The effect of a mixed-management system on the release of oxytocin, prolactin, and cortisol in ewes during suckling and machine milking

Milk yield and plasma oxytocin (OT), prolactin (PRL), and cortisol (CORT) during suckling and machine milking were measured in multiparous ewes subjected to a mixed management system of 3 sucklings and two daily milkings. Peak hormones were significantly increased and were similar during suckling and milking for PRL (181 vs. 163.3 ng x mL(-1)) and CORT (12.5 vs. 11.5 ng x mL(-1)). During the period of exclusive suckling, OT was always significantly released (90.3 pg x mL(-1)); however, during the period of mixed management, OT concentrations only increased during suckling compared to milking (91.7 vs. 13.1 pg x mL(-1)). The mean volume of milk obtained during suckling (632 mL) was significantly higher than during milking (255 mL). Thus, during a mixed management system, oxytocin and prolactin releases are not under similar central regulation. A mixed system, without OT release during milking, does not contribute to accelerate the conditioning of ewes for machine milking.     

The ovulatory and LH responses to the male effect in dominant and subordinate goats

The objective of this study was to evaluate the LH and ovulatory response of dominant and subordinate dairy does following the introduction of males. A behavioral study was carried out to determine the individual success index (SI) of 35 anestrous does according to their ability to dominate other females. The 8 highest-ranking (highest SI) and the 8 lowest-ranking does (lowest SI) in terms of dominance were separated from the rest of the herd and placed together in the same pen, where a male was later introduced. Blood samples for plasma LH determinations were obtained from the 16 females at 30 min intervals from 0 to 6, 12 to 18 and 33 to 39 h after the introduction of the male, using an intravenous catheter. After day 8, plasma progesterone was also measured daily in order to determine the occurrence of ovulation. None of the does showed LH pulses during the sampling period prior to the introduction of the male. The dominant does showed significantly (p < 0.05) more LH pulses (2.0 ± 0.18 ng/ml vs. 1.2 ± 0.25 ng/ml) and a higher mean plasma LH concentration (0.25 ± 0.03 ng/ml vs. 0.14 ± 0.03 ng/ml) than the subordinate goats during the first 6 h of exposure to the male. There were no differences in LH pulsatility or concentrations at other times. The frequency of goats that ovulated tended to be greater in high-ranked than low-ranked does (87% vs. 37%). It could be concluded that the immediate LH response to the presence of the male (number of LH pulses) is higher in the dominant, compared to the subordinate goats, and this is associated with a higher number of dominant goats ovulating in response to the male effect.     

The influence of androgens on hibernation phenology of free-living male arctic ground squirrels

Free-living ground squirrel species are sexually dimorphic in hibernation phenology. The underlying causes of these differences are not yet known. Androgens, testosterone (T) in particular, inhibit hibernation. To determine the influence of endogenous androgens on annual timing of hibernation we first measured circulating levels of T and dehydroepiandrosterone (DHEA), an adrenal androgen implicated in non-mating season aggression in other species, in free-living male arctic ground squirrels (Urocitellus parryii, AGS). We also manipulated endogenous androgen levels by surgical castration, and consequently compared body temperature records from intact (n = 24) and castrated (n = 9) males to elucidate the influence of endogenous androgens on annual body temperature cycles. The highest T levels (0.53 ± 0.10 ng/mL) were in reproductively mature male AGS in spring; whereas, both immature males in spring and all males in late summer had T levels an order of magnitude lower (0.07 ± 0.01 and 0.06 ± 0.00 ng/mL, respectively). DHEA levels were higher in males during the late summer compared to reproductively mature males in spring (120.6 ± 18.9 and 35.9 ± 2.3 pg/mL, respectively). Eliminating gonadal androgens via castration resulted in males delaying euthermy by extending heterothermy significantly in spring (Apr 22 ± 2.9) than reproductive males (Mar 28 ± 3.9) but did not change the timing of hibernation onset (castrate: Oct 12 ± 1.0 vs. intact: Oct 3 ± 3.1). We conclude that while androgens play a significant role in spring hibernation phenology of males, their role in fall hibernation onset is unclear.     

Resistance exercise modulates lipid plasma profile and cytokine content in the adipose tissue of tumour-bearing rats

Cancer cachexia is a multifactorial syndrome characterised by progressive weight loss, frequently accompanied by anorexia, sarcopenia, and chronic systemic inflammation. The white adipose tissue is markedly affected by cachexia and contributes to this syndrome throught the secretion of pro-inflammatory factors which reach the adjacent tissues and the circulation. A nonpharmacologic intervention that may attenuate cancer cachexia is chronic physical activity, but the effect of resistance training upon adipose tissue inflammation in cachexia has never been examined. For that purpose we designed a protocol in which animals were randomly assigned to a control group (CT, n = 7), a Tumour bearing group (TB, n = 7), a Resistance Trained group (RT, n = 7) and a Resistance Trained tumour bearing group (RTTB, n = 7). Trained rats climbed a vertical ladder with an extra load attached to the tail, representing 75–90% of total body mass, 3 times per week, for 8 weeks. In the 6th week of resistance training, tumour cells (3 × 10⁷ Walker 256 carcinosarcoma) were inoculated in the tumour groups. Body, adipose tissue, muscle and tumour mass was determined, as well a blood biochemical parameters, and the hormone and cytokine profile assessed. The glycogen content of the liver and muscle was measured. IL-10, IL-6 and TNF-α protein expression was evaluated in the mesenteric adipose tissue (MEAT) examined. Resistance training increased by 9% body weight gain in RTTB (final weight 310.8 ± 9.8 g), when compared with TB (final weight 288.3 ± 4.9 g). LDL-c levels were decreased in RTTB (0.28 ± 0.9 mmol/L) by 43% when compared with TB (0.57 ± 0.1 mmol/L). HDL-c levels were increased in RTTB (1.31 ± 0.12 mmol/L) by 15% in regard to CT (1.13 ± 0.7 mmol/L) and 22% as compared with TB (1.07 ± 0.07 mmol/L). RTTB testosterone levels (577 ± 131 ng/mL) were 55% higher when compared with CT (254 ± 41.3 ng/mL) and 63% higher when compared with TB (221 ± 23.1 ng/mL). Adiponectin levels were augmented in RT (23 μg/mL) by 43% when compared with TB (11 μg/mL). Protein expression of IL-6 was increased 38% in TB MEAT (5.95 pg/μg), as compared with CT (3.64 pg/μg) and 50% compared with RTTB (2.91 pg/μg). Similar results with respect to TNF-α TB (7.18 pg/μg) were observed: 39% and 46%, higher protein expression in comparison with CT (4.63 pg/μg) and RTTB (3.8 pg/μg), respectively. IL-10 protein expression was found to be increased in TB (4.4 pg/μg) and RTTB (3.2 pg/μg) 50% and 47%, respectively, in comparison with CT (1.2 pu/μg). The IL-10/TNF-α ratio was higher in RTTB in relation to all others experimental groups. The results show a robust effect of resistance exercise training in preventing important symptoms of cancer cachexia, thus strongly suggesting it may appear as an alternative to endurance exercise as a non-pharmacological therapy in the management of this syndrome.     

Menstrual Disorders and Androgen-Related Traits in Young Women with Type 1 Diabetes Mellitus: a Clinical Study

Objective: To investigate possible causes of menstrual disorders and androgen-related traits in young women with type 1 diabetes mellitus (T1DM).Methods: Fifty-three women with T1DM (duration 8.0 ± 5.6 years), 41 women with (polycystic ovary syndrome) PCOS, and 51 controls matched for age (19.4 ± 4.3 years vs. 21.2 ± 2.7 years vs. 20.8 ± 3.1 years; P>.05) and body mass index (BMI) (22.2 ± 2.7 kg/m² vs. 21.9 ± 2.0 kg/m² vs. 21.4 ± 1.9 kg/m²; P>.05) were prospectively recruited.Results: Two women (3.8%) in the T1DM group had not experienced menarche (at 15.5 and 16.6 years); of the rest, 23.5% had oligomenorrhea, 32.1% hirsutism, and 45.3% had acne. The age at menarche was delayed in the T1DM group compared to controls (12.7 ± 1.3 vs. 12.0 ± 1.0 years; P = .004), while no difference was observed with the polycystic ovary syndrome (PCOS) group (12.4 ± 1.2 years). There were no differences in total testosterone (0.43 ± 0.14 ng/mL vs. 0.39 ± 0.14 ng/mL; P>.05), dehydroepiandrosterone sulfate (DHEA-S) (269 ± 112 μg/dL vs. 238 ± 106 μg/dL; P>.05) or Δ4-androstenedione (2.4 ± 1.3 ng/mL vs. 1.9 ± 0.5 ng/mL; P>.05) concentrations between T1DM and controls. However, patients with T1DM had lower sex hormone binding globulin (SHBG) concentrations than controls (61 ± 17 nmol/L vs. 83 ± 18.1 nmol/L; P = .001), which were even lower in the PCOS group (39.5 ± 12.9 nmol/L; P = .001 compared with T1DM). The free androgen index (FAI) was higher in the PCOS group compared with both other groups (T1DM vs. PCOS vs. controls: 2.53 ± 0.54 vs. 7.88 ± 1.21 vs. 1.6 ± 0.68; P<.001). FAI was higher in patients with T1DM compared to controls as well (P = .038). There was no difference in DHEA-S concentrations between T1DM and PCOS patients (269 ± 112 μg/dL vs. 297 ± 100 μg/dL; P>.05).Conclusion: Menstrual disorders and androgen-related traits in young women with T1DM may be attributed to an increase in androgen bioavailability due to decreased SHBG concentrations.     

Decreased plasma nesfatin-1 levels in patients with acute myocardial infarction

Nesfatin-1 is a novel anorexigenic hormone which has close relationship with diabetes, obese, anorexia nervosa, psychiatric disorders and neurogenic diseases. The aim of our study was to evaluate levels of plasma nesfatin-1 among patients presenting with coronary artery disease and the correlation between nesfatin-1 levels and other clinical parameters. Fasting plasma levels of nesfatin-1 were tested in 48 acute myocardial infarction (AMI) patients, 74 stable angina pectoris (SAP) patients and 34 control subjects. All of them were examined by coronary angiography. The severity of coronary atherosclerosis was assessed using the Gensini score. Plasma nesfatin-1 levels were significantly lower in AMI group than SAP group or control group (0.91 ± 0.08 ng/mL vs. 0.98 ± 0.19 ng/mL and 1.09 ± 0.39 ng/mL, respectively, P < 0.05). In AMI patients, plasma nesfatin-1 levels were negatively correlated with high-sensitivity C-reactive protein, neutrophil% or Gensini scores. Such information implies that lower nesfatin-1 concentration may play a very important role in the development of AMI.     

Influence of organic systems on milk fatty acid profile and CLA in goats

The effect of organic system on the fatty acid profile of milk and CLA content was evaluated using 30 pregnant pluriparous goats, divided into two homogeneous groups (S and O) of 15 goats each. Group S was housed in a stable and received alfalfa hay as forage, while group O was raised according EC Regulation 834/2007 and led to pasture. After the kids weaning, goats were milked twice a day for 5 months. Daily milk yield was recorded and, monthly, representative milk samples from the two daily milkings were analysed for chemical and fatty acid profile. Average milk yield did not differ statistically between the groups. The goats of the O group had significantly higher fat content in milk than those of group S (65.9 g/day vs. 54.3 g/day, P < 0.01). Among milk fatty acids, organic system significantly affected the percentages of C18:1 c9, C18:1 t11, linoleic acid, alpha-linolenic acid, monounsaturated fatty acid and polyunsaturated fatty acid. Organic system highly influenced the c9 t11 conjugated linoleic acid (CLA) (0.810 g/100 g of fat vs. 0.542 g/100 g of fat, for groups O and S, respectively, P < 0.01), t10 c12 CLA (0.041 g/100 g of fat vs. 0.024 g/100 g of fat, for groups O and S, respectively, P < 0.01) and ∑CLA (0.87 g/100 g of fat vs. 0.58 g/100 g of fat for groups O and S, respectively, P < 0.01) concentrations of milk.     

Vitamin D-Binding Protein in Healthy Pre- and Postmenopausal Women: Relationship with Estradiol Concentrations

Objective: To examine the relationship between endogenous serum estradiol and vitamin D–binding protein (DBP) and total, free, and bioavailable 25-hydroxyvitamin D (25OHD) concentrations in pre- and postmenopausal women.Methods: In 165 healthy women (ages, 26 to 75 years) not taking any form of exogenous estrogen, the serum concentrations of estradiol, 25OHD, DBP, parathyroid hormone, and albumin were measured. Free and bioavailable 25OHD (free + albumin-bound) levels were calculated from total 25OHD, DBP, and serum albumin levels.Results: Premenopausal women had higher serum 25OHD (31.5 ± 7.9 ng/mL), DBP (45.3 ± 6.2 mg/dL), and estradiol (52.8 ± 35.0 pg/mL) levels than postmenopausal women (26.5 ± 4.9 ng/mL, 41.7 ± 5.7 mg/dL, and 12.9 ± 4.9 pg/mL), respectively. In addition, the calculated free and bioavailable 25OHD levels were higher in prethan postmenopausal women (P<.05). Serum estradiol correlated with DBP (r = 0.22; P<.01) and total 25OHD (r = 0.27; P<.01). In multivariate regression models (with or without serum 25OHD), estradiol was independently associated with DBP (P<.05).Conclusion: Lower estradiol level is one of the factors that contribute to lower DBP levels in older women. Our data indicate that besides well-known factors such as age, gender, and race, serum estradiol concentrations are also a physiologic predictor of DBP concentration.Abbreviations: 25OHD = 25-hydroxyvitamin D BMI = body mass index CV = coefficient of variation DBP = vitamin D–binding protein PTH = parathyroid hormone SHBG = sex hormone–binding globulin     

Mn and Cu concentrations in mixed saliva of elementary school children in relation to sex,age, and dental caries

To examine the standard Mn and Cu concentrations in mixed saliva from children and the relationship between these levels and dental caries, resting mixed saliva samples obtained from 527 children of an elementary school in Kitakyushu City were collected at 10:00–11:30 a.m. during December 2004. The Mn and Cu concentrations were determined using simultaneous multi-element atomic absorption spectrometry. The standard Mn and Cu levels were 22.0±15.2 and 3.8±4.1 ng/mL, respectively, in the sound teeth group. Mn levels were significantly higher in boys (25.4±17.4 ng/mL) than girls (19.1±12.3 ng/mL) and also higher in upper (25.5±16.4 ng/mL) than lower (19.0±13.5 ng/mL) grades. The Cu level was unaffected by sex and age in the sound teeth group. The Cu level in children with caries experience (5.7±5.3 ng/mL) was significantly higher than that of the sound teeth group. Moreover, the Cu levels in children with untreated caries were significantly higher than that of the sound teeth group, and increased with the number of untreated teeth. No significant difference was found in the Cu concentrations between the group in which all decayed teeth were treated and the sound teeth group. The Mn levels were similar with or without caries and treatment. These findings indicate that the Mn level in mixed saliva depended on sex and age, and suggest the possibility of Cu dissolving into mixed saliva by demineralization due to dental caries.     

Performance of Toggenburg dairy goats in smallholder production systems of the eastern highlands of Kenya

The use of exotic dairy goats in breeding programmes for smallholder production systems is popular in Eastern Africa. However, information on the performance of exotic breeds within these systems is scarce. This paper presents information on performance of Toggenburg dairy goats under smallholder production systems in a medium to high agricultural potential environment in Kenya under a community-based set-up as part of the characterization of its adaptive and productive attributes. Environmental factors affecting growth of 646 goats born in the environment, and fertility and milk production of 160 does from 1997 to 2005 were evaluated. Genetic parameters were also estimated for early growth traits. The average birth weight (BW) for 607 kids was 3.27 kg. Corrected weaning weights (CW), and average daily gain to weaning (ADG) for 646 kids were 19.12 kg and 136 g/day, respectively. The results indicated that the smallholder farmers were able to maintain comparably high levels of milk production in the first three parities (LMY), with yields of 475 ± 9 l in 201 days for 160 does in the first parity, 507 ± 9 l in 264 days from 130 does in the second parity and 513 ± 13 l in 296 days for 82 does in the third parity. Kidding intervals though initially long decreased with time to reasonable levels (302 ± 117 days). The heritability estimates obtained were low (0.23 ± 0.13 for BW, 0.18 ± 0.11 for CW and 0.14 ± 0.11 for ADG). Genetic correlations between the traits were also low. Genetic and phenotypic trends indicated little change in BW, CW and LMY over the years. The phenotypic trend in the kidding interval showed a reducing interval over time. The results demonstrated that the Toggenburg goats were able to perform and thrive reasonably well under the low-input farming conditions.     

A sensitive LC–MS/MS method for quantification of a nucleoside analog in plasma: Application to in vivo rat pharmacokinetic studies

A LC–MS/MS method was developed and validated for determination of nucleoside analog (NA) in rat plasma. The method run time was 6 min and the limit of quantification (LOQ) was estimated at 100 pg/mL. The extraction procedure consisted on plasma samples protein precipitation with an acetonitrile solution which contained the stable isotope labeled internal standard (IS). Chromatography was performed on a newly developed C₁₆ column (150 mm × 4.6 mm, 5 μm) in order to avoid the use ion pair salts. The samples were eluted at 0.8 mL/min with a gradient of mobile phase made of water and acetonitrile both acidified with 0.5% acetic acid and 0.025% trifluoroacetic acid (TFA). A tandem mass spectrometer was used as a detector for quantitative analysis. Intra-run and inter-run precision and accuracy within ±15% were achieved during a 3-run validation for quality control samples at four concentration levels in rat plasma, over a concentration ranging between 0.1 and 1000 ng/mL. The data indicate that our LC–MS/MS assay is an effective method for the pharmacokinetics study of NA in rat plasma.     

Influencia del inmunoensayo empleado en la determinación de vitamina D sérica

IntroductionSerum 25-hydroxyvitamin D [25(OH)D] levels are the best indicator of vitamin D levels in the body. Precision, reproducibility, and lack of standardization are the main problems in such measurements. The aim of this study was to compare the 25(OH)D levels measured using Elecsys Vitamin D Total (Roche) and ADVIA Centaur Vitamin D Total (Siemens).Material and methods25(OH)D levels were tested in 166 patients using both methods. Patients were subsequently divided into two groups: a «supplemented group» consisting of patients receiving vitamin D supplements, and an «untreated group» consisting of the rest of patients.Results25(OH)D mean levels measured by the Roche and Siemens methods in the overall group were 33.6 ± 16.0 and 19.8 ± 12.4 ng/mL respectively. 54.2% of patients were receiving vitamin D supplements. In this group, mean 25(OH)D levels measured by the Roche and Siemens methods were 40.6 ± 14.5 and 25.4 ± 13.1 ng/mL respectively. In the untreated group, the respective values were 24.9 ± 13.2 and 12.8 ± 6.6 ng/mL. Prevalence of vitamin D deficiency (serum 25(OH)D levels less than 20 ng/mL) was higher in samples analyzed using the Siemens method (60.2%) as compared to those tested using the Roche method (23.5%).ConclusionThe assays evaluated are not comparable to each other. Laboratory specialists should inform clinicians of the features of the method used for measuring 25(OH)D because this will have a direct impact on interpretation of the results and medical decisions.     

Improvement in Pancreatic β-Cell Function with Vitamin D and Calcium Supplementation in Vitamin D-Deficient Nondiabetic Subjects

ObjectiveThere are varied reports on the effect of vitamin D supplementation on β-cell function and plasma glucose levels. The objective of this study was to examine the effect of vitamin D and calcium supplementation on β-cell function and plasma glucose levels in subjects with vitamin D deficiency.MethodsNondiabetic subjects (N = 48) were screened for their serum 25-hydroxyvitamin D (25-OHD), albumin, creatinine, calcium, phosphorus, alkaline phosphatase, and intact parathyroid hormone (PTH) status. Subjects with 25-OHD deficiency underwent a 2-hour oral glucose tolerance test. Cholecalciferol (9,570 international units [IU]/day; tolerable upper intake level, 10,000 IU/day; according to the Endocrine Society guidelines for vitamin D supplementation) and calcium (1 g/day) were supplemented.ResultsThirty-seven patients with 25-OHD deficiency participated in the study. The baseline and postvitamin D/calcium supplementation and the difference (corrected) were: serum calcium, 9 ± 0.33 and 8.33 ± 1.09 mg/dL (− 0.66 ± 1.11 mg/dL); 25-OHD, 8.75 ± 4.75 and 36.83 ± 18.68 ng/mL (28.00 ± 18.33 ng/mL); PTH, 57.9 ± 29.3 and 36.33 ± 22.48 pg/mL (− 20.25 ± 22.45 pg/mL); fasting plasma glucose, 78.23 ± 7.60 and 73.47 ± 9.82 mg/dL (− 4.88 ± 10.65 mg/dL); and homeostasis model assessment-2–percent β-cell function C-peptide secretion (HOMA-2–%B C-PEP), 183.17 ± 88.74 and 194.67 ± 54.71 (11.38 ± 94.27). Significant differences were observed between baseline and post-vitamin D/calcium supplementation serum levels of corrected calcium (Z, − 3.751; P < .0001), 25-OHD (Z, − 4.9; P < .0001), intact PTH (Z, − 4.04; P < .0001), fasting plasma glucose (Z, − 2.7; P < .007), and HOMA-2–%B C-PEP (Z, − 1.923; P < .05) as determined by Wilcoxon signed rank test. Insulin resistance as measured by HOMA was unchanged.ConclusionOptimizing serum 25-OHD concentrations and supplementation with calcium improves fasting plasma glucose levels and β-cell secretory reserve. Larger randomized control studies are needed to determine if correction of 25-OHD deficiency will improve insulin secretion and prevent abnormalities of glucose homeostasis. (Endocr Pract. 2014;20:129-138)     

Serum cytokine profiles of Khorasan veterans 23 years after sulfur mustard exposure

Sulfur mustard (SM) is an incapacitating chemical warfare agent that was used against Iranian soldiers during the period from 1983 to 1988. We have investigated serum cytokines profiles of Khorasan veterans who were exposed to SM >23 years earlier. Forty-four male Iranian veterans who had >40% disabilities due to delayed complications of SM poisoning and had disabilities were investigated. A total of 30 healthy male volunteers (relatives of the veterans) were selected as the control group. Cytokine levels were measured in the serum of case and control subjects using commercial ELISA kits. Hematologic parameters (white/red blood cell counts, hemoglobin levels, immune cell differentials) were also performed on blood samples from the study subjects. The results indicated that serum levels of ICAM-1 were significantly higher in the samples from SM-exposed veterans (772.8 [±15.1] ng/ml [p = 0.014] vs. control values of 710.2 [±20.0] ng/ml). On the other hand, serum IL-1β, IL-8 levels and TNFα, were significantly lower for the veterans than the controls (IL-1β: 3.8 [±0.1] vs. 4.3 [±0.2] pg/ml, p = 0.037; IL-8: 21.0 [±6.1] vs. 84.6 [±20.3] pg/ml, p = 0.002; TNFα: 4.5 [±0.1] vs. 5.5 [± 0.1] pg/ml, p = 0.027). Levels of other assayed cytokines, e.g., IL-2, -4, -5, -6, -10, and -12, IFNγ, TNFβ, and sVCAM-1 were not significantly different between the study populations. None of the assayed hematologic parameters appeared to differ as well. It seems possible that dysfunctions could have been induced in the innate immune functions of the SM-exposed veterans as a result of these changes in cytokine expression and that these, in turn, may have contributed to the increased incidence of a myriad of diseases that have been documented in these veterans, including cancers. Future studies must focus on examining the significance of these changes in circulating cytokines and their potential contribution to the development of different diseases in veterans exposed to SM.     

Necrotic cell death and suppression of T-cell immunity characterized acute liver failure due to drug-induced liver injury

Background & aims: The aim of this study was to investigate the clinical characteristics and pathophysiology of drug-induced liver injury (DILI) – acute liver failure (ALF). Methods: The patients with acute liver injury (ALI) including ALF from 2009 to 2014 were analyzed. The hepatic encephalopathy (HE) development rate was compared with the findings from a national survey in Japan. The serum cytokines levels and the findings of a liver function test were evaluated in the DILI patients. Results: The HE development rate substantially decreased for autoimmune hepatitis (AIH) – and undetermined cause-induced ALI owing to the early prediction system, but not in DILI-ALI. Among the DILI-ALF and AIH-ALF cases, the CK-18 fragment (1480.1 U/L, 3945.4 U/L), IL-8 (82.9 pg/mL, 207.5 pg/mL), IP-10 (1379.6 pg/mL, 3731.2 pg/mL) and MIP-1β (1017.7 pg/mL, 2273.3 pg/mL) levels were lower in the DILI-ALF cases. Among the DILI-ALI and DILI-ALF cases, IL-4 (19.8 pg/mL, 25.4 pg/mL) and RANTES (14028.0 pg/mL, 17804.7 pg/mL) were higher in DILI-ALI, and HMGB-1 (397.1 pg/μL, 326.2 pg/μL) and HGF (2.41 ng/mL, 0.55 ng/mL) were higher in DILI-ALF. We observed that HGF independently associated with DLI-ALF development. Conclusions: Despite the low grade apoptosis and inflammation, DILI patients progressed to ALF comparable with that of the AIH patients.     

Gomesin acts in the immune system and promotes myeloid differentiation and monocyte/macrophage activation in mouse

Due to the cytotoxic effect of antimicrobial peptides (AMP) against several microorganism and tumor cells has been proposed their association with the immune system. However, just a few reports have shown this relationship. In this study, mice were treated with gomesin, a β-hairpin AMP that exhibit high cytotoxicity against bacterial and tumor cells. Different effects in the immune system were observed, such as, decrease of CD3⁺ in T lymphocytes (Control: 17.7 ± 1.4%; Gomesin: 7.67 ± 1.2%) and in hematopoietic progenitors and increase of hematopoietic stem cell (Control: 0.046 ± 0.004%; Gomesin: 0.067 ± 0.003%), B220⁺ B lymphocytes (Control: 38.63 ± 1.5%; Gomesin: 47.83 ± 0.48%), and Mac-1⁺F4/80⁺ macrophages (Control: 11.76 ± 3.4%; Gomesin: 27.13 ± 4.0%). Additionally, macrophage increase was accompanied by an increase of macrophage phagocytosis (Control 20.85 ± 1.53; Gomesin 31.32 ± 1 Geometric mean), interleukin 6 (Control: 47.24 ± 1.9 ng/mL; Gomesin: 138.68 ± 33.68 ng/mL) and monocyte chemoattractant protein-1 (Control: 0.872 ± 0.093 ng/mL; Gomesin: 1.83 ± 0.067 ng/mL). Thus, this report showed immunomodulatory activity of gomesin in the immune system of mice.     

Assessment of the reproductive parameters,laparoscopic oocyte recovery and the first embryos produced in vitro from endangered Canindé goats (Capra hircus)

The Canindé breed of goats (Capra hircus) is currently endangered. The aims of this study were to characterize the estrus behavior, ovulatory responses and progesterone profiles, and to evaluate the in vitro embryo production (IVP) in this breed. In Experiment 1, ten nulliparous and seven pluriparous females received medroxyprogesterone acetate (MAP)-containing sponges (60 mg) plus 75 μg d-cloprostenol for estrus synchronization and their reproductive parameters were evaluated. In Experiment 2, oocytes obtained by laparascopy from hormonally stimulated females (n = 15) were used for IVP. There was no difference (p > 0.05) between nulliparous and pluriparous goats in terms of estrus response (40.0% vs. 85.7%), time from progestagen sponge removal to the onset of estrus (62.0 ± 15.5 vs. 50.7 ± 19.2 h; mean ± SEM), duration of estrus (25.0 ± 16.1 vs. 30.0 ± 15.1 h), percentage of ovulating animals (60.0% vs. 85.7%), number of ovulations (1.2 ± 0.4 vs. 1.3 ± 0.8), and diameter of the preovulatory follicle (5.8 ± 0.5 vs. 6.1 ± 0.3 mm). Progesterone concentrations were also similar (p > 0.05) in both groups. During laparoscopic recovery, there were average 12.2 aspirated follicles and 9.1 oocytes per goat, resulting in a high recovery rate (74.3%, 182/245). A total of 78 embryos were produced (51.0%). The mean number of cells in the blastocysts at day 7 of in vitro culture was 170.3 ± 12.5. In conclusion, nulliparous and pluriparous Canindé goats exhibited similar reproductive profiles. It was possible to produce embryos in vitro, allowing the instigation of an embryo bank for preservation of this breed.     

Signals from fat after injury: Plasma adipokines and ghrelin concentrations in the severely burned

IntroductionHypermetabolism is universal in the severely burned and is characterized by catabolism of lean mass and body fat with associated insulin resistance. Adipokines are likely to play a role in these changes but have not been identified to date in burn patients.MethodsFrom a single burn ICU, 17 burn patients with an expected stay >14 days were studied. Study period began within 14 days of admission. Over 7 days, plasma samples were collected for measurement of leptin, adiponectin, resistin, ghrelin, insulin, and cortisol by ELISA. For comparison, samples from 15 healthy controls of similar age, BMI, and blood glucose were obtained.ResultsMean age was 33 ± 17 years and BMI 26 ± 3.4. Average burn size was 45 ± 20% TBSA and ISS 32 ± 10 with 72% having inhalation injury; in-hospital mortality was 29%. Estimated energy needs were 3626 ± 710 kcal, of which 84 ± 21% were met by enteral feeding with intensive insulin treatment (glucose 80–110 mg/ml). Using the homeostasis model assessment of insulin resistance, burned subjects were more resistant than controls (17 ± 11.3 and 8 ± 10.0). Insulin levels were elevated (57 ± 35.6 μU/ml in burned subject vs. 26 ± 31.1 μU/ml in controls), and cortisol concentrations increased (50 ± 41.2 μg/dl vs. 12 ± 3.9 μg/dl). These traditional hormone changes were associated with increased resistin (16.6 ± 5.5 ng/ml vs. 3.8 ± 0.9 ng/ml) and decreased leptin (8.8 ± 8.9 ng/ml vs. 19.4 ± 23.5 ng/ml), adiponectin (9 ± 3.5 ng/ml vs. 17 ± 10.2 ng/ml), and ghrelin (0.37 ± 0.14 ng/ml vs.0.56 ± 0.26 ng/ml).ConclusionPatients with burns, who are characteristically hypermetabolic with hypercortisolism and insulin resistant, have significant changes in adipokine levels that appear independent of the magnitude of initial injury or metabolic derangement. In addition, suppression of ghrelin in the presence of decreased leptin and adiponectin levels in combination with increased insulin and resistin levels represent unexpected changes in the metabolic milieu of the injured patient possibly due to dramatic activation of inflammatory pathways, indicating strategies for treatment.     

Repeated lipopolysaccharide exposure causes corticosteroid insensitive airway inflammation via activation of phosphoinositide-3-kinase δ pathway

Corticosteroid resistance is one of major barriers to effective management of chronic inflammatory respiratory diseases, such as chronic obstructive pulmonary disease (COPD) and severe asthma. These patients often experience exacerbations with viral and/or bacterial infection, which may cause continuous corticosteroid insensitive inflammation. In this study, we observed that repeated exposure of lipopolysaccharide (LPS) intranasally attenuated the anti-inflammatory effects of the corticosteroid fluticasone propionate (FP) on neutrophils and CXCL1 levels in bronchoalveolar lavage (BAL) fluid in an in vivo murine model. Histone deacetylase-2 (HDAC2) and NF-E2 related factor 2 (Nrf2) levels in lungs after LPS administration for 3 consecutive days were significantly decreased to 38.9±6.3% (mean±SEM) and 77.5±2.7% of the levels seen after only one day of LPS exposure, respectively. In addition, 3 days LPS exposure resulted in an increase of Akt phosphorylation, indicating activation of the phosphoinositide-3-kinase (PI3K) pathway by 4-fold in lungs compared with 1 day of exposure. Furthermore, combination treatment with theophylline and FP significantly decreased the neutrophil accumulation and CXCL1 concentrations in BAL fluid from 22.5±1.8×10⁴ cells/mL and 214.6±20.6 pg/mL to 7.9±0.5×10⁴ cells/mL and 61.9±13.3 pg/mL, respectively. Combination treatment with IC87114, a selective PI3Kδ inhibitor, and FP also significantly decreased neutrophils and CXCL1 levels from 16.8±0.7×10⁴ cells/mL and 182.4±4.6 pg/mL to 5.9±0.3×10⁴ cells/mL and 71.4±2.7 pg/mL, respectively. Taken together, repeated exposure of LPS causes corticosteroid-insensitive airway inflammation in vivo, and the corticosteroid-resistance induced by LPS is at least partly mediated through the activation of PI3Kδ, resulting in decreased levels of HDAC2 and Nrf2. These findings provide a potentially new therapeutic approach to COPD and severe asthma.