Low ovarian responders produce more progesterone per follicle than normal and high responders.

OBJECTIVE: Late follicular premature progesterone rise is a complex phenomenon encountered during assisted reproductive technology (ART) treatments; different etiologies can occur in the same patient. Low ovarian responders may be the best example, since higher FSH doses and ovarian aging-related changes may interact and generate a premature progesterone rise. This study aims to explore the correlation between progesterone levels on hCG day and the progesterone-to-follicle index and compare the progesterone-to-follicle index according to ovarian response. METHODS: We performed a retrospective, observational, analytic, cross-sectional, and cohort study at the Reproductive Endocrinology Department at Centro Médico Nacional 20 de November between January 2015 to January 2020. After verifying for normalcy, a Spearman Rho, Principal Component Analysis, and a simple linear regression model were performed. Treatment cycles were classified according to their ovarian response. Low-ovarian responders were classified according to the Bologna Criteria. Then an ANOVA test was performed to compare each group. RESULTS: Our results show that the progesterone-to-follicle index correlates best with progesterone levels on hCG day. Comparing all the ovarian responses, low ovarian responders have the highest progesterone-to-follicle index of the four groups. CONCLUSIONS: Low ovarian responders produce more progesterone per follicle than regular and high responders.

Antibody and T-Cell Subsets Analysis Unveils an Immune Profile Heterogeneity Mediating Long-term Responses in Individuals Vaccinated Against SARS-CoV-2.

BACKGROUND: Based on the fact that coronavirus disease 2019 (COVID-19) is still spreading despite worldwide vaccine administration, there is an imperative need to understand the underlying mechanisms of vaccine-induced interindividual immune response variations. METHODS: We compared humoral and cellular immune responses in 127 individuals vaccinated with either BNT162b2, mRNA-1273, or ChAdOx1-nCoV-19 vaccine. RESULTS: Both mRNA vaccines induced faster and stronger humoral responses as assessed by high spike- and RBD-specific antibody titers and neutralizing efficacy in comparison to ChAdOx1-nCoV-19 vaccine. At 7 months postvaccination, a decreasing trend in humoral responses was observed, irrespective of the vaccine administered. Correlation analysis between anti-S1 IgG and interferon- (IFN-) production unveiled a heterogeneous immune profile among BNT162b2-vaccinated individuals. Specifically, vaccination in the high-responder group induced sizable populations of polyfunctional memory CD4 helper T cells (TH1), follicular helper T cells (TFH), and T cells with features of stemness (TSCM), along with high neutralizing antibody production that persisted up to 7 months. In contrast, low responders were characterized by significantly lower antibody titers and memory T cells and a considerably lower capacity for interleukin-2 and IFN- production. CONCLUSIONS: We identified that long-term humoral responses correlate with the individuals ability to produce antigen-specific persistent memory T-cell populations.

Predictors of muscle hypertrophy responsiveness to electrically evoked resistance training after spinal cord injury.

The purpose of the study was to identify potential predictors of muscle hypertrophy responsiveness following neuromuscular electrical stimulation resistance training (NMES-RT) in persons with chronic spinal cord injury (SCI). Data for twenty individuals with motor complete SCI who completed twice weekly NMES-RT lasting 12-16 weeks as part of their participation in one of two separate clinical trials were pooled and retrospectively analyzed. Magnetic resonance imaging (MRI) was used to measure muscle cross-sectional area (CSA) of the whole thigh and knee extensor muscle before and after NMES-RT. Muscle biopsies and fasting biomarkers were also measured. Following the completion of the respective NMES-RT trials, participants were classified into either high-responders (n = 8; muscle CSA > 20%) or low-responders (n = 12; muscle CSA < 20%) based on whole thigh muscle CSA hypertrophy. Whole thigh muscle and knee extensors CSAs were significantly greater (P < 0.0001) in high-responders (29 ± 7% and 47 ± 15%, respectively) compared to low-responders (12 ± 3% and 19 ± 6%, respectively). There were no differences in total caloric intake or macronutrient intake between groups. Extensor spasticity was lower in the high-responders compared to the low-responders as was the dosage of baclofen. Prior to the intervention, the high-responders had greater body mass compared to the low-responders with SCI (87.8 ± 13.7 vs. 70.4 ± 15.8 kg; P = 0.012), body mass index (BMI: 27.6 ± 2.7 vs. 22.9 ± 6.0 kg/m2; P = 0.04), as well as greater percentage in whole body and regional fat mass (P < 0.05). Furthermore, high-responders had a 69% greater increase (P = 0.086) in total Akt protein expression than low-responders. High-responders also exhibited reduced circulating IGF-1 with a concomitant increase in IGFBP-3. Exploratory analyses revealed upregulation of mRNAs for muscle hypertrophy markers [IRS-1, Akt, mTOR] and downregulation of protein degradation markers [myostatin, MurF-1, and PDK4] in the high-responders compared to low-responders. The findings indicate that body composition, spasticity, baclofen usage, and multiple signaling pathways (anabolic and catabolic) are involved in the differential muscle hypertrophy response to NMES-RT in persons with chronic SCI.

Association between interindividual variability in training volume and strength gain.

This study aimed to examine the association between interindividual variability in strength changes and in training volume. A total of 26 untrained men completed 4-weeks of isometric knee extension (KE group, n = 12) and hip flexion (HF group, n = 14) training. Each training session comprised four sets of ten isometric contractions, 3-s contractions every 20 s. Training volume, which was defined as impulse during contractions, and maximal voluntary contraction (MVC) torque during KE and HF were evaluated. Based on the magnitude of MVC torque changes, the participants were divided into the high and low responders (n = 13; KE = 6 and HF = 7 per responders). The MVC torque changes (KE, 20.8%; HF, 22.4%) and total training volume did not significantly differ between the two groups. A higher training volume was demonstrated in the low responders than the high responders. The total training volume was positively associated with the MVC torque changes in low responders (r = 0.869%, 95% confidence interval [0.610, 0.960], p < 0.001), but not in high responders [r = 0.229, 95% confidence interval (-0.368, 0.693), p = 0.451], KE or HF group. Results showed that training volume was an important factor in determining the magnitude of strength gains in low responders, and MVC torque could improve by approximately 20% with the use of the study protocol regardless of joint actions involved during training.

Alteration of final maturation and laboratory techniques in low responders.

The number and quality of embryos generated from the limited number of oocytes retrieved from low responders are important aspects of infertility treatment for these patients. This article focuses on 5 aspects relating to final maturation and laboratory techniques: follicular size at trigger, dual trigger, artificial oocyte activation (AOA), blastocyst transfer, and the role of preimplantation genetic testing for aneuploidy (PGT-A). There is lack of data regarding the role of follicular size, specifically in low-responder patients, but consideration should be given to using broader follicular size criteria when retrieving oocytes in this patient group. Use of dual trigger seems to be a good strategy in low-responder patients on the basis of initial evidence. Use of AOA with calcium ionophore may improve fertilization, embryonic development, and outcomes in cases with previous developmental problems. There is lack of data for low responders, but this promising technique deserves further study. In unselected patients, clinical trial data on blastocyst transfer are conflicting, and no high-quality studies have evaluated whether the live birth rate is higher after blastocyst transfer than after cleavage-stage embryo transfer in low responders. Specific evidence for PGT-A in low-responder patients is also lacking. Preimplantation genetic testing for aneuploidy should be considered in POSEIDON group 2 patients, especially those aged >38 years. Overall, applying the limited data available in combination with patient preference and individual patient characteristics will ensure a patient-centered and evidence-based approach that should optimize fertility outcomes for low responders.

Serum Free Triiodothyronine and the Responsiveness to Clopidogrel in Patients Undergoing Elective Percutaneous Coronary Intervention.

INTRODUCTION: Both thyroid dysfunction and low responsiveness to clopidogrel have been reported to be associated with increased cardiovascular risk. Our study aims at determining the relationship between free triiodothyronine (FT3) and low responsiveness to clopidogrel in patients undergoing elective percutaneous coronary intervention (PCI). METHODS: Consecutive patients undergoing elective PCI were enrolled. All patients received a loading dose of 300 mg clopidogrel, and platelet function was assessed by thromboelastography at least 12 h later. Low responsiveness to clopidogrel was defined by an adenosine diphosphate-induced platelet-fibrin clot strength > 47 mm and adenosine diphosphate-induced platelet inhibition rate < 50%. Major adverse cardiovascular events (MACEs) were defined as a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, and ischemia-driven revascularization. RESULTS: Of 812 patients included in the study, 289 showed low responsiveness to clopidogrel. The FT3 level was significantly lower in low responders (4.61 ± 0.60 pmol/l versus 4.94 ± 4.66 pmol/l, p = 0.002). Moreover, the percentage of low responders was greater among patients with low FT3 level than among those without (56.1% versus 34.5%, p = 0.007). Logistic regression analysis showed that a FT3 level was independently associated with the risk of low responsiveness to clopidogrel (odds ratio 0.720, 95% confidence interval [CI] 0.533-0.973, p = 0.033). In patients with low responsiveness to clopidogrel, low FT3 was independently associated with increased risk of MACEs (adjusted hazard ratio 3.040, 95% CI 1.077-8.580, p = 0.036) at a median of 19-month follow-up. CONCLUSIONS: Low FT3 was independently associated with increased risks of both low responsiveness to clopidogrel and cardiovascular events in patients undergoing elective PCI.

Effects of 5-HT2C receptor modulation and the NA reuptake inhibitor atomoxetine in tests of compulsive and impulsive behaviour.

Drug repositioning has gained strategic value as a reaction to high attrition rates of new drugs as they pass through the clinical development process. The 5-HT2C receptor agonist lorcaserin (Belviq®), and the selective NA reuptake inhibitor atomoxetine (Strattera®) represent two drugs FDA approved for obesity and ADHD respectively. Although both drugs are of differing pharmacological class, each share a property of regulating impulsive behaviours in preclinical studies, and thus represent candidates for consideration in clinical conditions labelled as 'impulsive-compulsive disorders'. The present studies investigated both drugs, as well as the highly selective 5-HT2C agonist CP-809101 in two tests of compulsive action: schedule-induced polydipsia (SIP) and increased perseverative [PSV] (and premature [PREM]) responses emitted during an extended ITI 5-choice task. While lorcaserin (0.06-0.6 mg/kg), CP-809101 (0.1-1 mg/kg) and atomoxetine (0.1-1 mg/kg) each reduced both PREM and PSV measures in the 5-choice task, at equivalent doses only lorcaserin and CP-809101 affected excessive water intake in the SIP task, atomoxetine (0.1-2 mg/kg) was essentially ineffective. Further evidence supporting a role of the 5-HT2C receptor as an important regulator of impulsive-compulsive behaviours, the selective antagonist SB-242084 produced the opposing effects to lorcaserin, i.e promoting both impulsive and compulsive behaviours. The profile of atomoxetine may suggest differences in the nature of compulsive action measured either as non-regulatory drinking in the SIP task, and PSV responses made in a 5-choice task. These studies support the consideration of 5-HT2C receptor agonists, typified by lorcaserin, and atomoxetine as potential treatments for clinical conditions categorised as 'impulsive-compulsive disorders'. This article is part of the special issue entitled 'Serotonin Research: Crossing Scales and Boundaries'.

Individual Differences in Ethanol Drinking and Seeking Behaviors in Rats Exposed to Chronic Intermittent Ethanol Vapor Exposure is Associated with Altered CaMKII Autophosphorylation in the Nucleus Accumbens Shell.

Chronic intermittent ethanol vapor exposure (CIE) in rodents produces reliable and high blood ethanol concentration and behavioral symptoms associated with moderate to severe alcohol use disorder (AUD)-for example, escalation of operant ethanol self-administration, a feature suggestive of transition from recreational to addictive use, is a widely replicated behavior in rats that experience CIE. Herein, we present evidence from a subset of rats that do not demonstrate escalation of ethanol self-administration following seven weeks of CIE. These low responders (LR) maintain low ethanol self-administration during CIE, demonstrate lower relapse to drinking during abstinence and reduced reinstatement of ethanol seeking triggered by ethanol cues when compared with high responders (HR). We examined the blood ethanol levels in LR and HR rats during CIE and show higher levels in LR compared with HR. We also examined peak corticosterone levels during CIE and show that LR rats have higher levels compared with HR rats. Lastly, we evaluated the levels of Ca2+/calmodulin-dependent protein kinase II (CaMKII) in the nucleus accumbens shell and reveal that the activity of CaMKII, which is autophosphorylated at site Tyr-286, is significantly reduced in HR rats compared with LR rats. These findings demonstrate that dysregulation of the hypothalamic-pituitary-adrenal axis activity and plasticity-related proteins regulating molecular memory in the nucleus accumbens shell are associated with higher ethanol-drinking and -seeking in HR rats. Future mechanistic studies should evaluate CaMKII autophosphorylation-dependent remodeling of glutamatergic synapses in the ventral striatum as a plausible mechanism for the CIE-induced enhanced ethanol drinking and seeking behaviors.

Impact of a novel environment on alcohol-induced locomotor activity in Wistar rats.

Clinical studies have shown a positive correlation between novelty-seeking behavior and the susceptibility to consume drugs of abuse. Although several animal studies have demonstrated this correlation with psychostimulants or morphine, studies with alcohol have shown conflicting results. The aim of this work was to investigate alcohol-induced motor effects in Wistar rats with different responses to novelty. Animals were classified as Low- (LR) or High-Responders (HR) to novelty, depending on their horizontal activity in an automated open field. Motor activity was recorded in naïve, saline, and alcohol-administered rats at different doses (0.1, 0.25, 0.5, 1.0, or 2.5 g/kg). Horizontal movements, rearings, and stereotyped behaviors were evaluated. After the behavioral test, animals were sacrificed and blood alcohol concentrations (BACs) were measured. Low (0.1 and 0.25 g/kg) and high (2.5 g/kg) alcohol doses decreased horizontal movements in LR animals, whereas 1.0 g/kg increased this parameter in HR rats. Rearings were increased by alcohol 1.0 g/kg in LR animals. In HR rats, alcohol doses of 0.5 and 1.0 g/kg also increased this parameter. Stereotyped behaviors were decreased by an alcohol dose of 2.5 g/kg in LR animals, but were increased by an intermediate dose (1.0 g/kg) in HR rats. Differences in horizontal movements and rearings were found between LR and HR animals at certain ethanol doses. Horizontal movements (0.25 g/kg) and rearings (0.5 g/kg) were lower in LR than HR rats; however, rearings were lower in HR than LR rats at 1.0 g/kg. BACs were similar between LR and HR rats at all ethanol doses. These findings suggest that HR rats are more responsive to the stimulant effects of intermediate alcohol doses, whereas LR animals are sensitive to low/high doses of the drug. Sensitivity to alcohol motor effects may substantially depend on the initial animal's response to a novel environment. The stimulant effects of alcohol may constitute important behavioral traits significantly associated with the rewarding properties of the drug.

[Anti-HBs persistence after revaccination with three doses of hepatitis B vaccine among low-responder infants following primary vaccination: 4-year of follow-up].

Objective: Assess the 4-year antibody against hepatitis B surface antigen (anti-HBs) persistence after revaccination with 3-dose of hepatitis B vaccine (HepB) among low-responder infants following primary vaccination. Methods: According to stratified cluster sampling, a total of 4 147 infants were enrolled and primarily vaccinated with 5 µg HepB derived in Saccharomyces Cerevisiae (HepB-SC) at 0-1-6 months schedule from 75 towns of Jinan, Weifang, Yantai, Weihai prefectures, Shandong Province, China in Aug and Sep 2009. Blood samples were collected one to six months after the third dose of primary immunization and tested for anti-HBs using chemiluminescence microparticle immunoassay (CMIA). 717 infants who appeared low response (10 mU/ml ≤ anti-HBs<100 mU/ml) were revaccinated with 3-dose of HepB. Blood samples were collected from a total of 315 infants one month (T(0)), four years (T(1)) after revaccination and anti-HBs, antibody against hepatitis B core antigen (anti-HBc) and hepatitis B surface antigen (HBsAg) were detected by CMIA. Information about their birth, primary vaccination were collected. The risk factors associated with positive rate of anti-HBs and GMC of anti-HBs were identified by multiple non-conditional logistic regression analysis and multifactor linear regression model analysis, respectively. Results: Among 315 children, 165 (52.38%) were male and 150 (47.62%) were female. The positive rate was 83.81% (264/315) at T(0) and it decreased to 16.51% (149/529) at T(1). The corresponding GMC decreased from 473.15 mU/ml to 17.37 mU/ml. The average annual decreasing rate of positive rate and GMC was 33.38% and 56.23% from T(0) to T(1). Multivariable analysis showed the positive rate and GMC among those whose anti-HBs titer higher at T(0) were significantly higher at T(1). The positive rate at T(1) among those whose anti-HBs titer 400-<600, 600-<800, 800-<1 000, ≥1 000 mU/ml at T(0) were significantly higher than those whose anti-HBs titer less than 200 mU/ml. The OR (95%CI) of the positive rate was 4.29 (1.03-17.84), 4.53 (1.25-16.47), 4.19 (1.10-15.97) and 9.13 (2.91-28.63), respectively. The GMC at T(1) among those whose anti-HBs titer 400-<600, 600-<800, 800-<1 000 mU/ml and those whose anti-HBs titer ≥1 000 mU/ml at T(0) were higher than those whose anti-HBs titer<200 mU/ml. The b value (95% CI) of GMC was 0.84 (0.06-1.62), 1.13 (0.46-1.79), 1.33 (0.65-2.01) and 1.88 (1.33-2.44), respectively. GMC among full-term infants were significantly higher than premature infants at T(1). The b value (95% CI) of GMC was 0.86 (0.04-1.68). Conclusion: Anti-HBs GMC decreased rapidly 4 years after revaccination among low-responder infants, but still kept good protection. The anti-HBs persistence after revaccination was associated with anti-HBs level of titer one month after revaccination.

Anti-HBs persistence after revaccination with three doses of hepatitis B vaccine among low-responder infants following primary vaccination: 4-year of follow-up / 中华预防医学杂志

Objective@#Assess the 4-year antibody against hepatitis B surface antigen (anti-HBs) persistence after revaccination with 3-dose of hepatitis B vaccine (HepB) among low-responder infants following primary vaccination.@*Methods@#According to stratified cluster sampling, a total of 4 147 infants were enrolled and primarily vaccinated with 5 μg HepB derived in Saccharomyces Cerevisiae (HepB-SC) at 0-1-6 months schedule from 75 towns of Jinan, Weifang, Yantai, Weihai prefectures, Shandong Province, China in Aug and Sep 2009. Blood samples were collected one to six months after the third dose of primary immunization and tested for anti-HBs using chemiluminescence microparticle immunoassay (CMIA). 717 infants who appeared low response (10 mU/ml ≤ anti-HBs<100 mU/ml) were revaccinated with 3-dose of HepB. Blood samples were collected from a total of 315 infants one month (T0), four years (T1) after revaccination and anti-HBs, antibody against hepatitis B core antigen (anti-HBc) and hepatitis B surface antigen (HBsAg) were detected by CMIA. Information about their birth, primary vaccination were collected. The risk factors associated with positive rate of anti-HBs and GMC of anti-HBs were identified by multiple non-conditional logistic regression analysis and multifactor linear regression model analysis, respectively.@*Results@#Among 315 children, 165 (52.38%) were male and 150 (47.62%) were female. The positive rate was 83.81% (264/315) at T0 and it decreased to 16.51% (149/529) at T1. The corresponding GMC decreased from 473.15 mU/ml to 17.37 mU/ml. The average annual decreasing rate of positive rate and GMC was 33.38% and 56.23% from T0 to T1. Multivariable analysis showed the positive rate and GMC among those whose anti-HBs titer higher at T0 were significantly higher at T1. The positive rate at T1 among those whose anti-HBs titer 400-<600, 600-<800, 800-<1 000, ≥1 000 mU/ml at T0 were significantly higher than those whose anti-HBs titer less than 200 mU/ml. The OR (95%CI) of the positive rate was 4.29 (1.03-17.84), 4.53 (1.25-16.47), 4.19 (1.10-15.97) and 9.13 (2.91-28.63), respectively. The GMC at T1 among those whose anti-HBs titer 400-<600, 600-<800, 800-<1 000 mU/ml and those whose anti-HBs titer ≥1 000 mU/ml at T0 were higher than those whose anti-HBs titer<200 mU/ml. The b value (95% CI) of GMC was 0.84 (0.06-1.62), 1.13 (0.46-1.79), 1.33 (0.65-2.01) and 1.88 (1.33-2.44), respectively. GMC among full-term infants were significantly higher than premature infants at T1. The b value (95% CI) of GMC was 0.86 (0.04-1.68).@*Conclusion@#Anti-HBs GMC decreased rapidly 4 years after revaccination among low-responder infants, but still kept good protection. The anti-HBs persistence after revaccination was associated with anti-HBs level of titer one month after revaccination.

The state of "freeze-for-all" in human ARTs.

The recent development of vitrification technologies and the good outcomes obtained in assisted reproduction technologies have supported new indications for freezing and segmentation of treatment. Beyond OHSS prevention and avoidance of embryo transfers in the setting of an adverse endocrinological profile or endometrial cavity, we have witnessed a trend to shift fresh embryo transfers to frozen embryo transfers in many programs. We critically review the available evidence and suggest that freeze-all is not "for all," but should be individualized.

Effect of Tetanus-diphtheria Vaccine on Immune Response to Hepatitis B Vaccine in Low-responder Individuals.

BACKGROUND: Conventional hepatitis B virus (HBV) vaccination fails to achieve efficient protection in about 5-10% of the world population. Hence, different strategies have been adopted to ameliorate HBV antibody titers. This study aimed to evaluate the concurrent application of tetanus-diphtheria (Td) and HBV vaccination on hepatitis B surface (HBs) antibody titer in low-responder healthy individuals. METHODS: This was a randomized clinical trial, which was implemented among 140 of medical staff working as health-care workers assumed as low-responders. The subjects were randomly allocated to either control or interventional groups. The control and interventional groups received HBV recombinant vaccine while the latter group was also vaccinated through Td. Enzyme-linked immunosorbent assay was applied to measure HBs antibody (HBsAb) titers just before and 6 months after the last vaccination. All data were entered into SPSS software. Independent t-test, paired t-test, and Chi-square or Fisher's exact test were applied for data comparison. RESULTS: Antibody titers of the subjects in the intervention and control groups soared from 49.08 ± 20.08 IU/L to 917.78 ± 204.80 IU/L and from 46.95 ± 18.55 to 586.81 ± 351.77 IU/L, respectively (both P < 0.001); nevertheless, by comparison with control group, variation of antibody titer in the interventional group was significantly higher (P < 0.001). CONCLUSIONS: Concurrent application of Td and HBV vaccine could effectively enhance protective levels of HBsAb titers in low-responder individuals.

Failure of intrauterine insemination as rescue treatment in low responders with adequate HCG timing with no oocytes retrieved.

In this retrospective study, the efficiency of carrying out rescue intrauterine insemination (IUI) in low-responder patients undergoing IVF when no oocytes were retrieved after follicular aspiration and when HCG timing was adequate was analysed. A historical control group was used. Over 13 years, women undergoing IVF with failure to obtain oocytes at follicular aspiration underwent rescue IUI if the following criteria were met: adequate HCG timing; one normal tube; motile sperm count after preparation over 3 million/ml; and ultrasound visualization of one to six follicles over 13 mm. The rescue IUI was carried out 1 h after follicular aspiration. Results were compared with those of a standard IUI population (5394 cycles) in the same period. Confidence intervals were calculated using Poisson 97.5% confidence upper tail limits when no event was observed in the study sample. No pregnancies were achieved among the 54 cases who underwent rescue IUI (confidence interval: 0 to 6.8%). This pregnancy rate was lower than that observed in the general IUI population (17.5%) (relative risk, 19.2). After adjusting for age and endometriosis, the relative risk was 11.7. The rescue IUI is an inefficient procedure. Its efficacy is unlikely to exceed 7% pregnancy rate per IUI.

A novel pathogenic peptide of thyroglobulin (2208-2227) induces autoreactive T-cell and B-cell responses in both high and low responder mouse strains.

Experimental autoimmune thyroiditis (EAT) is commonly induced by thyroglobulin (Tg) or Tg peptides in mice genetically susceptible to thyroiditis. In the present study, we investigated the immunogenic and pathogenic potential of a novel 20mer human Tg peptide, p2208 (amino acids 2208-2227), in mouse strains classified as low (LR) or high (HR) responders in EAT. The peptide was selected for its content in overlapping binding motifs for MHC class II products, associated with either resistance (A(b)), or susceptibility (A(s), E(k)) to EAT. We therefore immunized LR BALB/c (H-2(d)) and C57BL/6 (H-2(b)) strains, as well as HR CBA/J (H-2(k)) and SJL/J (H-2(s)) mice with 100 nmol of p2208 in adjuvant and collected their sera, lymph nodes and thyroid glands for further analysis. The p2208 peptide was found to contain B-cell and cryptic T-cell epitope(s) in two of the four strains examined, one LR and one HR. Specifically, it elicited direct EAT in C57BL/6 mice (two of seven mice, infiltration index 1-3), as well as in SJL/J mice (two of six mice, infiltration index 1-2). Such an EAT model could provide insights into the immunoregulatory cascades taking place in resistant hosts.

Interaction between cholecystokinin and the fibroblast growth factor system in the ventral tegmental area of selectively bred high- and low-responder rats.

Individual differences in the locomotor response to novelty have been linked to basal differences in dopaminergic neurotransmission. Mesolimbic dopaminergic outputs are regulated by cholecystokinin (CCK), a neuropeptide implicated in anxiety. In turn, CCK expression is regulated by fibroblast growth factor-2 (FGF2), which has recently been identified as an endogenous regulator of anxiety. FGF2 binds to the high-affinity fibroblast growth factor receptor-1 (FGF-R1) to regulate the development and maintenance of dopamine neurons in the ventral tegmental area (VTA). However, the relationship between the FGF and CCK systems in the VTA is not well understood. Therefore, we utilized the selectively-bred low-responder (bLR; high-anxiety) and high-responder (bHR; low-anxiety) rats to examine the effects of repeated (21-day) FGF2 treatment on CCK and FGF-R1 mRNA in the rostral VTA (VTAr). In vehicle-treated controls, both CCK and FGF-R1 mRNA levels were increased in the VTAr of bLR rats relative to bHR rats. Following FGF2 treatment, however, bHR-bLR differences in CCK and FGF-R1 mRNA expression were eliminated, due to decreased CCK mRNA levels in the VTAr of bLR rats and increased FGF-R1 expression in bHR rats. Differences after FGF2 treatment may denote distinct interactions between the CCK and FGF systems in the VTAr of bHR vs. bLR rats. Indeed, significant correlations between CCK and FGF-R1 mRNA expression were found in bHR, but not bLR rats. Colocalization studies suggest that CCK and FGF-R1 are coexpressed in some VTAr neurons. Taken together, our findings suggest that the FGF system is poised to modulate both CCK and FGF-R1 expression in the VTAr, which may be associated with individual differences in mesolimbic pathways associated with anxiety-like behavior.

The efficacy of oral contraceptive pre-treatment in controlled ovarian hyperstimulation using a GnRH antagonist in low responders / 대한산부인과학회지

OBJECTIVE: This study was performed to evaluate the efficacy of GnRH antagonist multidose protocol (GnRH-ant MDP) with or without oral contraceptive (OC) pretreatment in low responders undergoing IVF-ET, compared with standard GnRH agonist (GnRH-a) lowdose long protocol (LP). METHODS: Eighty-two patients, aged 28-42 years who were defined as low responders were recruited for this prospective study and they were randomized to undergo GnRH-ant MDP after OC pretreatment (group 1) or GnRH-ant MDP without OC pretreatment (group 2) or GnRH-a luteal lowdose LP (group 3). All of the subjects were administered recombinant human FSH (rhFSH) for ovarian stimulation. RESULTS: Patients' characteristics were comparable among three groups. Total dose and duration of rhFSH used for COH were significantly higher in group 3 than those in group 1 or 2. The number of mature oocytes, fertilization rate and the number of grade I, II embryos were significantly lower in group 2 than those in other groups. The clinical pregnancy rate seemed to be lower in group 2 but the difference did not achieve statistical significance. There were also no differences in the miscarriage rate and multiple pregnancy rate among three groups. CONCLUSION: This study demonstrates that GnRH-ant MDP with OC pretreatment is as effective as GnRH-a lowdose LP and might be considered more advantageous because of the short-term and small dose application in low responders.