Update in the Treatment of Pleural Tumors: Robotic Surgery Combined with Hyperthermic Intrathoracic Chemotherapy.

(1) Background. Intracavitary hyperthermic chemotherapy (HITHOC) remains part of the complex mosaic that is the multimodal approach for advanced stage thymoma and pleural malignancies. However, robotic pleurectomy/removal of pleural lesions in combination with intrathoracic chemotherapy is not currently being investigated. The aim of this study is to evaluate the safety of robotic pleurectomy/removal of relapses and HITHOC in patients with pleural recurrence of thymoma or MPM. (2) Methods: The data of nine consecutive patients affected by thymoma relapses or MPM who underwent robotic surgery in combination with HITHOC from February 2017 to November 2022 were collected and analyzed. Surgery performed prior to intrathoracic infusion of high-temperature chemotherapy consisted of removal of recurrences (three patients) or pleurectomy (six patients). All surgeries were performed with a four-port, fully robotic technique. (3) Results: No intraoperative complications occurred. No renal complications related to infusion were recorded. One patient, who underwent pleurectomy for MPM, had a grade II Clavien-Dindo postoperative complication. Oncological follow-up showed results in line with the literature. (4) Conclusions: With the limitation of the small number of patients, robotic surgery in combination with HITHOC seems to be safe in patients with pleural relapses of thymoma and early-stage MPM.

Ticagrelor Enhances the Cardioprotective Effects of Ischemic Preconditioning in Stable Patients Undergoing Percutaneous Coronary Intervention: the TAPER-S Randomized Study.

BACKGROUND: Ticagrelor improves clinical outcomes in patients with acute coronary syndrome compared with clopidogrel. Ticagrelor also inhibits cell uptake of adenosine and has been associated with cardioprotective effects in animal models. We sought to investigate the potential cardioprotective effects of ticagrelor, as compared with clopidogrel, in stable patients undergoing percutaneous coronary intervention (PCI). METHODS AND RESULTS: This was a Prospective Randomized Open Blinded End-points (PROBE) trial enrolling stable patients with coronary artery disease (CAD) requiring fractional flow reserve (FFR)-guided PCI of intermediate epicardial coronary lesions. ST-segment elevation at intracoronary (IC)-ECG during a two-step sequential coronary balloon inflations in the reference vessel during PCI was used as an indirect marker of cardioprotection induced by ischemic preconditioning. The primary endpoint of the study was the comparison of the delta (Δ) (difference) ST-segment elevation measured by intracoronary-ECG during two-step sequential coronary balloon inflations. RESULTS: Fifty-three patients were randomized to either clopidogrel or ticagrelor. The study was stopped earlier because the primary endpoint was met at a pre-specified interim analysis. ΔST-segment elevation was significantly higher in ticagrelor as compared to clopidogrel arms (p<0.0001). Ticagrelor was associated with lower angina score during coronary balloon inflations. There was no difference in coronary microvascular resistance between groups. Adenosine serum concentrations were increased in patients treated with ticagrelor as compared to those treated with clopidogrel. CONCLUSIONS: Ticagrelor enhances the cardioprotective effects of ischemic preconditioning compared with clopidogrel in stable patients with CAD undergoing PCI. Further studies are warranted to fully elucidate the mechanisms through which ticagrelor may exert cardioprotective effects in humans. Clinical Trial Registration: http://www.clinicaltrials.gov. Unique Identifier: NCT02701140.

Unradical Surgery for Locally-Advanced Thymoma: Is it time to evolve Perspectives?

OBJECTIVES: Nearly-one-third of thymomas are locally-advanced at diagnosis. The traditional dogma that surgery is justified in case a complete resection can be achieved has remained unmovable until today. This study aimed to investigate feasibility and oncologic efficacy of incomplete resection for locally-advanced thymomas in a contest of multimodality therapy. MATERIALS AND METHODS: A retrospective analysis was conducted using data of prospectively maintained thymomas database in a single high-volume centre. Data on 285 consecutive patients undergoing surgery for stage III and IVa thymomas between 1995 and 2019 were reviewed. Patients who underwent incomplete resection with curative-intent (removal of at least 90% of tumour burden) were included. Long-term outcomes and predictors of cancer-specific survival (CSS) and progression-free survival (PFS) were analyzed. Secondary endpoint was to assess adjuvant therapy efficacy. RESULTS: The study included 79 patients, 60 with microscopic residual tumour (76%, R1) and 19 with macroscopic residual disease (24%, R2). Masaoka-Koga stage was: III in 41 patients (52%) and IVa in 38 (48%). Histology was B2-thymomas (n = 31, 39.2%) followed by B3 (n = 27, 34.2%). Five- and 10-years CSS was 88% and 80%. Seventy patients (90%) underwent adjuvant treatment; they showed CSS comparable to radical resected patients (5-years: 89.1% vs 98.9%, respectively; 10-years: 81.8% vs 92.7%, respectively, p = 0.43). The site of residual disease, Masaoka-Koga stage and WHO histology did not affect prognosis. Stepwise multivariable analysis confirmed adjuvant therapy as a favourable CSS prognostic factor (HR, 0.51; 95% CI, 0.33-0.79, p = 0.003). Stratifying by subgroups, R2-patients who received postoperative chemo(radio)therapy (pCRT) showed a significantly better prognosis than R2-patients treated by consolidation radiotherapy alone (10-years CSS: 60%, p < 0.001). CONCLUSION: In locally-advanced thymomas, whenever a radical surgery cannot be achieved, incomplete resection has proved to be effective in a contest of multimodality strategy, independently of WHO histology, Masaoka-Koga stage and site of residual disease.

Women in thoracic, cardiac and vascular surgery claim for a change in the working situation: an Italian national survey.

Background: Women's participation in the surgical workforce has increased. The aim of the study is to acquire objective data regarding practice, training, satisfaction, and discrimination of women surgeons working in cardiothoracic and vascular surgery in Italy. Methods: An 83-item questionnaire was distributed through social media and sent to e-mails of women surgeons from November through December 2020. A sub-analysis on women working in cardiac, thoracic, and vascular surgery was performed. Results: Overall, 222 respondents were included (48 cardiac, 62 thoracic, and 112 vascular surgeons). Thirty-six percent partially abandoned surgical activities in favor of other professional activities, not including the operating room. On average, our respondents took part in 33% of all surgical cases performed in their units; however, of 12 high complexity surgeries per month, less than one is performed by them. Only 7 female participants who answered the questionnaire were in leadership positions. Many respondents struggle with lack of mentorship and missing opportunities in operating room. A high percentage of women experienced discrimination due to their gender in their professional life, and 59% claimed to have been subject to sexual harassment. Conclusions: In Italy, women thoracic, cardiac, and vascular surgeons face lack of mentorship, opportunities in the operating room, and gender-related issues including some episodes of sexual harassment. Diversity, equity, and inclusion should become strategic priorities in all institutions. Among our respondents, surgical exposure is limited, which may deter a surgical career and play a crucial role in surgeons' dissatisfaction, that also include poor work-life-balance, and a large amount of administrative work. Surgical societies may address these issues by providing structured mentorship programs and networking opportunities. Societies' contributions might substantially impact supporting and retaining women at different stages of their careers.

Age and training intensity differently affect male runners' endocrine and sexual parameters.

Physical activity is widely recognized to improve health and its inclusion in daily life at all ages is highly recommended. Gonadal hormones are known to be affected by physical activity. The exercise-induced effects on male runners of different ages were investigated by dividing 31 runners by age (Young, Y, 30-55 years; Old, O, 56-70 years) and amount of training (Light, L, <50 km/week; Heavy, H, 50 or more km/week). To test the somatic, sexual, and psychological health aspects, the Aging Male's Symptoms Scale (AMS) and the International Index of Erectile Function-6 (IIEF-6) questionnaires were administered and blood samples were drawn for adrenocorticotropic hormone, testosterone (Total-TT), free testosterone (Free-T), cortisol (C), dihydrotestosterone (DHT), estradiol, and sex hormone-binding globulin determinations. Clinical evaluations and questionnaire results showed the presence in all groups of some subclinical symptoms and "Light" dysfunctions. TT in the old-heavy (OH) group was significantly lower than in the OL group (2.38 ± 0.18 ng/mL vs. 3.36 ± 0.44 ng/ml, P = 0.05). The TT/DHT ratio was significantly higher in YH than in OH (3.64 ± 0.16 vs. 2.92 ± 0.23, P < 0.05). TT was positively correlated with AMS sexual subscale and negatively correlated with IIEF-6. Physical activity can significantly affect andrological health and testosterone levels in runners at all ages. Thus, due to the important testosterone-mediated vital functions in men, the evaluation of these parameters would be indicated in old as well as in young subjects.

Estrogens and phytoestrogens in body functions.

Estrogens are the hormones of reproduction in women as well as of many other important functions in the male and female body. They undergo significant changes in the different phases of life, e.g. during puberty, pregnancy or at menopause/andropause. Phytoestrogens are natural non-steroidal phenolic plant compounds that can mimic the activity of estrogens and their beneficial effects in women and in men. This narrative review summarizes the literature on the physiological role of estrogens and the several potential health benefits of phytoestrogens, with particular attention given to the possible role of phytoestrogens in aging.

Robotic thymectomy: A surgical point of view.

Robotic thymectomy is the most innovative surgical approach for treating disease of the anterior mediastinum. Robotic surgery offers low postoperative morbidity, faster recovery, shorter hospital stay, and better cosmetic results, without compromising surgical radicality. During the operation, the patient is placed in a supine position at the left edge of the operating table with the left hemithorax upward; the position is maintained with sandbags. The target area for the autodocking should be toward the jugulum. The first surgical step is to isolate the inferior thymic horns via the dissection that starts from the inferior portion of the mediastinal tissue and proceeds toward the right side, following the contralateral pleural reflection. Afterward, it is necessary to move toward the superior horns, following the phrenic nerve, the first landmark, to the innominate vein, our second landmark. Finally, we dissect the superior horns while searching for the thymic veins, which could appear atrophic, and clip the vessels to safely isolate the innominate vein. During this step, it is useful to use a retraction movement to progressively dissect the horns from the jugulum. The thymus gland is removed en bloc with the perithymus fat using an endoscopic bag inserted through the right port incision.

Robotic thymectomy for thymoma in patients with myasthenia gravis: neurological and oncological outcomes.

OBJECTIVES: The goal of this study was to analyse the outcomes in 53 patients with thymoma, 34 of whom had myasthenia gravis (MG), who were treated with robotic surgery. The oncological outcomes of the whole series of patients were analysed. Furthermore, because consistent data are not yet available in the literature, the main focus was the analysis of the neurological results of the patients affected by MG and thymoma. METHODS: The clinical outcomes of 53 patients with a diagnosis of thymoma who underwent robotic thymectomy between January 2014 and December 2019 in our institution were collected and evaluated; 34 of these patients had a concomitant diagnosis of MG. The neurological status of the patients was determined from a clinical evaluation according to the Osserman classification and on pre- and post-surgery Myasthenia Gravis Composite scores, whereas neurological clinical outcomes were assessed using the Myasthenia Gravis Foundation of America Post-Intervention Score. Reduction of steroid therapy was also considered. The recurrence rate, adjuvant radiotherapy and overall survival of the patients with a thymoma were evaluated. RESULTS: Neurological outcomes: improvement of the clinical conditions was obtained in 26 patients (76.5%) following the operation: complete stable remission was observed in 5 patients (14.7%), pharmacological remission in 10 (29.4%) and minimal manifestation in 11 (32.3%). Four patients (11.8%) exhibited no substantial change from the pretreatment clinical manifestations or reduction in MG medication and 4 (11.8%) patients experienced worsening of clinical conditions. In 21 patients (61.7%) a reduction of the dosage of steroid therapy was obtained. Oncological outcomes: at an average follow-up of 36 months, the overall survival was 96%, 4 patients (7.5%) had pleural relapses and 12 patients (22.6%) underwent postoperative radiotherapy, according to their stage. In accordance with Masaoka staging, 34% were in stage I, 56.6% in stage II and 9.4% in stage III. CONCLUSIONS: Our results suggest that robotic surgical treatment of patients with thymoma and concomitant MG is effective in improving the neurological outcomes. Moreover, the oncological results obtained in this series confirm the efficacy of robotic surgery for the treatment of thymic malignancies, with results in line with those of open surgery. However, due to the indolent growth of thymomas, further observations with longer follow-up are necessary.

A risk stratification scheme for synchronous oligometastatic non-small cell lung cancer developed by a multicentre analysis.

BACKGROUNDS: Oligometastatic Non-Small Cell Lung Cancer (NSCLC) patients represent a category without a standard therapeutic approach. However, in selected oligometastatic NSCLC, radical surgery seems to offer a good prognosis. This retrospective study aimed to analyse the long-term outcomes of synchronous oligometastatic patients treated with curative intent and identify the factors associated with better results and the proposal of a risk stratification system for classifying the synchronous oligometastatic NSCLC. METHODS: The medical records of patients from 18 centres with pathologically diagnosed synchronous oligometastatic NSCLC were retrospectively reviewed. The inclusion criteria were synchronous oligometastatic NSCLC, radical surgical treatment of the primary tumour with or without neoadjuvant/adjuvant therapy and radical treatment of all metastatic sites. The Kaplan - Meier method estimated survivals. A stratified backward stepwise Cox regression model was assessed for multivariable survival analyses. RESULTS: 281 patients were included. The most common site of metastasis was the brain, in 50.89 % patients. Median overall survival was 40 months (95 % CI: 29-53). Age ≤65 years (HR = 1.02, 95 % CI: 1.00-1.05; p = 0.019), single metastasis (HR = 0.71, 95 % CI: 0.45-1.13; p = 0.15) and presence of contralateral lung metastases (HR = 0.30, 95 % CI: 0.15 - 0.62; p = 0.001) were associated with a good prognosis. The presence of pathological N2 metastases negatively affected survival (HR = 2.00, 95 % CI: 1.21-3.32; p = 0.0065). These prognostic factors were used to build a simple risk classification scheme. CONCLUSIONS: Treatment of selected synchronous oligometastatic NSCLC with curative purpose could be conducted safely and at acceptable 5-year survival levels, especially in younger patients with pN0 disease.

Physiological effects of high-altitude trekking on gonadal, thyroid hormones and macrophage migration inhibitory factor (MIF) responses in young lowlander women.

Altitude hypoxia is often associated with impairment of human reproduction. In this study, hormones and macrophage migration inhibitory factor (MIF, a proinflammatory cytokine with key roles in human reproduction) were determined in seven regularly menstruating, lowlander native women living at sea level participating in 14 days of trekking at moderate and high altitude. Blood and saliva samples were collected from each subject at high altitude (5050 m a.s.l. [above sea level]), and at sea level before and after the expedition. Testosterone level was lowered by high altitude and was restored after the end of the expedition, while progesterone decreased significantly in all participants at the end of the expedition, although most of the participants were in the luteal phase. The salivary concentration of MIF decreased greatly at altitude, but its levels were completely restored after the return to sea level. Our findings showed high sensitivity and rapid changes in the determined parameters in response to the high-altitude hypoxic environment, particularly MIF.

Recombinant Adeno Associated Viral (AAV) vector type 9 delivery of Ex1-Q138-mutant huntingtin in the rat striatum as a short-time model for in vivo studies in drug discovery.

Huntington's disease (HD) is an inherited neurodegenerative disorder characterized by dyskinesia, cognitive impairment and emotional disturbances, presenting progressive neurodegeneration in the striatum and intracellular mutant Huntingtin (mHTT) aggregates in various areas of the brain. Recombinant Adeno Associated Viral (rAAV) vectors have been successfully used to transfer foreign genes to the brain of adult animals. In the present study we report a novel in vivo rat HD model obtained by stereotaxic injection of rAAV serotype2/9 containing Exon1-Q138 mHTT (Q138) and Exon1-Q17 wild type HTT (Q17; control), respectively in the right and in the left striatum, and expressed as C-terminal GFP fusions to facilitate detection of infected cells and aggregate production. Immunohistochemical analysis of brain slices from animals sacrificed twenty-one days after viral infection showed that Q138 injection resulted in robust formation of GFP-positive aggregates in the striatum, increased GFAP and microglial activation and neurodegeneration, with little evidence of any of these events in contralateral tissue infected with wild type (Q17) expressing construct. Differences in the relative metabolite concentrations (N-Acetyl Aspartate/Creatine and Myo-Inositol/Creatine) were observed by H1 MR Spectroscopy. By quantitative RT-PCR we also demonstrated that mHTT induced changes in the expression of genes previously shown to be altered in other rodent HD models. Importantly, administration of reference compounds previously shown to ameliorate the aggregation and neurodegeneration phenotypes in preclinical HD models was demonstrated to revert the mutant HTT-dependent effects in our model. In conclusion, the AAV2/9-Q138/Q17 exon 1 HTT stereotaxic injection represents a useful first-line in vivo preclinical model for studying the biology of mutant HTT exon 1 in the striatum and to provide early evidence of efficacy of therapeutic approaches.

N-[5-(5-fluoropyridin-3-yl)-1H-pyrazol-3-yl]-4-piperidin-1-ylbutyramide (SEN78702, WYE-308775): a medicinal chemistry effort toward an α7 nicotinic acetylcholine receptor agonist preclinical candidate.

α7 Nicotinic acetylcholine receptors (α7 nAChR) represent promising therapeutic candidates for the treatment of cognitive impairment associated with Alzheimer's disease (AD) and schizophrenia. A medicinal chemistry effort around previously reported compound 1 (SEN15924, WAY-361789) led to the identification of 12 (SEN78702, WYE-308775) a potent and selective full agonist of the α7 nAChR that demonstrated improved plasma stability, brain levels, and efficacy in behavioral cognition models.

Endocrine and behavioural effects of transdermal buprenorphine in pain-suffering women of different reproductive ages.

Chronic pain is a common problem in clinical practice and women are affected more often than men. Morphine is often used for long-term pain relief, but it induces side effects including endocrine alterations. The aim of the present study was to assess the behavioural and hormonal effects of transdermal buprenorphine in women suffering from persistent non-malignant pain. Hormones (LH, FSH, total and free testosterone, estradiol, cortisol) and pain measures (visual analogue scale, McGill Pain questionnaire, present pain intensity test) were evaluated at baseline and after 1, 3 and 6 months. Subjects were recruited in the Second University of Naples Pain Research Centre. Eighteen chronic pain women were included in the study, divided into pre- and post-menopausal groups. A transdermal buprenorphine patch (Buprenorphine TDS, 35 µg/h) was administered every 72 h. As expected, buprenorphine administration led to a decrease in pain intensity and no side effects suggestive of hypogonadism were recorded. Pain measures decreased at the first control visit (T1) in both groups. Total and free testosterone were not reduced by treatment (they tended to increase in both groups) while cortisol progressively recovered from the quite low levels detected at the beginning of treatment. These data confirm that buprenorphine is a safe and effective drug for pain relief in women. It is free from the adverse effects on gonadal hormones frequently associated with other opioid treatments. The lack of opioid-induced effects on gonadal hormones (i.e., hypogonadism) is important to guarantee safe long-term pain treatment.

Sex differences in the analgesic effects of ICI 182,780 and Flutamide on ureteral calculosis in rats.

To better define the involvement of gonadal hormones in the sex differences observed in experimental visceral pain, we administered antagonists of estrogen receptors (ICI 182,780 [ICI]) or androgen receptors (Flutamide [FLU]) to adult male and female rats suffering from artificial ureteral calculosis. Subjects were divided into groups and treated with one of the substances (ICI, FLU) or sweet almond oil (OIL, vehicle) for 5 days, starting 2 days before surgery. On day 3, animals underwent surgery, with half receiving an artificial calculosis (Stone) and half only a sham procedure. The animals' behavior (number and duration of ureteral crises) and blood hormone levels (estradiol and testosterone) were determined in all groups. In OIL-treated rats the number and duration of crises were higher in females than in males. The administration of ICI or FLU resulted in hormonal effects in males and behavioral effects in females. In males ICI treatment increased estradiol plasma levels and FLU increased testosterone plasma levels; in females ICI and FLU treatments both decreased the number and duration of the ureteral crises. These results, confirming previous findings of higher sensitivity of females than males to urinary tract pain, showed the modulatory effects of estrogen and androgen antagonists on the behavioral responses induced by pain but only in females.

Estradiol and testosterone differently affect visceral pain-related behavioural responses in male and female rats.

In the study of pain, the presence of sex differences is well known, with female subjects being more affected in a number of chronic painful conditions; however, the underlying mechanisms and the involvement of gonadal hormones, are still controversial. This study evaluated visceral pain in a validated rat model of artificial calculosis and the effects of estradiol and testosterone administration. Adult male and female rats were divided into groups and treated with one of the substances or Oil (vehicle) for 5 days, starting 2 days before surgery, with half receiving an artificial calculosis (Stone) and half only a sham (Sham) procedure. The animals' behaviour (ureteral crises, frequency and duration) were recorded for 72 h; estradiol and testosterone plasma levels were determined in all groups at the end of the observation period. After surgery, only Stone rats showed ureteral pain crises, with a significant sex difference in the Oil-treated groups in which the number and duration of crises were higher in females than in males. This difference was not present in the estradiol-treated groups in which ureteral crises were decreased only in females while testosterone treatment had no effect in either sex. Estradiol and testosterone plasma levels were affected by treatments in both sexes. These results confirm that, also in this model of visceral pain, females experience more pain than males; moreover, they show that supraphysiological levels of estradiol, but not of testosterone, are analgesic only in females. A dose and sex-dependent efficacy of gonadal hormones is suggested and discussed.

Effects of morphine on testosterone levels in rat C6 glioma cells: modulation by anastrozole.

Rat C6 glioma cells are commonly used to investigate the functions of glial cells. To evaluate the presence of testosterone and its metabolism in rat C6 glioma cells, we cultured them in media with or without the addition of testosterone propionate and anastrozole, a blocker of aromatase, the enzyme needed to transform testosterone into estradiol. The same procedure was repeated with morphine (10 and 100 microM), known to decrease testosterone levels in the brain (in rats) and plasma (in rats and humans). Confluent cells were exposed to the test media for 48 h and then collected. Cell pellets were used to determine testosterone by radioimmunoassay. The C6 cells contained detectable levels of testosterone and the levels increased with the addition of testosterone to the medium. Aromatase blockage by anastrozole increased cellular levels of testosterone regardless of the addition of exogenous testosterone. Both concentrations of morphine dose-dependently decreased testosterone levels in the C6 cells; this effect was also present with the contemporary administration of anastrozole. Our findings show that testosterone is present in rat C6 glioma cells and can be metabolized by aromatase. Moreover, the presence of morphine in the culture medium strongly decreased testosterone, demonstrating that the glia would be a target of the morphine-induced hypogonadal effect.

Perinatal exposure to xenoestrogens affects pain in adult female rats.

Estrogens have a variety of effects in addition to their action on reproductive structures, including permanent effects on the Central Nervous System (CNS). Therefore environmental chemicals with estrogenic activity (xenoestrogens) can potentially affect a number of CNS functions. In the present experiment, female rats receiving ethynylestradiol (EE) or methoxychlor (MXC) via the mothers during pregnancy (pre) or lactation (post) were tested in comparison with females born from mothers treated with OIL. The Object Recognition, Plantar and Formalin tests were carried out to evaluate the effects of these compounds on integrated functions such as memory and pain. Testosterone and estradiol plasma levels were determined by RIA. The results of the Object Recognition and Plantar tests did not differ among groups. However the groups differed in the Formalin test since flexing duration was higher in the EE- and MXC-pre groups than in the EE- and MXC-post and OIL groups. Estradiol plasma levels were higher in EE-pre than in the other groups. These results confirm the possibility that estrogen-like compounds (EE and MXC) can affect complex neural processes like pain when taken during critical stages of CNS development.

Effects of 17beta-estradiol on rat urinary bladder: gender differences in anoxia-glucopenia and reperfusion damage.

AIM: To study the effect of 17beta-estradiol (E(2)) as a neuroprotective agent in male and female rat urinary bladders subjected to anoxia-glucopenia and reperfusion (A/G-R) damage. METHODS: Rat urinary bladders were exposed to 1 hour of A-G and 2 hours of reperfusion (R). Intrinsic nerves underwent electrical field stimulation. The effect of E(2) on the contractile response and its recovery in R phase, was monitored by adding it to the bath medium, at different concentrations, 60 min before A-G, during the A-G and the first 30 min of R. Furthermore, on both genders, in vivo treatments with E(2), testosterone, IC1 182,780 and anastrozole were performed. RESULTS: After A-G the recovery of the nerve function in female bladders were significantly higher than in male. E(2) given both in vivo (increased of E(2) plasma levels were monitored) and in vitro, resulted to be neuroprotective in male bladder subjected to A-G/R damage. When rats were treated with anastrozole, a lower recovery of nerve responses both in male and female bladders was observed. Finally, treatments with E2 receptor antagonist ICI 182,780 increased E(2) plasma levels and showed to abolished E(2) neuroprotection, thus suggesting that E2 promotes neuronal survival likely through a rapid estrogen receptor mediated response. CONCLUSIONS: Male rat urinary bladder serves are more susceptible to A-G/R damage than female. E(2) exhibits neuroprotective properties and could be a lead for novel agents capable to protect the urinary bladder from ischaemia/reperfusion damage associated with urinary bladder disorders.

Cross-sex hormone administration changes pain in transsexual women and men.

Chronic pain is gender-related, since there is a clear predominance of one sex with respect to the other in most pain syndromes. Gonadal hormones are known to affect the occurrence and incidence of pain. Transsexuals receive cross-sex hormones to develop and maintain somatic characteristics of the opposite sex: male to female transsexuals (MtF) are administered estrogens and anti-androgens, while female to male transsexuals (FtM) are administered androgens. Hence, these subjects represent a model to study the relationship between sex hormones and pain. Questionnaires dealing with sociodemographic data and pain (occurrence, frequency, duration, intensity, location and associated symptoms) were administered to both MtF and FtM transsexuals under hormone treatment for sex reassignment for at least 1 year. Forty-seven MtF and 26 FtM completed the questionnaires. Fourteen of the 47 MtF (29.8%) reported painful conditions, which in 11 subjects were not present before the beginning of hormone treatment. Pain consisted mainly of headaches and breast and musculoskeletal pain. Five subjects suffered from more than one pain condition. Sixteen of the 26 FtM (61.5%) reported pain. In 11 subjects, the pain was present before the beginning of hormone intake, and in 6 of them it improved after testosterone administration. These data suggest that marked changes in sex hormones affect the occurrence of pain in a high percentage of humans but not in all of them. Whether these effects are due to peripheral or central actions of sex steroids is unknown.

Estrogenic chemicals at puberty change ERalpha in the hypothalamus of male and female rats.

The effects of two environmental endocrine disruptors, the synthetic pharmaceutical estrogen 17-ethinylestradiol (EE) and bisphenol-A (BPA), were analysed in male and female rats in a very sensitive developmental period, puberty. Immunohistochemistry was used to evaluate changes in the number of cells expressing estrogen receptors (ER-alpha) in the arcuate nucleus (ARC), ventromedial nucleus (VMH) and medial preoptic area (MPA) of the hypothalamus. Animals were treated during early puberty, from PND 23 to PND 30, with EE and BPA given orally every day. They were then sacrificed and perfused on PND 37 or PND 90, and blood and brains were collected for hormonal determination (testosterone and estradiol) and immunohistochemistry (estrogen receptors, ER). At PND 37, ER-labelled neurons were higher in males than in females in the ARC and MPA. EE and BPA increased ER-labelled neurons in the ARC and MPA. At PND 90, females showed higher ER-labelled neurons in the VMH. EE and BPA increased ER-labelled neurons in the MPA in females. EE increased testosterone in males at PND 37 and estradiol in females at PND 90. These results indicate the ability of estrogenic chemicals to change the reproductive neural circuits during puberty in male and female rats.