Plasma IGF-I Research Articles

In Vivo Effects of a GHR Synthesis Inhibitor during Prolonged Treatment in Dogs

Background: The activation of the growth hormone receptor (GHR) is a major determinant of body growth. Defective GHR signaling, as seen in human Laron dwarfism, resulted in low plasma IGF-1 concentrations and limited growth, but also marked absence in the development of breast cancer and type 2 diabetes. In vitro, we identified a small molecule (C#1) that inhibits the translation of GHR mRNA to receptor protein. Methods: Before its application in humans as a potential anticancer drug, C#1 was tested in animals to evaluate whether it could be administered to achieve a plasma concentration in vivo that inhibits cell proliferation in vitro without causing unwanted toxicity. To evaluate the efficacy and toxicity of C#1, a group of six intact female Beagle dogs was treated daily each morning for 90 days with an oral solution of C#1 in Soiae oleum emulgatum at a dose of 0.1 mg/kg body weight. During treatment, dogs were closely monitored clinically, and blood samples were taken to measure plasma C#1 concentrations, complete blood counts (CBC), clinical chemistry, and endocrinology. At the end of the treatment, dogs were euthanized for gross and histopathological analysis. An additional group of six female Beagle dogs was included for statistical reasons and only evaluated for efficacy during treatment for 30 days. Results: Daily administration of C#1 resulted in a constant mean plasma concentration of approximately 50 nmol/L. In both groups, two out of six dogs developed decreased appetite and food refusal after 4–5 weeks, and occasionally diarrhea. No significant effects in CBC or routine clinical chemistry were seen. Plasma IGF-1 concentrations, used as biomarkers for defective GHR signaling, significantly decreased by 31% over time. As plasma growth hormone (GH) concentrations decreased by 51% as well, no proof of GHR dysfunction could be established. The measured 43% decrease in plasma acylated/non-acylated ghrelin ratios will also lower plasma GH concentrations by reducing activation of the GH secretagogue receptor (GHSR). C#1 did not directly inhibit the GHSR in vivo, as shown in vitro. There were no significant effects on glucose, lipid, or folate/homocysteine metabolism. Conclusions: It is concluded that with daily dosing of 0.1 mg C#1/kg body weight, the induction of toxic effects prevented further increases in dosage. Due to the concomitant decrease in both IGF-1 and GH, in vivo inhibition of GHR could not be confirmed. Since the concept of specific inhibition of GHR synthesis by small molecules remains a promising strategy, searching for compounds similar to C#1 with lower toxicity should be worthwhile.

Effect of Time-Restricted Eating on Circulating Levels of IGF1 and Its Binding Proteins in Obesity: An Exploratory Analysis of a Randomized Controlled Trial

Obesity is associated with alterations in circulating IGF1, IGF1-binding proteins (IGFBPs), insulin, inflammatory markers, and hormones implicated in cardiovascular disease, diabetes, cancer, and aging. However, the effects of 4 and 6 h time-restricted eating (TRE) on circulating IGF1 and IGFBPs is uncertain. Objective: This study aimed to investigate the effects of TRE on plasma IGF1, IGFBP1, IGFBP2, and IGFBP3, and whether these effects were mediated by weight loss or body composition changes. Insulin sensitivity, glucose control, adipokines, and inflammatory markers were also examined. Design: An exploratory analysis of an 8-week randomized controlled trial implementing a daily TRE intervention was carried out. Participants/Setting: This study was conducted at the University of Illinois at Chicago in 2019. Participants with obesity were randomized to 4 or 6 h TRE (n = 35) or a control (n = 14) group. Plasma biomarkers were measured by ELISA at baseline and week 8. In a sub-analysis, participants were stratified into higher- (>3.5%) and lower- (≤3.5%) weight-loss groups. Intervention: Participants fasted daily from 7 p.m. to 3 p.m. in the 4 h TRE group (20 h) and from 7 p.m. to 1 p.m. in the 6 h TRE group (18 h), followed by ad libitum eating for the remainder of the day. Controls received no dietary recommendations. Main outcome measures: IGF1, IGFBPs, hsCRP, and adipokines were the main outcome measures of this analysis. Statistical Analysis: Repeated measures ANOVA and mediation analysis were conducted. Results: Body weight significantly decreased with TRE (−3.6 ± 0.3%), contrasting with controls (+0.2 ± 0.5%, p < 0.001). Significant effects of TRE over time were observed on plasma IGFBP2, insulin, HOMA-IR, and 8-isoprostane levels, without affecting other biomarkers. In the sub-analysis, IGFBP2 increased while leptin and 8-isoprostane decreased significantly only in the “higher weight loss” subgroup. Changes in insulin and HOMA-IR were related to TRE adherence. Conclusions: Eight-week daily 4 to 6 h TRE did not affect IGF1, IGFBP1, or IGFBP3 levels but improved insulin, HOMA-IR, and 8-isoprostane. IGFBP2 increased and leptin decreased when weight loss exceeded 3.5% of baseline.

Predictive value of IGF-1/IGFBP-3 ratio for thyroid nodules in type 2 diabetic mellitus.

To explore the predictive value of the IGF-1/IGFBP-3 ratio for the presence of thyroid nodules in patients with type 2 diabetes mellitus (T2DM). This observational study prospectively enrolled patients with T2DM at the Second Hospital of Jilin University between May 2021 and January 2022. Thyroid nodule (TN) status was determined by ultrasonography. Receiver operating characteristic (ROC) curve analysis was performed to assess the predictive value of the serum IGF-1/IGFBP-3 molar ratio for TNs. Multivariable logistic regression analysis was conducted to identify risk factors for thyroid nodules in patients with T2DM. A total of 122 patients (mean age ± standard deviation: 52.57 ± 11.71 years; 74 males) were enrolled. 37.7% (n=46) of patients did not have TNs, while 62.3% (n=76) had TNs. The duration of diabetes, age, and HDL-C level were significantly higher in the T2DM group with TNs compared to the group without TNs (all P < 0.05). The area under the ROC curve (AUC) for the combination of IGF-1, IGFBP-3, and the serum IGF-1/IGFBP-3 molar ratio in predicting TNs in T2DM patients was 0.619 (P < 0.001). Additionally, multivariable logistic regression analysis revealed that the duration of diabetes, age, fasting plasma glucose (FPG), fasting insulin (FINS), thyroid-stimulating hormone (TSH), IGF-1, and IGFBP-3 levels were independent risk factors for thyroid nodules, while the serum IGF-1/IGFBP-3 molar ratio level was an independent protective factor for thyroid nodules in patients with T2DM (all P < 0.05). The combination of IGF-1, IGFBP-3, and the serum IGF-1/IGFBP-3 molar ratio may have a better predictive value for TNs in T2DM patients than using any single marker alone. The duration of diabetes, age, FPG, FINS, TSH, IGF-1, IGFBP-3, and the serum IGF-1/IGFBP-3 molar ratio levels were independently associated with thyroid nodules in patients with T2DM.

8539 Curcumin a Double Edged Sword: A Case of Curcumin Induced Pituitary Macroadenoma Apoplexy

Abstract Disclosure: P. Balozian: None. D. Alfakara: None. M. Linz: None. &amp;lt;Curcumin, the active component of turmeric, exerts numerous beneficial anti-inflammatory, antiplatelet, and anticoagulant effects. Recent literature has shown however that curcumin inhibits proliferation and induces apoptosis of pituitary cells. Despite these findings, there are limited clinical cases reporting an association between curcumin and pituitary adenoma apoplexy.We report the case of a 39-year old G9P6A3 female with Hashimoto’s disease and class II obesity who presented with a constant bifrontal excruciating headache, blurry vision, photophobia, and nausea. She also had fatigue and amenorrhea for two years. Her exam showed normal vitals, decreased visual acuity, diplopia, and bitemporal hemianopsia. Data showed a serum prolactin of 69 ug/L , plasma IGF-1 of 133 ng/ml (Z score -0.4), TSH of 2.58 with a free T4 of 0.47 ng/dl [0.61-1.12 ng/dL], a random cortisol of 12.7 mcg/dl despite her stress and pain, ACTH of 27 pg/ml, DHEA-S of 46 mcg/dl, an LH of 0.5 IU/L, and an FSH of 4mIU/ml with an estradiol of 25 pg/ml. MRI of the pituitary revealed a 1.8 cm macroadenoma with a mass effect on the overlying optic chiasm and a T1 intrinsic hyperintense signal indicative of a hemorrhagic component. She was given IV dexamethasone for 24 hours then underwent transsphenoidal resection of the hemorrhagic tumor that resulted in rapid resolution of headaches and visual symptoms. She was not given any glucocorticoids during or after surgery. Labs immediately after surgery revealed a prolactin of &amp;lt;1ug/L and a cortisol of 26.7 mcg/dl. Pathology showed corticotroph tumor with hemosiderin deposition with a 4.2% Ki67 and negative ACTH immunostaining. On medication review, patient had been taking large doses of curcumin. In the absence of other recent precipitating factors, it was highly likely that she had curcumin-triggered apoplexy of a pituitary macroadenoma. Most recent bloodwork, about 20 months from presentation, revealed a serum prolactin of 5.0 ug/L, IGF-1 of 123ng/mL (Z score -0.6), TSH of 0.97 mIU/L with a free T4 of 0.85 ng/dL, a random cortisol of 5.3 ug/dL, ACTH of 18.2 pg/mL, DHEA-S of 94 ug/dL, LH of 2.5 IU/L, FSH of 4.3 IU/L, and an estradiol of 45 pg/mL. Regular menstrual cycles had resumed. Headaches, nausea, and vision abnormalities completely resolved.The case illustrates the need to identify any herbal remedies and supplements a patient is taking, particularly turmeric, as supplements may contribute to increased bleeding tendency of an already existing adenoma. The case also emphasizes the potential rapid recovery of pituitary function after surgical resection of an apoplectic pituitary tumor.&amp;gt; Presentation: 6/3/2024

Injection of antioxidant trace minerals/vitamins into peripartum crossbred cows improves the nutritional and immunological properties of colostrum/milk and the health of their calves under heat stress conditions.

Multimineral and vitamin injections can provide better nutrient availability at the cellular level, which is essential for mitigating transition period stress and improving the wellbeing and productivity of dairy cows. The present study was conducted to assess the colostrum quality and calf health after intramuscular injection of multi-minerals (MM) and multi-vitamins (MV) to peripartum cows during winter (THI = 58 to 66) and summer (THI = 78 to 82) months. In each season, twenty-four pregnant crossbred Karan Fries cows were grouped into four, each consisting of six cows. Group I, referred to as the Control, received solely the basal diet, without any additional supplements. Groups II, III, and IV were administered additional MM (T1), MV (T2), and a combined MM and MV (T3) along with their basal diet, starting 30days before calving and continuing for 30days after calving. Blood samples were collected from the calves, while colostrum/milk samples were obtained from the cows on days 1, 3, 7, and 15 after calving. The somatic cell counts (SCC) in the milk were determined using a cell counter. Cortisol, IgG, IGF1 and total immunoglobulins (TIG) in whey and plasma from cow colostrum/milk or calf blood samples were estimated by ELISA. Cows that calved in the summer exhibited notably reduced levels (P < 0.05) of IgG, milk, and plasma IGF1, along with lower calf body weights, in comparison to those calving in the winter season. Furthermore, the summer months saw significant increases (P < 0.05) in plasma and milk cortisol levels, as well as total somatic cell counts (SCC) in both colostrum and milk samples. Maximum beneficial effect was observed in T3 group. Results indicate that injections to peripartum cows could be an important strategy for improving colostrum quality and calf health during the summer seasons.

Association between metabolic parameters and embryo production in superovulated dairy cattle.

This study aims to investigate the relationship between metabolic parameters and the number of embryos produced in superovulated cows with high genetic characteristics in milk yield. Eighteen Holstein donors were treated with classic superovulation protocols, AI and flushing. During superovulation, decreasing doses of FSH (follicle-stimulating hormone) were administered at 12-h intervals for 4 days. Plasma insulin-like growth factor (IGF1), glucose (GLU), beta-hydroxybutyric acid (BHB), non-esterified fatty acid (NEFA), blood urea nitrogen (BUN) and total protein (TP) levels were determined by using an autoanalyzer. The mixed model analysis of variance was used for statistical analysis. As a result, plasma IGF1, BHB and BUN had significant interactions with both groups and days (p < .05). Additionally, plasma TP-days interactions were significant (p < .05). Furthermore, there was a negative correlation between the number of embryos and plasma BHB levels (p < .05). In conclusion, under appropriate environmental conditions, metabolic profile control of donors can contribute to the embryo production process and to the studies on the metabolic infrastructure.

Preoperative Plasma Insulin-Like Growth Factor-I and Its Binding Proteins-Based Risk Stratification of Patients Treated With Radical Nephroureterectomy for Upper Tract Urothelial Carcinoma

IntroductionWe evaluate the predictive and prognostic value of insulin-like growth factor-I (IGF-1), IGF binding protein-2 (IGFBP-2) and -3 (IGFBP-3) in patients treated with radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). MethodsThis is a retrospective analysis of a multi-institutional database comprising 753 patients who underwent RNU for UTUC and had a preoperative plasma available. Logistic and Cox regression analyses were performed. The discriminative ability and clinical utility of the models was calculated using the lasso regression test, area under receiver operating characteristics curves, C-index, and decision curve analysis (DCA). ResultsLower preoperative plasma levels of IGFBP-2 and -3 independently correlated with increased risks of lymph node metastasis, pT3/4 disease, nonorgan confined disease, and worse recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) (all P ≤ .004). The addition of both IGFBP-2 and -3 to a postoperative multivariable model, that included standard clinicopathologic characteristics, improved the model's concordance index by 10%, 9%, and 8% for RFS, CSS, and OS, respectively. On DCA, addition of both IGFBP-2 and -3 to base models improved their performance for RFS, CSS, and OS by a statistically and clinically significant margin. Plasma IGF-1 was not associated with any of outcomes. ConclusionsWe confirmed that a lower plasma levels of IGFBP-2 and -3 both are independent and clinically significant predictors of adverse pathological features and survival outcomes in UTUC patients treated with RNU. These findings might help guide the clinical decision-making regarding perioperative systemic therapy and follow-up scheduling.

Effects of calving interval of dairy cows on development, metabolism, and milk performance of their offspring

Extending the voluntary waiting period (VWP) for insemination in dairy cows is of interest as a strategy to reduce the frequency of calving events and inseminate at a moment with fewer fertility problems. Little is known about the calves born from dams with a different VWP followed by a different calving interval (CInt). The objective of the current study was to identify the effect of dam's CInt on body condition, metabolic status, and milk production of their offspring from birth until 100 DIM of the offspring's first lactation. Holstein-Friesian dairy cows (n = 154, 41 primiparous, 113 multiparous) were blocked according to parity, milk yield, and SCC and randomly assigned to a VWP of 50, 125, or 200 d. Female calves (n = 62) from cows with different CInt were monitored from birth until their first calving event as heifer. Certain dams were not successfully inseminated soon after the planned VWP, resulting in differences between the intended VWP and the actual CInt. Calves were regrouped according to their dam's actual CInt (CInt_1: 324-408 d; CInt_2: 409-468 d; CInt_3: 469-586 d). The dam's CInt did not affect calf birth weight. From birth to weaning, the calves born to dams in CInt_1 had a higher plasma nonesterified fatty acids (NEFA) concentration (0.34 mmol/L; CI: 0.30, 0.37) than CInt_2 (0.28 mmol/L; CI: 0.26, 0.31) and CInt_3 (0.26 mmol/L; CI: 0.24, 0.29) calves. Calves born to dams with a shorter CInt (CInt_1) had greater IgG and IgM against keyhole limpet hemocyanin (KLH) than CInt_3 (IgG: 6.05 ± 0.30 vs. 4.64 ± 0.30; IgM: 6.45 ± 0.17 vs. 5.89 ± 0.16, respectively; mean ± SE) before weaning. After weaning till calving, CInt_1 calves tended to have greater plasma NEFA concentration than CInt_3-calves. During the first 100 DIM, a longer CInt of the dams resulted in lower plasma IGF_1 (CInt_2), lower milk lactose (CInt_3), and lower fat- and protein-corrected milk (FPCM; CInt_2) in offspring, compared with shorter CInt of the dams (CInt_1). Collectively, a longer CInt in dams did not affect birth weight of their calves or BW during the weaning or rearing phase. From birth till weaning, a longer CInt in dams resulted in less anti-KLH IgG and lower plasma NEFA concentration in plasma of the calves. During the first lactation of their offspring, a longer CInt in dams can result in a lower plasma IGF_1 and FPCM during the first 100 DIM, although effects were not present in all CInt categories.

NGF, EPO, and IGF-1 in the Male Reproductive System.

Several studies have demonstrated interesting results considering the implication of three growth factors (GFs), namely nerve growth factor (NGF), erythropoietin (EPO), and the insulin-like growth factor-I (IGF-1) in the physiology of male reproductive functions. This review provides insights into the effects of NGF, EPO, and IGF-1 on the male reproductive system, emphasizing mainly their effects on sperm motility and vitality. In the male reproductive system, the expression pattern of the NGF system varies according to the species and testicular development, playing a crucial role in morphogenesis and spermatogenesis. In humans, it seems that NGF positively affects sperm motility parameters and NGF supplementation in cryopreservation media improves post-thaw sperm motility. In animals, EPO is found in various male reproductive tissues, and in humans, the protein is present in seminal plasma and testicular germ cells. EPO receptors have been discovered in the plasma membrane of human spermatozoa, suggesting potential roles in sperm motility and vitality. In humans, IGF-1 is expressed mainly in Sertoli cells and is present in seminal plasma, contributing to cell development and the maturation of spermatozoa. IGF-1 seems to modulate sperm motility, and treatment with IGF-1 has a positive effect on sperm motility and vitality. Furthermore, lower levels of NGF or IGF-1 in seminal plasma are associated with infertility. Understanding the mechanisms of actions of these GFs in the male reproductive system may improve the outcome of sperm processing techniques.

Toward new biomarkers of cold tolerance: microRNAs regulating cold adaptation in fish are differentially expressed in cold-tolerant and cold-sensitive Nile tilapia (Oreochromis niloticus)

Overcoming the negative effects of cold stress in Nile tilapia (Oreochromis niloticus) is of great interest for the overall aquaculture economy. Recent evidence suggests that microRNAs may regulate mechanisms of cold adaptation in fish and could be potential biomarkers of cold tolerance in these animals. However, information on how microRNAs regulating cold adaptation in fish are expressed in cold-tolerant and cold-sensitive fish is still scarce. Therefore, the aim of the present study is to investigate the relationship between a panel of previously identified differentially expressed microRNAs in fish exposed to low temperatures and their association with cold tolerance in Nile tilapia. To this end, fish were individualized based on their weight and length, and subjected to a critical thermal minimum (CTmin) test. Blood samples were collected before and after the CTmin test. After the CTmin, brain and liver tissues were collected. Fish were separated into cold-tolerant and cold-sensitive based on their CTmin results. Untreated fish were used as control. The relative expression of miR-9-3p, miR-135c, miR-9-5p, miR-30b, miR-122, miR-92a was assessed through qPCR. Additionally, qPCR was used to measure the mRNA relative expression of IGF-I and SCD in the tissues. Cortisol and biochemical parameters were determined in plasma samples. As a result, miR-92a was up-regulated in the liver of cold-sensitive fish and in the blood of cold-tolerant fish post-CTmin. miR-30b was up-regulated in the blood and liver of cold stressed fish. In the brain, miR-9-5p and miR-9-3p were up-regulated in cold-tolerant fish post-CTmin. Furthermore, miR-122 and miR-135c expression levels remained similar to the control post-CTmin. In addition, miR-122 and miR-92a were differentially expressed in the blood of cold-tolerant and cold-sensitive Nile tilapia pre-CTmin. Therefore, besides regulating fish cold acclimation responses differently in cold-tolerant and cold-sensitive fish, miRNAs may also regulate pre-existing physiological conditions that are determinant to cold tolerance in Nile tilapia. In the transcriptional level, SCD expression increased in both cold-tolerant and cold-sensitive fish post-CTmin. Cold-tolerant Nile tilapia post-CTmin had increased levels of plasma cholesterol and IGF-I mRNA in the liver, which could mean an adaptive advantage. The present findings provide new insights on the role of post-transcriptional regulation of cold tolerance in Nile tilapia. Furthermore, miRNAs differentially expressed in cold-tolerant Nile tilapia may be potential targets for the development of new biomarkers and aid in the breeding of cold-tolerant strains in this species.

Unveiling the Role of IGF-I in Fertility: Effect of Long-Acting Bovine Somatotropin (bST) on Terminal Follicular Development and Fertility during an Annual Reproductive Cycle in Sheep.

The study aimed to assess the effect of long-acting bST treatment, in a dose that only increases IGF-I plasma concentrations, on ovarian and fertility markers of estrous synchronized ewes that were fed to keep their bodyweight. Three experiments were designed to evaluate this effect: in Experiment 1, 18 ewes were distributed in groups (bST 0, 30, 50 mg) to measure plasma IGF-I and insulin for 15 days; in Experiment 2, 92 ewes (5 replicates) in two groups (0 and 30 mg bST) were synchronized using a 6-day progesterone protocol during the breeding season to assess the effect of bST on follicular and luteal performances, estrous and ovulation, and fertility after mating. In Experiment 3, 50 ewes (3 replicates) were used to repeat the study before but during anestrus. Results indicate that 50 mg bST increased IGF-I and insulin plasma concentrations, but 30 mg bST only increased IGF-I concentrations; and that only during the breeding season did 30 mg bST increase the number of lambs born and the reproductive success of ovulatory-sized follicles compared to controls. This occurred without it affecting any other reproductive marker. In conclusion, 30 mg bST treatment may improve oocyte competence for fertility during the breeding season.

Fucoidan Supplementation Improves Antioxidant Capacity via Regulating the Keap1/Nrf2 Signaling Pathway and Mitochondrial Function in Low-Weaning Weight Piglets.

Fucoidan (FC) is known for its antioxidant properties, but it has unclear effects and mechanisms on weaned piglets. Two experiments were conducted to determine the optimal FC dosage in piglet diets and its protective effect against lipopolysaccharide (LPS)-induced oxidative stress. In experiment one, 24 low weight weaned piglets were randomly assigned to four dietary treatments: a basal diet (FC 0), or a diet supplemented with 150 (FC 150), 300 (FC 300), or 600 mg/kg FC (FC 600). In experiment two, 72 low-weaning weight piglets were randomly allocated into four treatments: a basal diet (CON), or 300 mg/kg of fucoidan added to a basal diet challenged with LPS (100 µg LPS/kg body weight) or not. The results showed that FC treatments increased the G:F ratio, and dietary FC 300 reduced the diarrhea incidence and increased the plasma IGF-1 concentrations. In addition, FC 300 and FC 600 supplementation increased the plasma SOD activity and reduced the plasma MDA concentration. LPS challenge triggered a strong systemic redox imbalance and mitochondrial dysfunction. However, dietary FC (300 mg/kg) supplementation increased the activity of antioxidant enzymes, including SOD, decreased the MDA concentration in the plasma and liver, down-regulated Keap1 gene expression, and up-regulated Nrf2, CAT, MFN2, SDHA, and UQCRB gene expression in the liver. These results indicated that dietary fucoidan (300 mg/kg) supplementation improved the growth performance and antioxidant capacity of low-weaning weight piglets, which might be attributed to the modulation of the Keap1/Nrf2 signaling pathway and the mitochondrial function in the liver.

Exploring the impact of high-energy diets on cattle: Insights into subacute rumen acidosis, insulin resistance, and hoof health

Cattle lameness remains a significant concern, causing economic losses and compromising animal welfare. Claw horn lesions have been identified as a major cause of lameness in dairy cows but its correlation with high-energy diet and ruminal acidosis remains unclear. Hence, the primary objective of this study was to assess the effects of a high starch and a conventional diet on the rumen environment, acute phase proteins, and metabolic alterations, with a particular focus on insulin resistance and the consequent implications for the histology of the hooves in Holstein steers. Sixteen animals were divided into the high-starch (HS; 37% starch) and conventional (CON; 16.8% starch) groups. Glucose tolerance tests (GTT), blood, rumen fluid analysis, and histological evaluations of the hoof tissue were conducted over a 102-d experimental period. The HS group showed a lower ruminal pH than the CON group, and with values indicating subacute ruminal acidosis (SARA). The plasma glucose and IGF-1 concentrations were higher in the HS group, suggesting an anabolic state. Both groups exhibited an increase in the insulin area under the curve (AUC) after the GTT on d 102. Histological analysis of the hooves showed a reduction in the length and width of the epidermal lamella in both groups. There was a significant negative correlation between the insulin AUC and the length and width of the epidermal lamella. Since both groups were similarly affected, the hypothesis that histological alterations were caused by the experimental diets still needs confirmation. Additionally, the development of SARA was not essential for the observed histological changes in the hoof. Further studies are warranted to thoroughly investigate the role of insulin and IGF-1 imbalances in claw health.

Hormonal profile changes under the influence of environmental factors in children residing in the Aral environmental disaster region

BACKGROUND: Since the mid 20th century, the Southern Aral Sea Region is notorious as a region of ecological disaster, where anthropogenic influence led to the desiccation of the Aral Sea. Aridization of these territories is the cause of accumulation of endocrine disrupting chemicals — pesticides and toxic metals in soil and water.&#x0D; AIM: The aim of this study was to assess the changes in hormonal profile under the influence of environmental factors in prepubertal children living at different distances from the epicenter of the Aral ecological disaster.&#x0D; MATERIALS AND METHODS: The study included 58 male children aged 11–13 years. All children from birth lived in two regions of the Aral Sea Region and were divided into two groups depending on their place of residence. The group “North” (unfavorable conditions) consisted of 27 children from Muynak, Kungrad, Karauzyak, Takhtakupyr districts. The “Nukus” group (relatively favorable conditions) included 31 volunteers from Nukus city. All children were determined the concentration of IGF-1 — Insulin-like growth factor 1, GH — growth gormone, TT — total testosterone, E2 — estradiol, FSH — follicle-stimulating hormone, LH — luteinizing hormone, TSH — thyroid-stimulating hormone, TT3 — total triiodothyronine in blood sample. The statistical significance of the differences of the mentioned hormones in children from the “North” and “Nukus” groups was checked using the Mann–Whitney test.&#x0D; RESULTS: This analysis revealed statistically significantly higher values of TT, FSH and LH in children from the “Nukus” group compared to their peers from the “North” group. The concentrations of IGF-1, GH, E2, TTG and T3 in blood plasma in volunteers from both groups were not statistically significantly different.&#x0D; CONCLUSIONS: The environment of the Aral ecological disaster region with increased content of organochlorine compounds, pesticides and heavy metals changes the endocrine status in local prepubertal children. This is expressed in a moderate decrease in the activity of androgens (but not estrogens) and gonadotropic hormones. This research work can be considered as a pilot study, which determines the need for further monitoring of endocrine disorders in children and adults living in negative environmental conditions.

Mating Season Influences Placental Characteristics, Plasma IGF Concentration, and mRNA Expression without Affecting Lamb Birth Weight in Akkaraman Ewes

Seasonal variations significantly impact lambs’ birth weight and post-natal growth of lambs, yet the underlying physiological mechanisms remain insufficiently explored. Therefore, this study examined the effects of mating season on lamb birth weight, placental characteristics, maternal concentrations of insulin-like growth factors (IGFs) in plasma, and placental mRNA expression levels of IGFs in Akkaraman ewes reared under extensive conditions. Ewes were mated in the breeding season (September; n = 35) and out-of-breeding season (April; n = 27). Blood samples were taken from the jugular vein of all ewes using a vacutainer in sterile heparin tubes every month from mating to parturition. Post-lambing, both dam and lamb weights were recorded, and placental characteristics were documented within 12 hours of parturition in both seasons. The number and weight of cotyledons were higher (P&lt;0.05) in ewes mated during the breeding season than those mated during the out-of-breeding season. Also, ewes mated during the breeding season demonstrated thicker large cotyledons (P&lt;0.05). Although placental and cotyledonal efficiencies were similar in both mating seasons, volumetric cotyledon efficiency was higher (P&lt;0.05) in ewes mated during the out-of-breeding season than in those bred during the breeding season. Additionally, ewes mated in the breeding season exhibited higher plasma concentration of IGF-I at three months of gestation than ewes mated in the out-of-breeding season (123.8 ± 9.8 vs. 99.3 ± 11.4 ng/ml, respectively; P&lt;0.05). Although the mating season did not affect the IGF-I gene’s placental mRNA expression levels, the IGF-II gene’s expression level was notably higher (P&lt;0.05; fold change: 2.84) in ewes mated during the breeding season. The results suggest that mating season influences placental characteristics, maternal plasma IGF-I concentrations, and IGF-II gene expression levels of cotyledons due to alterations in cotyledon numbers and size on the surface of the placenta.

Variability in residual feed intake, nutrient utilisation and blood parametersin Murrah buffalo calves fed on total mixed ration

The present study was conducted on 18 female Murrah buffalo calves divided into two treatment groups to determine the residual feed intake, nutrient digestibility and blood metabolite parameters when fed with ration containing wheat (Triticum aestivum) straw, berseem (Trifolium alexandrinum) fodder as roughages and concentrate mixture to meet their requirements. Regular recording of body weight and feed intake was done during 90-day trial period. Residual feed intake (RFI) values were determined for individual animals based on which they were divided into low and high RFI groups. DM intake was lower in low RFI animals than high RFI animals. The blood glucose level and growth hormone level in low and high RFI group was comparable in both groups. Low RFI group had greater concentration of creatinine (1.62 vs. 1.21 mg/dL) as well as IGF-1 (136.70 vs. 120.38 ng/mL) whereas, concentration of total plasma protein level (6.80 vs 7.43 g/dL), albumin (3.46 vs 3.71 g/dl), aspartate aminotransferase (102.20 vs. 122.60 IU/L) and cortisol (3.48 vs. 5.32 ng/mL) were lesser in low RFI group with respect to high RFI group, indicating a positive correlation of RFI with total plasma protein, albumin, aspartate aminotransferase and cortisol and a negative correlation with plasma creatinine and IGF-1 levels in female Murrah buffalo calves. It was concluded that low RFI group of female Murrah buffalo calves showed better performance when fed with total mixed ration.

Effect of Different Herbage Allowances from Mid to Late Gestation on Nellore Cow Performance and Female Offspring Growth until Weaning.

This study evaluated different herbage allowances from mid to late pregnancy on pre- and postpartum physiological responses, milk production, and the performance of Nellore cows and the preweaning growth of their female offspring. Sixty multiparous Nellore cows were blocked by their body weight (BW; 425 ± 36 kg) and body condition score (BCS; 3.67 ± 0.23, scale 1-5) and randomly allocated to twelve pastures. Treatments consisted of two different herbage allowances (HA) during pregnancy: low HA (LHA; 2.80 kg DM/kg of BW) and high HA (HHA; 7.60 kg DM/kg of BW). Both treatment groups were fed 1 g/kg BW of a protein supplement. After calving, all cow-calf pairs were combined in a single group. The effects of maternal treatment × day of the study were detected for herbage mass and allowance, the stocking rate and forage crude protein, and for cow BW, BCS, and carcass measures (p < 0.01). Milk yield corrected to 4% fat, while the levels of fat total solids and cow plasma IGF-1 and urea were different (p ≤ 0.04) between treatments. HHA offspring was heavier (p ≤ 0.05) at 120 days and at weaning. A high herbage allowance can be implemented from mid-gestation until calving to increase cow prepartum performance, post-partum milk yield and composition, and positively modulate female offspring preweaning growth.

Effects of starch content of calf starter on rumen properties and blood concentrations of metabolites and hormones in dairy calves under a high plane of milk feeding.

The objective of this study was to investigate the effects of calf starters with different starch content on rumen and blood properties in calves fed under a high plane of nutrition program. Twenty-seven Holstein calves (14 female, 13 male) were assigned to one of three starter treatment groups in a randomized block design: high-starch (41.8%) (n= 9), H; medium-starch (31.9%) (n= 9), M; low-starch (22.0%) (n= 9), L. Milk replacer on powder basis was fed up to 1.2kg/day as fed, gradually reduced from 6weeks of age; calves were weaned at 8weeks of age. Each starter (up to 3.5kg/day as fed) and chopped hay were provided ad libitum from 5days of age. Blood was collected from 4 to 13 weeks of age. Rumen fluid was collected at 6, 8, 10, and 13 weeks of age. Serum urea nitrogen concentration after weaning was the lowest in H. Plasma IGF-1 concentrations were higher in H than in L. Ruminal pH was not different, but the molar proportion of ruminal propionate was higher in H than in L throughout the study period. In summary, a high-starch starter may increase propionate production and microbial protein synthesis in the rumen, inducing higher plasma IGF-1 concentrations.

Effect of semaglutide on global longitudinal strain and global myocardial work efficiency in patients with uncontrolled type 2 diabetes mellitus and obesity

Abstract Background Type 2 Diabetes mellitus (T2DM) increases of two-to three-fold the risk of cardiovascular disease (CVD). Cardiovascular outcome trials (CVOTs) demonstrated that glucagon-like peptide 1-receptor agonists (GLP1-RAs), as semaglutide in SUSTAIN-6 study, have effectively reduced CV risk in T2DM patients, so their use is recommended by guidelines. Purpose The objective of our work was to evaluate the effect of Semaglutide administration in a cohort of uncontrolled diabetic patients (within 5 years from diagnosis) on oxidative stress validated markers (8-isoprostane and NOX-2), platelet activation indicators (Sp-Selectin) and subclinical myocardial damage evaluated by measurement of deformation and efficiency parameters, obtained by speckle tracking echocardiography (STE). Methods We enrolled 70 Caucasian patients (mean age 65.5±8.2) with T2DM and obesity, 54 men and 16 women, 85.7% with hypertension, 14.2% with chronic obstructive pulmonary disease, 57.1% with sleep apnea syndrome, 18.5% with chronic kidney disease, and 41.4% with dyslipidemia. All patients were treated with statins and metformin, 42.8% with insulin, 24.2% with diuretics, 37.1% with ACE inhibitors, and 48.5% with angiotensin receptor antagonists. In the study the mean dose of semaglutide was 0.59±0.29 mg/week, no serious adverse events were reported. Results After 6 months of follow-up a significant improvement in fasting plasma glucose, insulinemia, HOMA, IGF-1, HbA1c and BMI (p&amp;lt;0.0001) was reported. In addition, there was a significant reduction in biomarkers of oxidative stress such as 8-isoprostane, Nox-2 and uric acid (p&amp;lt;0.0001), biomarkers of platelet activity such as Sp-Selectin and high-sensitivity C-reactive protein (hs-CRP) (p&amp;lt;0.0001). Moreover, we observed a significant improvement in left ventricular myocardial deformation parameters such as Global longitudinal strain (GLS) (p&amp;lt;0.0001) and global myocardial work efficiency (GWE) (p&amp;lt;0.0001). The linear correlation analysis showed that variation (Δ) GLS was inversely correlated with ΔHOMA (p=0.011), Δuric acid (p=0.025) and ΔSp-selectin (p&amp;lt;0.0001); ΔGWE was inversely correlated with ΔHOMA (p=0.011), Δuric acid (p=0.025) and ΔSp-selectin (p&amp;lt;0.0001). From stepwise multivariate linear regression model, ΔSp-selectin, ΔHOMA and Δuric acid justifying 27.8%(p&amp;lt;0.0001), 5.6%(p=0.010) and 4.4%(p=0.023) of ΔGLS variation, respectively. Instead ΔNOX-2, Δhs-CRP and ΔBMI justifying 22.3%(p&amp;lt;0.0001), 15.6%(p&amp;lt;0.0001), and 4.0%(p=0.022) of ΔGWE variation, respectively. Conclusion Treatment for 6 months with Semaglutide, in patients with uncontrolled T2DM and obesity, improved GLS and GWE. It’s plausible that this improvement may be justified by the reduction of inflammatory, oxidative stress and platelet activation parameters together with favorable metabolic changes; thus promoting coronary microcirculation protection with positive effects on myocardial contractility.

Colostrum supplement, IGF-1, and diarrhea in mechanically-ventilated patients: A double-blind, randomized, placebo-controlled study

BackgroundDiarrhea is relatively common in critically-ill mechanically-ventilated patients. This study investigated the effect of bovine colostrum supplement in the prevention of diarrhea. MethodsMechanically-ventilated patients expected to require enteral nutrition for at least five days were randomly assigned to the intervention or placebo groups. The intervention group received enteral diet providing 30g of bovine colostrum daily, and the control group received a similar diet except for whey protein as a placebo. The duration of the intervention was ten days. Serum levels of IGF-1 were measured at baseline and the end of the intervention. Patients were followed up for the occurrence of diarrhea. ResultsOut of 136 participants, 45 patients in the colostrum group and 45 patients in the control group were included in the final analysis of the outcomes. Plasma IGF-1 concentration increased significantly in the colostrum group after the intervention (P=0.02). In the between-group comparison, the increase in IGF-1 was significantly higher in the colostrum group compared with the placebo group (P=0.04). Furthermore, the incidence of diarrhea was significantly lower in the colostrum group compared to the control group. ConclusionBovine colostrum supplementation increased serum levels of IGF-1 and may reduce the incidence of diarrhea in critically-ill mechanically-ventilated patients.