Evaluation of testis hormonal and histopathological alterations in type I and type II diabetic rats.

BACKGROUND: Diabetes is a devastating metabolic disease that causes long-term damage to various organs. An important leading complication of diabetes is a degenerative effect on the reproductive system including infertility and gonadal dysfunction. This study aimed to evaluate the effects of experimental type I and II diabetes on the levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone. METHODS: Male Wistar rats were randomly divided into four separate groups: (1) type I diabetes (T1DM), (2) type II diabetes (T2DM), (3) cetrorelix acetate-treated nondiabetic control group, and (4) normal untreated group (n = 6). T1DM was experimentally induced by a single injection of alloxan (135 mg/kg) while T2DM was induced by feeding the animals with drinking water enriched with fructose (10%). Cetrorelix acetate (100 mg/kg, intraperitoneal for 1 week) treatment group was used as a positive control. All rats were killed and blood and testes were collected after 8 weeks of the study. The effects of induced diabetes on the levels of blood glucose and insulin were assessed. The levels of sex hormones and insulin were determined by radioimmunoassay. Histological staining was used to check abnormal patterns of testicular morphology, the diameter of seminiferous tubules, testicular diameter, and germinal layer thickness. RESULTS: A significant reduction in the testosterone, FSH, and LH levels were observed in T1DM, T2DM, and also in cetrorelix acetate-treated groups. Analysis of testicular histology sections revealed significantly reduced thickness of cell layer in T1DM and cetrorelix acetate-treated groups compared with the T2DM group. In T2DM, the cell numbers, the thickness of cell layer, the diameter of seminiferous tubules, and weight of testicles were slightly increased. In contrast, total tubules of empty seminiferous increased significantly in T1D and cetrorelix treated groups compared with the control group. CONCLUSION: Overall, diabetes can induce hypothalamus-pituitary-gonad axis dysfunction, affects hormonal secretion, and causes histological damage to testes, collectively leading to deleterious effects on male fertility.

Type 1 Diabetes and the Menstrual Cycle: Where/How Does Exercise Fit in?

Regular exercise is associated with substantial health benefits for individuals with type 1 diabetes (T1D). However, the fear of hypoglycemia (low blood glucose) due to activity-induced declines in blood glucose levels acts as a major barrier to partaking in exercise in this population. For females with T1D, hormonal fluctuations during the menstrual cycle and their effects on blood glucose levels can act as an additional barrier. The impact that these cyclic changes may have on blood glucose and insulin needs and the consequent risk of hypoglycemia during or after exercise are still unknown in this population. Therefore, in this narrative review, we gathered existing knowledge about the menstrual cycle in T1D and the effects of different cyclic phases on substrate metabolism and glucose response to exercise in females with T1D to increase knowledge and understanding around exercise in this underrepresented population. This increased knowledge in such an understudied area can help to better inform exercise guidelines for females with T1D. It can also play an important role in eliminating a significant barrier to exercise in this population, which has the potential to increase activity, improve mental health and quality of life, and decrease the risk of diabetes-related complications.

The Effect of Starting Blood Glucose Levels on Serum Electrolyte Concentrations during and after Exercise in Type 1 Diabetes.

Fear of hypoglycemia is a major exercise barrier for people with type 1 diabetes (PWT1D). Consequently, although guidelines recommend starting exercise with blood glucose (BG) concentration at 7-10 mmol/L, PWT1D often start higher, potentially affecting hydration and serum electrolyte concentrations. To test this, we examined serum and urine electrolyte concentrations during aerobic exercise (cycling 45 min at 60%VO2peak) in 12 PWT1D (10F/2M, mean ± SEM: age 29 ± 2.3 years, VO2peak 37.9 ± 2.2 mL·kg-1·min-1) with starting BG levels: 8-10 (MOD), and 12-14 (HI) mmol/L. Age, sex, and fitness-matched controls without diabetes (CON) completed one exercise session with BG in the normal physiological range. Serum glucose was significantly higher during exercise and recovery in HI versus MOD (p = 0.0002 and p < 0.0001, respectively) and in MOD versus CON (p < 0.0001). During exercise and recovery, MOD and HI were not significantly different in serum insulin (p = 0.59 and p = 0.63), sodium (p = 0.058 and p = 0.08), potassium (p = 0.17 and p = 0.16), calcium (p = 0.75 and 0.19), and magnesium p = 0.24 and p = 0.09). Our findings suggest that exercise of moderate intensity and duration with higher BG levels may not pose an immediate risk to hydration or serum electrolyte concentrations for PWT1D.

Global prevalence of suicide in patients living with HIV/AIDS: A systematic review and meta-analysis.

BACKGROUND: In fact, people living with HIV are at a greater risk of mental health disorders. Based on lack of necessary information in this area the present systematic review and meta-analysis study was conducted to determine the magnitude of committed suicides among HIV/AIDS people as well as their associated factors in a global setting. METHOD: Firstly we registered the protocol of study in PROSPRO. Then the publications were searched in the 4 main databases from January 2000 to April 2022. After removing duplication and inappropriate studies we applied inclusion and exclusion criteria. Finally 60 studies were included for analysis. Comprehensive meta-analysis software were used for analyzing. RESULTS: After reviewing 60 articles published from January 2000 to April 2021 in 24 countries, the total prevalence rate of suicide among 61,904 patients was estimated at 0.249 (95 % CI, 0.2-0.306). Findings indicated that the highest suicide prevalence was related to single patients estimated at 0.257 (95 % CI, 0.184-0.347). A gender-based meta-analysis depicted that the prevalence of suicide/ suicidal ideation was higher among females estimated at 0.22 (95 % CI, 0.15-0.29) compared with men at 0.17 (95 % CI, 0.11-0.23). CONCLUSION: Health planners and policymakers should develop suicide-prevention strategies aimed at female patients in younger age groups who live alone and are deprived of social support to effectively promote their self-efficacy in successful management of the disease. Integrating mental health services into anti-retroviral therapy for HIV/AIDS patients is also suggested in order to effectively design integrated programs for the management of individuals living with HIV/AIDS.

Can Resistance Exercise Be a Tool for Healthy Aging in Post-Menopausal Women with Type 1 Diabetes?

Due to improvements in diabetes care, people with type 1 diabetes (T1D) are living longer. Studies show that post-menopausal T1D women have a substantially elevated cardiovascular risk compared to those without T1D. As T1D may also accelerate age-related bone and muscle loss, the risk of frailty may be considerable for T1D women. Exercise and physical activity may be optimal preventative therapies to maintain health and prevent complications in this population: They are associated with improvements in, or maintenance of, cardiovascular health, bone mineral density, and muscle mass in older adults. Resistance exercise, in particular, may provide important protection against age-related frailty, due to its specific effects on bone and muscle. Fear of hypoglycemia can be a barrier to exercise in those with T1D, and resistance exercise may cause less hypoglycemia than aerobic exercise. There are currently no exercise studies involving older, post-menopausal women with T1D. As such, it is unknown whether current guidelines for insulin adjustment/carbohydrate intake for activity are appropriate for this population. This review focuses on existing knowledge about exercise in older adults and considers potential future directions around resistance exercise as a therapeutic intervention for post-menopausal T1D women.

RAGE signaling is required for AMPA receptor dysfunction in the hippocampus of hyperglycemic mice.

Diabetes in humans has been associated for a long time with cognitive dysfunction. In rodent animal models, cognitive dysfunction can manifest as impaired hippocampal synaptic plasticity. Particular attention has been concentrated on the receptor for advanced glycation end products (RAGE), which is implicated in multiple diabetic complications involving the development of vascular and peripheral nerve abnormalities. In this study, we hypothesize that RAGE signaling alters glutamate receptor function and expression, impairing synaptic transmission in the hippocampus. Using preparations of hippocampal slices from male mice, we show a RAGE-dependent decrease in long-term potentiation (LTP) and an increase in paired-pulse facilitation (PPF) following streptozotocin (STZ)-induced diabetes. Consistently, in hippocampal cultures from male and female neonatal mice, high glucose caused a RAGE-dependent reduction of AMPA- but not NMDA-evoked currents, and an increase in cytosolic reactive oxygen species (ROS). Consistently, when cultures were co-treated with high glucose and the RAGE antagonist FPS-ZM1, AMPA-evoked currents were unchanged. Hippocampi from STZ-induced hyperglycemic wild type (WT) mice showed increased RAGE expression concomitant with a decrease of both expression and phosphorylation (Ser 831 and 845) of the AMPA GluA1 subunit. We found these changes correlated to activation of the MAPK pathway, consistent with decreased pJNK/JNK ratio and the JNK kinase, pMEK7. As no changes in expression or phosphorylation of regulatory proteins were observed in hippocampi from STZ-induced hyperglycemic RAGE-KO mice, we report a RAGE-dependent impairment in the hippocampi of hyperglycemic WT mice, with reduced AMPA receptor expression/function and LTP deficits.

Hyperglycemia induces RAGE-dependent hippocampal spatial memory impairments.

Diabetes is a prevalent metabolic disorder that has long been associated with changes in different regions of the brain, including the hippocampus. Changes in hippocampal synaptic plasticity and subsequent impairment in cognitive functions such as learning and memory, are well documented in animal models of type 1 and type 2 diabetes. It is known that RAGE contributes to peripheral micro- and macro-vascular complications of diabetes. However, it is still unknown if RAGE plays a similar role in the development of CNS complications of diabetes. Therefore, we hypothesize that RAGE contributes to cognitive dysfunction, such as learning and memory impairments, in a mouse model of STZ-induced hyperglycemia. Control and STZ-induced hyperglycemic mice from WT and RAGE-KO groups were used for the behavioral experiments. While STZ-induced hyperglycemia decreased locomotor activity in the open field (OF) test, it did not affect the recognition memory in the novel object recognition (NOR) test in either genotype. Spatial memory, however, was impaired in STZ-induced hyperglycemic mice in WT but not in RAGE-KO group in both the Barnes maze (BM) and the Morris water maze (MWM) tests. Consistently, the RAGE antagonist FPS-ZM1 protected WT STZ-induced hyperglycemic mice from spatial memory impairment in the BM test. Our findings indicate that the parameters associated with locomotor activity and recognition memory were independent of RAGE in STZ-induced hyperglycemic mice. In contrast, the parameters associated with hippocampal-dependent spatial memory were dependent on RAGE expression.

Lipopolysaccharides induce a RAGE-mediated sensitization of sensory neurons and fluid hypersecretion in the upper airways.

Thoracic dorsal root ganglia (tDRG) contribute to fluid secretion in the upper airways. Inflammation potentiates DRG responses, but the mechanisms remain under investigation. The receptor for advanced glycation end-products (RAGE) underlies potentiation of DRG responses in pain pathologies; however, its role in other sensory modalities is less understood. We hypothesize that RAGE contributes to electrophysiological and biochemical changes in tDRGs during inflammation. We used tDRGs and tracheas from wild types (WT), RAGE knock-out (RAGE-KO), and with the RAGE antagonist FPS-ZM1, and exposed them to lipopolysaccharides (LPS). We studied: capsaicin (CAP)-evoked currents and action potentials (AP), tracheal submucosal gland secretion, RAGE expression and downstream pathways. In WT neurons, LPS increased CAP-evoked currents and AP generation, and it caused submucosal gland hypersecretion in tracheas from WT mice exposed to LPS. In contrast, LPS had no effect on tDRG excitability or gland secretion in RAGE-KO mice or mice treated with FPS-ZM1. LPS upregulated full-length RAGE (encoded by Tv1-RAGE) and downregulated a soluble (sRAGE) splice variant (encoded by MmusRAGEv4) in tDRG neurons. These data suggest that sensitization of tDRG neurons contributes to hypersecretion in the upper airways during inflammation. And at least two RAGE variants may be involved in these effects of LPS.

Estimation of the Thyroid Secondary Cancer Risk on the Patient of Standard Breast External Beam Radiotherapy.

BACKGROUND: The purpose of this study was to estimate the secondary cancer risk of thyroid in standard radiotherapy methods which are commonly used for breast cancer patients. METHODS: A total of 64 breast cancer patients (their age range was around 50 years old) who referred to Seyed-Al-Shohada hospital (Isfahan, Iran) were included in this study. The radiotherapy of the mentioned patients was performed using 6-MV photon beams. Dose measurements were also done using thermoluminescent dosimeters. Calculation of the risk of developing secondary cancer in thyroid was done using the Biological Effects of Ionizing Radiation Committee VII and recommended quantity of the International Radiation Protection Commission, excess relative risk. RESULTS: The mean radiation dose to thyroid for the tangential beams, tangential field with supraclavicular (SC) field, and also a tangential field with SC field in modified radical mastectomy (MRM) were 0.883 ± 0.472, 1.512 ± 0.365, and 1.587 ± 0.37, respectively. The risk of developing secondary thyroid cancer over a period of 5 years after breast cancer therapy in the tangential, tangential with a SC field, and also tangential beam with SC field in MRM were 9.974 ± 4.318, 17.891 ± 0.365, and 18.783 ± 4.384, respectively. The mean of the measured thyroid doses in patients treated with tangent fields was significantly lower than the patients under the irradiation of the tangent fields with SC field (P < 0.001). CONCLUSIONS: Using radiation protection equipment is suggested for breast cancer patients who treated with the studied radiotherapy methods.

RAGE-dependent potentiation of TRPV1 currents in sensory neurons exposed to high glucose.

Diabetes mellitus is associated with sensory abnormalities, including exacerbated responses to painful (hyperalgesia) or non-painful (allodynia) stimuli. These abnormalities are symptoms of diabetic peripheral neuropathy (DPN), which is the most common complication that affects approximately 50% of diabetic patients. Yet, the underlying mechanisms linking hyperglycemia and symptoms of DPN remain poorly understood. The transient receptor potential vanilloid 1 (TRPV1) channel plays a central role in such sensory abnormalities and shows elevated expression levels in animal models of diabetes. Here, we investigated the function of TRPV1 channels in sensory neurons cultured from the dorsal root ganglion (DRG) of neonatal mice, under control (5mM) and high glucose (25mM) conditions. After maintaining DRG neurons in high glucose for 1 week, we observed a significant increase in capsaicin (CAP)-evoked currents and CAP-evoked depolarizations, independent of TRPV1 channel expression. These functional changes were largely dependent on the expression of the receptor for Advanced Glycation End-products (RAGE), calcium influx, cytoplasmic ROS accumulation, PKC, and Src kinase activity. Like cultured neurons from neonates, mature neurons from adult mice also displayed a similar potentiation of CAP-evoked currents in the high glucose condition. Taken together, our data demonstrate that under the diabetic condition, DRG neurons are directly affected by elevated levels of glucose, independent of vascular or glial signals, and dependent on RAGE expression. These early cellular and molecular changes to sensory neurons in vitro are potential mechanisms that might contribute to sensory abnormalities that can occur in the very early stages of diabetes.

Effects of hydro-alcoholic extract of Launaea acanthodes on serum gonadotropin and testosterone levels and the structure of seminiferous tubules in hyperglycemic rats.

OBJECTIVE: To investigate the effects of hydro-alcoholic extract of Launaea acanthodes, a blood glucose lowering plant in folk medicine of Iran, on the structure of seminiferous tubules and serum gonadotropin and testosterone levels in hyperglycemic rats. METHODS: Twenty-four Wistar rats were randomly allocated into 4 groups (n=6): control, streptozotocin (STZ), STZ + insulin [STZ + Ins, 5 IU/(kg•day)], and STZ + Launaea acanthodes extract [STZ + Ext, 150 mg/(kg•day)]. Blood samples were collected at the 2nd and 4th weeks for detection of testosterone, follicle stimulating hormone (FSH) and luteinizing hormone (LH) with enzyme-linked immuno sorbent assay (ELISA), and the right testes of rats were removed at the 7th week for the evaluation of diameter and wall thickness of seminiferous tubules and number of Leydig cells using unbiased stereological techniques. RESULTS: In comparison with the control group, at the 2nd week FSH (0.45 vs 0.03, 0.02, 0.02 IU/L in STZ, STZ + Ins and STZ + Ext groups, respectively) and LH (1.02 vs 0.37, 0.2, 0.29 IU/L) showed significant decreases (all P<0.05) and testosterone (4.2 vs 8.37, 7.78, 11.8 ng/mL) showed a remarkable increase (all P<0.05). The levels of these hormones became closer in the STZ + Ext and the STZ + Ins groups to the control at the 4th week. A significant decrease in diameter and wall thickness of seminiferous tubules and number of Leydig cells were observed in the STZ group as compared with the control (P<0.01). CONCLUSIONS: Administration of Launaea extract demonstrated a beneficial impact on the protection of testis from pathogenic and degenerative effects of hyperglycemia which may be partly due to its potential antioxidative effects.