The Influence of Soy Isoflavones and Soy Isoflavones with Inulin on Kidney Morphology, Fatty Acids, and Associated Parameters in Rats with and without Induced Diabetes Type 2.

Diabetes mellitus resulting from hyperglycemia stands as the primary cause of diabetic kidney disease. Emerging evidence suggests that plasma concentrations of soy isoflavones, substances with well-established antidiabetic properties, rise following supplemental inulin administration. The investigation encompassed 36 male Sprague-Dawley (SD) rats segregated into two cohorts: non-diabetic and diabetic, induced with type 2 diabetes (high-fat diet + two intraperitoneal streptozotocin injections). Each cohort was further divided into three subgroups (n = 6): control, isoflavone-treated, and isoflavone plus inulin-treated rats. Tail blood glucose and ketone levels were gauged. Upon termination, blood samples were drawn directly from the heart for urea, creatinine, and HbA1c/HbF analyses. One kidney per rat underwent histological (H-E) and immunohistochemical assessments (anti-AQP1, anti-AQP2, anti-AVPR2, anti-SLC22A2, anti-ACC-alpha, anti-SREBP-1). The remaining kidney underwent fatty acid methyl ester analysis. Results unveiled notable alterations in water intake, body and kidney mass, kidney morphology, fatty acids, AQP2, AVPR2, AcetylCoA, SREBP-1, blood urea, creatinine, and glucose levels in control rats with induced type 2 diabetes. Isoflavone supplementation exhibited favorable effects on plasma urea, plasma urea/creatinine ratio, glycemia, water intake, and kidney mass, morphology, and function in type 2 diabetic rats. Additional inulin supplementation frequently modulated the action of soy isoflavones.

Effects of Letrozole Treatment and Vitamin C Supplementation on Morphology, Endoplasmic Reticulum Stress, Programmed Cell Death, and Oxidative Stress in the Small Intestine of Adult Male Rats.

Estrogens are hormones that play an important role in the digestive tract, including in men. Letrozole is an inhibitor of cytochrome P450 aromatase, an enzyme converting androgens to estrogens. The use of letrozole may cause oxidative stress and endoplasmic reticulum stress in the cells. Factors modulating cellular stress may include vitamin C. The purpose of this study was to examine whether letrozole and/or vitamin C supplementation can affect the morphology of the small intestine, the parameters of endoplasmic reticulum stress, programmed cell death markers, and oxidative damage. Three-month-old male rats were divided into four groups and treated with the following: (I) CTRL-water; (II) CTRL+C-L-ascorbic acid; (III) LET-letrozole; and (IV) LET+C-letrozole + L-ascorbic acid. The morphometrical measurements included epithelial thickness, crypt and lumen area, crypt perimeter, nuclei number in the crypt, and the cell size of crypts. The expression levels of PERK, caspase-3, and catalase were determined. Significant differences in the morphometrical measurements and immunoexpression were observed. This may indicate that chronic treatment with letrozole can affect morphology and induce ER stress, oxidative stress, and programmed cell death in the epithelial cells of the small intestine of adult male rats. Vitamin C supplementation exerts an effect on some parameters of the molecular processes.

Pilot Study: FSHR Expression in Neuroendocrine Tumors of the Appendix.

Appendix neuroendocrine neoplasm (ANEN) treatment is based on tumor size and proliferation markers. Recently, the role of the follicle-stimulating hormone receptor (FSHR) from the clinical perspective has also been increasingly discussed. The FSHR is expressed in the endothelial cells of both intratumoral and peritumoral blood vessels, where it contributes to neoangiogenesis and blood vessel remodeling. FSHR expression is associated with a range of tumor types, such as gastrointestinal tumors, and it is not detected in healthy tissues located more than 10 mm from the tumor site or in tumor lymphatics. In this study, we evaluated the expression of FSHR and CD31 in the blood vessels of ANENs in females and males with confirmed histopathology. We conducted a quantitative analysis of the immunohistochemical reactions and found a higher number of microvessels in the mucosa and submucosa of neuroendocrine tumors in the appendix. A higher level of FSHR expression was observed in women. Future research should consider whether an elevated number of blood vessels along with a strong pattern of FSHR expression may influence future treatment strategies.

Prenatal Exposition to Different Immunosuppressive Protocols Results in Vacuolar Degeneration of Hepatocytes.

Immunosuppressive drugs are essential for transplant recipients, since they prolong proper function of graft; however, they affect the morphology and function of organs, including liver. One commonly observed alteration in hepatocytes is vacuolar degeneration. Numerous medications are contraindicated in pregnancy and breastfeeding, mostly due to a lack of data concerning their advert effects. The aim of the current study was to compare the effects of prenatal exposition to different protocols of immunosuppressants on vacuolar degeneration in the hepatocytes of livers of rats. Thirty-two livers of rats with usage of digital analysis of the images were examined. Area, perimeter, axis length, eccentricity and circularity regarding vacuolar degeneration were analysed. The most prominent vacuolar degeneration in hepatocytes in the aspects of presence, area and perimeter was observed in rats exposed to tacrolimus, mycophenolate mofetil and glucocorticoids, and cyclosporine A, everolimus with glucocorticoids.This is the first study that demonstrates the results of the influence of multidrug immnunosuppression distributed in utero on the hepatic tissue of offspring.

Morphology of the male rat gonad after in Utero exposure to immunosuppressants.

The protocol for immunosuppression of pregnant women is based on immunosuppressant panels. The aim of the study was to determine the influence of commonly applied combinations of immunosuppressants to pregnant rats on the morphology of the offspring' testes. Pregnant rats were treated with cyclosporin A (CsA), mycophenolate mofetil (MMF) and prednisone (Pred) (CMG); tacrolimus (Tc), MMF and Pred (TMG); CsA, everolimus (Ev) and Pred (CEG). Testes of mature offspring underwent morphological analysis. Mainly in the testes of CMG and TMG rats the morphological and functional changes were observed: immature germ cells (GCs) in the seminiferous tubule (ST) lumen, invaginations of the basement membrane, infolding to the seminiferous epithelium (SE), the ST wall thickening, increased acidophilia of Sertoli cells' (SCs) cytoplasm, large residual bodies near the lumen, dystrophic ST and tubules look like the Sertoli cell-only syndrome, Leydig cells with abnormal cell nucleus, hypertrophy of the interstitium, blurring of the boundary between ST wall and interstitium, a reduced number of GCs in the SE, vacuolation of the SE. In the CEG there were only a reduced number of GCs in some tubules and vacuolization of SCs. The safest combination of drugs was CEG, while the TMG and CMG were gonadotoxic.

Hyaluronic Acid and Radiofrequency in Patients with Urogenital Atrophy and Vaginal Laxity.

Vaginal laxity (VL) and genitourinary syndrome of menopause (GSM), as well as aesthetic changes in the vulvar skin, often occur together and cause physical, psychological, and functional problems for women and their partners. The current study evaluated the efficacy of a nonsurgical radiofrequency device (RF) procedure combined with hyaluronic acid (HA) injection into the skin of the labia majora on clinical, histological, and aesthetic levels. Twenty women with GSM and VL, aged between 36 and 72 (mean age 53.4), were treated with bipolar RF SECTUM, vaginal and vulvar application, as well as with a hyaluronic acid (HA) injection into the skin of the labia majora. The Vaginal Laxity Questionnaire (VLQ), Vaginal Health Index (VHI), and Female Sexual Function Index (FSFI) were used to examine the clinical effects of the operations. The Global Aesthetic Improvement Scale was utilized to measure patient satisfaction. On a histochemical level, the concentrations of elastin and collagen in the vaginal wall and vulvar skin were examined. Results: There was significantly higher patient satisfaction and a considerable clinical improvement across all areas of analysis. On the histochemical level, elastin and collagen fiber concentration increased after the treatment protocol both in the vulvar skin and in the vaginal wall: elastin in the vaginal wall, 11.4%, and in the vulvar skin, 61%; collagen in the vaginal wall, 26%, and in the vulvar skin, 27%. The current study demonstrated the efficacy and safety of this nonsurgical RF procedure combined with a hyaluronic acid (HA) injection into the skin of the labia majora on clinical, histochemical, and aesthetic levels.

The Interplay between Finasteride-Induced Androgen Imbalance, Endoplasmic Reticulum Stress, Oxidative Stress, and Liver Disorders in Paternal and Filial Generation.

Finasteride (Fin) causes androgen imbalance by inhibiting the conversion of testosterone (T) to its more active metabolite, dihydrotestosterone (DHT). Androgen receptors (AR) are present (e.g., in hepatocytes), which have well-developed endoplasmic reticulum (ERet). Cellular protein quality control is carried out by ERet in two paths: (i) unfolded protein response (UPR) and/or (ii) endoplasmic reticulum associated degradation (ERAD). ERet under continuous stress can generate changes in the UPR and can direct the cell on the pathway of life or death. It has been demonstrated that genes involved in ERet stress are among the genes controlled by androgens in some tissues. Oxidative stress is also one of the factors affecting the functions of ERet and androgens are one of the regulators of antioxidant enzyme activity. In this paper, we discuss/analyze a possible relationship between androgen imbalance in paternal generation with ERet stress and liver disorders in both paternal and filial generation. In our rat model, hyperglycemia and subsequent higher accumulation of hepatic glycogen were observed in all filial generation obtained from females fertilized by Fin-treated males (F1:Fin). Importantly, genes encoding enzymes involved in glucose and glycogen metabolism have been previously recognized among UPR targets.

Colostrum-Induced Temporary Changes in the Expression of Proteins Regulating the Epithelial Barrier Function in the Intestine.

The intestinal wall and epithelial cells are interconnected by numerous intercellular junctions. Colostrum (Col), in its natural form, is a secretion of the mammary gland of mammals at the end of pregnancy and up to 72 h after birth. Recently, it has been used as a biologically active dietary supplement with a high content of lactoferrin (Lf). Lf, a glycoprotein with a broad spectrum of activity, is becoming more popular in health-promoting supplements. This study aims to investigate whether Col supplementation can affect small and large intestine morphology by modulating the expression of selected proteins involved in tissue integrity. We examined the thickness of the epithelium, and the length of the microvilli, and assessed the expression of CDH1, CDH2, CTNNB, CX43, VCL, OCLN, HP, MYH9, and ACTG2 gene levels using qRT-PCR and at the protein level using IHC. Additionally, to evaluate whether the effect of Col supplementation is temporary or persistent, we performed all analyses on tissues collected from animals receiving Col for 1, 3, or 6 months. We noticed a decrease in CDH1 and CDH2 expression, especially after 3 months of supplementation in the large intestine and in CTNNB in the small intestine as well as increased levels of CX43 and CTNNB1 in the small intestine. The present data indicate that Col can temporarily alter some components of the cell adhesion molecules involved in the formation of the cellular barrier.

Morphological and morphometric changes and epithelial apoptosis are induced in the rat epididymis by long-term letrozole treatment.

The epididymis is an organ that plays a key role in sperm maturation. The aim of this study was to examine the association between the chronic treatment of mature male rats with letrozole and morphological evaluation and morphometric values of epididymis as well as changes in the number of apoptotic cells in epididymal epithelium. Adult rats were treated with letrozole for 6 months and the epididymis weight, morphology, morphometric values and the number of apoptotic cells in  the epithelium were examined. Long-term aromatase inhibition resulted in presence of intraepithelial clear vacuoles, hyperplasia of clear cells and a hyperplastic alteration in the epithelium known as a cribriform change. Moreover, changes in diameters of the epididymal duct and the epididymal lumen and changes in the epididymal epithelium height were observed. The number of apoptotic epithelial cells was increased in letrozole-treated group. It can be indicated that chronic treatment with letrozole can affect morphology, morphometric values and apoptosis in the epididymis of adult male rats. Observed changes are similar to that observed in the aging processes and may also be important for patients treated with aromatase inhibitors.

Paternal Finasteride Treatment Can Influence the Testicular Transcriptome Profile of Male Offspring-Preliminary Study.

(1) Background: Hormone-dependent events that occur throughout spermatogenesis during postnatal testis maturation are significant for adult male fertility. Any disturbances in the T/DHT ratio in male progeny born from females fertilized by finasteride-treated male rats (F0:Fin) can result in the impairment of testicular physiology. The goal of this work was to profile the testicular transcriptome in the male filial generation (F1:Fin) from paternal F0:Fin rats. (2) Methods: The subject material for the study were testis from immature and mature male rats born from females fertilized by finasteride-treated rats. Testicular tissues from the offspring were used in microarray analyses. (3) Results: The top 10 genes having the highest and lowest fold change values were mainly those that encoded odoriferous (Olfr: 31, 331, 365, 633, 774, 814, 890, 935, 1109, 1112, 1173, 1251, 1259, 1253, 1383) and vomeronasal (Vmn1r: 50, 103, 210, 211; Vmn2r: 3, 23, 99) receptors and RIKEN cDNA 5430402E10, also known as odorant-binding protein. (4) Conclusions: Finasteride treatment of male adult rats may cause changes in the testicular transcriptome of their male offspring, leading to a defective function of spermatozoa in response to odorant-like signals, which are recently more and more often noticed as significant players in male fertility.

Tacrolimus-Based Immunosuppressive Therapy Influences Sex Hormone Profile in Renal-Transplant Recipients-A Research Study.

It is estimated that approximately 20% of couples suffer from infertility worldwide and within renal-transplant recipients, this problem is 10 times more common. An intake of immunosuppressants may lead to hormonal imbalance. The aim of the study was to investigate the influence of tacrolimus-based therapy on the hormonal status of grafted patients. Blood samples were obtained from patients from the Department of Nephrology, Transplantology, and Internal Medicine of Independent Public Clinical Hospital No. 2, Pomeranian Medical University. All 121 patients had stable graft function for over 6 months. The blood plasma concentrations of luteinizing hormone, follicle-stimulating hormone, prolactin, testosterone, estradiol, cortisol were assessed by the electrochemiluminescence method. We observed decreased levels of prolactin (11.9 ng/mL) and cortisol (87.4 µg/mL) in patients under tacrolimus-based therapy. Tacrolimus-based therapy was also associated with increased testosterone and follicle-stimulating hormone in males, 4.04 ng/mL and 6.9 mLU/mL, respectively, and decreased testosterone levels in females, 0.121 ng/mL. We also assessed that immunosuppressive therapy based on tacrolimus is less nephrotoxic in comparison to other regimens. Concluding, tacrolimus-based therapy may influence the hormonal status of transplant recipients in the current study. Results presented here are believed to be helpful for clinicians and patients, especially within the aspect of willingness for biological offspring.

The Obscure Effect of Tribulus terrestris Saponins Plus Inulin on Liver Morphology, Liver Fatty Acids, Plasma Glucose, and Lipid Profile in SD Rats with and without Induced Type 2 Diabetes Mellitus.

Diabetes is a predictor of nonalcoholic fatty liver disease (NAFLD). There are data suggesting that Tribulus terrestris (TT) saponins act as antidiabetic agents and protect against NAFLD. The effect of saponins may be increased by fermentable fibers such as inulin. The aim of the present study was to investigate the influence of TT saponins and TT saponins plus inulin on the plasma lipid profile and liver fatty acids of rats with induced diabetes mellitus type 2 (T2DM). The study was performed on 36 male Sprague-Dawley rats divided into two main groups: control and diabetic. Animals of the diabetic (DM) group were fed a high-fat diet and injected with streptozotocin (low doses). Animals of the control group (nDM) were on a regular diet and were injected with buffer. After the injections, the animals were split into subgroups: three non-diabetic (nDM): (i) control (c-C); (ii) saponin-treated rats (C-Sap); (iii) rats treated with saponins + inulin (C-Sap + IN), and three diabetic subgroups (DM): (iv) control (c-DM); (v) saponin-treated rats (DM-Sap); (vi) rats treated with saponins + inulin (DM-Sap + IN). Liver fatty acids were extracted and analyzed by gas chromatography, and plasma glucose and lipids were measured. The study showed significant changes in liver morphology, liver fatty acids, plasma lipid profile, and plasma glucose. In summary, supplementation with TT saponins or saponins with inulin for one month decreased the level of steatosis in rats with induced type 2 diabetes. Moreover, there were favorable effects on the plasma lipid profile in the rats. However, additional supplementation with inulin had a negative effect on liver morphology (with a microvesicular type of steatosis) in the non-diabetes group. Moreover, supplementation with inulin had a negative effect on plasma glucose in both diabetic and non-diabetic rats. These data show that a diet enriched with fermentable fibers reveals different effects in different organisms, and not all sources and forms of fiber are beneficial to health.

Hormonal (Im)Balance and Reproductive System's Disorders in Transplant Recipients-A Review.

The rising need for treatment of end stage of organ failure results in an increased number of graft recipients yearly. The most commonly transplanted organs are kidney, heart, liver, bone marrow, lung and skin. The procedure of transplantation saves and prolongs the lives of chronically ill patients or at least improves the quality. However, following transplantation recipients must take immunosuppressive drugs on a daily basis. Usually, the immunosuppressive therapy comprises two or three drugs from different groups, as the mechanism of their action varies. Although the benefits of intake of immunosuppressants is undeniable, numerous side effects are associated with them. To different extents, they are neurotoxic, nephrotoxic and may influence the function of the reproductive system. Nowadays, when infertility is an urgent problem even among healthy pairs, transplant recipients face the problem of disturbance in the hypothalamic-pituitary axis. This review will provide an overview of the most common disturbances among the concentration of sex-related hormones in recipients of both sexes at different ages, including sexually immature children, adults of reproductive age as well as elderly women and men. We have also focused on the numerous side effects of immunosuppressive therapy regarding function and morphology of reproductive organs both in males and females. The current review also presents the regimen of immunosuppressive therapy and time since transplantation.

Global Gene Expression of Cultured Human Dermal Fibroblasts: Focus on Cell Cycle and Proliferation Status in Improving the Condition of Face Skin.

Chronological skin ageing is an inevitable physiological process that results in thin and sagging skin, fine wrinkles, and gradual dermal atrophy. The main therapeutic approaches to soft tissue augmentation involve using dermal fillers, where natural fillers, such as autologous fibroblasts, are involved in generating dermal matrix proteins. The aim of this study was to determine the global transcriptome profile of three passages of dermal autologous fibroblasts from a male volunteer, focusing on the processes of the cell cycle and cell proliferation status to estimate the optimal passage of the tested cells with respect to their reimplantation. We performed K-means clustering and validation of the expression of the selected mRNA by qRT-PCR. Ten genes were selected (ANLN, BUB1, CDC20, CCNA2, DLGAP5, MKI67, PLK1, PRC1, SPAG5, and TPX2) from the top five processes annotated to cluster 5. Detailed microarray analysis of the fibroblast genes indicated that the cell population of the third passage exhibited the highest number of upregulated genes involved in the cell cycle and cell proliferation. In all cases, the results of qRT-PCR confirmed the differences in expression of the selected mRNAs between fibroblasts from the primary culture (C0) and from the first (C1), second (C2), and third (C3) cell passage. Our results thus suggest that these cells might be useful for increasing fibroblast numbers after reimplantation into a recipient's skin, and the method used in this study seems to be an excellent tool for autologous transplantation allowing the rejuvenation of aging skin.

Analysis of Cadmium, Mercury, and Lead Concentrations in Erythrocytes of Renal Transplant Recipients from Northwestern Poland.

Cadmium (Cd), mercury (Hg), and lead (Pb) exhibit highly nephrotoxic properties, and their high concentrations can lead to renal failure. Much research has been conducted on the concentrations of heavy metals, microelements, and macroelements in the blood, but little is known about the concentration of Cd, Pb, and Hg in erythrocytes of renal recipients. The aim of this study is to determine the blood erythrocyte concentrations of toxic metals (Cd, Pb, and Hg) in renal transplant recipients (RTRs). Additionally, we analyzed the effect of selected biological and environmental factors, including the intake of various immunosuppressive drug regimens and smoking, on these xenobiotic concentrations. The material consisted of erythrocyte samples from 115 patients of the Department of Nephrology, Transplantology, and Internal Medicine at Independent Public Clinical Hospital No. 2, Pomeranian Medical University, Szczecin, in northwestern Poland. Cd, Hg, and Pb levels in the erythrocytes were quantified by inductively coupled mass spectroscopy (ICP-MS). Equal concentrations of Cd were found in erythrocytes of both female and male transplant recipients. The highest level of Hg was seen in women, and women overall had statistically higher concentrations of Pb than men. Comparison of metal concentrations between those over 50 years and those under it showed that Pb concentration was also significantly higher in renal transplant recipients over 50. Pb concentration was almost twice as high in RTRs who used tacrolimus with mycophenolate mofetil than in RTRs who used cyclosporine A with mycophenolate mofetil. The highest level of Cd was seen in smokers, who had 3.25 µg/L. This value was significantly higher than in ex-smokers (p = 0.001) and with RTRs who had never smoked. There were significantly higher levels of Pb in the erythrocytes of RTRs who were ex-smokers than in those who had never smoked. A statistically significant correlation was found between Cd and Pb concentrations. Additionally, we have noticed significant positive correlation between Pb and age (R = 0.37), gender (R = 0.24) and significant negative correlation of Pb with GFR (R = -0.33). We have also found significant positive correlation between Hg and age (R = 0.21). In summary, our data suggest that, smoking is associated with Pb and Cd concentrations, and gender, age change depending on Pb concentration in erythrocytes of RTRs. Additionally, this is the first research that suggests that immunosuppressive regimen, depending on type of immunosuppressive drugs combination affects Pb concentration in erythrocytes of RTRs. It seems to be crucial information for patients who use immunosuppressive drugs.

The Postnatal Offspring of Finasteride-Treated Male Rats Shows Hyperglycaemia, Elevated Hepatic Glycogen Storage and Altered GLUT2, IR, and AR Expression in the Liver.

BACKGROUND: A growing body of data indicates that the physiology of the liver is sex-hormone dependent, with some types of liver failure occurring more frequently in males, and some in females. In males, in physiological conditions, testosterone acts via androgen receptors (AR) to increase insulin receptor (IR) expression and glycogen synthesis, and to decrease glucose uptake controlled by liver-specific glucose transporter 2 (GLUT-2). Our previous study indicated that this mechanism may be impaired by finasteride, a popular drug used in urology and dermatology, inhibiting 5α-reductase 2, which converts testosterone (T) into dihydrotestosterone (DHT). Our research has also shown that the offspring of rats exposed to finasteride have an altered T-DHT ratio and show changes in their testes and epididymides. Therefore, the goal of this study was to assess whether the administration of finasteride had an trans-generational effect on (i) GLUT-2 dependent accumulation of glycogen in the liver, (ii) IR and AR expression in the hepatocytes of male rat offspring, (iii) a relation between serum T and DHT levels and the expression of GLUT2, IR, and AR mRNAs, (iv) a serum glucose level and it correlation with GLUT-2 mRNA. METHODS: The study was conducted on the liver (an androgen-dependent organ) from 7, 14, 21, 28, and 90-day old Wistar male rats (F1:Fin) born by females fertilized by finasteride-treated rats. The control group was the offspring (F1:Control) of untreated Wistar parents. In the histological sections of liver the Periodic Acid Schiff (PAS) staining (to visualize glycogen) and IHC (to detect GLUT-2, IR, and AR) were performed. The liver homogenates were used in qRT-PCR to assess GLUT2, IR, and AR mRNA expression. The percentage of PAS-positive glycogen areas were correlated with the immunoexpression of GLUT-2, serum levels of T and DHT were correlated with GLUT-2, IR, and AR transcript levels, and serum glucose concentration was correlated with the age of animals and with the GLUT-2 mRNA by Spearman's rank correlation coefficients. RESULTS: In each age group of F1:Fin rats, the accumulation of glycogen was elevated but did not correlate with changes in GLUT-2 expression. The levels of GLUT-2, IR, and AR transcripts and their immunoreactivity statistically significantly decreased in F1:Fin animals. In F1:Fin rats the serum levels of T and DHT negatively correlated with androgen receptor mRNA. The animals from F1:Fin group have statistically elevated level of glucose. Additionally, in adult F1:Fin rats, steatosis was observed in the liver (see Appendix A). CONCLUSIONS: It seems that treating male adult rats with finasteride causes changes in the carbohydrate metabolism in the liver of their offspring. This can lead to improper hepatic energy homeostasis or even hyperglycaemia, insulin resistance, as well as some symptoms of metabolic syndrome and liver steatosis.

Morphology and serum and bone tissue calcium and magnesium concentrations in the bones of male rats chronically treated with letrozole, a nonsteroidal cytochrome P450 aromatase inhibitor.

Purpose/Aim of the study: The role of estrogen (E) in the regulation of bone turnover in women is well established, though the contributions of E versus testosterone (T) in the control of bone turnover in men are poorly understood. The aim of this study was to examine the association between chronic treatment with letrozole, a nonsteroidal inhibitor blocking the aromatase activity and thus the conversion of androgens into estrogens, and cortical bone morphology in the femur and humerus of male adult rats.Materials and Methods: Adult male rats were treated with letrozole for 6 months and the body and femur weight, morphology, collagen structure, blood serum, and bone tissue concentrations of calcium and magnesium were examined.Results: Long-term aromatase inhibition resulted in a decrease in femur mass, a wavelike arrangement of bone and lamellae with an altered organization of collagen in compact bone, a increased concentration of calcium in blood serum, and no change in calcium bone tissue concentration, magnesium serum, or bone tissue concentration. MicroCT study of the humerus revealed significant decreases of whole bone tissue volume, cortical bone thickness, cortical bone volume, and external cortical bone thickness with letrozole treatment.Conclusion: Chronic treatment with letrozole affected cortical bone structure and produced histomorphological changes in male rat bone similar to that observed in the aging processes.

Neuroendocrine Tumors: Clinical, Histological and Immunohistochemical Perspectives and Case Report-Mature Teratoma in a 16-Year-Old Girl.

A mature teratoma is a germinal neoplasm that differentiates from embryonic multipotent cells into three germ layers. There may also be glandular tissue. The literature describes a total of 658 cases of ovarian neuroendocrine neoplasms, mainly in women over 40 years of age. The authors, together with a systemic review, present a case of a 16-year-old girl diagnosed with and treated for a neuroendocrine tumor. Case description: A 16-year-old girl visited the Paediatric Gynaecology Outpatient Clinic because of abdominal pains that intensified during menstruation. Standard painkillers and diastolic drugs were ineffective. An ultrasound examination revealed a large tumor with a heterogeneous structure in her right ovary. A sparing operation was carried out. During laparotomy, the lesion was enucleated, leaving healthy tissue. Histopathological examination revealed the typical features of teratoma, as well as the coexistence of a G1 neuroendocrine tumor. Immunohistochemical examination (IHC) showed the presence of markers characteristic for this type of tumor. The patient requires constant monitoring in the Endocrinology and Oncological Gynaecology Clinic. Conclusion: Tissue of neuroendocrine neoplasm within a teratoma is rare in this age group of patients; thus, there are currently no standards for long-term follow-up. This case adds to the body of evidence and demonstrates a possible good prognosis with non-aggressive behavior in G1 neuroendocrine tumors and teratomas in young patients.

Morphological and Functional Changes in Skin of Adult Male Rats Chronically Treated with Letrozole, a Nonsteroidal Inhibitor of Cytochrome P450 Aromatase.

Skin is a target for hormones and a site of hormone production. Aromatase inhibitors such as letrozole reduce circulating estrogen. The aim of the study was to investigate the morphology of the dermis and immunoexpression of androgen receptor (AR), estrogen receptor α and ß (ERα, ERß), luteinizing hormone receptor (LHR), follicle-stimulating hormone receptor (FSHR), and cytochrome P450 aromatase (P450arom) in male rats with a deficit of estradiol. Experiments were performed on skin of 12 male rats. Rats in the experimental group received per os letrozole for 6 months. For morphological analysis, van Gieson, Sirius Red and orcein staining of sections was performed. In immunohistochemistry, reactions with specific antibodies (anti-P450arom, LHR, FSHR, ERα, ERß) were used. In morphometric analysis, sections were stained with hematoxylin and eosin. Differences between groups were assessed by Mann-Whitney U-test. There were no differences in the diameter of collagen fibers. The dermis of letrozole-treated animals showed areas without collagen fibers, and expression of P450arom, ERα and ERß was diminished in the skin of these animals. This study indicates that estrogens exert an effect via ERs that has a role in maintaining proper skin morphology in males, together with androgen. This is also the first documented expression of FSHR in the skin of male rats.

Expression of SCD and FADS2 Is Lower in the Necrotic Core and Growing Tumor Area than in the Peritumoral Area of Glioblastoma Multiforme.

The expression of desaturases is higher in many types of cancer, and despite their recognized role in oncogenesis, there has been no research on the expression of desaturases in glioblastoma multiforme (GBM). Tumor tissue samples were collected during surgery from 28 patients (16 men and 12 women) diagnosed with GBM. The effect of necrotic conditions and nutritional deficiency (mimicking conditions in the studied tumor zones) was studied in an in vitro culture of human brain (glioblastoma astrocytoma) U-87 MG cells. Analysis of desaturase expression was made by qRT-PCR and the immunohistochemistry method. In the tumor, the expression of stearoyl-coenzyme A desaturase (SCD) and fatty acid desaturases 2 (FADS2) was lower than in the peritumoral area. The expression of other desaturases did not differ in between the distinguished zones. We found no differences in the expression of SCD, fatty acid desaturases 1 (FADS1), or FADS2 between the sexes. Necrotic conditions and nutritional deficiency increased the expression of the studied desaturase in human brain (glioblastoma astrocytoma) U-87 MG cells. The obtained results suggest that (i) biosynthesis of monounsaturated fatty acids (MUFA) and polyunsaturated fatty acids (PUFA) in a GBM tumor is less intense than in the peritumoral area; (ii) expressions of SCD, SCD5, FADS1, and FADS2 correlate with each other in the necrotic core, growing tumor area, and peritumoral area; (iii) expressions of desaturases in a GBM tumor do not differ between the sexes; and (iv) nutritional deficiency increases the biosynthesis of MUFA and PUFA in GBM cells.