Effects of corticotropin-releasing hormone on proopiomelanocortin derivatives and monocytic HLA-DR expression in patients with septic shock

Little is known about interactions between immune and neuro-endocrine systems in patients with septic shock. We therefore evaluated whether the corticotropin-releasing hormone (CRH) and/or proopiomelanocortin (POMC) derivatives [ACTH, β-endorphin (β-END), β-lipotropin (β-LPH), α-melanocyte stimulating hormone (α-MSH) or N-acetyl-β-END (Nac-β-END)] have any influences on monocyte deactivation as a major factor of immunosuppression under septic shock conditions. Sixteen patients with septic shock were enrolled in a double-blind, cross-over and placebo controlled clinical study; 0.5 μg/(kg_bodyweight h) CRH (or placebo) were intravenously administered for 24 h. Using flow cytometry we investigated the immunosuppression in patients as far as related to the loss of leukocyte surface antigen-DR expression on circulating monocytes (mHLA-DR). ACTH, β-END immunoreacive material (IRM), β-LPH IRM, α-MSH and Nac-β-END IRM as well as TNF-α and mHLA-DR expression were determined before, during and after treatment with CRH (or placebo). A significant correlation between plasma concentration of α-MSH and mHLA-DR expression and an inverse correlation between mHLA-DR expression and TNF-α plasma level were found. Additionally, a significant increase of mHLA-DR expression was observed 16 h after starting the CRH infusion; 8 h later, the mHLA-DR expression had decreased again. Our results indicate that the up-regulation of mHLA-DR expression after CRH infusion is not dependent on the release of POMC derivatives. From the correlation between plasma concentration of α-MSH and mHLA-DR expression, we conclude that in patients with septic shock the down-regulation of mHAL-DR expression is accompanied by the loss of monocytic release of α-MSH into the cardiovascular compartment.     

The interface of hypothalamic–pituitary–adrenocortical axis and circulating brain natriuretic peptide in prediction of cardiopulmonary performance during physical stress

Brain natriuretic peptide (NT-pro-BNP) was implicated in the regulation of hypothalamic–pituitary–adrenocortical (HPA) responses to psychological stressors. However, HPA axis activation in different physical stress models and its interface with NT-pro-BNP in the prediction of cardiopulmonary performance is unclear. Cardiopulmonary test on a treadmill was used to assess cardiopulmonary parameters in 16 elite male wrestlers (W), 21 water polo player (WP) and 20 sedentary age-matched subjects (C). Plasma levels of NT-pro-BNP, cortisol and adrenocorticotropic hormone (ACTH) were measured using immunoassay sandwich technique, radioimmunoassay and radioimmunometric techniques, respectively, 10 min before test (1), at beginning (2), at maximal effort (3), at 3rd min of recovery (4). In all groups, NT-pro-BNP decreased between 1 and 2; increased from 2 to 3; and remained unchanged until 4. ACTH increased from 1 to 4, whereas cortisol increased from 1 to 3 and stayed elevated at 4. In all groups together, ΔNT-pro-BNP2/1 predicted peak oxygen consumption (B = 37.40, r = 0.38, p = 0.007); cortisol at 3 predicted heart rate increase between 2 and 3 (r = −0.38,B = −0.06, p = 0.005); cortisol at 2 predicted peak carbon-dioxide output (B = 2.27, r = 0.35, p < 0.001); ΔACTH3/2 predicted peak ventilatory equivalent for carbon-dioxide (B = 0.03, r = 0.33, p = 0.003). The relation of cortisol at 1 with NT-pro-BNP at 1 and 3 was demonstrated using logistic function in all the participants together (for 1/cortisol at 1 B = 63.40, 58.52; r = 0.41, 0.34; p = 0.003, 0.013, respectively). ΔNT-pro-BNP2/1 linearly correlated with ΔACTH4/3 in WP and W (r = −0.45, −0.48; p = 0.04, 0.04, respectively). These results demonstrate for the first time that HPA axis and NT-pro-BNP interface in physical stress probably contribute to integrative regulation of cardiopulmonary performance.     

Influences of the number of fetuses and levels of CP and ME in gestation and lactation supplements on performance of Spanish does and kids during suckling and post-weaning

Forty-eight mature US Spanish does (40 kg BW), from a herd selected for cashmere fiber growth, were used to investigate influences of the number of fetuses and levels of ME and CP in supplements during gestation and lactation on doe and kid performance. At 60 days of gestation, does with single or twin fetuses consumed mature Bermudagrass hay ad libitum and 1% BW (DM basis) of supplements with 18.6% or 28.5% CP (LP and HP, respectively) and 2.2 or 2.8 Mcal/kg ME (DM basis; LE and HE, respectively). The HE-HP supplement was offered at 1.5% BW (DM basis) for 15 days after birth, and does received the same supplement treatments as in gestation thereafter until weaning at 50 days after parturition. For a 50-day post-weaning period, kids consumed ad libitum the HE-LP supplement. BW at 90 days of gestation (41.4 vs 38.4 kg; P<0.10), BW before parturition (46.1 vs 41.7 kg; P<0.05), BW loss from parturition to day 21 of lactation (8.38 vs 5.25 kg; P<0.05), litter birth weight (5.47 vs 2.75 kg; P<0.05) and plasma concentrations of β-hydroxybutyrate (0.33 vs 0.29 mM; P<0.05) and NEFA (538 vs 434 mEq/l; P<0.05) were greater for does with twin vs single kids. BW at weaning was similar between single and twin kids (P>0.10; 8.31 and 7.63, respectively). Kid BW and cashmere fiber weight after the post-weaning period were affected by interactions (P<0.05) between number of fetuses and supplement ME level; kid BW was 12.3, 14.7, 14.6 and 13.2 kg (SE = 1.12 and 0.68 kg for singles and twins, respectively), and kid cashmere weight was 86, 109, 106 and 102 g (SE = 8.5 and 5.0 g for singles and twins, respectively) for single-HE, single-LE, twin-HE and twin-LE, respectively. In conclusion, effects of supplements differing in levels of ME and in ingredient composition for US Spanish does in gestation and lactation had dissimilar impacts on post-weaning BW and cashmere weight of single and twin kids. However, because of the limited number of observations and the high variability among animals in measures such as cashmere fibre growth, further experimentation concerning the potential for effects of nutritional plane of does on cashmere growth by kids is warranted.     

Heifer nutrition during early- and mid-pregnancy alters fetal growth trajectory and birth weight

Maternal nutrient intake during gestation can alter fetal growth. Whilst this has been studied extensively in the sheep, less is known about effects in the bovine. Composite-breed beef heifers were allocated to either a high (H/? = 76 MJ metabolisable energy (ME) and 1.4 kg crude protein (CP)) or low (L/? = 62 MJ ME and 0.4 kg CP daily) nutritional treatment at artificial insemination. Half of each nutritional group changed to an opposite nutritional group at the end of the first trimester (?/H = 82 MJ ME and 1.4 kg CP; ?/L = 62 MJ ME and 0.4 kg CP daily), resulting in 4 treatment groups: HH (n = 16); HL (n = 19); LH (n = 17); LL (n = 19). During the third trimester all heifers were fed the same diets. Fetuses were measured at 4-weekly intervals beginning at day 39 of gestation. Calves were also measured at birth for physical body variables. Low maternal nutrient intake was associated with decreased crown-rump length at day 39 (P < 0.01) and increased thoracic diameter at day 95 (P < 0.01). Umbilical cord diameter was reduced in L/? fetuses in the first trimester (P < 0.05) but was greater in ?/L fetuses in the second trimester compared to their respective H counterparts (P < 0.05). Calf birth weight was decreased in association with ?/L maternal diets (P < 0.05). In conclusion, fetal development of cattle may be affected by maternal nutrition as early as day 39 of gestation. This may be followed by either compensatory fetal growth, or alternatively, preferential fetal tissue growth that is dependant upon maternal nutrition. Clearly, calf birth weight may be altered by maternal nutrition during mid-gestation.     

Alarin-induced antidepressant-like effects and their relationship with hypothalamus–pituitary–adrenal axis activity and brain derived neurotrophic factor levels in mice

Alarin is a newly identified member of the galanin family of peptides. Galanin has been shown to exert regulatory effects on depression. Similar to galanin in distribution, alarin is also expressed in the medial amygdala and hypothalamus, i.e., regions interrelated with depression. However, it remains a puzzle whether alarin is involved in depression. Accordingly, we established the depression-like mouse model using behavioral tests to ascertain the possible involvement of alarin, with fluoxetine as a positive control. With the positive antidepressant-like effects of alarin, we further examined its relationship to HPA axis activity and brain-derived neurotrophic factor (BDNF) levels in different brain areas in a chronic unpredictable mild stress (CUMS) paradigm. In the acute studies, alarin produced a dose-related reduction in the immobility duration in tail suspension test (TST) in mice. In the open-field test, intracerebroventricular (i.c.v.) injection of alarin (1.0 nmol) did not impair locomotion or motor coordination in the treated mice. In the CUMS paradigm, alarin administration (1.0 nmol, i.c.v.) significantly improved murine behaviors (FST and locomotor activity), which was associated with a decrease in corticotropin-releasing hormone (CRH) mRNA levels in the hypothalamus, as well as a decline in serum levels of CRH, adrenocorticotropic hormone (ACTH) and corticosterone (CORT), all of which are key hormones of the HPA axis. Furthermore, alarin upregulated BDNF mRNA levels in the prefrontal cortex and hippocampus. These findings suggest that alarin may potentiate the development of new antidepressants, which would be further secured with the identification of its receptor(s).     

Growth and cashmere production by Spanish goats consuming ad libitum diets differing in protein and energy levels

Thirty-six Spanish goat wethers (196 ± 12.9 days of age and 17.5 ± 4.60 kg BW at experiment initiation) from a herd previously selected for cashmere growth were used to determine effects and interactions of ad libitum consumption of diets differing in concentrations of CP (10% and 15%) and ME (2.00, 2.35 and 2.70 Mcal/kg; DM basis) on growth and cashmere fiber production in an 84-day, fall-season experiment. DM intake was greater (P < 0.05) for diets with 15% vs. 10% CP (736 vs. 655 g/day) but similar among ME concentrations (P > 0.10). ADG was greater (P < 0.02) for 15% vs. 10% CP (79 vs. 53 g/day) and increased linearly (P < 0.10) as dietary ME level increased (58, 62 and 78 g/day for 2.00, 2.35 and 2.70 Mcal/kg ME, respectively). Total fleece weight at the end of the experiment was similar (P > 0.10) between CP levels but increased linearly (P < 0.03) as ME concentration in the diet increased (197, 239 and 227 g/day). Guard hair weight was not affected by dietary treatments (P > 0.10); cashmere length was similar among treatments (P > 0.10); and cashmere fiber diameter was not altered by dietary ME level (P > 0.10) but was greater (P < 0.05) for 15% vs. 10% CP (16.92 vs. 16.06 μm). Cashmere weight was influenced by an interaction between CP and ME levels (P < 0.05); cashmere fiber weight with 10% CP was 92, 82 and 95 g, and with 15% CP was 63, 115 and 99 g for 2.00, 2.35 and 2.70 Mcal ME/kg diets, respectively (SE = 10.2). However, the ranking of treatment means for initial cashmere fiber weight was similar to that at the end of the experiment, although differences at the beginning were non-significant and of lesser magnitude than at the end. In conclusion, further research with influences of concentrations of CP and ME in diets consumed ad libitum on cashmere fiber growth of growing US Spanish wether goats is required, and animal numbers and allocation to treatments deserve careful consideration in studies of cashmere fiber production.     

Anti-herpes virus activities of Achyranthes aspera: An Indian ethnomedicine,and its triterpene acid

The aim of this study was to evaluate the antiviral potential of methanolic extract (ME) of Achyranthes aspera, an Indian folk medicine and one of its pure compound oleanolic acid (OA) against herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2). The ME possessed weak anti-herpes virus activity (EC₅₀ 64.4 μg/ml for HSV-1 and 72.8 μg/ml for HSV-2). While OA exhibited potent antiherpesvirus activity against both HSV-1 (EC₅₀ 6.8 μg/ml) and HSV-2 (EC₅₀ 7.8 μg/ml). The time response study revealed that the antiviral activity of ME and OA is highest at 2–6 h post infection. The infected and drug-treated peritoneal macrophage at specific time showed increased level of pro-inflammatory cytokines (IL6 and IL12). Further, the PCR of DNA from infected cultures treated with ME and OA, at various time intervals, failed to show amplification at 48–72 h, similar to that of HSV infected cells treated with acyclovir, indicating that the ME and OA probably inhibit the early stage of multiplication (post infection of 2–6 h). Thus, our study demonstrated that ME and OA have good anti-HSV activity, with SI values of 12, suggesting the potential use of this plant.     

Ecological-economic assessment of ecological sanitation development in the cities of Chinese Loess Plateau

Many cities in Chinese Loess Plateau have inadequate sanitation. Ecological sanitation (ecosan) is a systemic approach to solve environmental and sanitary problems. Thus, suitable ecosan technologies and systems were analyzed, and three alternative developing models of sanitation were compared, namely, centralized traditional (CT) model, centralized ecosan (CE) model, and centralized and decentralized mixed ecosan (ME) model. Their ecological-economic assessment was made in the theoretical framework of social–economic–natural complex ecological system. Main results were (1) CE and ME reduced the emission of greenhouse gases, and the maximum reduction was 96.8% of CT. (2) ME reduced the water pollutants at a comparatively lower capital and running cost, and BOD₅ emission could be reduced to 85–88% of CT. (3) CE and ME reclaimed more nutrients than CT. Attributing to reclaiming nutrients, CE and ME could produce 461.4 and 809.9 Gg foods, respectively, and CT was 32.1 Gg. (4) The sequence of health risk caused by sanitation was CT > CE > ME. (5) Urban ecosan system could bring forward a maximum net benefit of 0.267 billion RMB. In addition, the bottlenecks of developing ecosan in China were also discussed in this paper.     

Prevalence and resting behaviour of dengue vectors,Aedes aegypti and Aedes albopictus in dengue high risk urban settings in Colombo,Sri Lanka

Understanding local geographical variation in vector density and bionomics related to virus transmission are critical for planning effective vector control programs to control dengue virus transmission. This study investigated the prevalence and resting behaviour of Aedes aegypti and Ae. albopictus in three dengue high-risk areas in the Colombo District, Sri Lanka. Monthly sampling of resting adult mosquitoes was conducted from August 2019 to February 2020. Thirty-seven percent of the households (289/776) harboured Aedes mosquitoes, and 603 Aedes mosquitoes were collected. The proportion of Ae. aegypti was higher in the overall collection during the collection period (94% [569/603]), and 62% (352/569) were females. Significant monthly variations in Ae. aegypti were observed with respect to the indices: number of females per surveyed house (F/SH; p = 0.001), number of females per Aedes positive house (F/PH; p = 0.029), adult house index (AHI; p = 0.001), adult density (AD; p = 0.005) and resting ratio (RR; p = 0.001). AHI, AD, and RR had statistically significant positive correlations with monthly rainfall (p = 0.001, p = 0.011, and p = 0.002 respectively) and one-month lagged dengue cases (p = 0.002, p = 0.005, and p < 0.001 respectively). A statistically significantly higher proportion of Ae. aegypti females were caught resting indoors (N = 309, 88%) than outdoors (N = 43, 12%; p < 0.001). The most common resting areas were bedrooms (51%) & living/dining rooms (37%), and places were under or on furniture (47%) & hangings (34%) for Ae. aegypti. Conversely, 74% of female Ae. albopictus were collected outdoors. Results of this study could have strong implications to improve vector surveillance and control by early detection of dengue to detect outbreaks and minimization of disease transmission.     

Effects of daily protein intake levels on the oral stereotypic behaviours in energy restricted lambs

Effects of daily protein intake levels on oral stereotypic behaviours (OSB) in energy restricted lambs were investigated. Thirty-eight male lambs were randomly allotted to three treatments. Lambs in the first group (AL) received their ration (12.1 MJ ME/kg DM; 148.6 g CP/kg DM) at ad libitum level, whereas the second group (RP1) (12.1 MJ ME/kg DM; 177.4 g CP/kg DM) and the third group (RP2) (12.1 MJ ME/kg DM; 214.9 g CP/kg DM) received their rations at restricted levels. Recording of behaviours was carried out once a week using time sampling technique during a 7-week experimental period. OSB were significantly (P<0.001) affected by the treatments. RP2 group showed higher oral stereotypies than the others. It was concluded that increasing the daily protein intake under energy restricted conditions may have additive effects on the development of stereotypic oral behaviours.     

Whole crop rice silage: Predictions of yield and content of metabolizable energy,metabolizable protein and other nutrients for dairy cows from crop maturity and botanical fractions at harvest

The study investigated the suitability of stage of maturity and botanical fractions of whole crop rice (WCR) to predict yield and nutritive value of ensiled WCR for dairy cows. Eight varieties of WCR (i.e., Akichikara, Fukuhibiki, Habataki, Hamasari, Hokuriku 168, Kusanami, Tamakei 96, Yumetoiro) were harvested at four stages of maturity (i.e., 10, 22, 34, 45 days after flowering [DAF]) and ensiled. Dry matter (DM) yield at each harvest was determined. Silage samples were fractionated into four botanical fractions being: leaf blade, leaf sheath, stem and head. Silage samples were also analyzed for chemical composition, fermentation characteristics, in situ DM and N disappearance. Metabolizable energy (ME) and metabolizable protein (MP) content of samples were estimated according to Terada et al. (1988) and AFRC (1993), respectively. Relationships between maturity or proportions of botanical fractions and contents of WCR silage in terms of DM, ME and MP, and their yields, were estimated by correlation and regression analysis. Stage of maturity was positively related (P<0.001) to ME content (R² = 0.46; y = 4.53 + 0.08X) and MP content (R² = 0.56; y = 22.26 + 0.76X), and DM yield (R² = 0.63; y = 9.21 + 0.12X), ME yield (R² = 0.68, y = 36931 + 1708X) and MP yield (R² = 0.72, y = 161.0 + 14.15X) of WCR. Proportion of leaf was negatively related to yields and nutritive value of ensiled WCR, whilst proportion of head was positively related (P<0.05 to <0.001). Proportion of head was best related to the ME content (R² = 0.72; y = 3.26 + 0.009X), MP content (R² = 0.72; y = 12.31 + 0.079X), and DM yield (R² = 0.41; y = 9.02 + 0.009X), ME yield (R² = 0.76, y = 19494 + 165.5X), and MP yield (R² = 0.75, y = 34.37 + 1.32X) of WCR. Results suggest that to optimize yield and nutritive value, WCR should be ensiled within 40 DAF and the proportion of head should be equal to or more than 500 g per kg DM of WCR silage. Stage of maturity and proportion of head of WCR predict yields of DM, ME and MP of WCR, and their contents, in WCR silage with acceptable accuracy. However, these relationships need to be validated using large data sets and in vivo studies.     

Medial gastrocnemius muscle-tendon interaction and architecture change during exhaustive hopping exercise

Background: Previous literature has shown in vivo changes in muscle-tendon interaction during exhaustive stretch-shortening cycle (SSC) exercise. It is unclear whether these changes in muscle-tendon length during exhaustive SSC exercise are associated with changes in mechanical efficiency (ME). The purpose of the study was to investigate whether changes in platarflexor contractile component (CC) length, tendon length, and changes in plantarflexor muscle activity could explain reduction in ME during exhaustive SSC exercise. Methods: Eight males participated in an exhaustive hopping task to fatigue. Mechanical work and energy expenditure were calculated at different time-points during the hopping task. Furthermore, hopping kinetics and kinematics, medial gastrocnemius (MG) muscle activity, and in vivo ultrasound of the MG were also collected at different time-points throughout the hopping task. Results: ME did not change during the hopping protocol despite shorter tendon and longer CC lengths as subjects approached exhaustion. Percent decreases in pennation angle and muscle thickness were most strongly correlated to time to exhaustion (r = 0.94, p ⩽ 0.05; r = 0.87, p ⩽ 0.05; respectively). Percent changes in CC length change and pennation angle were strongly correlated to percent decrease in maximal voluntary isometric plantarflexion (MVIP) force (r = −0.71, p ⩽ 0.04; r = 0.70, p ⩽ 0.05; respectively). Braking/push-off EMG ratio increased from initial pre-fatigue values to all other time points showing neuromuscular adaptations to altered muscle lengths. Conclusion: Findings from the current study suggest that changes in CC and tendon lengths occur during repetitive hopping to exhaustion, with the amount change strongly related to time to exhaustion. ME of hopping remained unchanged in the presence of altered CC and tendon lengths.     

Oxytocin promotes functional coupling between paraventricular nucleus and both sympathetic and parasympathetic cardioregulatory nuclei

The neuropeptide oxytocin (OXT) facilitates prosocial behavior and selective sociality. In the context of stress, OXT also can down-regulate hypothalamic–pituitary–adrenal (HPA) axis activity, leading to consideration of OXT as a potential treatment for many socioaffective disorders. However, the mechanisms through which administration of exogenous OXT modulates social behavior in stressful environmental contexts are not fully understood. Here, we investigate the hypothesis that autonomic pathways are components of the mechanisms through which OXT aids the recruitment of social resources in stressful contexts that may elicit mobilized behavioral responses. Female prairie voles (Microtus ochrogaster) underwent a stressor (walking in shallow water) following pretreatment with intraperitoneal OXT (0.25 mg/kg) or OXT antagonist (OXT-A, 20 mg/kg), and were allowed to recover with or without their sibling cagemate. Administration of OXT resulted in elevated OXT concentrations in plasma, but did not dampen the HPA axis response to a stressor. However, OXT, but not OXT-A, pretreatment prevented the functional coupling, usually seen in the absence of OXT, between paraventricular nucleus (PVN) activity as measured by c-Fos immunoreactivity and HPA output (i.e. corticosterone release). Furthermore, OXT pretreatment resulted in functional coupling between PVN activity and brain regions regulating both sympathetic (i.e. rostral ventrolateral medulla) and parasympathetic (i.e. dorsal vagal complex and nucleus ambiguous) branches of the autonomic nervous system. These findings suggest that OXT increases central neural control of autonomic activity, rather than strictly dampening HPA axis activity, and provides a potential mechanism through which OXT may facilitate adaptive and context-dependent behavioral and physiological responses to stressors.     

Efficiency of energy use for pregnancy by meat goat does with different litter size

Twenty-four Boer × Spanish does (3 years of age, having kidded once previously and with an initial BW of 42.7 ± 1.2 kg) were used to determine the efficiency of ME utilization for pregnancy (k_preg). Six does were nonpregnant and, based on ultrasound determination on day 45 of gestation, six had a litter size (LS) of 1, 2, and 3. However, only 10 of the pregnant does delivered the expected number of kids (3, 4, and 3 with LS of 1, 2, and 3, respectively). Does were fed a diet of approximately 50% concentrate in accordance with assumed maintenance plus pregnancy energy requirements based on estimated nonpregnancy tissue BW and LS. Recovered energy (RE) was determined by subtraction of energy expenditure (EE; respiration calorimetry) near days 80, 100, 120, and 140 of gestation from ME intake (MEI). RE was assumed attributable to pregnancy tissues (fetus, fetal fluids and membranes, uterus, and mammary gland), and ME used for pregnancy (ME_preg) was estimated by subtracting ME_m determined with nonpregnant goats from MEI by those pregnant. For does with actual LS equal to that expected, the no-intercept equation for the regression of RE against ME_preg was: RE = ME_preg × 0.252 (S.E. = 0.030; R² = 0.64), indicating a k_preg of 25%. A regression including LS (1 versus 2 or 3) suggested greater k_preg for LS of 1 (40.2 ± 5.6%) versus 2 or 3 (20.5 ± 3.2%). Regressions for goats with LS different from expected suggested positive effects of use of energy mobilized from nonpregnancy tissues on k_preg and of use of dietary ME for energy accretion in nonpregnancy tissues on the efficiency of whole body ME utilization. In conclusion, the average efficiency of ME use for pregnancy regardless of LS in goats was near 25%, which when considering the expected proportion of all pregnancy tissues attributable to fetal or conceptus tissues implies an energy requirement for pregnancy of goats similar to common recommendations for sheep and cattle.     

Utility of Adrenocorticotropic Hormone in Assessing the Response to Transsphenoidal Surgery for Cushing’s Disease

ObjectivesTo compare adrenocorticotrophic hormone (ACTH) and cortisol dynamics in subjects with Cushing’s disease (CD) following transsphenoidal surgery (TSS) and to determine the value of early postoperative ACTH levels in predicting subsequent hypocortisolemia.MethodsFollowing TSS for CD, serum cortisol and plasma ACTH were measured every 6 hours in the absence of empiric glucocorticoid coverage.ResultsA total of 26 subjects (25 female) underwent 28 operations. Hypocortisolemia was achieved in 21 (81%) subjects after the initial TSS. Repeat TSS was performed in 2 subjects, resulting in hypocortisolemia in 1. Subjects who achieved hypocortisolemia had significantly lower ACTH levels by 19 hours postoperatively (P = .007). Plasma ACTH fell to < 30 pg/mL in 86% and < 20 pg/mL in 82% of subjects who subsequently achieved hypocorti- solemia. Plasma ACTH declined to < 30 pg/mL by a mean of 10 hours and to < 20 pg/mL by 13 hours prior to hypo- cortisolemia. Follow-up data were available on 25 patients for a median of 23 months. Three subjects who achieved initial surgical remission had disease recurrence at 19, 24, and 36 months; all of these subjects had a postoperative nadir serum cortisol levels < 3 μg/dL and plasma ACTH < 20 pg/mL.ConclusionFollowing TSS for CD, plasma ACTH declined prior to achievement of hypocortisolemia in most subjects. In the majority, the ACTH level reached a nadir of < 20 pg/mL. Low early postoperative ACTH levels predict early hypocortisolemia but may not accurately predict long-term remission. (Endocr Pract. 2014;20:1159-1164)     

Efficiency of energy use for maintenance and gain by growing crossbred Boer and Spanish Goats consuming diets differing in forage level

Eight Boer (75%) × Spanish (BS) and eight Spanish (S) wether goats (155 ± 8 days of age and 19.2 ± 2.3 kg BW, initial) were used in a replicated crossover design experiment with a 2 × 2 factorial arrangement of treatments to determine the effects of genotype and diet quality on heat production with ad libitum, near maintenance and fasting levels of feed intake. Diets were 65% concentrate (CON 15% CP, DM basis) and coarsely ground alfalfa hay (FOR 23% CP). There were no significant interactions between genotype and diet. ME intake was similar between genotypes and greater (P < 0.05) for CON versus FOR both when intake was ad libitum (7.60 versus 5.43 MJ/day) and near maintenance (4.31 versus 4.09 MJ/day). DE concentration was greater (P < 0.05) for CON than for FOR with ad libitum (74.4 versus 55.5%) and restricted intake (77.0 versus 59.6%). Energy expenditure (EE), determined by respiration calorimetry, at all levels of intake was similar between genotypes. EE was greater (P < 0.05) for CON than for FOR at each of the three levels of intake, ad libitum (573 and 521 kJ/kg BW^0.75 while fasting), near maintenance (426 and 400 kJ/kg BW^0.75) and fasting (280 and 255 kJ/kg BW^0.75). Efficiencies of ME utilization for maintenance (k_m) and gain (k_g) and the ME requirement for maintenance (ME_m) were similar between genotypes. k_m was similar between diets (0.705 and 0.690 for CON and FOR, respectively), although k_g was greater (P < 0.05) for CON than for FOR (0.603 versus 0.387). ME_m was numerically greater (P < 0.17) for CON than for FOR (407 versus 379 kJ/kg BW^0.75), which may have involved higher ME intake with CON. In conclusion, under the conditions of this experiment energy requirements and efficiency of utilization were not different between growing Boer crossbred and Spanish goats regardless of diet quality.     

Predicting toxicity for head and neck cancer patients undergoing radiation therapy: an independent and external validation of MDASI-HN based nomogram

AimWe conducted a study to validate the MDASI-HN based nomogram, which is used to predict the acute toxicities in head and neck cancer patients undergoing radiation therapy with or without chemotherapy.BackgroundTolerance to radiation varies from patient to patient and also depends on various other factors like tumor volume, dose of radiation, chemotherapy. Predicting the toxicities allow us to identify potential candidates who are likely to have a higher toxicity and, in addition, evaluates the nomogram when done on an independent group of patients.Materials and MethodsSixty biopsy confirmed head and neck cancer patients undergoing radiation were the subjects of the study. The patients completed patient reported outcome instrument (PRO) MDASI-HN questionnaire at the beginning and at the fifth week of radiation. The baseline score obtained was used to obtain the predicted score using nomogram. The nomogram was also externally validated as per the TRIPOD guidelines.ResultsThe mean baseline, predicted and score at the fifth week were 27.28 ± 11.04, 73.33 ± 15.51 and 82.62 ± 17.67, respectively, for all sub-sites. A positive, significant correlation (p < 0.01) between the predicted score and the score at the fifth week was seen across all sub sites such as Oral cavity (p = 0.05), Oropharynx (p = 0.02), Hypo pharynx (p = 0.02) and Larynx (p = 0.02).ConclusionThe MDASI-HN questionnaire based nomogram is simple, easily doable and takes into consideration the initial symptoms as well the treatment details; thereby, it is able to predict the toxicities accurately.     

Genistein stimulates the hypothalamo-pituitary-adrenal axis in adult rats: morphological and hormonal study

Genistein, the soy isoflavone structurally similar to estradiol, is widely consumed for putative beneficial health effects. However, there is a lack of data about the genisteins' effects in adult males, especially its effects on the hipothalamo-pituitary-adrenal (HPA) axis. Therefore, the present study was carried out to investigate the effects of genistein on the HPA axis in orchidectomized adult rats, and to create a parallel with those of estradiol. Changes in the hypothalamic corticotrophin-releasing hormone (CRH) neurons and pituitary corticotrophs (ACTH cells) were evaluated stereologically, while corticosterone and ACTH levels were determined biochemically. Orchidectomy (Orx) provoked the enlargement (p<0.05) of: hypothalamic paraventricular nucleus volume (60%), percentage of CRH neurons (23%), percentage of activated CRH neurons (45%); pituitary weight (15%) and ACTH level (57%). In comparison with Orx, estradiol treatment provoked the enlargement (p<0.05) of: percentage of CRH neurons (28%), percentage of activated CRH neurons (2.7-fold), pituitary weight (131%) and volume (82%), ACTH level (69%), the serum (103%) and adrenal tissue (4.8 fold) level of corticosterone. Clearly, Orx has induced the increase in HPA axis activity, which even augments after estradiol treatment. Also, compared to Orx, genistein treatment provoked the enhancement (p<0.05) of: percentage of activated CRH neurons (2.3-fold), pituitary weight (28%) and volume (21%), total number of ACTH cells (22%) ACTH level (45%), the serum (2.6-fold) and adrenal tissue (2.8 fold) level of corticosterone. It can be concluded that an identical tendency, concerning the HPA axis parameters, follows estradiol and genistein administration to the orchidectomized adult rats.