The Selective NMDA Receptor GluN2B Subunit Antagonist CP-101,606 with Antidepressant Properties Modulates Cytochrome P450 Expression in the Liver

Recent research indicates that selective NMDA receptor GluN2B subunit antagonists may become useful for the treatment of major depressive disorders. We aimed to examine in parallel the effect of the selective NMDA receptor GluN2B subunit antagonist CP-101,606 on the pituitary/serum hormone levels and on the regulation of cytochrome P450 in rat liver. CP-101,606 (20 mg/kg ip. for 5 days) decreased the activity of CYP1A, CYP2A, CYP2B, CYP2C11 and CYP3A, but not that of CYP2C6. The alterations in enzymatic activity were accompanied by changes in the CYP protein and mRNA levels. In parallel, a decrease in the pituitary growth hormone-releasing hormone, and in serum growth hormone and corticosterone (but not T3 and T4) concentration was observed. After a 3-week administration period of CP-101,606 less changes were found. A decrease in the CYP3A enzyme activity and protein level was still maintained, though no change in the mRNA level was found. A slight decrease in the serum concentration of corticosterone was also maintained, while GH level returned to the control value. The obtained results imply engagement of the glutamatergic system in the neuroendocrine regulation of cytochrome P450 and potential involvement of drugs acting on NMDA receptors in metabolic drug–drug interactions.

Cycled Lighting Versus Continuous Near Darkness in Preterm Infants: A Randomized Controlled Trial

ABSTRACT Objective To compare the effectiveness of cycled lighting (CL) or continuous near darkness (CND) on weight in preterm infants. Study Design Total 147 infants with a gestational age 25–32 weeks and/or a birth weight 750–1500 g were included in the study. The infants were classified into two groups: CL and CND. Weight on postnatal day 14, weight at corrected 35 weeks, mean rectal temperature and serum growth hormone, cortisol, melatonin levels at 35 weeks’ post menstrual age (PMA), weekly weight gain, full enteral feeding time, duration of mechanical ventilation, retinopathy of prematurity (ROP), length of stay in the hospital, weight and length at three and six months corrected age were compared between the groups. Results There were no differences between weights on postnatal day 14. Anthropometric parameters and mean rectal temperatures of groups also were not different at 35 weeks’ PMA. There were no differences among the groups in duration of full enteral feeding time, length of stay in hospitalization, duration of mechanical ventilation, ROP and anthropometric parameters. Further, serum growth hormone, cortisol, and melatonin levels were similar between the groups at 35 weeks’ PMA. Conclusion CL and CND did not have any advantages over each other.

The acute effect of resistance exercise on serum growth hormone and blood glucose in healthy non-obese adolescent subject

Background: The growth hormone (GH) response to resistance training is altered by many factors including sex steroid concentrations, fitness, intensity of exercise, age, gender, duration of exercise and glycemic state but the exact understanding of the interplay of different exercises to GH levels and its induced physiological adaptations is still obscure. This study aimed to see how resistance exercise affects GH levels and its correlation to plasma glucose levels in healthy non-obese adolescent subjects.Methods: 48 healthy non-obese adolescent subjects, 24 males and 24 females were included in the study. High volume exercise training regimen was used which involved major muscle group of arms, legs and trunk. Pre and post exercise levels of serum GH and random blood sugar were estimated in male and female groups.Results: The mean body mass index (BMI) of male and female groups was 23.22±3.12 kg/m2 and 20.40±4.49 kg/m2, respectively. The post-exercise serum GH levels in male and females increased significantly by 0.54±1.041 ng/ml (p<0.05) and 0.85±1.023 ng/ml (p<0.001) respectively. The random blood sugar levels in males after exercise significantly increased (p<0.05) by 7.16±12.61 mg/dl and in females by 6.20±12.09 mg/dl (p<0.05). There was significant correlation (p<0.05) between increase in serum GH levels and increase in random blood sugar levels in both male and female group.Conclusions: Exercise induced increase in GH and its interplay with serum glucose can be better gained access into via metanalytical/elaborate studies of the major hormones and fuels involved.

The effect of 8 weeks swimming training on secretion of growth hormone in 9-11 years old boys

The influence of exercise training on anabolic hormones is especially important for growth and development in childhood years. The aim of this study was determine effect of 8 weeks of swimming training on secretion of growth hormone in 9-11 years old boys. To test the research hypothesis, the people who were willing to cooperate with the investigator randomly assigned to experimental group (n=15: age: 9.33±0.30, height: 130.46±7.53, weight: 27.04±7.39) and control group (n=15: age: 9.39±0.39, height: 133.53±7.52, weight: 27.15±4.92). Experimental group participated in 8 weeks swimming training with intensity of 45-65% HRmax for 3 times per week and 1 hour per session. During this time control group did not participate in this protocol and continue to routine activity. Fasting blood sample were collected 48 hours before and after of 8 weeks swimming training to assess serum growth hormone. 8 weeks swimming training led to significant increase on growth hormone in experimental group (P= 0.000). But increase growth hormone in control group not significant (P= 0.383). In result, 8 week of swimming training led to significant increase on secretion growth hormone in 9-11 years old boys.

Nursing piglet ionomics-metabolome responses to different dietary copper levels in antibiotic-free creep feed

Background: Ionomics is a novel method to investigate the mechanism underlying the cross-talk and homeostasis of trace elements in animals. Research has not yet determined the composition and distribution of trace elements in piglets and their variations under diverse dietary high-level copper. Results: In this study, the growth performance was calculated from 180 nursing piglets which access to antibiotic-free creep feed including different copper level: 6, 20, and 300 mg·kg-1 Cu (CuSO4), and offered ad libitum from d 14 until weaning at 40 days of age. In HC (300 mg·kg-1 Cu ) group, the average daily gain (ADG) and average daily feed intake (ADFI) increased during d 14 to 28, but ADG was decreased with extension of feeding time (d 29 to 40). The ionomics profiles (hair, serum, and feces) and the correlations with serum and fecal metabolites were further analyzed. The hair Na, K, Cu, and fecal Cu concentrations were increased in HC group than other groups. The hair Na and K were negatively correlated with serum TNF-α and fecal inosine, while positively correlated with serum insulin-like growth factors-1 (IGF-1); the hair Cu was negatively correlated with serum malondialdehyde (MDA), total bile acid (TBA) and fecal putrescine, glucose-6-phosphate, fumaric acid; the fecal Cu was positively correlated with serum growth hormone, negatively correlated with fecal methionine, pantothenic acid, and uracil. Further metabolic pathway enrichment analysis showed that the hair Cu was negatively correlated with phenylalanine and tyrosine metabolism and mitochondrial electron transport chain pathways; fecal Cu was negatively correlated with betaine metabolism, and pantothenate, and CoA biosynthesis pathways. Conclusions: Dietary 300 mg·kg-1 copper promoted growth in the short term, and altered the ion balance, further affected the metabolic homeostasis, harm to the health of piglets; dietary 20 mg·kg-1 copper maintain ion homeostasis due to preservation of the interactions between macro and micro elements and suitable to meet the nutritional needs of nursing piglets. These results may benefit people to understand the molecular mechanism of ionomics effects on human and piglets’ health.

The Protective Role of Alpha-Ketoglutaric Acid on the Growth and Bone Development of Experimentally Induced Perinatal Growth-Retarded Piglets

The effect of alpha-ketoglutaric acid (AKG) supplementation to experimentally-induced, perinatal growth-retarded piglets was examined. Sows were treated with a synthetic glucocorticoid (Gc) during the last 25 days of pregnancy, and after the birth, piglets were randomly divided into three groups depending on the treatment. The Gc/Gc + AKG and Gc/AKG groups born by Gc-treated sows after the birth were treated with Gc or Gc + AKG for 35 days. Significantly lower serum growth hormone, IGF-I, osteocalcin, leptin, and cortisol concentrations were observed in the Gc/Gc + AKG group, while the bone alkaline phosphatase activity was significantly higher. Serum insulin concentration was higher in the control group. Serum alanine, lysine, histidine, and tryptophan concentrations were higher in the Gc/Gc + AKG and Gc/AKG groups. The perinatal action of Gc significantly affects histomorphometry of articular cartilage and trabecular bone and bone mechanics. The results clearly showed that dietary AKG had positive effects with regards to the profile of free amino acids. Taking into account the function of AKG as an energy donor and stimulator of collagen synthesis, it can be concluded that the anabolic role of AKG may be the main mechanism responsible for its protective effect against the GC-induced perinatal intensified catabolic state.

Measuring IGF-1 and IGFBP-3 profiles in women seeking assisted reproduction; relationship to serum growth hormone levels (Study 3)

Extending from our first two studies examining the IGF profile (IGF-1, IGFBP-3 and the ratio of IGFBP-3/ IGF-1) in women presenting for assisted reproductive technologies (ART), this study examines its relevance to the testing of human growth hormone (hGH) levels on the same blood sample. These were taken in the morning during the early follicular phase of the woman’s menstrual cycle and included 408 women who were ART-naïve, undertaking the tests as part of an assessment cycle prior to any ART treatment. The growth hormone levels were also tested on a further 945 women classified as ART-interval cases. It was shown that the vast majority of hGH levels (73%) were very low at <1.0 ng/mL and 22% are extremely low <0.1 ng/mL, close to the detection level of the chemiluminescent immunoassay (0.03 ng/mL). Only 12% of hGH levels were recorded in the range ≥3.0 ng/mL, levels which exclude adult growth hormone deficiency (AGHD). Although IGF-1 levels are regarded as a screening test for AGHD, our studies showed no correlation between hGH levels and the entire range of IGF-1 levels, neither across IGFBP-3 levels, nor across IGF Ratios, albeit there was an apparent inverse trend for the latter. Across the entire age range, the hGH levels were not statistically different among neither the ART-naïve nor the ART-interval women. Furthermore, hGH levels were not different among the clinical parameters of stature or BMI; nor for ovarian reserve parameters AMH or AFC. It is concluded that serum hGH screening probably has very limited value as a screening test for potential AGHD.

A case of Luscan-Lumish syndrome: Possible involvement of enhanced GH signaling

Context Luscan-Lumish syndrome (LLS) is characterized by postnatal overgrowth, obesity, Chiari I malformation, seizures, and intellectual disability. SET domain-containing protein 2 (SETD2) is a histone methyltransferase, where mutations in the gene are associated with the development of LLS. However, mechanisms underlying LLS remain unclear. Case description A 20-year-old man was referred to our hospital because of tall stature. His body height was 188.2 cm (+3.18 SD) and he showed obesity with a body mass index of 28.4 kg/m 2. He exhibited acral overgrowth, jaw malocclusion, and prognathism, but no history of seizures, intellectual disability, or speech delay. Serum growth hormone (GH), insulin-like growth factor 1 (IGF-1), and nadir GH levels after administration of 75 g oral glucose were within normal range. Pituitary magnetic resonance imaging showed no pituitary adenoma, but Chiari I malformation. Whole exome sequencing analysis of the proband revealed a de novo heterozygous germline mutation in SETD2 (c.236T&gt;A, p.L79H). Skin fibroblasts derived from the patient grew faster than those from his father and the control subject. In addition, these cells showed enhanced tyrosine phosphorylation and transcriptional activity of signal transducer and activator of transcription 5b (STAT5b) and increased IGF-1 expression induced by GH. Conclusion This is a mild case of LLS with a novel mutation in SETD2 without neurological symptoms. LLS should be differentiated in a patient with gigantism without pituitary tumors. Although further investigation is necessary, this is the first study to suggest the involvement of aberrant GH signaling in the development of LLS.

Ocular manifestations of de-Morsiers syndrome

A two-year old male child presented to the ophthalmology outpatient department (OPD) with parents complaining of child’s inability to make an eye contact. On examination, the patient had horizontal manifest nystagmus with no fixing and following. The pupillary reactions and the anterior segment examination were normal. Fundus examination in both eyes revealed small optic disc with 360 degree hyperpigmented ring in both the eyes (Figure 1 A and B). The macula was >2 disc diameter (DD) in distance from optic disc, suggestive of optic nerve hypoplasia. Magnetic resonance imaging (MRI) brain showed absent septum pellucidum (Figure 1 C and D). Serum growth hormone levels were significantly high. Based on the examination and investigations, diagnosis of de Morsier’s syndrome was made.