Surgical Antimicrobial Prophylaxis Compliance in Turkey: Data from the Prospective, Observational, Multicenter Survey Including 7,978 Surgical Patients.

Background: Surgical antimicrobial prophylaxis (SAP) is the peri-operative administration of antimicrobial agents. Compliance rates vary worldwide from 15% to 84.3%, with studies in Turkey not exceeding 35%. The aim of this multicenter study was to determine the rate of appropriate antibiotic class, timing, and duration as well as discharge prescriptions in Turkey. Thus, we aimed to determine the rate of full compliance with SAP procedures in our country Patients and Methods: This multicenter, prospective, observational, descriptive study was conducted in 47 hospitals from 28 provinces in seven different regions of Turkey. Patients over 18 years of age in all surgical units between June 6, 2022, and June 10, 2022, were included in the study. Results: Of the 7,978 patients included in the study, 332 were excluded from further analyses because of pre-existing infection, and SAP compliance analyses were performed on the remaining 7,646 cases. The antibiotic most commonly used for SAP was cefazolin (n = 4,701; 61.5%), followed by third-generation cephalosporins (n = 596; 7.8%). The most common time to start SAP was within 30 minutes before surgery (n = 2,252; 32.5%), followed by 30 to 60 minutes before surgery (n = 1,638; 23.6%). Surgical antimicrobial prophylaxis duration was <24 hours in 3,516 (50.7%) patients and prolonged until discharge in 1,505 (21.7%) patients. Finally, the actual proportion of patients compliant with SAP was 19% (n = 1,452) after omitting 4,458 (58.3%) patients who were prescribed oral antibiotic agents at discharge as part of a prolonged SAP. Conclusions: Surgical antimicrobial prophylaxis compliance rates are still very low in Turkey. Prolonged duration of SAP and especially high rate of antibiotic prescription at discharge are the main reasons for non-compliance with SAP.

Prediction of Antibiotic Resistance in Patients With a Urinary Tract Infection: Algorithm Development and Validation.

BACKGROUND: The early prediction of antibiotic resistance in patients with a urinary tract infection (UTI) is important to guide appropriate antibiotic therapy selection. OBJECTIVE: In this study, we aimed to predict antibiotic resistance in patients with a UTI. Additionally, we aimed to interpret the machine learning models we developed. METHODS: The electronic medical records of patients who were admitted to Yongin Severance Hospital, South Korea were used. A total of 71 features extracted from patients' admission, diagnosis, prescription, and microbiology records were used for classification. UTI pathogens were classified as either sensitive or resistant to cephalosporin, piperacillin-tazobactam (TZP), carbapenem, trimethoprim-sulfamethoxazole (TMP-SMX), and fluoroquinolone. To analyze how each variable contributed to the machine learning model's predictions of antibiotic resistance, we used the Shapley Additive Explanations method. Finally, a prototype machine learning-based clinical decision support system was proposed to provide clinicians the resistance probabilities for each antibiotic. RESULTS: The data set included 3535, 737, 708, 1582, and 1365 samples for cephalosporin, TZP, TMP-SMX, fluoroquinolone, and carbapenem resistance prediction models, respectively. The area under the receiver operating characteristic curve values of the random forest models were 0.777 (95% CI 0.775-0.779), 0.864 (95% CI 0.862-0.867), 0.877 (95% CI 0.874-0.880), 0.881 (95% CI 0.879-0.882), and 0.884 (95% CI 0.884-0.885) in the training set and 0.638 (95% CI 0.635-0.642), 0.630 (95% CI 0.626-0.634), 0.665 (95% CI 0.659-0.671), 0.670 (95% CI 0.666-0.673), and 0.721 (95% CI 0.718-0.724) in the test set for predicting resistance to cephalosporin, TZP, carbapenem, TMP-SMX, and fluoroquinolone, respectively. The number of previous visits, first culture after admission, chronic lower respiratory diseases, administration of drugs before infection, and exposure time to these drugs were found to be important variables for predicting antibiotic resistance. CONCLUSIONS: The study results demonstrated the potential of machine learning to predict antibiotic resistance in patients with a UTI. Machine learning can assist clinicians in making decisions regarding the selection of appropriate antibiotic therapy in patients with a UTI.

TRPM2 may be involved in high fructose corn syrup-induced anxiety-like behavior in adult male rats.

Excessive high fructose corn syrup (HFCS) consumption is known to cause oxidative stress, which induces transient receptor potential melastatin type 2 (TRPM2) channel gating. Oxidative stress-induced TRPM2 gating is suggested to play an important role in neurons, indicating a role for the TRPM2 channel in a variety of neuropsychiatric disorders including depression and anxiety. We investigated the effects of HFCS and chronic immobilization stress (CIS) on TRPM2 channel immunoreactivity, anxiety, and depressive-like behaviors in adult male rats. The male rats (n=8/group) were divided into 4 groups: Control, 20% HFCS (F20), 40% HFCS (F40), and stress. The control group received tap water, and F20 and F40 groups were exposed to HFCS 20% and 40% respectively for 14 consecutive days. Rats in the stress group were subjected to immobilization stress for 3 or 6 hours daily in the first and second weeks to induce CIS. Then, light/dark tests, open field tests (OFT), and tail suspension tests (TST) were performed, respectively. In the light/dark test, the time spent in the dark chamber significantly increased in all groups vs the control group (P<0.01). In support of this result, time spent in the light chamber significantly decreased in all groups vs the control group (P<0.01). Besides, CIS significantly increased depressive-like behavior in the stress group vs the control group (P<0.05). In serum hormone levels, corticosterone (CORT) levels significantly increased in the F40 and stress groups vs the control group (P<0.01). TRPM2 immunoreactivity significantly increased in the hippocampus, prefrontal cortex (PFC), nucleus accumbens (NaC), and amygdala regions by HFCS and CIS treatments. For the first time in the present study,  showed that f increased immunoreactivity of the TRPM2 cation channels may be linked to the anxiety-like behavior induced by HFCS.

Chronic levamisole exposure in male rats alters sexual behavior and induces apoptosis in the testis.

Levamisole is an anti-helminthic drug developed and introduced in veterinary medicine, and it has been used more frequently after the inclusion of its usage in human medicine regarding disorders with immunomodulatory properties. In recent years, it has started to attract attention since it has beneficial effects on the treatment of COVID-19 due to its immunomodulatory properties. To investigate the effects of levamisole on sexual behavior and the reproductive system in male rats, two groups were formed the vehicle (n = 10) and levamisole (n = 10) groups. The vehicle group was given purified water whereas the levamisole group was administered with levamisole (2 mg/kg) by oral gavage daily for 4 weeks. Levamisole treatment significantly increased the mount latency (ML, P < 0.001) as well as the intromission latency (IL, P < 0.01). It also significantly prolonged postejaculatory interval (PEI, P < 0.01), decreased copulatory rate (CR, P < 0.05), and sexual activity index (SAI, P < 0.05). It significantly decreased serum monoamine oxidase A (MAO-A) levels (P < 0.05). Additionally, levamisole induced disorganizations of germinal epithelial cells of seminiferous tubules, congestion, edema in the interstitial area, and metaphase arrest in some spermatocytes (P < 0.001), and it significantly increased the immunohistochemical expressions of apoptotic Bax and cytochrome c, which is crucial proapoptotic protein, in the testis (P < 0.001). Also, levamisole significantly upregulated the mRNA levels of the apoptosis-related key regulatory genes, including Bax (Bcl-2-associated X protein, P = 0.05) and Bax/Bcl-2 ratio (P < 0.01) in testis. The current research is the first to show that levamisole may decrease sexual performance, potency, sexual motivation, and libido and induce apoptosis in the testis.

Effects of chronic irisin treatment on brain monoamine levels in the hypothalamic and subcortical nuclei of adult male and female rats: An HPLC-ECD study.

Monoaminergic systems are known to be involved in the pathophysiology of neuropsychiatric disorders and vegetative functions due to their established influence on hypothalamic and subcortical areas. These systems can be modulated by lifestyle factors, especially exercise, which is known to produce several beneficial effects on reproduction, brain health, and mental disorders. The fact that exercise is sensed by the brain shows that muscle-stimulated secretion of myokines allows direct crosstalk between the muscles and the brain. One of such exercise-induced beneficial effects on the brain is exhibited by irisin-a recently discovered PGC-1α-dependent adipo-myokine mainly secreted from skeletal muscle during exercise. Thus, we hypothesized that irisin may affect central monoamine levels and thus play an important role in the muscle-brain endocrine loop. To test this assertion, for 10 weeks, vehicle (deionized water) or 100 ng/kg irisin was injected intraperitoneally once a day to 12 male and 12 female rats after which the levels of monoamines and their metabolites were determined by HPLC-ECD. In the hypothalamic nuclei, irisin significantly decreased dopamine (DA) metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) (p < 0.05), DOPAC/DA ratio (p < 0.01) and noradrenaline (NA, p < 0.05) levels in the anteroventral periventricular nucleus (AVPV), and DOPAC and NA levels in the medial preoptic area (mPOA) (p < 0.05), having a crucial role in reproduction and sexual motivation, respectively. On the other hand, irisin significantly increased DOPAC levels in the lateral hypothalamic area (LHA) (p < 0.05), which acts as a hunger center, while it significantly decreased the levels of DA, NA, and its metabolite 3,4-dihydroxyphenylglycol (DHPG) in the ventromedial hypothalamic nucleus (VMH) as a known satiety center (p < 0.05). In nucleus accumbens (NaC), irisin significantly reduced 5-hydroxyindoleacetic acid (5-HIAA) levels (p < 0.05), which are implicated in autism spectrum disorder (ASD) physiopathology. It also significantly increased DA levels in this area, thus exhibiting positive effects on depression and sexual dysfunction in men. On the other hand, it significantly decreased serotonin (5-HT) (p < 0.01) and its metabolite 5-HIAA levels in the medial amygdala (MeA) (p < 0.05), indicating that it may play a role in social behaviors. Moreover, it significantly attenuated NA levels in the same subcortical area (p < 0.01), which is directly involved in stress-induced activation of the central noradrenergic system. These findings demonstrate for the first time that irisin induces significant changes in monoamine levels in many hypothalamic nuclei involved in feeding behavior and vegetative functions, as well as in subcortical nuclei related to neuropsychiatric disorders.

The Effect of Irisin on Thyroid Hormone Levels in Chronic Paroxetine-Treated Rats.

It is known that serotonin reuptake inhibitors (SSRIs), which are widely used in mood disorders, affect the hypothalamic-pituitary-thyroid axis activity. In this study, we investigated the effect of paroxetine, an SSRI, on thyroid hormone levels in rats. We also examined the role of irisin, a newly discovered potential regulatory hormone for metabolism, on paroxetine-induced changes. A total of 64 Sprague-Dawley female and male rats were randomly divided into four subgroups for each gender and treated as follows: sham-operated control (vehicle), paroxetine (treated with 20 mg/kg paroxetine by oral gavage), irisin (100 ng/kg/day for 28 days with mini-osmotic pumps), and paroxetine + irisin group (n = 8). Serum fasting free triiodothyronine (fT3) and free thyroxine (fT4) levels were measured by automated chemiluminescence method. Serum thyroid-stimulating hormone (TSH) level was determined with enzyme-linked immunosorbent analysis (ELISA). Compared to the sham control group (p < 0.05), the significantly reduced fT4 and TSH serum levels in paroxetine-treated male animals were markedly increased by subcutaneous irisin perfusion. fT3 levels significantly increased in both irisin (4.35 ± 0.17 pq/mL) and paroxetine + irisin groups (4.51 ± 0.19 pq/mL) compared to sham control (3.60 ± 0.23 pq/mL) and paroxetine groups (3.57 ± 0.12 pq/mL) (p < 0.05). It was observed that serum fT3, fT4, and TSH levels decreased in female animals receiving paroxetine compared to the sham control group. Subcutaneous administration of irisin increased these hormone levels. However, these changes were not statistically significant. These results suggested that irisin may play a role in the mechanism underlying the beneficial effects of exercise in preventing SSRI-related side effects by increasing thyroid hormone levels, which were decreased by paroxetine.

Beneficial effects of irisin in experimental paroxetine-induced hyperprolactinemia.

OBJECTIVE: It is known that selective serotonin reuptake inhibitors (SSRIs), represent an important and effective treatment of depression and other psychological disorders, these medications can increase prolactin levels mainly through activation of the serotonergic pathway. In this study, we aimed to determine the beneficial effects of irisin on paroxetine, a SSRI, induced hyperprolectinemia and in some other reproductive hormonal changes associated with hyperprolactinemia. METHODS: Thirty two male Spraque-Dawley rats were used and divided into four groups including sham-operated control (vehicle), irisin (100 ng/kg/day for 28 days with mini-osmotic pumps), paroxetine (treated with 20 mg/kg paroxetine by oral gavage), irisin and paroxetine+irisin groups (n = 8). Serum prolactin (PRL), kisspeptin, luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone and 5-alpha reductase levels were determined with enzyme-linked immunosorbent analysis (ELISA). RESULTS: In animals treated with paroxetine, PRL level increased and testosterone level decreased significantly (p < 0.05). Serum LH level was significantly increased in the group, but no significant changes were observed in the FSH, kisspeptin and 5-alpha reductase levels. Serum prolactin levels was significantly decreased in the group treated with irisin. While no significant difference was observed in kisspeptin, FSH and 5-alpha reductase levels, an increase in serum LH and testosterone levels with irisin administration (p < 0.05). CONCLUSION: In conclusion, chronic irisin exposure may reverse paroxetine-induced hyperprolactinemia. These results indicate that irisin may have the potential to be used as a therapeutic agent by primarily affecting paroxetine-induced increased prolactin and decreased testosterone levels.

Irisin Improves High-Fat Diet-Induced Sexual Dysfunction in Obese Male Rats.

INTRODUCTION: Obesity is known to cause sexual dysfunction including erectile dysfunction and poor semen quality. Lifestyle modifications such as exercise have increasingly been more recognized to lower the likelihood of having sexual dysfunction or infertility in obese men. In this context, as an exercise-mimetic hormone, irisin has a potential to improve obesity-related reproductive dysfunctions. We aimed to elucidate possible effects of irisin on high-fat diet (HFD)-induced reproductive dysfunction in obese male rats. METHODS: Rats were divided into four groups: vehicle, irisin, obese, and obese + irisin. The rats in obese and obese+irisin groups were fed with HFD (60% kcal fat) pellets for 12 weeks to induce obesity, and then obesity-induced sexual dysfunction was confirmed by the sexual behavior test (SBT). Irisin and obese+irisin groups received irisin (100 ng/kg/day) infusion by an s.c. osmotic minipump for 4 weeks after HFD-induced obesity was formed. RESULTS: Irisin did improve a number of measures of copulation, including penile erection, ejaculation, and sexual performance, and also improved sperm morphology and motility and decreased fat-induced testicular damage. It decreased serum leptin levels. On the other hand, irisin did not affect serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone. It also increased gene expression of tyrosine hydroxylase (TH) and adrenoceptor alpha 1A (ADRA1A) in the medial preoptic area (mPOA) and nucleus accumbens (NAc). CONCLUSION: Irisin provided a marked enhancement of HFD-induced decrease in libido, potency, sexual performance, and erection in SBT. Taken together, our results emphasize that irisin has a restorative and improver role in HFD-induced reproductive dysfunctions in obese male rats.

The Role of Zinc Status on Spatial Memory, Hippocampal Synaptic Plasticity, and Insulin Signaling in icv-STZ-Induced Sporadic Alzheimer's-Like Disease in Rats.

Alzheimer's disease (AD), especially its sporadic form (sAD), is of multifactorial nature. Brain insulin resistance and disrupted zinc homeostasis are two key aspects of AD that remain to be elucidated. Here, we investigated the effects of dietary zinc deficiency and supplementation on memory, hippocampal synaptic plasticity, and insulin signaling in intracerebroventricular streptozotocin (icv-STZ)-induced sAD in rats. The memory performance was evaluated by Morris water maze. The expression of hippocampal protein and mRNA levels of targets related to synaptic plasticity and insulin pathway was assessed by Western blot and real-time quantitative PCR. We found memory deficits in icv-STZ rats, which were fully recovered by zinc supplementation. Western blot analysis revealed that icv-STZ treatment significantly reduced hippocampal PSD95 and p-GSK3ß, and zinc supplementation restored the normal protein levels. mRNA levels of BDNF, PSD95, SIRT1, GLUT4, insulin receptor, and ZnT3 were found to be reduced by icv-STZ and reestablished by zinc supplementation. Our data suggest that zinc supplementation improves cognitive deficits and rescues the decline in key molecular targets of synaptic plasticity and insulin signaling in hippocampus caused by icv-STZ induced sAD in rats.

Irisin ameliorates male sexual dysfunction in paroxetine-treated male rats.

Sexual dysfunction is a common clinical condition due to different causes including the use of selective serotonin reuptake inhibitors (SSRI). Especially, SSRI paroxetine is known to cause numerous types of sexual dysfunction in men. There is growing interest in exercise as a non-pharmacological approach for the treatment of SSRI-induced sexual dysfunction. With these in mind, we investigated the effects of irisin, which is a recently detected exercise-linked hormone, on paroxetine-induced sexual dysfunction in male rats. Our findings showed that circulating irisin levels were lower in paroxetine-induced sexual dysfunction in male rats (20 mg/kg/day for 8 weeks by oral gavage than in vehicle-treated rats). In addition, results from sexual behavioral tests revealed that subcutaneous irisin perfusion (100 ng/kg/day via mini-osmotic pumps for 28 days) ameliorated sexual motivation and copulatory performance in sexually impaired male rats treated with paroxetine. The significantly reduced serum testosterone levels and α1-adrenoceptors (ADRA1A) and tyrosine hydroxylase gene (TH) expression levels in the nucleus accumbens (NAc) in paroxetine-induced sexually dysfunctioning male rats were markedly increased following irisin exposure. Similarly, the expression levels of ADRA1A and TH in the medial preoptic area (mPOA) significantly increased in male rats co-administered with paroxetine and irisin compared to the vehicle-treated male rats. These results demonstrate that irisin may be a therapeutic modality that mimics/supports the beneficial effects of exercise for improving SSRI-associated sexual dysfunction in men through increase in serum testosterone levels and increased expression of α1-adrenoceptors and TH in the NAc and mPOA associated with sexual motivation and copulatory behaviors.

The modulatory effects of irisin on asprosin, leptin, glucose levels and lipid profile in healthy and obese male and female rats.

OBJECTIVES: The main aim of this study was to investigate the effects of irisin on asprosin, leptin, glucose levels and lipid profile in healthy and obese male and female rats. METHODS: Irisin was subcutaneously administered with osmotic minipumps at the dose of 100 ng/kg/day for 28 days and then, the serum levels of asprosin, leptin, glucose and lipid profile were investigated. RESULTS: Irisin infusion increased asprosin levels in male rats (p = .02) but not in female rats. Irisin inhibited obesity-induced high glucose, low-density lipoprotein (LDL), triglyceride (TG) and leptin levels in all groups; however, it did not lead to any change in asprosin levels in both obese female and male rats. CONCLUSIONS: It was determined that irisin increased serum asprosin levels and decreased LDL, TG, glucose and leptin levels, and this could indicate a protective role of irisin against obesity development.

Agomelatine, A Potential Multi-Target Treatment Alternative for Insomnia, Depression, and Osteoporosis in Postmenopausal Women: A Hypothetical Model.

Insomnia, which is associated with menopausal depression, is a common symptom of menopause. Both symptoms have a common etiology, and can affect each other significantly. Pharmacological interventions, including hypnotics and antidepressants, and non-pharmacological therapies are generally administered in clinical practice for insomnia treatment. As another menopausal disorder, osteoporosis is described as a disease of low bone mineral density (BMD), affecting nearly 200 million women worldwide. Postmenopausal osteoporosis is common among middle-aged women. Since postmenopausal osteoporosis mainly results from low estrogen levels, menopausal hormone therapy (HT) is considered the first-line option for the prevention of osteoporosis during the menopausal period. However, almost no study has evaluated novel treatments for the combined prevention of insomnia, depression, and osteoporosis. Hence, it is necessary to develop new multi-target strategies for the treatment of these disorders to improve the quality of life during this vulnerable period. Melatonin is the major regulator of sleep, and it has been suggested to be safe and effective for bone loss therapy by MT-2 receptor activity. As a result, we hypothesize that agomelatine, an MT-1 and MT-2 receptor agonist and 5-HT2C receptor antagonist, holds promise in the combined treatment of insomnia, depression, and osteoporosis in middle-aged women during menopause.

Chronic irisin exposure decreases sexual incentive motivation in female rats.

Irisin is a novel myokine/adipokine that is released into the circulation in response to types of exercise and increases energy expenditure. Disorders in the endocrine system related to reproduction, which occur due to the chronic or excessive exercise, cause a decrease in women's sexual desire. However, the role of irisin hormone on sexual desire in women has not been elucidated. We hypothesized that chronic irisin exposure would decrease sexual incentive motivation for male partners by affecting the endocrine system in female rats. We tested this by quantifying and comparing of both sexual incentive motivation and active investigation for sexual partner, and also changes in the serum hormone levels in chronically irisin-treated female rats. As a result, chronic irisin exposure decreased the time spent near the male rat, male preference ratio, and male investigation preference ratio. Furthermore, serum testosterone and progesterone levels significantly decreased and estradiol levels increased while kisspeptin-1 levels were not changed by chronic irisin exposure in female rats. These data indicate that chronic irisin exposure may cause low sexual incentive motivation for opposite-sex partners in female rats via changes in reproductive hormones. The results suggest that irisin hormone may play a role in decreased sexual desire due to long-term exercise in women.

Chronic effects of maternal tobacco-smoke exposure and/or α-lipoic acid treatment on reproductive parameters in female rat offspring.

Prenatal tobacco-smoke exposure negatively affects the reproductive functions of female offspring and oxidative stress plays a major role at this point. Alpha-lipoic acid (ALA), well known as a biological antioxidant, has been used as a nutritional supplement and as a therapeutic agent in the treatment of certain complications during pregnancy. We aimed to investigate the effects of maternal tobacco-smoke exposure and/or ALA administration on puberty onset, sexual behavior, gonadotrophin levels, apoptosis-related genes, apoptotic cell numbers and oxidative stress markers in the adult female rat offspring. Sprague-Dawley rats were divided into four groups; control, tobacco smoke (TS), TS+ALA and ALA groups. Animals were exposed to TS and/or ALA for 8 weeks before pregnancy and throughout pregnancy. All treatments ended with birth and later newborn female rats were selected for each experimental group. The experiment ended at postnatal day 74-77. Maternal tobacco smoke advanced the onset of puberty in the female offspring of the TS group (p < 0.05). In all treatment groups; the mean number of anogenital investigations and lordosis quality scores showed a decline, serum luteinizing hormone levels significantly increased (p < 0.05) and several histopathological changes in ovaries were observed compared to the control group. In addition, an increase in apoptotic marker levels and apoptotic cell numbers was detected in the ovaries of all treatment groups. Decreased TAS and increased TOS levels were detected in all treatment groups compared to control. These findings suggested that maternal tobacco smoke and/or ALA administration may be leading to the impaired reproductive health of female offspring. Abbreviations: ALA: alpha-lipoic acid; LH: luteinizing hormone; FSH: follicle-stimulating hormone; TAS: total antioxidant status; TOS: total oxidant status; Apaf1: apoptotic protease-activating factor 1; Casp3: caspase 3; Casp9: caspase 9; CF: cyst follicles; 4-HNE: 4-Hidroxynonenal; 8-OHdG: 8-hydroxydeoxyguanosine; TUNEL: terminal deoxynucleotidyl transferase-mediated deoxyuridine-biotin nick end labeling; ROS: reactive oxygen species; GnRHR: gonadotropin-releasing hormone receptor; HPG: hypothalamic-pituitary-gonadal; AMPK: AMP-activated protein kinase; ELISA: enzyme-linked immunosorbent assay; cDNA: complementary DNA; qPCR: quantitative real-time PCR; FC: follicular cysts; PF: primary follicle; SF: secondary follicle; GF: graafian follicle; CL: corpus luteum; DF: degenerated follicle; AF: atretic follicle.

Chronic Maternal Tobacco Smoke Exposure and/or Alpha-Lipoic Acid Treatment Causes Long-Term Deterioration of Testis and Sexual Behavior in Adult Male Rats.

BACKGROUND: Tobacco use during pregnancy is known to have several negative effects on the offspring's reproductive health in the long term. The use of alpha-lipoic acid (ALA) as a dietary supplement during pregnancy has increased greatly in recent years and has been known to have positive effects on various pregnancy outcomes including miscarriage, diabetic embryopathy, preterm delivery, and congenital malformations. AIM: To evaluate the effects of tobacco smoke exposure (TSE) on sexual behavior, reproductive parameters, and testicles in adult male rats and to reveal the possible role of ALA administration on these parameters. METHODS: Pregnant rats (n = 7 per group) were treated with tobacco smoke (TS), ALA (20 mg/kg), and TS + ALA for a total of 11 weeks. The following parameters were compared with 8 control rats: puberty parameters, sexual behavior; levels of serum gonadotropins and testosterone, total antioxidant status, and total oxidant status; the expression of the apoptotic protease-activating factor-1 and caspase 9 mRNA levels in the testis; and assessment of immunohistochemistry and terminal deoxynucleotidyl transferase dUTP nick end labeling assay of testis. MAIN OUTCOME MEASURE: Sexual behavior, changes in puberty parameters, and hormonal and genetic alterations were the outcomes analyzed in this study. RESULTS: Maternal TSE caused a significant decrease in the number of intromissions compared to the control group. Similarly, ALA decreased erectile function in sexual behavior by decreasing the number of intromissions and intromission ratio in the ALA group compared to the control group. In addition, TSE and ALA treatment caused an impairment of some consummatory sexual behaviors. Also, in parallel with this inhibitory effect, the age of pubertal onset was significantly delayed in the TS + ALA group compared to other groups. Also, histopathological changes in testicular tissue, oxidative stress markers, apoptotic index, and mRNA levels of apoptosis-related genes increased in all treatment groups. CLINICAL IMPLICATIONS: The use of ALA and/or tobacco products during pregnancy may adversely affect the reproductive health of male newborns in the long term. STRENGTHS & LIMITATIONS: To the best of our knowledge, this study is the first to show the effects of maternal ALA treatment and/or TSE on the sexual behavior and reproductive parameters in male rats; however, the study is based on an animal model, and the present findings partially reflect the characteristics of human sexual behavior. CONCLUSION: Maternal TSE and/or ALA treatment may impair sexual behavior in adulthood in male rats because of testicular damage caused by oxidative stress during gonadal development. Yardimci A, Akkoc RF, Tektemur A, et al. Chronic Maternal Tobacco Smoke Exposure and/or Alpha-Lipoic Acid Treatment Causes Long-Term Deterioration of Testis and Sexual Behavior in Adult Male Rats. J Sex Med 2020;17:1835-1847.

Irisin may have a role in pubertal development and regulation of reproductive function in rats.

Physical exercise and body muscle/fat mass are known to affect the endocrine system, puberty onset and reproductive health. However, the potential effects of irisin, an adipo-myokine and exercise-induced hormone, have not yet been fully elucidated on reproductive maturation. Therefore, the present study aimed to determine the effects of irisin administration on pubertal maturation and reproductive system in female and male rats. Daily i.p. injection of irisin (100 ng/kg; from postnatal day 21 for about 10 weeks) delayed the ages at the vaginal opening (as an external index of puberty onset) and first estrus. Furthermore, continuous administration of irisin to female rats caused a significant decrease in serum follicle-stimulating hormone levels and an increase in serum luteinizing hormone and 17ß-estradiol levels, as well as causing histopathological changes in the ovarian tissue. On the contrary, irisin administration to male rats did not modify the timing of puberty, as estimated by age at preputial separation. However, chronic exposure to irisin produced significant increases in serum luteinizing hormone and testosterone levels and also sperm concentration and seminiferous tubule diameter in male rats. In conclusion, irisin exposure has different effects on both pubertal maturation and reproductive system in female and male rats. The present findings reveal that chronic irisin exposure may lead to disorders in the female reproductive system and may have androgenic potential on the hypothalamic-pituitary-gonadal axis in males.

Chronic exposure to paroxetine or bupropion modulates the pubertal maturation and the reproductive system in female rats.

Antidepressant drugs are globally used to treat several psychiatric disorders in pediatric patients and their prescription has continued to increase in recent years, especially among girls. In addition to its well-known metabolic and gastrointestinal side effects, antidepressants can cause sexual dysfunction in adults. However, the effects of the antidepressants on puberty onset and reproductive system remain unclear in children and adolescents. Therefore, the goal of this study is to examine the effects of chronic postnatal antidepressant drugs, paroxetine or bupropion, treatments on puberty onset and reproductive system components in female rats weaned at postnatal day (PND) 21. Female rats (n = 10 for each group) were exposed to vehicle (0.2 mL of saline), paroxetine (3.6 mg/kg in 0.2 mL of saline) or bupropion (17 mg/kg in 0.2 mL of saline) daily by oral gavage from the PND 21 to PND 90-93. Chronic paroxetine or bupropion treatments advanced the puberty onset, but the difference was statistically significant in only the paroxetine group. The exposure to bupropion significantly decreased the serum anti-Müllerian hormone (AMH) levels and luteinizing hormone (LH) levels. There were increases in serum estradiol levels by both antidepressant treatments and the significance was found in only the paroxetine group. Consistent with these results, histopathologic changes were observed in the ovary and uterus tissues taken from both antidepressant-treated rats. The obtained results of chronic postnatal exposure to paroxetine or bupropion may change the timing of puberty onset and lead to disruption of reproductive functions in females.

Agomelatine potentiates anti-nociceptive effects of morphine in a mice model for diabetic neuropathy: involvement of NMDA receptor subtype NR1 within the raphe nucleus and periaqueductal grey.

OBJECTIVES: Opioid analgesics have been used for a long time in the treatment of acute and chronic pain. However, they have many side effects including tolerance development to a significant extent. Agomelatine, an atypical antidepressant, has been demonstrated to be effective in experimental studies on pain. However, the effect of agomelatine on morphine tolerance development and its mechanism of action are unknown. The antinociceptive effects of agomelatine, morphine and their combination were assessed in a mice model for painful diabetic neuropathy. The roles of glutamate ionotropic receptor N-methyl-D-aspartate (NMDA) type subunit-1 (GluN1) in raphe nucleus and periaqueductal gray (PAG) in the effect of agomelatine on neuropathic pain were also investigated in diabetic mice. METHODS: Agomelatine (10 mg/kg), morphine (10 mg/kg) and agomelatine + morphine were administered intraperitoneally for 15 consecutive days (twice per day), and the analgesic responses were assessed at days 1, 3, 6, 9, 12 and 15 in healthy and diabetic mice. Real time polymerase chain reaction (RT-PCR) was used to determine the changes in GluN1 expression. RESULTS: The tolerance development for morphine was evident, started at 6th day and remained thereafter, but not for agomelatine. GluN1 in raphe nucleus and PAG was upregulated in morphine treated but not in agomelatine-treated groups. DISCUSSION: The combination of agomelatine with morphine alone causes outlasting analgesic effects of repeated treatment, which can be interpreted as attenuated tolerance. Moreover, we also pointed out for the first time the modulatory effects of agomelatine on GluN1 expression in raphe nucleus and PAG after chronic morphine treatment. ABBREVIATIONS: Ca2+: Calcium; D2DR: Dopamine D2 receptor; GAPDH: Glyceraldehyde-3-phosphate dehydrogenase; GluN1: Glutamate ionotropic receptor N-methyl-D-aspartate type subunit-1; 5-HT: 5-hydroxytryptamine; i.p.: intraperitoneal injection; MPE: Maximal possible effect; MT: Melatonin; NMDA: N-methyl-D-aspartate; NMDAR1: NMDA receptors-1; PAG: Periaqueductal grey; PKCγ: Protein kinase C gamma; RT-PCR: Real time polymerase chain reaction; STZ: Streptozotocin.

Effects of long-term paroxetine or bupropion treatment on puberty onset, reproductive and feeding parameters in adolescent male rats.

Antidepressant use in adolescents has become more common in recent years. We have found several studies stating that prenatal antidepressant exposure can lead to delayed or earlier puberty onset but there was no study on postnatal paroxetine or bupropion. The main aim of this study was to investigate the effect of postnatal exposure to bupropion or paroxetine on puberty onset, reproductive and feeding results. The male rats (n = 8/group) aged 21 days were exposed to paroxetine (3.6 mg/kg) or bupropion (17 mg/kg) orally by gastric gavage every day from postnatal day 21-90. Also, control group received only saline orally as a vehicle. Postnatal exposure to bupropion or paroxetine delayed puberty onset compared to control group, but it was not significant. Sperm counts were significantly lower in the paroxetine and bupropion groups compared to control group. Sperm motility was significantly lower in only bupropion group. In addition, sperm motility was lower in paroxetine group, but it was not significant. In the histopathological examination, there was damage to the testicular structure in both treatments. Taken together, our result indicates that postnatal paroxetine or bupropion exposure may affect puberty onset and contribute to the impairment in fertility in male rats.

Rejection evaluation after renal transplantation using MR diffusion tensor imaging.

Background Renal allograft dysfunction monitoring is mainly performed using the serum creatinine (SC) level, Doppler ultrasound (US), or renal biopsy. Recently proposed diffusion-based magnetic resonance imaging (MRI) methods have been explored as new, non-invasive tools for assessing renal function after transplantation. Purpose To investigate the value of fractional anisotropy (FA) measurements in the evaluation of acute rejection cases after renal transplant. Material and Methods Doppler US and MRI diffusion tensor imaging (DTI) were performed in 21 patients with graft dysfunction requiring graft biopsy after renal transplantation and in 21 patients with normal graft function. The MR examinations were performed on a 1.5-T MRI using two b-values (0 and 800 s/mm2). FA values were measured from the cortex and medulla of the transplanted kidney at the upper, middle, and lower poles. Results Twenty-one transplant patients diagnosed with acute rejection (Group 1) were compared to the control group of 21 transplant patients with normal graft function (Group 2). The measured FA values of the medulla were 0.19 ± 0.02 and 0.22 ± 0.05 ( P = 0.017) for Groups 1 and 2, respectively. On the other hand, the measured FA values of the renal cortex were 0.18 ± 0.04 and 0.18 ± 0.04 ( P = 0.97) for Groups 1 and 2, respectively. Conclusion The good correlation between the renal medulla FA values and allograft function shows that MR DTI has potential for non-invasive functional assessment of transplanted kidneys. On the other hand, the renal cortex FA values had no correlation with the allograft function.