Knee and Hip Joint Kinematics Predict Quadriceps and Hamstrings Neuromuscular Activation Patterns in Drop Jump Landings

PurposeThe purpose was to assess if variation in sagittal plane landing kinematics is associated with variation in neuromuscular activation patterns of the quadriceps-hamstrings muscle groups during drop vertical jumps (DVJ).MethodsFifty female athletes performed three DVJ. The relationship between peak knee and hip flexion angles and the amplitude of four EMG vectors was investigated with trajectory-level canonical correlation analyses over the entire time period of the landing phase. EMG vectors consisted of the {vastus medialis(VM),vastus lateralis(VL)}, {vastus medialis(VM),hamstring medialis(HM)}, {hamstring medialis(HM),hamstring lateralis(HL)} and the {vastus lateralis(VL),hamstring lateralis(HL)}. To estimate the contribution of each individual muscle, linear regressions were also conducted using one-dimensional statistical parametric mapping.ResultsThe peak knee flexion angle was significantly positively associated with the amplitudes of the {VM,HM} and {HM,HL} during the preparatory and initial contact phase and with the {VL,HL} vector during the peak loading phase (p<0.05). Small peak knee flexion angles were significantly associated with higher HM amplitudes during the preparatory and initial contact phase (p<0.001). The amplitudes of the {VM,VL} and {VL,HL} were significantly positively associated with the peak hip flexion angle during the peak loading phase (p<0.05). Small peak hip flexion angles were significantly associated with higher VL amplitudes during the peak loading phase (p = 0.001). Higher external knee abduction and flexion moments were found in participants landing with less flexed knee and hip joints (p<0.001).ConclusionThis study demonstrated clear associations between neuromuscular activation patterns and landing kinematics in the sagittal plane during specific parts of the landing. These findings have indicated that an erect landing pattern, characterized by less hip and knee flexion, was significantly associated with an increased medial and posterior neuromuscular activation (dominant hamstrings medialis activity) during the preparatory and initial contact phase and an increased lateral neuromuscular activation (dominant vastus lateralis activity) during the peak loading phase.     

The Activity of the Hypothalamic‐Pituitary‐Adrenal Axis and the Sympathetic Nervous System in Relation to Waist/Hip Circumference Ratio in Men

Objective: To investigate possible differences, between generally and abdominally obese men, in activity and regulation of the hypothalamic‐pituitary‐adrenal (HPA) axis and the sympathetic nervous system. Research Methods and Procedures: Fifty non‐diabetic, middle‐aged men were selected to obtain two groups with similar body mass index (BMI) but different waist/hip circumference ratio (WHR). Measurements were performed of the activity of the HPA axis and the sympathetic nervous system, as well as metabolic and endocrine variables. Results: Men with a high WHR, in comparisons with men with a low WHR, had higher insulin, glucose, and triglyceride values in the basal state and higher glucose and insulin after an oral glucose tolerance test. Men with high WHR had elevated diurnal adrenocorticotropic hormone (ACTH) values but similar cortisol values, except lower cortisol values in the morning. Diurnal growth hormone concentrations showed reduced peak size. Stimulation of the HPA axis with corticotropin‐releasing hormone (CRH) and laboratory stress showed no difference in ACTH values between groups, but cortisol values were lower in men with high WHR. In comparison with men with a low WHR, men with a high WHR had elevated pulse pressure and heart rate in the basal state and after challenges by CRH and laboratory stress. They also had increased urinary excretion of catecholamine metabolites. Discussion: These results suggest a mild dysregulation of the HPA axis, occurring with elevated WHR independent of the BMI. The results also indicate a central activation of the sympathetic nervous system, such as in the early phases of hypertension, correlating with insulin resistance.     

Elevated Hair Cortisol Levels among Heroin Addicts on Current Methadone Maintenance Compared to Controls

Whether methadone maintenance treatment (MMT) can improve the basal function of the hypothalamic–pituitary–adrenal (HPA) axis, which is suppressed by long-term heroin consumption, is a matter of debate. The stress state and depression and anxiety symptoms may affect the basal activity of the HPA axis in MMT patients. However, the effect of psychological factors on HPA activity was not simultaneously controlled in previous studies. This study investigated differences in HPA basal activity between MMT patients and controls using psychological variables as covariates. The participants included 52 MMT patients and 41 age-matched, non-heroin-dependent controls. Psychological states were self-reported with the Perceived Stress Scale, Self-Rating Depression Scale and Self-Rating Anxiety Scale. The hair cortisol level was adopted as a biomarker of HPA basal activity and was determined with liquid chromatography tandem mass spectrometry. The results revealed that MMT patients had significantly higher hair cortisol levels than the controls (p<0.05), but the difference was not significant (p>0.05) when the perceived stress, depression and anxiety scores were used as covariates. We concluded that patients with long-term MMT showed higher basal activity of the HPA axis. The high chronic stress state and increase in depression and anxiety symptoms may mask the suppression effect of methadone on the HPA activity.     

Effect of adding plyometric training to physical education sessions on specific biomechanical parameters in primary school girls

Objectives:The study aimed to determine the effect of adding a school-based plyometric training program (PMT) to physical education (PE) sessions on the strength, balance, and flexibility in primary school girls.Methods:Students from grades 3-6 were randomized equally to a plyometric or control group. In the control group, students took their regular PE classes twice a week. In the plyometric group, students performed PMT twice a week during the initial 20 minutes of every PE session. The Lido Linea closed kinetic chain isokinetic dynamometer, Star excursion balance test (SEBT), and sit-and-reach test were used to assess muscle strength, balance, and flexibility, respectively, before and after nine weeks of training.Results:The improvement in extension peak force (p=0.04) and extension total work (p<0.001) was more prevalent in the PMT group than in the control group. SEBT scores had improved significantly (p<0.05) for all directions in the PMT group, except in the anterior direction, which was highly significant (p<0.001). Hamstring and lower back flexibility had improved more in the PMT group than in the control group (p<0.001).Conclusion:Adding PMT to regular PE classes has a positive and notable effect on muscle strength, balance, and flexibility in primary school students.     

Investigation of Genetic Variants,Birthweight and Hypothalamic-Pituitary-Adrenal Axis Function Suggests a Genetic Variant in the SERPINA6 Gene Is Associated with Corticosteroid Binding Globulin in the Western Australia Pregnancy Cohort (Raine) Study

Background

The hypothalamic-pituitary-adrenal (HPA) axis regulates stress responses and HPA dysfunction has been associated with several chronic diseases. Low birthweight may be associated with HPA dysfunction in later life, yet human studies are inconclusive. The primary study aim was to identify genetic variants associated with HPA axis function. A secondary aim was to evaluate if these variants modify the association between birthweight and HPA axis function in adolescents.

Methods

Morning fasted blood samples were collected from children of the Western Australia Pregnancy Cohort (Raine) at age 17 (n = 1077). Basal HPA axis function was assessed by total cortisol, corticosteroid binding globulin (CBG), and adrenocorticotropic hormone (ACTH). The associations between 124 tag single nucleotide polymorphisms (SNPs) within 16 HPA pathway candidate genes and each hormone were evaluated using multivariate linear regression and penalized linear regression analysis using the HyperLasso method.

Results

The penalized regression analysis revealed one candidate gene SNP, rs11621961 in the CBG encoding gene (SERPINA6), significantly associated with total cortisol and CBG. No other candidate gene SNPs were significant after applying the penalty or adjusting for multiple comparisons; however, several SNPs approached significance. For example, rs907621 (p = 0.002) and rs3846326 (p = 0.003) in the mineralocorticoid receptor gene (NR3C2) were associated with ACTH and SERPINA6 SNPs rs941601 (p = 0.004) and rs11622665 (p = 0.008), were associated with CBG. To further investigate our findings for SERPINA6, rare and common SNPs in the gene were imputed from the 1,000 genomes data and 8 SNPs across the gene were significantly associated with CBG levels after adjustment for multiple comparisons. Birthweight was not associated with any HPA outcome, and none of the gene-birthweight interactions were significant after adjustment for multiple comparisons.

Conclusions

Our study suggests that genetic variation in the SERPINA6 gene may be associated with altered CBG levels during adolescence. Replication of these findings is required.     

Association of salivary steroid hormones and their ratios with time-domain heart rate variability indices in healthy individuals

BackgroundStress system consists of the hypothalamicpituitary-adrenal (HPA) axis and the locus caeruleus/norepinephrine-autonomic nervous system (ANS). Traditionally, HPA axis activity is evaluated by measuring its end-product cortisol, while the activity of ANS is assessed using heart rate variability (HRV) indices. Alterations in cortisol levels and HRV measures during laboratory-based stress tasks were extensively studied in previous research. However, scarce data exist on the associations of HRV measures with the levels of other adrenal steroid hormones under baseline conditions. Thus, we aimed to evaluate the activity of the HPA axis by measuring salivary cortisol, cortisone, dehydroepiandrosterone (DHEA) levels, and their ratios and to examine its association with HRV measures in a sample of healthy young and middle-aged adults.MethodsFor each participant (n=40), three data collection sessions taking place at the same time of the day were scheduled within five working days. Participants completed a self-reported questionnaire on sociodemographic and lifestyle characteristics, filled out t h e Perceived Stress Scale and State-Trait Anxiety Inventory. Also, saliva samples were collected, and physiological measures, including resting HR and HRV, were recorded during three data collection sessions.ResultsStatistically significant associations between diminished parasympathetic vagal tone evaluated by time domain HRV measures and higher salivary cortisol, lower DHEA levels, as well as decreased DHEA to cortisol ratio, were found. Also, physiological stress indicators (i.e., HRV) showed greater intraindividual stability compared with biochemical biomarkers (i.e., salivary steroid hormones) within five days.ConclusionsOur findings suggest that both cortisol and DHEA mediate the link between two stress-sensitive homeostatic systems.     

Achieving Shoulder Balance Using Medial and Lateral Radiological Measures in Adolescent Idiopathic Scoliosis

BackgroundResearch has shown that postoperative shoulder imbalance is a common problem after spinal fusion in adolescent idiopathic scoliosis (AIS). The best radiographic predictor has not yet been determined and results are inconsistent. This study was to investigate whether using medial and lateral shoulder parameters can effectively achieve postoperative shoulder balance.MethodsA prospective database of AIS undergoing posterior spinal fusion were reviewed. Patient demographics and radiological parameters including radiographic shoulder height (RSH), clavicle angle, T1-tilt and first-rib angle at baseline, 6 weeks and last minimal follow up of 2 years were recorded. Correlations between radiological parameters were assessed using Pearson’s correlation coefficients. Multivariable linear models identified predictors associated with increased RSH.Results219 patients (mean age:13.7 years; 81.7% female) were included. The mean follow-up time was 2.8 years (range:2.0-7.0). The mean RSH at baseline, 6 weeks and last follow up was improved significantly at 95.8%. Preoperative (r=0.8; p<0.001) and post-operative measurements of RSH at 6-week (r=0.9; p<0.001) and last follow up (r=0.9; p<0.001) correlated strongly with clavicle angle measured at respective time-points. In a multivariable linear model, we noted marginal increase in clavicle angle (+4.3°; p<0.001) to be associated with increased RSH. On the contrary, first rib angle and T1-tilt demonstrated moderate to weak correlation with RSH.ConclusionClavicle angle is strongly consistent with RSH. First rib angle and T1-tilt as demonstrate medial shoulder balance are moderate to weak correlation. Leveling T1 tilt and first rib angle do not guarantee the postoperative shoulder balance. Level of Evidence: IV     

Cortisol Patterns Are Associated with T Cell Activation in HIV

Objective

The level of T cell activation in untreated HIV disease is strongly and independently associated with risk of immunologic and clinical progression. The factors that influence the level of activation, however, are not fully defined. Since endogenous glucocorticoids are important in regulating inflammation, we sought to determine whether less optimal diurnal cortisol patterns are associated with greater T cell activation.

Methods

We studied 128 HIV-infected adults who were not on treatment and had a CD4⁺ T cell count above 250 cells/µl. We assessed T cell activation by CD38 expression using flow cytometry, and diurnal cortisol was assessed with salivary measurements.

Results

Lower waking cortisol levels correlated with greater T cell immune activation, measured by CD38 mean fluorescent intensity, on CD4⁺ T cells (r = −0.26, p = 0.006). Participants with lower waking cortisol also showed a trend toward greater activation on CD8⁺ T cells (r = −0.17, p = 0.08). A greater diurnal decline in cortisol, usually considered a healthy pattern, correlated with less CD4⁺ (r = 0.24, p = 0.018) and CD8⁺ (r = 0.24, p = 0.017) activation.

Conclusions

These data suggest that the hypothalamic-pituitary-adrenal (HPA) axis contributes to the regulation of T cell activation in HIV. This may represent an important pathway through which psychological states and the HPA axis influence progression of HIV.     

Increased Cortisol Bioavailability,Abdominal Obesity,and the Metabolic Syndrome in Obese Women

Objective: This study was conducted to obtain a detailed profile of hypothalamo‐pituitary‐adrenal (HPA) axis activity and reactivity and its differential relationships with body fat distribution and total fat mass in premenopausal obese women. Research Methods and Procedures: Cortisol responses to stimulation (awakening, food intake, exercise) and suppression (0.25 mg dexamethasone), cortisol metabolism, and tissue sensitivity to glucocorticoids were studied in 53 premenopausal obese women grouped according to their waist‐to hip ratio: women with abdominal body fat distribution (A‐BFD; n = 31) and women with peripheral fat distribution (P‐BFD; n = 22). Results: Comparatively, A‐BFD women had 1) lower awakening salivary cortisol levels; 2) increased salivary responsiveness to a standardized lunch; 3) similar pituitary sensitivity to dexamethasone but decreased sensitivity of monocytes to dexamethasone; 4) similar 24‐hour urinary free cortisol but increased 24‐hour urinary ratio of cortisone‐to‐cortisol; and 5) no difference in corticosteroid binding protein parameters. Discussion: Although abdominal obesity is not very different from generalized obesity in terms of HPA function, subtle variations in HPA axis activity and reactivity are evidenced in A‐BFD premenopausal obese women.     

Corticosteroid Binding Globulin Gene Polymorphism Influences Cortisol Driven Fat Distribution in Obese Women

Hypothalamo‐pituitary‐adrenal axis has been reported to influence fat mass distribution in obesity. We investigated the hypothesis that corticosteroid‐binding globulin (CBG) polymorphism could influence obesity, metabolic, or hypothalamo‐pituitary adrenal (HPA) axis activity parameters. In 44 obese pre‐menopausal women, a microsatellite located within the CBG gene was analyzed, providing three genotypes: 86/86 (n = 29), 86/90 (n = 14), and 90/90 (n = 1). No significant difference was found for obesity, metabolic, and HPA axis activity parameters between the genotypes 86/86 and 86/90. Looking for differences in correlations between HPA axis activity parameters and obesity or metabolic parameters between the two genotypes, genotype 86/90 showed a strong correlation between salivary cortisol after dexamethasone (0.25 mg) suppression test and waist‐to‐hip ratio (r = ?0.84, p = 0.0007), whereas this correlation was weaker for genotype 86/86 (r = ?0.34, p = 0.09). These data were completed with an analysis of the BclI polymorphism of the glucocorticoid receptor (GR) gene. There was an association between this GR polymorphism and both awakening salivary cortisol and postdexamethasone salivary cortisol but no association for obesity or metabolic parameters. We concluded that CBG gene polymorphisms might modulate the influence of the HPA axis on the fat mass distribution in this population.     

The Glucocorticoid Receptor and its Expression in the Anterior Pituitary and the Adrenal Cortex: A Source of Variation in Hypothalamic-Pituitary-Adrenal Axis Function; Implications for Pituitary and Adrenal Tumors

ObjectiveTo review the expression of the glucocorticoid receptor (GR) in anterior pituitary and adrenocortical cells and tumors derived from these tissues as well as factors that may influence its expression.MethodsWe present an overview of the relevant literature, with a focus on data generated from our studies.ResultsThe expression of the GR is an essential element of the negative feedback that closes the loop formed by corticotropin-releasing hormone, adrenocorticotropic hormone, and cortisol in the context of the hypothalamicpituitary-adrenal (HPA) axis. Although the GR expression in anterior pituitary cells—and in particular the corticotrophs—was first demonstrated several years ago, it was not known until relatively recently where, by what cells, and in what form the GR is expressed in the adrenal cortex.The variability in the expression of the GR in pituitary and adrenocortical cells may underlie the substantial differences in HPA axis function across individuals, especially when testing for tumors associated with hypercortisolemia. This expression is influenced by a multitude of tissue-specific factors, which may explain why it is so difficult to interpret (or reproduce) studies that are based on GR functional polymorphisms on different cohorts of patients or even different sets of laboratory animals.ConclusionThis review highlights the variability in expression and function of the GR in pituitary and adrenocortical cells as one of the reasons for the appreciable differences in HPA axis function across individuals. Particular attention was paid to interactions that may affect the interpretation of diagnostic testing of the HPA axis in patients with pituitary adenomas (Cushing disease) or adrenocortical tumors (Cushing syndrome). (Endocr Pract. 2011;17:941-948)     

Random Postoperative Day-3 Cortisol Concentration as a Predictor of Hypothalamic-Pituitary-Adrenal Axis Integrity after Transsphenoidal Surgery

ObjectiveTo determine whether a random postoperative day-3 cortisol value of 10 μg/dL or greater is predictive of adrenal sufficiency 3 to 10 weeks after transsphenoidal surgery (TSS) and during long-term clinical follow-up.MethodsWe retrospectively reviewed the case records of patients who underwent TSS at our institution between 1991 and 2008. Inclusion criteria were as follows: random cortisol measured on the morning of postoperative day 3, adrenal dynamic testing performed 3 to 10 weeks after TSS, and clinical assessment of the hypothalamicpituitary-adrenal (HPA) axis at least 6 months after TSS.ResultsA total of 466 patients underwent TSS at our institution during the study period. Eighty-three patients met study inclusion criteria. Sensitivity of a random postoperative day-3 serum cortisol value of 10 μg/dL or greater for the prediction of adrenal sufficiency at a median follow-up of 42 days was 64.81% (95% confidence interval, 50.6%-77.32%), with an odds ratio of 3.1 (95% confidence interval, 1.08-8.58). Specificity was 62.1% (95% confidence interval, 42.3%-79.3%). At a median follow-up of 500 days, only 2 patients with a postoperative day-3 cortisol value of 10 μg/dL or greater required hydrocortisone replacement, both of whom had multiple anterior pituitary hormone deficiencies and evidence of pituitary dysfunction during the perioperative period.ConclusionsIn the appropriate clinical context, a postoperative day-3 cortisol value of 10 μg/dL or greater accurately predicts the integrity of the HPA axis. The final decision regarding corticosteroid replacement should be personalized, considering the postoperative day-3 cortisol level, the clinical context in which the measurement was obtained, and any evidence of concomitant pituitary dysfunction in the perioperative period. (Endocr Pract. 2011;17:717-726)     

Efficacy of core stability training on upper extremity performance in collegiate athletes

Objective:To determine the efficacy of a five-week core stability training program for collegiate athletes on upper extremity performance measures.Methods:Seventy healthy collegiate athletes (age 21.6±1.7years; height 175±4.63 cm; body mass 65.31±5.63 kg) were randomly allocated to experimental (n=35) and control group (n=35). The experimental group has undergone a five-week core stabilisation protocol (three days /week) and regular training, whereas the control group maintained their regular training. The upper quarter Y balance test (UQ-YBT) and Functional throwing performance index (FTPI) were assessed pre and post-training.Results:The results of mixed ANOVA show that there was a significant interaction between time and group variables on YBT (p<0.001, η_p² =0.759) and FTPI (p<0.001, η_p² =0.411) after five weeks of core stability training. Statistically, significant improvement was shown in YBT (mean change=15.2, p<0.001) and FTPI (mean change=14.4, p<0.001) in the experimental group; however, there was no significant change observed in both outcomes in the control groups.Conclusion:After five weeks of core stabilisation training program, the measures of UQ-YBT and FTPI were improved, thus advocating the use of a core stabilisation training program among collegiate athletes to enhance their upper extremity performance.     

Analysis of Resin-Dentin Interface Morphology and Bond Strength Evaluation of Core Materials for One Stage Post-Endodontic Restorations

PurposeRestoration of endodontically treated teeth using fiber posts in a one-stage procedure gains more popularity and aims to create a secondary monoblock. Data of detailed analyses of so called “post-and-core-systems” with respect to morphological characteristics of the resin-dentin interface in combination with bond strength measurements of fiber posts luted with these materials are scarce. The present study aimed to analyze four different post-and-core-systems with two different adhesive approaches (self-etch and etch-and-rinse).ResultsCLSM analyses revealed significant differences between groups with respect to the factors hybrid layer thickness (p<0.0005) and number of resin tags (p = 0.02; ANOVA). Bond strength was significantly affected by core material (p = 0.001), location inside the root canal (p<0.0005) and incorporation of fluorescent dyes (p = 0.036; ANOVA). CX [7.7 (4.4) MPa] demonstrated significantly lower bond strength compared to LC [14.2 (8.7) MPa] and RB [13.3 (3.7) MPa] (p<0.05; Tukey HSD) but did not differ significantly from MC [11.5 (3.5) MPa].ConclusionIt can be concluded that bond strengths inside the root canal were not affected by the adhesive approach of the post-and-core-system. All systems demonstrated homogenous hybrid layer formation and penetration into the dentinal tubules in spite of the complicating conditions for adhesion inside the root canal.     

冷刺激诱导的弱精子症大鼠模型肾上腺轴与甲状腺轴功能改变的研究

目的:研究冷刺激诱导建立的弱精子症模型大鼠HPA轴与HPT轴功能改变,探讨其生殖生物学意义。方法:取28只SPF级性成熟雄性SD大鼠随机分为正常对照组(N组,12只)与冷刺激组(C组,16只)。造模结束前对大鼠一般情况包括精神状态、体重、核心体温、尿量等进行检测。23周后通过精子功能的评定筛选弱精子症大鼠并建立弱精子症组(CA组),同时取外周血清、HPA轴、HPT轴相关组织;ELISA法和放射免疫法测定各组大鼠外周血清HPA、HPT轴相关激素水平,并在光镜下观察HPA轴和HPT轴相关组织形态学改变。结果:与N组相比,CA组大鼠反应迟钝,活动能力降低,夹尾试验评分显著降低,核心体温及尿量升高,差异显著(P0.05)。血清激素结果表现为CA组EPI显著升高,T3/T4比值亦显著升高,差异均具有统计学意义(P0.05)。光镜下可见N组各组织形态正常,与N组相比,CA组下丘脑室旁核神经细胞增生,排列紊乱;垂体细胞水肿,血窦不明显,嗜酸性细胞增多;肾上腺以皮、髓质水肿改变为主;甲状腺滤泡萎缩,上皮细胞增生。结论:冷刺激诱导建立的弱精子症大鼠模型可发生HPA轴功能改变,呈现慢性应激反应现象,提示,HPA轴功能改变参与该模型弱精子症的的发生发展过程。     

Sex difference in the relationship between the hypothalamic-pituitary-adrenal axis and sex hormones in obesity

Objective: This study was carried out to investigate the role of sex in the regulation of the hypothalamic‐pituitary‐adrenal (HPA) axis and its relationship with testosterone levels in male and female obesity. Research Methods and Procedures: Twenty‐two obese men (OB‐M) and 29 obese women (OB‐W) participated in the study. Two groups of normal weight men (NW‐M) and women (NW‐W), respectively, served as controls. In basal conditions, blood concentrations of major androgens, sex hormone—binding protein, and gonadotropins were assessed, and the free androgen index (testosterone ×100/ sex hormone‐binding globulin) was calculated. All subjects underwent a combined corticotropin‐releasing hormone plus arginine‐vasopressin stimulation test. Results: OB‐M and NW‐M had higher basal adrenal cortical tropic hormone (ACTH) and cortisol levels than their female counterparts. In addition, ACTH, but not cortisol basal, levels were significantly higher in obese than in normal weight controls in both sexes. OB‐W had a higher response than OB‐M to the combined corticotropin‐releasing hormone plus arginine‐vasopressin test of both ACTH and cortisol [expressed as incremental percentage of area under the curve (AUC%)]. The same finding was present between NW‐W and NW‐M. Basal luteinizing hormone levels were negatively correlated to ACTH_AUC% in both OB‐W and OB‐M. In the OB‐W, however, a positive correlation was found between cortisol_AUC% and testosterone (r = 0.48; p = 0.002), whereas a tendency toward a negative correlation was present in OB‐M. Discussion: In conclusion, we have shown a significant positive relationship between the activity of the HPA axis and testosterone in obese women, which suggests a partial responsibility of increased HPA axis activity in determining testosterone levels. In addition, it clearly seems that, as reported in normal weight subjects, a sex difference in the HPA axis activity still persists even in the presence of obesity.     

Modeling the influence of chronopharmacological administration of synthetic glucocorticoids on the hypothalamic-pituitary-adrenal axis

ABSTRACT

Natural glucocorticoids, a class of cholesterol-derived hormones, modulate an array of metabolic, anti-inflammatory, immunosuppressive and cognitive signaling. The synthesis of natural glucocorticoids, largely cortisol in humans, is regulated by the hypothalamic-pituitary-adrenal (HPA) axis and exhibits pronounced circadian variation. Considering the central regulatory function of endogenous glucocorticoids, maintenance of the circadian activity of the HPA axis is essential to host survival and chronic disruption of such activity leads to systemic complications. There is a great deal of interest in synthetic glucocorticoids due to the immunosuppressive and anti-inflammatory properties and the development of novel dosing regimens that can minimize the disruption of endogenous activity, while still maintaining the pharmacological benefits of long-term synthetic glucocorticoid therapy. Synthetic glucocorticoids are associated with an increased risk of developing the pathological disorders related to chronic suppression of cortisol rhythmicity as a result of the potent negative feedback by synthetic glucocorticoids on the HPA axis precursors. In this study, a mathematical model was developed to explore the influence of chronopharmacological dosing of exogenous glucocorticoids on the endogenous cortisol rhythm considering intra-venous and oral dosing. Chronic daily dosing resulted in modification of the circadian rhythmicity of endogenous cortisol with the amplitude and acrophase of the altered rhythm dependent on the administration time. Simulations revealed that the circadian features of the endogenous cortisol rhythm can be preserved by proper timing of administration. The response following a single dose was not indicative of the response following long-term, repeated chronopharmacological dosing of synthetic glucocorticoids. Furthermore, simulations revealed the inductive influence of long-term treatment was only associated with low to moderate doses, while high doses generally led to suppression of endogenous activity regardless of the chronopharmacological dose. Finally, chronic daily dosing was found to alter the responsiveness of the HPA axis, such that a decrease in the amplitude of the cortisol rhythm resulted in a partial loss in the time-of-day dependent response to CRH stimulation, while an increase in the amplitude was associated with a more pronounced time-of-day dependence of the response.     

Association of vitamin D,BMD and knee osteoarthritis in postmenopausal women

Objectives:The aim of this study was to analyze the association of knee OA with bone mineral density (BMD) and vitamin D serum levels in postmenopausal women.Methods:A cross-sectional study including 240 postmenopausal women with knee OA was conducted. Demographic data were recorded along with balance and functionality scores. Knee OA severity was assessed by the radiological Kellgren & Lawrence scale. BMD and T-scores were calculated in hips and lumbar spine. Serum levels of vitamin D were also measured.Results:High BMI (p<0.005), high number of children (p=0.022) and family history of hip fracture (p=0.011) are significantly associated with knee OA severity. Lumbar spine OP is negatively associated with knee OA (p<0.005). A significant difference was detected between vitamin D deficiency and severe knee OA, adjusted for BMD [OR (95%CI); 3.1 (1.6-6.1), p=0.001]. BMD does not affect the relationship of vitamin D levels in relation to OA and vitamin D levels do not affect the relationship of BMD with OA.Conclusions:Low BMD has a protective role against knee OA while vitamin D deficiency contributes significantly to knee OA severity. However, the association between OA and OP is not affected by vitamin D deficiency and the association of OA and vitamin D serum levels is not affected by BMD.     

Cross training effects of non-paralytic dorsiflexion muscle strengthening exercise on paralytic dorsiflexor muscle activity,gait ability,and balancing ability in patients with chronic stroke: A randomized,controlled, pilot trial

Objective:To investigate the effects of non-paralytic dorsiflexion muscle strengthening exercise on functional abilities in chronic hemiplegic patients after stroke.Methods:A total of 21 patients with chronic stroke underwent dorsiflexion muscle strengthening exercise (MST) 5 times a week for 6 weeks (the experimental group, MST to non-paralytic dorsiflexion muscles, n=11; the control group, MST to paralytic dorsiflexion muscles; n=10). Paralytic dorsiflexor muscle activities (DFA) and 10 m walking tests (10MWT) and timed up and go tests (TUG) were measured before and after intervention.Results:A significant increase in DFA was observed after intervention in the experimental and control groups (p<0.05) (experimental 886.6% for reference voluntary contraction (RVC), control 931.6% for RVC). TUG and 10MWT results showed significant reductions post-intervention in the experimental and control groups (experimental group -5.6 sec, control -4.8 sec; experimental group -3.1 sec, control, -3.9 sec; respectively). No significant intergroup difference was observed between changes in DFA or between changes in TUG and 10MWT results after intervention (p>.05).Conclusion:Strengthening exercise performed on non-paralytic dorsiflexion muscles had positive cross-training effects on paralytic dorsiflexor muscle activities, balance abilities, and walking abilities in patients with chronic stroke.