Gland Weight Research Articles

Lockbox enrichment facilitates manipulative and cognitive activities for mice

Background Due to the lack of complexity and variety of stimuli, conventional housing conditions of laboratory mice do not allow these animals to fully express their behavioral repertoire, including manipulative and cognitive activities. Therefore, we designed mechanical puzzles, so-called lockboxes, for mice that can be provided in their home cages. We investigated the impact of the lockbox enrichment on their phenotype and affective state when compared to conventional housing and super-environmental enrichment. Methods Young adult female C57BL/6JCrl mice were examined before and after 2-month exposure to the different types of enrichment in a phenotyping test battery, including tests for trait and state anxiety-related behavior, calorimetric measurements, body weight measurements, and the analysis of stress hormone metabolite concentrations as well as sequential problem-solving abilities. At the end of the study, adrenal gland weights were determined and pathohistological evaluation was performed. For all continuous variables, the relative variability was calculated. Results We demonstrated that lockbox enrichment decreased trait anxiety-related behavior compared to conventional housing in the Grid Exploratory Paradigm. In contrast, the different types of enrichment neither influenced state anxiety-related behavior in the Open Field and Elevated Plus Maze Test nor physiological variables (i.e., bodyweight, resting metabolic rate, stress hormone metabolite concentrations, and adrenal gland weights). Lockbox enrichment improved sequential problem-solving when compared to super-environmental enrichment. Regardless of the housing condition, the relative variability increased in most variables over time, although the coefficient of variation decreased for some variables, especially in animals with access to the lockbox enrichment. A pathohistological evaluation revealed no evidence of toxicopathological effects associated with the material from which the lockbox enrichment was made. Conclusions Overall, the lockbox enrichment revealed beneficial effects on the affective state and sequential problem-solving abilities of laboratory mice. The reproducibility was demonstrated not to be compromised by lockbox enrichment, similar to super-environmental enrichment.

Tetrabromobisphenol A reduces male rats reproductive organ coefficients and disrupting sexual hormone by causing oxidative stress

Tetrabromobisphenol A (TBBPA) has become a topic of public attention due to its pervasive detection in the environment and organisms in recent decades. However, limited information is available regarding the toxicity of TBBPA on reproductive ability of male mammals. Herein, the reproductive toxicity of TBBPA was investigated in male rats to fill the knowledge gap. In this study, male rats were exposed to TBBPA (0, 10, 100, and 1000 mg/kg) for 6 weeks. Subsequently, body and organ indexes, histopathological evaluation of testis and epididymis, ultrastructural observation of sperm, testosterone and progesterone levels, and oxidative stress indicators were conducted to reveal corresponding mechanisms. Results obtained showed that compare to the control group, the body weight, testes weight, epididymis weight, seminal vesicle and coagulation glands weight of rats in the 1000 mg/kg group lost 8.30%, 16.84%, 20.16%, 19.72% and 26.42%, respectively. Intriguingly, exposure to TBBPA (10, 100, 100 mg/kg) resulted in substantial pathological damage in testis, epididymis and sperm. TBBPA exposure also increased malondialdehyde (MDA) and hydrogen peroxide (H2O2) contents, as well as superoxide dismutase (T-SOD) and catalase (CAT) activities in testicular tissue. What’s more, the testosterone and progesterone levels in male rat serum were significantly decreased after exposure to TBBPA for 6 weeks. Meanwhile, results of molecular docking showed that TBBPA has a strong affinity with estrogen receptors (ERs). These findings demonstrated that TBBPA exposure negatively impacts the reproductive ability of male rats, thus providing new insights for risk assessment for reproductive health under TBBPA exposure.

138 Growth performance and physiological response of nursery pigs fed a high canola meal diet with acidifiers

Abstract This study investigated the impact of feed additives aimed at reducing gut pH on the growth performance and physiological responses of nursery pigs when fed a high canola meal (CM) diet. A total of 315 nursery pigs, 6.0 ± 1.2 kg body weight (BW), were allotted to one of five dietary treatments with 9 replicates (7 pigs/pen) in a randomized complete block design. Dietary treatments were PC: corn-soybean meal-based diet with 20% CM, NC: corn-soybean meal-based diet with 40% CM; NC+A: NC diet with acidifier at 1,500 ppm, NC+B: NC diet with encapsulated butyrate at 500 ppm, and NC+A+B: NC diet with acidifier and encapsulated butyrate. All diets were formulated to meet or exceed the nutrient requirements of NRC (2012). All pigs received a common Phase 1 nursery diet during week 1 following weaning. Experimental diets were provided in Phase 2 (wk 2 and 3) and Phase 3 (wk 4 to 6). Individual pig BW and pen feed consumption were measured for each phase to calculate growth performance. At the conclusion of each phase, blood samples were collected from one pig per pen for analysis of serum triiodothyronine (T3) and thyroxine (T4) concentrations. The selected pig was euthanized within 24 h, and its organ weights and pH of digesta were measured. The results were analyzed using MIXED procedure in SAS with the pen as an experimental unit. There was no difference in BW and average daily gain throughout the overall period. However, PC treatment exhibited greater (P < 0.05) average daily feed intake in phase 3 by 18.2% and overall period by 13.4% compared with NC treatment and no difference with NC+A+B treatment. The NC+A and NC+A+B treatments tended to improve (P ≤ 0.10) gain to feed ratio in phase 3 by 17.9% and overall period by 16.1% compared with PC treatment, respectively. At the end of phase 3, the PC treatment tended (P < 0.10) to have greater serum T4 concentrations compared with NC and NC+A treatments (3.2 vs 2.5 and 2.4 ug/dL, respectively), whereas there was no difference between PC and NC+A+B treatments. In phase 3, the thyroid gland weight for PC treatment was less (P < 0.05) than for NC treatment (0.156 vs 0.202 g/kg), whereas there was no difference among PC, NC+B, and NC+A+B treatments. In phase 3, dietary encapsulated butyrate decreased (P < 0.05) the pH of jejunal digesta compared with PC treatment (6.28 vs 7.01), and dietary encapsulated butyrate treatments (NC+B and NC+A+B) tended to decrease (P < 0.10) the pH of hind-colonic digesta compared with the pH of PC treatment by 6.2% and 7.2%. In conclusion, dietary encapsulated butyrate in combination with acidifier may alleviate thyroid dysfunction that is anti-nutritional effect of high canola meal diets.

The Concurrent Administration of Dexamethasone and Aldosterone Effectively Mitigates the Pronounced Pro-ulcerogenic Effect of Dexamethasone on the Gastric Mucosa in Rats

We previously established that the effect of dexamethasone (Dex) on the gastric ulceration is time dependent. Administering Dex 1 hour before an ulcerogenic stimulus provides gastroprotection, but extending the interval to 24 hours transforms its effect into a pro-ulcerogenic one. The prolonged maintenance of blood glucose levels induced by Dex, accompanied by catabolic effects, may, in part, account for its pro-ulcerogenic nature (Filaretova et., Inflammopharmacology 2009). Given the evidence that Dex primarily binds to glucocorticoid receptors (GRs), we hypothesized that Dex-induced imbalance in the activation of GRs and mineralocorticoid receptors (MRs) could contribute to the pro-ulcerogenic effect of Dex. We partly confirmed this (Filaretova and Sudalina, FASEB J. 2019). To further validate this hypothesis, we conducted a study to determine whether correcting the imbalance in the activation of GRs and the MRs, induced by Dex, through co-administering Dex with the MR agonist aldosterone (Aldo), can mitigate the pro-ulcerogenic effect of Dex. The effects of separate and combined administration of Dex and Aldo at a dose of 1 mg/kg (i.p.) 1 hour and 24 hours before the onset of ulcerogenic stimulus on the gastric erosions was evaluated in rats. Gastric injury was induced by indomethacin (IM, 35 mg/kg, sc) in preliminary fasted rats. Four hours after IM administration, the rats were decapitated, the stomachs were removed to estimate the erosion area; the adrenal glands, thymus and spleen were remove to estimate their weight, and trunk blood was collected to test the corticosterone and glucose levels. We confirmed the gastroprotective effect of Dex administered 1 hour and the pronounced pro-ulcerogenic effect of Dex administered 24 hours before IM. Aldo itself, administered 1 hour before IM had no effect on the gastric erosions, however, when administered 24 hours before IM, it led to a pro-ulcerogenic effect of IM, but much less pronounced comparing with that of Dex. Co-administration Dex and Aldo 1 hour before IM resulted in the gastroprotection similar to that of Dex alone. Co-administration Dex and Aldo 24 hours before IM effectively mitigates the pronounced pro-ulcerogenic effect of dexamethasone on the gastric mucosa. Dex administration resulted in a sharp decrease in the blood corticosterone level both when administered 1 hour and 24 hours before IM, however, the corticosterone levels in 24 hours were significantly lower than in 1 hour. Aldo itself did not lead to a significant decrease the corticosterone levels neither after 1 hour nor after 24 hours. We confirmed our previous results that Dex administration both 1 hour and 24 hours before IM leads to an increase in blood glucose levels. Administration of Aldo alone did change glucose levels. The effect of the combined administration of Dex and Aldo on glucose levels did not differ from that of Dex alone. 24 hours after Dex administration alone or co-administration Dex with Aldo, pronounced catabolic effects appeared: a decrease in the relative weight of the adrenal glands, thymus and spleen. In conclusion, the concurrent administration of Dex and Aldo effectively mitigates the pronounced pro-ulcerogenic effect of Dex on the gastric mucosa in rats. The results further confirmed our hypothesis. State Program 47 SP “Scientific and Technological Development of the Russian Federation” (2019-2030), 0134-2019-0001. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Effects of Insulin and Metformin on Indomethacin-Induced Gastric Injury in Streptozotocin-Induced Diabetic and Non-Diabetic Rats

Diabetes is one of the major health issues globally. Diabetic gastropathy is a well-documented phenomenon. Current treatments for diabetes and its complications have proven to be unsatisfactory. Currently, standard insulin therapy alone is still not the best treatment for type 1 diabetes (T1D). Metformin, besides use in type 2 diabetes (T2D), might be considered for a treatment of T1D. This study analyzed the effects of insulin and metformin on the gastric injury caused by indomethacin in the streptozotocin (STZ)-induced diabetic (T1D) and control non-diabetic rats. STZ (60 mg/kg, i.p.) was administered once 2 weeks before indomethacin (IM, 35 mg/kg, s.c.) in rats. Control non-diabetic rats were injected with STZ vehicle. The development of diabetes was assessed by blood glucose levels, changes in the rats' body weight, and water consumption. Insulin (2 IU/kg, i.p.) and metformin (100 mg/kg, orally) were administered daily, separately to different groups of rats, starting from the 8th day after the administration of STZ, for 7 days. After the last administration of the drugs, the rats were fasted for 22 hours before IM administration. Four hours after IM administration, the rats were decapitated, the stomachs were removed to estimate the erosion area; the adrenal glands and thymus were removed to estimate their weight, and trunk blood was collected to test the corticosterone and glucose levels. During the first week after STZ administration characteristic signs of diabetes developed: increased blood glucose, increased water consumption, and slower body weight gain. A week after daily insulin administration (on the 14th day), the glucose level in diabetic rats was lower compared to the corresponding level on the 7th day (before insulin administration). At the same time, the glucose levels before (day 7) and after administration (day 14) of metformin did not differ significantly. The development of STZ-induced diabetes led to a pronounced worsening of the ulcerogenic effect of IM: the average area of erosions caused by IM was increased significantly compared to that in control non-diabetic rats. Administration of both insulin and metformin for 7 days prevented the ulcer-promoting effect of STZ. In addition, insulin, but not metformin, also had a gastroprotective effect in non-diabetic rats: it reduced the average area of IM-induced erosions. The development of STZ-induced diabetes was accompanied by the manifestation of signs of chronic stress: an increase in plasma corticosterone level, an increase in the relative weight of the adrenal glands, and a decrease in the relative weight of the thymus. Daily administration of insulin for 7 days, but not metformin, resulted in a decrease in corticosterone levels on day 14 in diabetic rats. In conclusion, both insulin and metformin effectively prevented the pronounced ulcer-promoting effect of STZ-induced diabetes on the gastric injury caused by indomethacin in rats. However, only insulin, but not metformin, also exerted gastroprotective effect against IM-induced injury in non-diabetic rats under our experimental conditions. Grant for the creation and development of the world-class scientific center "Pavlov Center “Integrative Physiology - to medicine, high-tech healthcare and technologies of stress resistance” and with financial support from the Ministry of Education and Science of the Russian Federation (No 075-15-2022-303 от 21.04.2022.). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Long-term effect of exposure to triethylene glycol dimethacrylate (TEGDMA) on male mouse reproduction.

Our study investigated the impact on male mouse fertility and reproduction of long-term (14 weeks) exposure to triethylene glycol dimethacrylate (TEGDMA), a co-monomer of resin-based compounds, at doses of 0.01, 0.1, 1, and 10ppm. Test and control mice were then paired with sexually mature untreated female mice and their fertility evaluated. Females paired with males exposed to all TEGDMA doses exhibited a significant decline in pregnancy rates, and significant increases in the total embryonic resorption-to-implantation ratio, except for males exposed to 0.01ppm TEGDMA. Males in the highest dose group (10ppm) showed significant increases in seminal vesicle and preputial gland weights. They also had significantly higher serum levels of luteinizing hormone (LH) and follicle stimulating hormone (FSH) than the controls, and the 0.01ppm dosage group for FSH levels. TEGDMA exposure resulted in notable histopathological alterations in the testis, with detachment of germ cells and shedding of germinal epithelium into the tubule lumen. These results strongly indicate that TEGDMA exposure has detrimental consequences on the reproductive abilities and functions in male mice through disruption of the standard hormonal regulation of the reproductive system, leading to changes in spermatogenesis and ultimately leading to decreased fertility.

Overweight as a biomarker for concomitant thyroid cancer in patients with Graves' disease.

The incidence of concomitant thyroid cancer in Graves' disease varies and Graves' disease can make the diagnosis and management of thyroid nodules more challenging. Since the majority of Graves' disease patients primarily received non-surgical treatment, identifying biomarkers for concomitant thyroid cancer in patients with Graves' disease may facilitate planning the surgery. The aim of this study is to identify the biomarkers for concurrent thyroid cancer in Graves' disease patients and evaluate the impact of being overweight on cancer risk. This retrospective cohort study analyzed 122 patients with Graves' disease who underwent thyroid surgery at Seoul St. Mary's Hospital (Seoul, Korea) from May 2010 to December 2022. Body mass index (BMI), preoperative thyroid function test, and thyroid stimulating hormone receptor antibody (TR-Ab) were measured. Overweight was defined as a BMI of 25 kg/m² or higher according to the World Health Organization (WHO). Most patients (88.5%) underwent total or near-total thyroidectomy. Multivariate analysis revealed that patients who were overweight had a higher risk of malignancy (Odds ratios, 3.108; 95% confidence intervals, 1.196-8.831; p = 0.021). Lower gland weight and lower preoperative TR-Ab were also biomarkers for malignancy in Graves' disease. Overweight patients with Graves' disease had a higher risk of thyroid cancer than non-overweight patients. A comprehensive assessment of overweight patients with Graves' disease is imperative for identifying concomitant thyroid cancer.

Melatonin Modulates Immunity in Broilers Exposed to Heat Stress

Previously thought to be a pharmaceutical for regulating sleep and rhythm, Melatonin has demonstrated its potential as a co-adjuvant treatment by modulating mast cells, macrophages, dendritic cells, and T/B cells. Melatonin is immunomodulatory, which means it regulates T-cell differentiation, interrupts T/B cell interaction, and reduces the production of pro-inflammatory factors; it acts as an antioxidant through specific receptors. Therefore, this study investigates the effect of Melatonin in improving broiler immunity using four hundred broiler chicks divided into five treatments. There was a significant increase (p≤0.05) for the T2, T3, T4 and T5 treatments in total protein, albumin, globulin and immunoglobulins compared to the T1 treatment. Significant increase (p≤0.05) for the T3, T4 and, T5 treatments in antibody titer for Newcastle (ND), infection bronchitis (IB), influenza daises (INFLU). Significant improvements (p≤0.05) for the T2 and T4 treatments in the relative weight of Fabricius gland and Fabricius index.

Macroscopic and microscopic characteristics of uropygial gland of budgerigars (Melopsittacus undulatus)

Objective: This study was carried out to investigate the anatomical, morphometric, topographic, and histological features of the uropygial gland in adult male and female budgerigars (Melopsittacus undulatus).
 Material-Method: For this study, the glandula uropygialis of fourteen adult budgerigars (7 male, 7 female) were used in the study. This glandular structure located between the caudal vertebrae and pygostyle was removed by careful dissection. Morphological and histological characteristics of the dissected glandula uropygialis were determined. In addition, morphometric measurements and index calculations were performed. Tissue samples taken to determine the histological structure of the gland were stained with Hematoxylin & Eosin (H&E), Masson Trichrome's and Periodic Acid Schiff-Alcian Blue.
 Result: In the study, it was determined that the gland structure was heart shaped and consisted of two lobes, a papilla and a draining duct system. Uropygial gland weight was determined as 1.57±0.96 g in male birds and 1.52±0.09 g in female birds. As a result of the statistical evaluation, there were significant differences between the sexes in the parameters of lobe width (P

Abstract 3575: The estrogenic endocrine disrupting compounds bisphenol-a (BPA) and alpha-zeranol (aZAL) induce early mammary hyperplasia in female ACI rats

Abstract Endocrine disrupting compounds (EDCs) found in food-grade plastics, drinking water, and foodstuffs, pose a threat to human health. Estrogenic EDCs are capable of binding and activating the estrogen receptor (ER). Since breast tissue relies on estrogen signaling for growth and renewal, excessive estrogen stimulation is associated with breast cancer development. Breast cancer is a leading cause of cancer-related death in women. Only 5-10% of all breast cancer cases can be attributed to genetic causes, and the proportion of breast cancers of the luminal subtype are increasing in the United States for reasons unknown. Estrogenic EDCs may be able to initiate breast cancers through their estrogenic activities. The present study assessed two EDCs: the plasticizer bisphenol-A (BPA) and the mycotoxin alpha-zeranol (aZAL). To assess the estrogenic effects of these EDCs in an in vivo model, we utilized the ACI rat strain due to its sensitivity to estrogen-induced mammary carcinogenesis. The hypothesis of this work was that BPA and aZAL will induce mammary gland proliferation and estrogen signaling at early timepoints post-exposure. Estrogen, BPA, or aZAL were implanted into the backs of female ACI rats in silastic tubes at either a 9 gram doses. At a timepoint of 5 days post implantation, we saw no overt toxicity of our treatment. Both BPA and aZAL resulted in increased glandular proliferation and hyperplasia in a comparable manner to estrogen. Immunohistochemistry and qPCR revealed that the estrogen signaling marker progesterone receptor (PGR) was significantly upregulated in the estrogen, BPA, and aZAL treatment groups compared to control. The percent positivity of PGR staining in the mammary glands were 21.5% +/- 4.2%, 25.7% +/- 1.7%, 27.9% +/- 3.8%, and 8.18% +/- 2.5% respectively. Additionally, PCNA, a marker of cell proliferation, was significantly upregulated in the estrogen and aZAL treatment groups. The percent positivity of PCNA staining in the mammary glands were 7.67% +/- 2.56%, 49.6% +/- 5.2%, and 41.0% +/- 11.5% respectively. Additionally, the weight of the pituitary gland, an estrogen-sensitive endocrine organ, significantly increased in both the estrogen and aZAL treatment groups. Overall, this study demonstrated that the estrogenic EDCs BPA and aZAL induced mammary gland proliferation and hyperplasia in a comparable manner to estrogen. This is concerning due to the routine detection of these two compounds in human biosamples. More information is needed to assess the risk of exposure to these compounds as it pertains to breast cancer and other hormonal cancers. Citation Format: Cassandra Winz, Ba Liu, Caroline Xie, Shlok Rohatagi, Eric Li, Philip Furmanski, Nanjoo Suh. The estrogenic endocrine disrupting compounds bisphenol-a (BPA) and alpha-zeranol (aZAL) induce early mammary hyperplasia in female ACI rats [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3575.

Gross morpho-biometry, histometry and immunohistochemical investigations of pituitary gland in the juvenile and adult male African giant rats (Cricetomys gambianus)

This work was designed to investigate the morphometry and immunohistochemical features of pituitary glands in the African Giant Rats (AGR). Adult and juvenile AGR were sacrificed and their brains harvested, and the pituitary glands were carefully dissected. The weight, length and width of brains and pituitary glands were subsequently measured. Sections were prepared and stained using Haematoxylin and Eosin (H&E), Cresyl-violet and periodic-acid-Schiff (PAS) for histological analysis. Immunohistochemical analysis was carried out with Glial-Fibrillary-Acidic-Protein (GFAP) and Ionized-Calcium-Binding-Adapter-Molecule 1 (Iba1). Grossly, the AGR pituitary gland is a somehow laterally extended, saddle-shaped organ that is dorso-ventrally flattened. The gray-coloured adenohypophysis (anterior-pituitary lobe) was bigger in size than the whitish neurohypophysis (posterior-pituitary lobe) on physical examination. Histometrically, the adenohypophyseal length was noticeably greater than that of neurohypophysis in both juvenile and adult. Similarly, the adenohypophyseal and neurohypophyseal width in adult were found to be more than that of juvenile. Also, the histological staining of the neurohypophysis and adenohypophysis were distinct. In the neurohypophysis, fibrous and protoplasmic pituicytes were observed among fibres and Herring-bodies. Chromophils and chromophobes were identified in the adenohypophysis and melanotrophs in the intermediate lobe. Immunohistochemistry showed pituicytes in the neurohypophysis, which was positive with GFAP-antibody. With Iba1-antibody, the neurohypophysis expressed a stronger positive immunolabelling to microglia as compared to macrophages in the adenohypophysis. In conclusion, the gross and microscopic characteristics of pituitary glands of the AGR are found to be similar to other rodents and mammals. We recommend further study to compare morphometrical parameters between male and females of this model.

Stress-induced changes in cognitive function and intestinal barrier integrity can be ameliorated by venlafaxine and synbiotic supplementations.

Stress profoundly impacts various aspects of both physical and psychological well-being. Our previous study demonstrated that venlafaxine (Vlx) and synbiotic (Syn) treatment attenuated learned fear-like behavior and recognition memory impairment in immobilized-stressed rats. In this study, we further investigated the physical, behavior, and cellular mechanisms underlying the effects of Syn and/or Vlx treatment on brain and intestinal functions in stressed rats. Adult male Wistar rats, aged 8 weeks old were subjected to 14 days of immobilization stress showed a decrease in body weight gain and food intake as well as an increase in water consumption, urinary corticosterone levels, and adrenal gland weight. Supplementation of Syn and/or Vlx in stressed rats resulted in mitigation of weight loss, restoration of normal food and fluid intake, and normalization of corticosterone levels. Behavioral analysis showed that treatment with Syn and/or Vlx enhanced depressive-like behaviors and improved spatial learning-memory impairment in stressed rats. Hippocampal dentate gyrus showed stress-induced neuronal cell death, which was attenuated by Syn and/or Vlx treatment. Stress-induced ileum inflammation and increased intestinal permeability were both effectively reduced by the supplementation of Syn. In addition, Syn and Vlx partly contributed to affecting the expression of the glial cell-derived neurotrophic factor in the hippocampus and intestines of stressed rats, suggesting particularly protective effects on both the gut barrier and the brain. This study highlights the intricate interplay between stress physiological responses in the brain and gut. Syn intervention alleviate stress-induced neuronal cell death and modulate depression- and memory impairment-like behaviors, and improve stress-induced gut barrier dysfunction which were similar to those of Vlx. These findings enhance our understanding of stress-related health conditions and suggest the synbiotic intervention may be a promising approach to ameliorate deleterious effects of stress on the gut-brain axis.

Sexual dimorphism during integrative endocrine and immune responses to ionizing radiation in mice

Exposure to cosmic ionizing radiation is an innate risk of the spaceflight environment that can cause DNA damage and altered cellular function. In astronauts, longitudinal monitoring of physiological systems and interactions between these systems are important to consider for mitigation strategies. In addition, assessments of sex-specific biological responses in the unique environment of spaceflight are vital to support future exploration missions that include both females and males. Here we assessed sex-specific, multi-system immune and endocrine responses to simulated cosmic radiation. For this, 24-week-old, male and female C57Bl/6J mice were exposed to simplified five-ion, space-relevant galactic cosmic ray (GCRsim) radiation at 15 and 50 cGy, to simulate predicted radiation exposures that would be experienced during lunar and Martian missions, respectively. Blood and adrenal tissues were collected at 3- and 14-days post-irradiation for analysis of immune and endocrine biosignatures and pathways. Sexually dimorphic adrenal gland weights and morphology, differential total RNA expression with corresponding gene ontology, and unique immune phenotypes were altered by GCRsim. In brief, this study offers new insights into sexually dimorphic immune and endocrine kinetics following simulated cosmic radiation exposure and highlights the necessity for personalized translational approaches for astronauts during exploration missions.

High-dose exposure to butylparaben impairs thyroid ultrastructure and function in rats

Parabens (PBs) are a class of preservatives commonly used in cosmetics and pharmaceuticals. Studies have shown that these compounds may act as endocrine disruptors, affecting thyroxine levels in humans. PBs with longer chain substituents, such as butylparaben (BuP), are less prone to complete biotransformation and are therefore more likely to accumulate in the body. In this study, the effect of high-dose exposure to BuP on thyroid microstructure, ultrastructure, and function was investigated in rats. 50 mg/kg bw per day of BuP was injected subcutaneously into the neck of rats for 4 weeks. Rat thyroid weight, microstructure, and ultrastructure were determined, and the levels of thyroid sodium/iodide symporter (NIS), serum thyroid hormones, and thyroid autoantibodies were measured. The human thyroid cell line was used to study the mechanism of BuP on thyroid epithelial cells. The weight of the thyroid gland of BuP-exposed rats was increased, the structure of the thyroid follicles was irregular and damaged, the mitochondria and rough endoplasmic reticulum were swollen and damaged, and the microvilli at the tip of the epithelium were reduced and disappeared. Serum total T3, total T4, free T3, and free T4 were decreased in BuP-exposed rats, and TSH, peroxidase antibody, and thyroglobulin antibody were increased. In vitro, BuP decreased the level of NIS in thyroid epithelial cells, inhibited proliferation and viability, and induced apoptosis in a dose-dependent manner. This study demonstrated that high-dose exposure to BuP induced structural, ultrastructural, and functional impairment to the thyroid gland of rats, which may be one of the factors leading to hypothyroidism.

Gingival-derived mesenchymal stem cell therapy regenerated the radiated salivary glands: functional and histological evidence in murine model

BackgroundRadiotherapy in head and neck cancer management causes degeneration of the salivary glands (SG). This study was designed to determine the potential of gingival mesenchymal stem cells (GMSCs) as a cell-based therapy to regenerate irradiated parotid SG tissues and restore their function using a murine model.MethodsCultured isolated cells from gingival tissues of 4 healthy guinea pigs at passage 3 were characterized as GMSCSs using flow cytometry for surface markers and multilineage differentiation capacity. Twenty-one Guinea pigs were equally divided into three groups: Group I/Test, received single local irradiation of 15 Gy to the head and neck field followed by intravenous injection of labeled GMSCs, Group II/Positive control, which received the same irradiation dose followed by injection of phosphate buffer solution (PBS), and Group III/Negative control, received (PBS) injection only. Body weight and salivary flow rate (SFR) were measured at baseline, 11 days, 8-, 13- and 16-weeks post-irradiation. At 16 weeks, parotid glands were harvested for assessment of gland weight and histological and immunohistochemical analysis.ResultsThe injected GMSCs homed to degenerated glands, with subsequent restoration of the normal gland histological acinar and tubular structure associated with a significant increase in cell proliferation and reduction in apoptotic activity. Subsequently, a significant increase in body weight and SFR, as well as an increase in gland weight at 16 weeks in comparison with the irradiated non-treated group were observed.ConclusionThe study provided a new potential therapeutic strategy for the treatment of xerostomia by re-engineering radiated SG using GMSCs.

Correlation between remnant thyroid gland I-131 uptake and serum thyroglobulin levels: can we rely on I-131 whole body scans?

BackgroundI-131 treatment (RAI) decision relies heavily on serum thyroglobulin (Tg) levels, as higher Tg levels are assumed to be correlated with higher I-131 uptake. Tg elevation, negative iodine scintigraphy (TENIS) definition is becoming more clinically relevant as alternative treatment methods are available. This study examined the correlation between Tg levels with I-131 uptake in remnant thyroid gland to evaluate the reliability of serum Tg levels in predicting I-131 uptake.MethodsFrom March 2012 to July 2019, 281 papillary thyroid cancer patients treated with 150 mCi RAI were retrospectively enrolled. Early (2nd day) and Delayed (7th day) post-RAI whole-body scan (WBS) neck counts were correlated with clinical and pathologic findings. Patients with normal neck ultrasound and undetectable level of serum Tg (< 0.2 ng/mL) and thyroglobulin antibody (TgAb) (< 10 IU/mL) were defined as ablation success within 2 years after I-131 ablation.ResultsThyroid gland weight, tumor size and thyroiditis were independent factors of preoperative serum Tg levels. Serum off-Tg levels correlated with Early and Delayed WBS neck counts, and thyroiditis pathology contributed to lower neck counts in both Early and Delayed WBSs. In multivariable analysis, Delayed WBS neck count, serum off-Tg and off-TgAb were significant factors for predicting ablation success.ConclusionI-131 uptake and retention in remnant thyroid gland correlates with serum off-Tg levels, thyroiditis, and ablation success in thyroid cancer patients receiving high-dose I-131 therapy. Semi-quantitative I-131 analysis with Early and Delayed WBSs provides additional information in evaluating ablation success, with the potential application for metastasis treatment response evaluation.

Perfluorotetradecanoic acid exposure to adult male rats stimulates corticosterone biosynthesis but inhibits aldosterone production.

Perfluorotetradecanoic acid (PFTeDA) is a novel perfluoroalkyl substance that ubiquitously exists in the environment. However, whether PFTeDA affects adrenal cortex function remains unclear. Male Sprague-Dawley rats (age of 60 days) were daily administered with PFTeDA (0, 1, 5, and 10 mg/kg body weight) through gavage for 28 days. PFTeDA did not change body and adrenal gland weights. PFTeDA markedly elevated serum corticosterone level at 10 mg/kg but lowering serum aldosterone level at this dosage without influencing serum adrenocorticotropic hormone level. PFTeDA thickened zona fasciculata without affecting zona glomerulosa. PFTeDA remarkably upregulated the expression of corticosterone biosynthetic genes (Mc2r, Scarb1, Star, Cyp21, Cyp11b1, and Hsd11b1) and their proteins, whereas downregulating aldosterone biosynthetic enzyme Cyp11b2 and its protein, thereby distinctly altering their serum levels. PFTeDA markedly downregulated the expression of antioxidant genes (Sod1 and Sod2) and their proteins at 10 mg/kg. PFTeDA significantly decreased SIRT1/PGC1α and AMPK signaling while stimulating AKT1/mTOR signaling. Corticosterone significantly inhibited testosterone production by adult Leydig cells at >0.1 μM in vitro; however aldosterone significantly stimulated testosterone production at 0.1 nM. In conclusion, exposure to PFTeDA at male rat adulthood causes corticosterone excess and aldosterone deficiency via SIRT1/PGC1α, AMPK, and AKT1/mTOR signals, which in turn additively leads to testosterone deficiency.

Sodium Hydrosulfide Reverts Chronic Stress-Induced Cardiovascular Alterations by Reducing Oxidative Stress.

Chronic stress induces a group of unrecognized cardiovascular impairments, including elevated hemodynamic variables and vascular dysfunction. Moreover, hydrogen sulfide (H 2 S), a gasotransmitter that regulates the cardiovascular system decreases under chronic stress. Thus, this study assessed the impact of sodium hydrosulfide (NaHS) (H 2 S donor) on chronic restraint stress (CRS)-induced cardiovascular changes. For that purpose, male Wistar rats were restrained for 2 hours a day in a transparent acrylic tube over 8 weeks. Then, body weight, relative adrenal gland weight, serum corticosterone, H 2 S-synthesizing enzymes, endothelial nitric oxide synthetize expression, reactive oxygen species levels, lipid peroxidation, and reduced glutathione-to-oxidized glutathione (GSH 2 :GSSG) ratio were determined in the thoracic aorta. The hemodynamic variables were measured in vivo by the plethysmograph method. The vascular function was evaluated in vitro as vasorelaxant responses induced by carbachol or sodium nitroprusside, and norepinephrine (NE)-mediated vasocontractile responses in the thoracic aorta. CRS increased (1) relative adrenal gland weight; (2) hemodynamic variables; (3) vasoconstrictor responses induced by NE, (4) reactive oxygen species levels, and (5) lipid peroxidation in the thoracic aorta. In addition, CRS decreased (1) body weight; (2) vasorelaxant responses induced by carbachol; (3) GSH content, and (4) GSH 2 :GSSG ratio. Notably, NaHS administration (5.6 mg/kg) restored hemodynamic variables and lipid peroxidation and attenuated the vasoconstrictor responses induced by NE in the thoracic aorta. In addition, NaHS treatment increased relative adrenal gland weight and the GSH 2 :GSSG ratio. Taken together, our results demonstrate that NaHS alleviates CRS-induced hypertension by reducing oxidative stress and restoring vascular function in the thoracic aorta.

Olanzapine during lactation: impact on testicular morphometry and endocrine parameters in adult wistar rats.

Olanzapine (OLZ) is an antipsychotic medication used to treat postpartum psychiatric symptoms. It aimed to evaluate the effects of administering OLZ to lactating rats on testicular parameters of adult Wistar rats. Mothers received 2.5, 5 or 10 mg/kg until weaning. Adult male rats showed decrease in body weight, weight of testes, epididymis, prostate, seminal gland and gonadosomatic index when higher doses of OLZ were administered. Testicular volumetric parameters, as well as the length of seminiferous tubules, were also reduced in animals treated with the highest doses of OLZ. The diameter of the seminiferous tubules and the height of the seminiferous epithelium were reduced. There was also a relevant decrease in the population of Sertoli cells and a relevant reduction in the volume of individual Leydig cells. Histopathological analysis of the testes showed lesions compatible with testicular degeneration in rats treated with the highest dose of OLZ. There was a significant reduction in plasma testosterone levels in all treatments. It is noted, therefore, that the adverse impact on the testes of the highest doses of the drug during the neonatal period persisted into adulthood, with the dose of 2.5 mg/kg of OLZ proving to be safer than the others.

Effect of early intravenous calcium replacement after total thyroidectomy

Aim: This study was to evaluate the need for postoperative calcium replacement in patients undergoing total thyroidectomy, to evaluate the effect of intravenous calcium therapy given in the early postoperative period regardless of serum calcium level and physical examination on the length of stay of the patients, parathormone levels, and the need for oral calcium after discharge. Materials and Methods: The files of 73 patients who underwent bilateral total thyroidectomy between January 2018 and July 2023 were retrospectively reviewed, and the demographic characteristics, anti-TG, anti-TPO, postoperative calcium, parathormone, thyroid gland weight of the patients were recorded. The effect of intravenous calcium replacement on calcium requirement, parathormone levels, and length of hospitalization was evaluated independently of calcium levels. Results: It has been observed that replacement is associated with long-term calcium requirement in patients who underwent bilateral total thyroidectomy and received intravenous calcium in the early period. The length of stay was found to be longer in patients who underwent calcium replacement. Conclusion: Various treatment methods are used to prevent hypocalcemia. One of these treatment methods is early intravenous calcium replacement. In clinical practice, treatments given to prevent the development of complications and to discharge patients early may sometimes lead to the occurrence of complications that are tried to be prevented. The purpose of calcium replacement is to prevent the development of hypocalcemia, to reduce the complication rate and to provide early discharge. It was evaluated that intravenous calcium replacement therapy, which was applied in the early period to prevent postoperative hypocalcemia, caused patients to need longer-term calcium replacement and prolonged hospitalization. It is important to avoid calcium replacement in the early period and to evaluate the physical examination findings along with the serum calcium level of the patients for replacement.