Ginsenoside Rb2 exhibits therapeutic value for male osteoporosis in orchiectomy mice by suppressing osteoclastogenesis and modulating NF-κB/MAPK signaling pathways.

Osteoporosis (OP) is a systemic disorder characterized by decreased bone mass as well as deteriorated microarchitecture. Although OP in men is common, it has received much less attention than that in women. Ginseng, a famous traditional herb in Asia, is used to strengthen and repair bones by invigorating vital bioenergy and maintaining body homeostasis in dietary intake and clinical applications. However, there is currently no study investigating the impact of ginseng and its active compounds on male osteoporosis. In this study, RNA sequencing and bioinformatic analysis were conducted to reveal the influence of Ginsenoside-Rb2 on RAW264.7 cells and its underlying signaling pathways. The potential anti-osteoporosis effects of Rb2 as well as its molecular mechanisms were elucidated in RAW264.7 cells and BMMs by TRAP staining, F-actin belt staining, qRT-PCR and WB. Moreover, orchiectomy (ORX) was utilized to demonstrate the influence of Rb2 on bone mass loss in vivo by micro-CT scanning, and H&E, TRAP, and IHC staining. The results suggested that Rb2 suppressed osteoclastogenesis and mitigated bone loss in orchiectomy mice through NF-κB/MAPK signaling pathways. These findings indicate that ginseng as well as its active component Rb2 have potential therapeutic value in the management of osteoporosis in men.

Testosterone regulates thymic remodeling by altering metabolic reprogramming in male rats.

The thymus is an energy-consuming organ, and its metabolism changes with atrophy. Testosterone regulates thymus remodeling (atrophy and regeneration). However, the characteristics of the energy metabolism during testosterone-mediated thymic atrophy and regeneration remain unclear. In this study, we demonstrated that testosterone ablation (implemented by immunocastration and surgical castration) induced global metabolic changes in the thymus. Kyoto Encyclopedia of Genes and Genomes pathway enrichment for differential metabolites and metabolite set enrichment analysis for total metabolites revealed that testosterone ablation affected thymic glycolysis, glutamate metabolism, and fatty acid ß-oxidation. Testosterone ablation-induced thymic regeneration was accompanied by attenuated glycolysis and glutamate metabolism and changed fatty acid composition and content. Testosterone supplementation in immunocastrated and surgically castrated rats enhanced glutaminolysis, reduced the level of unsaturated fatty acids, enhanced the ß-oxidation of unsaturated fatty acids in the mitochondria, boosted the tricarboxylic acid (TCA) cycle, and accelerated thymic atrophy. Overall, these results imply that metabolic reprogramming is directly related to thymic remodeling.

Advances in radiation therapy for testicular seminoma.

PURPOSE: Novel techniques and advances in radiation therapy (RT) have been explored to treat testicular seminoma, a highly radiosensitive and curable histology. We evaluated the historical and current indications for radiation therapy (RT) in testicular seminoma. METHODS: A narrative literature review was performed. Studies of RT for testicular seminoma were included. Additionally, recent trials testing the use of combination or surgical therapies for clinical stage (CS) II were included. Search parameters included radiation therapy, testicular seminoma, surgery, and chemoradiation. Parameters and outcomes assessed were progression-free survival (PFS), overall survival (OS), acute toxicities, long-term sequelae, and rates of secondary malignancies. RESULTS: Practice defining and changing studies in the use or omission of radiation therapy for testicular seminoma were identified along with resultant changes in National Comprehensive Cancer Network (NCCN) and European guidelines. Recent trials in combined chemoradiation and upfront surgical approaches to CS II disease were reviewed. CONCLUSION: RT has historically been used as adjuvant treatment for CS I disease and is highly effective at treating CS II (A/B) testicular seminoma. The drive to maintain therapeutic efficacy and reduce acute and long-term side effects, namely secondary malignancies, is being tested using new radiation technologies, combined modality therapy in the form of chemoradiation and with upfront surgical approaches. Also, as guidelines now "strongly prefer" surveillance instead of adjuvant RT for CS I disease, the current CS II population comprises patients presenting with CS II disease ("de novo") and those who present with CSII after relapsing post orchiectomy for CS I ("relapsed"). Emerging evidence suggests that these two groups have different outcomes with respect to RT and chemoradiation. Consequently, future trials may need to sub-stratify according to these groups.

Application of a topical anesthetic reduces pain-associated parameters during spermatic cord transection in piglet castration using a minimal anesthesia model.

OBJECTIVE: This study assessed the use of a topical anesthetic as a feasible approach to reduce pain during piglet castration using a minimal anesthesia protocol. ANIMALS: 18 male piglets, aged 3-6 days, were included in this study. METHODS: A minimal anesthetic state was induced with isoflurane administered by facemask, with anesthetic depth individually adjusted based on responses to interdigital pinch. To desensitize the scrotal skin, a vapocoolant was applied 3 times. Scrotal incisions were made subsequently and Tri-Solfen (TS) or Placebo (P) was administered in both incisional gaps. After 30 seconds, the spermatic cords were severed followed by a further application of TS/P to both incision edges. Nociception-related variables, such as mean arterial blood pressure (MAP), heart rate (HR), and nocifensive movements, were assessed. RESULTS: Significant differences in MAP changes were assessed between the TS (14 ± 4 mmHg) and the P group (36 ± 8 mmHg) for cutting the spermatic cords. Furthermore, significantly fewer nocifensive movement score points appeared in the TS than in the P group (0; IQR = 0 vs 5; IQR = 6). CLINICAL RELEVANCE: In this anesthesia model, the application of TS after skin incision significantly reduced MAP responses and nocifensive movements with spermatic cord transection compared with the application of P. However, the waiting period between TS-application and spermatic cord transection might limit the benefit of the method in conscious piglets, as pain during castration is reduced but additional stress is caused by the prolonged handling. Furthermore, using a vapocoolant did not provide anesthesia for skin incisions.

Effects of testosterone replacement on lipid profile, hepatotoxicity, oxidative stress, and cognitive performance in castrated wistar rats.

OBJECTIVE: Androgen deficiency is associated with multiple biochemical and behavioral disorders. This study investigated the effects of testosterone replacement and Spirulina Platensis association on testosterone deficiency-induced metabolic disorders and memory impairment. METHODS: Adult male rats were randomly and equally divided into four groups and received the following treatments for 20 consecutive days. CONTROL GROUP: non-castrated rats received distilled water. Castrated group received distilled water. Testosterone treated group: castrated rats received 0.20 mg of testosterone dissolved in corn oil by subcutaneous injection (i.p.). Spirulina co-treated group: castrated rats received 0.20 mg of testosterone (i.p.) dissolved in corn oil followed by 1000 mg/kg of Spirulina per os. RESULTS: Data showed that castration induced an increase in plasma ALT, AST, alkaline phosphatase (PAL), cholesterol, and triglycerides level. Castrated rats showed a great elevation in SOD and CAT activities and MDA and H2O2 levels in the prostate, seminal vesicles, and brain. Testosterone deficiency was also associated with alteration of the spatial memory and exploratory behaviour. Testosterone replacement either alone or with Spirulina combination efficiently improved most of these biochemical parameters and ameliorated cognitive abilities in castrated rats. CONCLUSIONS: Testosterone replacement either alone or in combination with Spirulina improved castration-induced metabolic, oxidative, and cognitive alterations.

Ketamine-dexmedetomidine combined with local anesthesia, with or without different doses of atipamezole in the postoperative period, for orchiectomy in cats.

OBJECTIVE: To evaluate the anesthetic and cardiopulmonary effects of ketamine-dexmedetomidine combined with local anesthesia, associated or not in the postoperative period with different doses of atipamezole, for orchiectomy in cats. ANIMALS: 24 healthy cats. PROCEDURES: Cats received ketamine (7 mg/kg) combined with dexmedetomidine (10 µg/kg) IM, and 1 mL of saline (group KDSAL), 25 µg/kg (group KDAT25), or 50 µg/kg (group KDAT50) of atipamezole IV, postoperatively. All cats received local anesthesia (2 mg/kg of lidocaine) intratesticular and SC. Physiologic variables were recorded at baseline and at time points during anesthesia. Ketamine rescue dose (1 mg/kg) was recorded. The quality of recovery, the degree of sedation, and side effects were evaluated postoperatively. RESULTS: 2 cats received a single additional bolus of ketamine to perform local anesthesia. Heart rate was lower in KDSAL, KDAT25, and KDAT50 during anesthesia, compared with baseline. Hypertension was observed intraoperatively in all groups. The time to head up, pedal reflex regained time, time to sternal recumbency, and time to standing were shorter in KDAT25 and KDAT50 compared to KDSAL. Lower sedation scores were assigned sooner to KDAT25 and KDAT50 than KDSAL. All groups resulted in low recovery quality scores and no side effects. CLINICAL RELEVANCE: At the doses used, ketamine-dexmedetomidine combined with local anesthesia allowed the performance of orchiectomy. Rescue dose of ketamine for performing local anesthesia may be required. This combination can result in hypertension. Both atipamezole doses shortened the anesthetic recovery, without differences among them, and side effects.

The importance of pigs' castration strategy on carbon footprint of feed intake, nitrogen and phosphorus efficiency under different management conditions.

The environmental impact of livestock production is under scrutiny nowadays and is being situated both on a global level and local level. On a global level, the global warming potential (GWP) of meat production is criticised. On a local level, the excretion of nitrogen (N) and phosphorus (P) is of concern as excess nutrients may lead to water eutrophication and soil acidification. The ERA-NET project SuSI evaluated if immunocastration may act as an ecologically, socially and economic more sustainable alternative compared to pork production with surgical castrates (SCs) and boars (BOs). Here, we report the environmental impact of immunocastrates (ICs) vs SC and BO, based on four trials carried out by European SuSi partners. More specifically, we aimed to compare IC with SC and BO in terms of GWP, N and P excretion per kg of pork production and test if this differed between experiments. There was an interaction between trial and sex category (PTrial × Sex category < 0.005) for all environmental sustainability parameters. Surgical castrates performed worse (higher carbon footprint of the feed intake, N and P excretion, lower N and P efficiency) compared to IC and BO, but the size of the effect was trial dependent. Immunocastrates scored intermediate, with mostly no significant differences from BO in most trials, but with significantly better values compared to SC. Over trials, the carbon footprint of the feed intake (land use change inclusive) per kg lean meat gain in the growing-finishing phase was 9-16% lower for IC vs SC and 9-22% lower for BO vs SC. Nitrogen efficiency of IC and BO was 7-10% and 9-14%, respectively, higher compared to SC. Phosphorus efficiency of IC and BO was higher than that of SC by 6-14% and 9-17%, respectively. Per kg of lean meat gain in the growing-finishing phase, IC excreted between 14 and 19% less N and between 14 and 24% less P than SC. For BO, it was between 14 and 27% less N and between 14 and 31% less P than SC. Differences between trials were larger than differences between castration strategies and trial design may have amplified the observed effects. Improving feed efficiency, adapting the feed to the needs of the animal (avoiding excess nutrients) and choosing low-impact ingredients are key for improving the environmental sustainability of pig production. Ending physical castration is another step to attain this goal.

A Phytomolecule Icariin Protects from Sarcopenia Partially by Suppressing Myosin Heavy Chain Degradation in Orchiectomized Rats.

Treatments are lacking for sarcopenia, which is an age-related disease characterized by loss of skeletal muscle mass, strength, and/or physical performance. Icariin is a phytomolecule from herbal Epimedium, a traditional Chinese medicine widely used to treat musculoskeletal disorders for thousands of years. Here the effects of icariin against sarcopenia are investigated and the underlying mechanism is elucidated. A classic rat model of bilaterally orchiectomized (ORX) is used to induce sarcopenia. After administration for 8 weeks, compared to the control group, the forelimb grip strength, the specific tetanic forces of the soleus (SOL) and extensor digitorum longus muscle (EDL) are higher, and the fiber cross-sectional areas (CSAs) of the gastrocnemius and tibialis anterior muscle are larger in the icariin group. In addition, icariin promotes mRNA and protein expressions of myosin heavy chain (MyHC) both in SOL and EDL. Mechanistically, icariin significantly suppresses the mRNA and protein expressions of FOXO3a, atrogin-1, and MuRF-1, which are related to the degradation of myosin heavy chain. Collectively, icariin protects from sarcopenia in ORX rats characterized by enhancing grip strength and skeletal muscle contraction, as well as increasing skeletal muscle CSA by inhibiting the ubiquitination degradation of the MyHC in skeletal muscle fibers.

Effects of dissociative anesthesia opioid-free protocols combined with local anesthesia, with or without flumazenil or atipamezole postoperatively, for orchiectomy in cats.

OBJECTIVE: To evaluate the anesthetic effects of two drug combinations with local anesthesia, with or without postoperative antagonists, for orchiectomy in cats. STUDY DESIGN: Prospective, randomized blinded clinical study. ANIMALS: A total of 64 healthy cats. METHODS: Cats were assigned to four equal groups: ketamine (5 mg kg-1) and dexmedetomidine (10 µg kg-1) were administered intramuscularly (IM), followed postoperatively with intravenous (IV) saline (5 mL; group KDS) or atipamezole (50 µg kg-1; group KDA); and ketamine (14 mg kg-1) with midazolam (0.5 mg kg-1) and acepromazine (0.1 mg kg-1) IM, with postoperative IV saline (5 mL; group KMAS) or flumazenil (0.1 mg kg-1; group KMAF). Lidocaine (2 mg kg-1) was divided between subcutaneous and intratesticular injection. Physiologic variables were recorded at time points during anesthesia. Ketamine rescue dose was recorded. The degree of sedation and the quality of recovery were evaluated postoperatively. RESULTS: Time to loss of pedal reflex was longer in groups KMAS and KMAF than in groups KDS and KDA (p = 0.010). Total rescue dose of ketamine was higher in KMAS and KMAF than in KDS and KDA (p = 0.003). Heart rate (HR) during anesthesia was higher in KMAS and KMAF than in KDS and KDA (p = 0.001). Times to head up (p = 0.0005) and to sternal recumbency (p = 0.0003) were shorter in KDA than in KDS, KMAS and KMAF. Lower sedation scores were assigned sooner to KDA than KDS, KMAS and KMAF (p < 0.001). Recovery quality scores were good in all groups. CONCLUSIONS AND CLINICAL RELEVANCE: Both anesthetic protocols allowed the performance of orchiectomy. Groups KMAS and KMAF required higher rescue doses of ketamine before injecting lidocaine. HR and oscillometric systolic pressure were minimally changed in groups KD and tachycardia was recorded in groups KMA. Only atipamezole shortened the anesthetic recovery.

Sexual dimorphism in glucose metabolism is shaped by androgen-driven gut microbiome.

Males are generally more susceptible to impaired glucose metabolism and type 2 diabetes (T2D) than females. However, the underlying mechanisms remain to be determined. Here, we revealed that gut microbiome depletion abolished sexual dimorphism in glucose metabolism. The transfer of male donor microbiota into antibiotics-treated female mice led the recipients to be more insulin resistant. Depleting androgen via castration changed the gut microbiome of male mice to be more similar to that of females and improved glucose metabolism, while reintroducing dihydrotestosterone (DHT) reversed these alterations. More importantly, the effects of androgen on glucose metabolism were largely abolished when the gut microbiome was depleted. Next, we demonstrated that androgen modulated circulating glutamine and glutamine/glutamate (Gln/Glu) ratio partially depending on the gut microbiome, and glutamine supplementation increases insulin sensitivity in vitro. Our study identifies the effects of androgen in deteriorating glucose homeostasis partially by modulating the gut microbiome and circulating glutamine and Gln/Glu ratio, thereby contributing to the difference in glucose metabolism between the two sexes.

Co-Treatment of Purified Annatto Oil (Bixa orellana L.) and Its Granules (Chronic®) Improves the Blood Lipid Profile and Bone Protective Effects of Testosterone in the Orchiectomy-Induced Osteoporosis in Wistar Rats.

This study aimed to evaluate and compare the effects of co-treatment with purified annatto oil (PAO) or its granules (GRA, Chronic®) with that of testosterone on the orchiectomy-induced osteoporosis in Wistar rats. After surgery, rats were treated from day 7 until day 45 with testosterone only (TES, 7 mg/kg, IM) or TES + PAO or GRA (200 mg/kg, p.o.). The following parameters were evaluated: food/water intake, weight, HDL, LDL, glucose, triglycerides (TG), total cholesterol (TC), alkaline phosphatase levels, blood phosphorus and calcium contents, femur weight, structure (through scanning electron microscopy), and calcium content (through atomic absorption spectrophotometry). Our results show that orchiectomy could significantly change the blood lipid profile and decrease bone integrity parameters. Testosterone reposition alone could improve some endpoints, including LDL, TC, bone weight, and bone calcium concentration. However, other parameters were not significantly improved. Co-treatment with PAO or GRA improved the blood lipid profile and bone integrity more significantly and improved some endpoints not affected by testosterone reposition alone (such as TG levels and trabeculae sizes). The results suggest that co-treatment with annatto products improved the blood lipid profile and the anti-osteoporosis effects of testosterone. Overall, GRA had better results than PAO.

Combined Effects of Exercise and Phytoanabolic Extracts in Castrated Male and Female Mice.

Dry extracts from the Eurasian plants, Ajuga turkestanica, Eurycoma longifolia, and Urtica dioica have been used as anabolic supplements, despite the limited scientific data on these effects. To assess their actions on early sarcopenia signs, male and female castrated mice were supplemented with lyophilized extracts of the three plants, isolated or in association (named TLU), and submitted to resistance exercise. Ovariectomy (OVX) led to body weight increase and non-high-density cholesterol (HDL) cholesterol elevation, which had been restored by exercise plus U. dioica extract, or by exercise and TLU, respectively. Orchiectomy (ORX) caused skeletal muscle weight loss, accompanied by increased adiposity, being the latter parameter reduced by exercise plus E. longifolia or U. dioica extracts. General physical activity was improved by exercise plus herbal extracts in either OVX or ORX animals. Exercise combined with TLU improved resistance to fatigue in OVX animals, though A. turkestanica enhanced the grip strength in ORX mice. E. longifolia or TLU also reduced the ladder climbing time in ORX mice. Resistance exercise plus herbal extracts partly altered gastrocnemius fiber size frequencies in OVX or ORX mice. We provide novel data that tested ergogenic extracts, when combined with resistance exercise, improved early sarcopenia alterations in castrated male and female mice.

A patient-centric pathway for testicular cancer - A multicentre study investigating the uptake of semen cryopreservation and impact on treatment.

BACKGROUND: The option of semen cryopreservation following a diagnosis of testicular cancer shows a variable uptake with the option to cryopreserve before surgery often dependent on the preference of the treating clinician and the fertility laboratory resources available. OBJECTIVES: To assess whether the introduction of a patient-centric pathway for managing suspected testicular cancer increases the uptake of semen cryopreservation and the impact of this on surgical waiting times. MATERIALS AND METHODS: A multicentre retrospective analysis of patients treated as part of a patient-centric pathway was conducted for suspected testicular cancer at two specialist centres within a one-stop testicular clinic. Clinical information, including semen cryopreservation acceptance rate, time intervals to surgery and CT scan, TNM stage, histology and age, was recorded from an institutional database. RESULTS: Eighty nine patients (median age: 34 years (range: 14-89)) underwent orchidectomy for suspected testicular cancer over a 15-month period after the introduction of a patient-centric testicular cancer pathway at two UK centres. The overall uptake of semen cryopreservation was 68.5% (n = 61) with all men under the age of 33 years accepting this option. A microdissection oncoTESE was performed in 9/61 (14.8%) patients who attempted cryopreservation but were found to be azoospermic. Pre-operative CT imaging was completed for 85.4% of patients, and the median time from initial outpatient consultation to orchidectomy was 9 days. DISCUSSION AND CONCLUSIONS: A patient-centric pathway ensures that the uptake of semen cryopreservation remains high particularly for those men within the common age for paternity. It also identifies men who may benefit from microdissection oncoTESE for complex cases such as tumours in solitary testicles, bilateral tumours or an atrophic contralateral testicle as well as those diagnosed with de novo azoospermia. The additional time taken for semen cryopreservation to be performed did not significantly delay orchidectomy or influence the decisions for adjuvant treatment.

Cordyceps militaris Fruit Body Extract Decreases Testosterone Catabolism and Testosterone-Stimulated Prostate Hypertrophy.

The androgens testosterone and dihydrotestosterone (DHT) are essential for a variety of systemic functions in mature males. Alteration of these hormones results in late-onset hypogonadism (LOH) and benign prostate hyperplasia (BPH). The fruit bodies of fungi of the genus Cordyceps have been regarded as folk medicine or health food with tonic and antifatigue effects. The extract from the fruit body of Cordyceps militaris parasitizing Samia cynthia ricini (CM) was evaluated as a novel-candidate natural product for ameliorating male andropause symptoms. To explore the effects of CM on LOH and BPH, CM was applied to rat models and cultured testicular cells and prostate cells. The concentrations of androgens in the serum and culture media were determined by ELISA. Expression of steroidogenic enzymes and androgen-related genes was evaluated by qPCR, and prostatic cell proliferation was assessed with the cell-viability assay. CM maintained the serum levels of testosterone and DHT, but inhibited testosterone-induced prostate hypertrophy. CM also increased the secretion of testosterone and DHT by primary testicular cells, with no changes in the mRNA expression of steroidogenic enzymes, but decreased the growth of prostatic cell lines. Our data suggest that CM could improve both LOH and BPH in males.

[De-escalation: Testicular cancer.] / La desescalada en urología: cáncer de testículo.

OBJECTIVES: To provide a priority algorithm for determinate diagnostic, therapeutic and follow-up procedures regarding at testicular cancer, adjusted by institutional requirements. Testicular cancer patient assessment during COVID-19 Pandemia. MATERIAL AND METHODS: Review of relevant manuscript published up to date, draft creation correctedt hough modified nominal group until final corrected manuscript. RESULTS: A lack of scientific evidence exists through a large amount of manuscripts. The authors support prioritizing diagnostic and therapeutic procedures. Once priorities have been established, that will facilitate providing each patients the limited resources. Initial diagnostic procedures for testicular cancer such as scrotal US, orchiectomy, staging CT and adjuvant treatment (if required) are priority. Reducing the usage of chemotherapy with respiratory toxicity and increasing the usage ofgrowth factors during chemotherapy treatment are the main stakeholders of treatment. Besides, providing active surveillance on non-risk factor clinical stage I is alsoa priority. In case of positive COVID-19, it is important to high light that the vast majority of patients are tentatively cured. CONCLUSIONS: During de-escalation phases, patients diagnosed with testicular cancer should receive priority care during initial assessment. The follow-ups of patients with low -risk and without recurrence for a long time, might be delayed.

OBJETIVOS: Establecer la prioridad de los distintos procedimientos diagnósticos, terapéuticos y de seguimiento sobre el cáncer de testículo para adaptarse adecuadamente a la situación asistencial de cada centro. Valorar precauciones y adaptaciones durante la situación actual de desescalada en el curso de la pandemia COVID-19. Valoración del paciente con cáncer de testículo en presencia de pandemia infectiva.MATERIAL Y MÉTODOS: Revisión de la literatura relevante publicada hasta la fecha, elaboración de un borrador corregido por técnica de grupo nominal modificada, hasta obtener un documento de consenso entre los autores. RESULTADOS: En ausencia de evidencia científica relevante la mayor parte de las publicaciones, y la conclusiónde los autores, abogan por priorizar los procedimientos diagnósticos y terapéuticos de los pacientes. Una vez priorizados será menos complejo adaptar los recursos limitados a las necesidades más perentorias de los pacientes. En el cáncer de testículo los procedimientos iniciales que incluyen ecografía escrotal, orquiectomía, estudio de extensión, y tratamiento complementario si necesario, son de máxima necesidad. Se propone disminuir el uso de fármacos con potencial toxicidad respiratoria, y aumentar la utilización de los estimulantes de colonias hematopoyéticas, asi como promover seguimiento activo en estadio clínico I sin factores de riesgo. En caso de infección activa subrayamos que la mayoría de los pacientes son potencialmente curables. CONCLUSIONES: En el proceso de desescalada los pacientes con cáncer de testículo deben ser atendidos de forma preferente, especialmente durante evaluación y tratamiento iniciales. Las revisiones de pacientes con remisiones estables pueden retrasarse razonablemente sin excesivo riesgo de progresion en estadios bajos.

Androgen action on renal calcium and phosphate handling: Effects of bisphosphonate treatment and low calcium diet.

Renal calcium and phosphate handling is an important contributor to mineral homeostasis and bone health and the androgen receptor (AR) is highly expressed in the kidney. We investigated the short term effects of androgen deprivation on renal calcium and phosphate reabsorption, independent of their effects on bone. Two weeks following orchidectomy (ORX) of adult mice, bone loss occurred along with hypercalciuria, which was similarly prevented by testosterone and dihydrotestosterone supplementation. Treatment with bisphosphonates prior to ORX also inhibited hypercalciuria, indicating that the calcium flux originated from the bone. Renal calcium and phosphate transporter expression was increased post-ORX, independent of bisphosphonates. Furthermore, androgen deprivation appeared to stimulate local synthesis of 1,25(OH)2D3. When bisphosphonate-treated mice were fed a low calcium diet, bone resorption was no longer blocked and secondary hyperparathyroidism developed, which was more pronounced in ORX mice than sham-operated mice. In conclusion, this study shows that androgen deprivation increased renal calcium and phosphate transporter expression, independent of bone, and underlines the importance of adequate intestinal calcium supply in circumstances of androgen deprivation and bisphosphonate treatment.

Immune modulating effects of additional supplementation of estradiol combined with testosterone in murine testosterone-deficient NAFLD model.

Nonalcoholic fatty liver disease (NAFLD) is associated with testosterone deficiency. However, NAFLD patients generally do not respond to treatment with testosterone alone. We investigated the innate immune mechanisms underlying the effects of treatment with testosterone alone, estrogen alone, or combined testosterone and estrogen on high-fat diet (HFD)-induced NAFLD due to testosterone deficiency. Orchiectomized (OCX) male Rag2-/- mice were used as a model of testosterone deficiency. To assess NAFLD severity, NAFLD activity score (NAS) is adopted. Moreover, immunological change was analyzed by multicolor flow cytometry. Treatment with both testosterone and estrogen significantly decreased body weight to that of the sham mice/normal diet (ND). NAS and liver fibrosis in OCX-HFD mice were significantly deteriorated, and treatment with testosterone and estrogen improved same as sham-ND mice. HFD increased the ratio of both type 2 and 3 innate lymphoid cells (ILC2s and ILC3s) to CD45-positive cells in the liver. Treatment with testosterone alone decreased the ratio of ILC2 to CD45 but not the ILC3-to-CD45 ratio. Addition of estrogen to the treatment reduced the ratios of ILC2-to-CD45 and ILC3-to-CD45 to the same level observed in sham-HFD mice. Moreover, OCX-HFD mice had a decreased proportion of M2 macrophages compared with sham-ND mice. Treatment with testosterone alone did not restore the proportion of M2 macrophages; however, combination treatment with both estrogen and testosterone increased that to the same level as that in sham-HFD mice. Treatment with both testosterone and estrogen improves liver fibrosis and decreases ILC3 and increases M2 macrophage abundance in the liver.NEW & NOTEWORTHY The progression of nonalcoholic fatty liver disease (NAFLD) is associated with testosterone deficiency. NAFLD patients generally do not respond to treatment with testosterone alone. In animal studies, treatment with testosterone and estrogen reduced the ratios of ILC2:CD45 and ILC3:CD45 and increased M2 macrophages in liver. Our study suggests, based on our immunological data, that a combination of estrogen and testosterone may be clinically relevant for the treatment of NAFLD in patients with male menopause.

Dietary Tomato or Lycopene Do Not Reduce Castration-Resistant Prostate Cancer Progression in a Murine Model.

BACKGROUND: Dietary tomato products or lycopene protect against prostate carcinogenesis, but their impact on the emergence of castration-resistant prostate cancer (CRPC) is unknown. OBJECTIVE: We hypothesized that tomato or lycopene products would reduce the emergence of CRPC. METHODS: Transgenic adenocarcinoma of the mouse prostate (TRAMP) mice were castrated at 12-13 wk and the emergence of CRPC was monitored by ultrasound in each study. In Study 1, TRAMP mice (n = 80) were weaned onto an AIN-93G-based control diet (Con-L, n = 28), a 10% tomato powder diet (TP-L, 10% lyophilized w/w, n = 26), or a control diet followed by a tomato powder diet after castration (TP-Int1, n = 26). In Study 2, TRAMP mice (n = 85) were randomized onto a control diet with placebo beadlets (Con-Int, n = 29), a tomato diet with placebo beadlets (TP-Int2, n = 29), or a control diet with lycopene beadlets (Lyc-Int, n = 27) following castration (aged 12 wk). Tumor incidence and growth were monitored by ultrasound beginning at an age of 10 wk. Mice were euthanized 4 wk after tumor detection or aged 30 wk if no tumor was detected. Tissue weights were compared by ANOVA followed by Dunnett's test. Tumor volumes were compared using generalized linear mixed model regression. RESULTS: Ultrasound estimates for the in vivo tumor volume were strongly correlated with tumor weight at necropsy (R2 = 0.75 and 0.94, P <0.001 for both Studies 1 and 2, respectively). Dietary treatments after castration did not significantly impact cancer incidence, time to tumor detection, or final tumor weight. CONCLUSIONS: In contrast to studies of de novo carcinogenesis in multiple preclinical models, tomato components had no significant impact on the emergence of CRPC in the TRAMP model. It is possible that specific mutant subclones of prostate cancer may continue to show some antiproliferative response to tomato components, but further studies are needed to confirm this.

Spondias mombin L. decoction utilization as antiseptic in cats submitted to castration / Uso de decocto de Spondias mombin L. como antisséptico em felinos submetidos à castração

This survey evaluated mombin leaves (Spondias mombin L.) decoction efficiency as an antiseptic during post-surgery period on cats submitted to orchiectomy and ovariosalpingohisterectomy. For this purpose, 45 castrated mongrels cats were divided into three groups, the first group as a positive control using 0.5% chlorhexidine-alcohol solution, the second a negative control group using sterile distilled water and, finally, the test group using mombin leaves decocted with a concentration of 100 mg/mL. All animals, independent of age and sex, had visibly healed in most cases in a similar time. Animals treated with mombin leaves decoction presented a significant reduction of bacterial growth. In addition, the animals treated in the test group had better surgical wound healing. All isolated bacterial strains presented inhibition halo for chlorhexidine and for Spondias mombin L. Thus, the decoction of Spondias mombin L. leaves proved antiseptic efficacy in the surgical wounds of cats submitted to orchiectomy and ovariosalpingohisterectomy.(AU)

Foi avaliada a eficiência do decocto das folhas de cajá (Spondias mombin L.) como antisséptico no pós-cirúrgico de gatos submetidos à orquiectomia e ovariosalpingohisterectomia. Para tal, foram submetidos à castração 45 gatos sem raça definida, divididos em três grupos. O primeiro grupo como controle positivo com Solução Alcoólica de Clorexidine a 0,5%; segundo grupo controle negativo com água destilada estéril; e o grupo teste com o decocto de cajá à concentração de 100 mg/mL. Todos os animais, independentemente da idade e sexo, tiveram cicatrização visível em tempo similar. Animais tratados com o decocto apresentaram uma redução significativa do crescimento bacteriano. Além disso, observou-se uma melhor cicatrização das feridas cirúrgicas dos animais tratados no grupo teste. Todas as estirpes bacterianas isoladas apresentaram halo de inibição para clorexidine e para Spondias mombin L. Portanto, o decocto das folhas da Spondias mombin L. apresentou eficácia antisséptica nas feridas cirúrgicas de gatos submetidos à orquiectomia e ovariosalpingohisterectomia.(AU)

The adrenal cortex after estradiol or daidzein application in a rat model of the andropause: Structural and hormonal study.

INTRODUCTION AND AIM: Daidzein application may represent an effective and less harmful alternative to indicated, classical estrogenization of ageing men. The aim of this study was to perform structural and hormonal analysis of the adrenal cortex, after estradiol or daidzein supplementation in a rat model of the andropause. MATERIAL AND METHODS: Middle-aged Wistar rats were divided into sham operated (SO; n = 8), orchidectomized (Orx; n = 8), estradiol treated orchidectomized (Orx + E; n = 8) and daidzein treated orchidectomized (Orx + D; n = 8) groups. Estradiol (0.625 mg/kg b.m./day) or daidzein (30 mg/kg b.m./day) were administered subcutaneously for three weeks, while the SO and Orx groups received the vehicle alone. Set objectives were achieved using stereology, histochemistry/immunohistochemistry, immunoassays and ultrastructural analysis. RESULTS: Both estradiol and daidzein treatment significantly increased volumes of the zona glomerulosa cell and nuclei, but decreased circulating aldosterone levels. Estradiol markedly increased volumes of the zona fasciculata cell and nuclei in parallel with significant decrease of the adrenal tissue level of corticosterone, while daidzein significantly decreased both the adrenal and circulating levels of corticosterone. Serum DHEA level and volumes of the zona reticularis cell and nuclei significantly increased upon estradiol treatment, whereas daidzein even stronger increased the circulating level of DHEA. Shunting of the corticosteroidogenesis pathways towards adrenal androgens production, after the treatments, corresponded to the ultrastructural findings and zonal capillary network rearrangements. CONCLUSIONS: Given the coherence of its effects and relative safety, daidzein could be the remedy of choice for the treatment of ageing-caused androgen deprivation and the hypothalamo-pituitary-adrenal axis hyperfunction/related metabolic issues in males.