence. Effects of estrogen and progesterone on waves of auditory brainstem responses (ABR) have been reported and a hypothesis has been proposed that sex steroids have more influence on central auditory pathways. As mid-latency responses (MLRs) and slow vertex responses (SVRs) are better indicators of central auditory pathways, so MLRs and SVRs were also recorded besides ABRs in the present study. Waves of ABRs, MLRs & SVRs were recorded in 20 normal cycling females in 4 different phases of menstrual cycles from Cz-A1 and Cz-A2 position with alternating 90dB sound pressure click stimuli. Contralateral ear was masked with a white noise of -40 dBHL. With the same setting by changing the number of click stimuli, intervals of stimuli and filter bandpass the above 3 recordings were taken. The evoked responses in females having ovulatory cycles were compared within the four phases using ANOVA test. There is a trend of increase in peak latencies of ABR waves III and V and IPL I-V in estrogen-peak midcycle while decrease in latencies in progesterone-peak (interpeak latency) midluteal phase. Peak latencies of MLR waves No, Po, Na, Pa and Pb also show a same trend. SVR waves P2 and N2 are significantly delayed in mid-cycle (178.80 +/- 20.49, 276.65 +/- 18.32) while conduction is faster in midluteal phase (166.45 +/- 17.41, 261.95 +/- 21.07). Smallest latencies of all the waves are occurring during menstruation. These findings are suggesting that normal cyclical variations in the levels of estrogen and progesterone during menstrual cycle do affect the auditory pathways and effects are better seen on the central component.     

Response of splanchnic and whole-body leucine kinetics to treatment of children with edematous protein-energy malnutrition accompanied by infection

BACKGROUND: Although the reduction in whole-body protein turnover and net protein loss induced by protein-energy malnutrition (PEM) has been well documented, it is unclear whether the protein-sparing mechanisms elicited by chronically inadequate intakes of dietary protein and energy are affected by the protein catabolic response to infection. OBJECTIVE: The objective of this study was to determine whether the presence of infection alters the PEM-induced reduction in whole-body protein metabolism. DESIGN: We determined whole-body leucine kinetics in 4 boys and 3 girls aged 6-15 mo with edematous PEM and infection approximately 3 d after admission (study 1), when they were both infected and malnourished; approximately 11 d after admission (study 2), when infection had resolved but they were still anthropometrically malnourished; and at recovery (study 3), when weight-for-length was at least 90% of that expected. RESULTS: The children had significantly less leucine flux in both study 1 and study 2 than they had in study 3. There were no significant differences in the amount of leucine released from protein breakdown or used for protein synthesis between study 1 and study 2. There were no significant differences in leucine balance or in either the amount or percentage of enteral leucine extracted by the splanchnic tissues among the 3 studies. CONCLUSIONS: When subjects are in the fed state, severe PEM induces a marked reduction in whole-body protein synthesis and breakdown rates, and the presence of infection does not alter this adaptation and hence the overall protein balance. A corollary is that children with severe PEM do not mount a protein catabolic response to infection.