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Background: Benign prostatic hyperplasia (BPH) is a disease linked to the hormonal imbalance that occurs during aging and over the last decades, complementary and alternative medicines have come on the scene as a treatment option for BPH, such as herbal medicines. Coconut oil has been shown to be capable of interfering in testosterone-induced BPH. However, until now there is no study of the effect of coconut oil during aging. The present study evaluated the effect of the intake of coconut oil on the prostate of aging gerbils (Meriones unguiculatus)., Methods: Two experimental groups were assigned: Gavage control (GC-animals subjected to gavage with water for 1 year, n = 11) and coconut oil (CO-animals subjected to gavage with coconut oil for 1 year, n = 11). Testosterone, and estradiol serum levels were determined by ELISA assay and histopathological analysis employed Hematoxylin-Eosin. Cell proliferation index was determined by PHH3 immunohistochemistry and TUNEL assay and receptors of androgen (AR) and estrogen (ERα and ERβ) were evaluated on the prostate., Results: The CO group exhibited a lower prostate weight (↓16.62%), decreased thickness of the prostate muscle stroma (↓18.27%), reduced expression of both AR (↓51.32) and ERα (↓14.26%) and reduced the percentage of BPH (↓1.53%) and intraepithelial neoplasms in the prostate (↓14.24%). Coconut oil intake mitigated age-related changes and increased the rate of apoptosis in prostatic cells (↑54.32)., Conclusions: Coconut oil treatment throughout aging helped counteract the negative effects of aging on prostate health., (© 2024 Wiley Periodicals LLC.)

This study aims to verify the effects of prolonged ingestion of coconut oil on the adrenal glands of Mongolian gerbils. Mongolian gerbils were used as an experimental model due to the morphological similarity of the adrenal glands to those of primates. Male Mongolian gerbils, 3 months of age, were divided into three experimental groups (n = 12): an intact control group, which received no treatment, a gavage control group, which received 0.1 ml of water daily by gavage, and a coconut oil-treated group, which received 0.1 ml of coconut oil daily for 12 months. The results showed that prolonged consumption of coconut oil caused an increase in cell area and thickness of the zona reticularis and the accumulation of lipid droplets, as well as reducing the amount of steroidogenic enzymes, such as CYP17, 3BHSD, and 17BHSD. It was also observed that the oil increased the expression of estrogen receptor alpha and their isoforms. These alterations allow us to conclude that changes in the lipid diet can cause alterations in the morphophysiology of the adrenal gland and, consequently, impact its functionality., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier Ltd. All rights reserved.)

The present study aimed to evaluate the effect of consumption of milk fermented by Lacticaseibacillus (Lc.) casei SJRP38 and Limosilactobacillus (Lm.) fermentum SJRP43 on bacterial translocation, stool analysis, and intestinal morphology of healthy BALB/c mice. Potentially probiotic lactic acid bacteria, Lc. casei SJRP38, and Lm. fermentum SJRP43 were evaluated and analyzed for translocation, fecal analysis, and intestinal morphology of four groups of mice: water control (WC), milk control (MC), milk fermented by Lc. casei SJRP38 (FMLC), and milk fermented by Lm. fermentum SJRP43 (FMLF), in co-culture with Streptococcus thermophilus ST080. The results of the animal assay indicate that the population of Lactobacilli and Bidobacterium sp. in the gastrointestinal tract of BALB/c mice was greater than 6.0 log 10 CFU/g, and there was no evidence of bacteremia due to the low incidence of bacterial translocation. Ingesting fermented milk containing Lc. casei SJRP38 and Lm. fermentum SJRP43 was found to promote a healthier microbiota, as it led to a reduction in Clostridium sp. and an increase in Lactobacilli and Bifidobacterium sp. in feces. Furthermore, the dairy treatments (MC, FMLC, and FMLF) resulted in taller intestinal villi and an increase in the frequency of goblet cells in the intestines. Overall, the consumption of fermented milk containing Lc. casei SJRP38 and Lm. fermentum SJRP43 strains was deemed safe and demonstrated beneficial effects on the intestines of BALB/c mice., Competing Interests: Declarations. Competing Interests: There are no financial interests directly or indirectly related to the work submitted for publication., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Aging causes changes in liver morphophysiology, altering hepatocyte morphology and organ function. Due to its antioxidant and anti-inflammatory properties, coconut oil has been used as a therapeutic agent in diets, in an attempt to attenuate alterations in the liver naturally caused by aging. Herein, we evaluated the effects of coconut oil consumption during aging on Mongolian gerbil liver morphophysiology. The animals were divided into three experimental groups: the gerbils in the Adult Control Group (AC) were euthanized at 3 months of age, the gerbils in the Old Control Group (OC) at 15 months of age, and the gerbils in the Coconut Oil Group (CO) received 0.1 ml/day of coconut oil for 12 months and were euthanized at 15 months of age. Prolonged consumption of coconut oil during aging prevented the animals and the liver from gaining mass. However, the other results showed that coconut oil intensified the morphophysiological alterations of aging, promoting an increase in the hepatocyte cytoplasm and nuclei. In addition, an increase in blood vessels, reticular fibers, lipid droplets, and lipofuscin granules were observed in the CO group. Finally, the results also demonstrated that coconut oil promotes an increase in lipid peroxidation, indicated by an increase in MDA levels. We therefore conclude that coconut oil has the potential to intensify the morphophysiological alterations that occur in the liver during aging., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The prostate undergoes normal or pathological morphological changes throughout life. An understanding of these changes is fundamental for the comprehension of aging-related pathological processes such as benign prostatic hyperplasia (BPH) and cancer. In the present study, we show some of these morphological changes, as well as histochemical techniques like Weigert's resorcin-fuchsin method, Picrosirius Red, and Gömöri's reticulin for use as tools in the study of prostate tissue under light microscopy. For this purpose, prostates of the Mongolian gerbil (n = 9), an experimental model that develops BPH spontaneously, were analyzed at three life stages: young (1 month old), adult (3 months old), and old (15 months old). The results showed that fibrillar components such as collagen, and reticular and elastic fibers, change throughout life. In young animals, the prostate has cuboidal epithelium surrounded by thin layers of smooth muscle, continuous collagen fibers, winding reticular fibers, and sporadic elastic fibers. With adulthood, the epithelium becomes columnar, encircled by compacted muscle cells among slender collagen fibers, elongated reticular fibers, and linear elastic fibers. In aging individuals, the prostate's epithelium stratifies, surrounded by thick muscle layers among dense collagen fibers, disordered reticular fibers, and elastic fibers in different planes. We also identified a few accumulations of lipid droplets and lipofuscin granules in adult animals and high accumulation in old animals evidenced by Oil red O and Gömöri-Halmi techniques, respectively. The histochemical techniques presented here have been demonstrated to be useful and accessible tools in prostate studies. RESEARCH HIGHLIGHTS: Cytochemical techniques to study prostate morphology. The prostate changes with age., (© 2024 Wiley Periodicals LLC.)

The adrenal gland produces steroid hormones that act in the homeostasis of organisms. During aging, alterations in the hormonal balance affect the adrenal glands, but these have not yet been fully described due to the lack of adequate animal models. The adrenal gland of the Mongolian gerbil has a morphology similar to the primate's adrenal gland, which makes it a possible animal model for endocrine studies. Therefore, the current study aimed to study the morphophysiology of the adrenal gland under the effect of aging. For this purpose, males Meriones unguiculatus, aged three, six, nine, twelve, and fifteen months were used. Morphometric, immunohistochemical, and hormonal analyses were performed. It was observed that during aging the adrenal gland presents hypertrophy of the fasciculata and reticularis zones. Lipofuscin accumulation was observed during aging, in addition to changes in proliferation, cell death, and cell receptors. The analyses also showed that the gerbil presents steroidogenic enzymes and the production of steroid hormones, such as DHEA, like that found in humans. The data provide the first comprehensive assessment of the morphophysiology of the Mongolian gerbil adrenal cortex during aging, indicating that this species is a possible experimental model for studies of the adrenal gland and aging., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Telocytes are interstitial cells that are present in various tissues, have long cytoplasmic projections known as telopodes, and are classified as CD34 + cells. Telopodes form extensive networks that permeate the stroma, and there is evidence that these networks connect several stromal cell types, giving them an important role in intercellular communication and the maintenance of tissue organisation. Data have also shown that these networks can be impaired and the number of telocytes reduced in association with many pathological conditions such as cancer and fibrosis. Thus, techniques that promote telocyte proliferation have become an important therapeutic target. In this study, ex vivo and in vitro assays were conducted to evaluate the impact on prostatic telocytes of SDF-1, a factor involved in the proliferation and migration of CD34 + cells. SDF-1 caused an increase in the number of telocytes in explants, as well as morphological changes that were possibly related to the proliferation of these cells. These changes involved the fusion of telopode segments, linked to an increase in cell body volume. In vitro assays also showed that SDF-1 enriched prostate stromal cells with telocytes. Altogether, the data indicate that SDF-1 may offer promising uses in therapies that aim to increase the number of telocytes. However, further studies are needed to confirm the efficiency of this factor in different tissues/pathological conditions., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Sexual transmission of Zika virus (ZIKV), an important arbovirus, and the virus persistence in semen raise several questions about how and where it circulates in the male reproductive system (MRS). Several studies reported detection of the virus in testes, epididymis, and prostate at 5 days post-infection (dpi) or more in animal models. In the present study, we investigated the interactions of ZIKV with mouse MRS using the AG129 strain, a ZIKV permissive immunodeficient mouse strain, at two dpi. Viral RNA was detected in blood, testes, epididymis, and prostatic complexes (prostate and seminal vesicles). Immunohistochemical (IHC) analyses, based on the envelope protein, showed an early infection in organs of MRS since ZIKV positive antigens were detected in cells within or surrounding blood vessels, Sertoli, and germ cells in testes and epithelial cells in epididymis and prostate. Positive antigens for NS5 protein, the virus RNA-dependent RNA polymerase, were also detected by IHC in these organs and circulating leukocytes, suggesting that the virus replicates in these sites as early as 2 days post-infection. Analysis of the early stages of ZIKV infection in MRS may improve the current knowledge about this issue and contribute to the development of therapies directed to the infection at this site., (© 2022. The Author(s) under exclusive licence to Sociedade Brasileira de Microbiologia.)

Background: The prostate is susceptible to changes in androgen levels, which can play an important role in the development of Benign Prostatic Hyperplasia (BPH). Natural compounds have beneficial properties for organisms and can be an important therapeutic strategy in the treatment of diseases. β-Caryophyllene (BCP) is a phytocannabinoid present in several medicinal and food plants species and has shown beneficial effects in different organs. However, little is known about its effects on the prostate. The present study seeks to evaluate the effects of exposure to BCP on the morphophysiology of the ventral prostate of adult gerbils supplemented with testosterone., Methods: Animals were distributed into four groups (n = 8/group): Intact control (C); β-Caryophyllene (BCP): β-Caryophyllene (50 mg/kg/day); Testosterone (T): animals received subcutaneous injections of Testosterone Cypionate (3 mg/Kg), on alternate days, for one month and were euthanized 30 days supplementation ended; Testosterone and β-Caryophyllene (TBCP): animals were exposed to testosterone cypionate (3 mg/Kg) to induce hyperplastic alterations followed by daily BCP (50 mg/kg). Morphological, biometric, immunohistochemical, and serological analyses were performed., Results: Proliferative disorders and inflammatory foci were present in the ventral prostate of all experimental groups. An increase in the multiplicity of benign intraepithelial neoplasm and subepithelial inflammatory foci was observed in T group. The incidence of intraluminal inflammatory foci and microinvasive carcinoma was verified only in the T group. Cellular rearrangement and tissue remodeling occurred in the prostate of groups exposed to phytocannabinoids. A reduction was observed in the frequency of PHH3 and Cox2 markers in the prostatic epithelium of TBCP in comparison with T. A decrease in F4/80 and CD163 positive macrophages were also observed in the prostatic stroma of the TBCP group in comparison with T. The results suggest that BCP had favorable effects on BPH, reducing the proliferation and frequency of some inflammatory cells., Conclusion: BCP impacts the tissue remodeling process in the premalignant prostate environment and that the use of this phytocannabinoid can have a promising effect in the handling of BPH., (© 2021 Wiley Periodicals LLC.)

The prostate is an important gland that contributes to the male reproductive process, producing secretions that are essential for maintaining ideal conditions for the survival of sperm. Studies indicate a wide variation in the occurrence, morphology, and physiology of this gland in mammals, especially in bats, with this variation being related not only to the number of regions and their degree of compaction/lobulation but also to fluctuations in their functioning throughout the year. Thus, the aim of this study was to evaluate the annual morphological and physiological variations of the male prostate of Artibeus lituratus and analyze their responses to annual abiotic variations and hormonal control. Sixty sexually adult males of A. lituratus were analyzed in this study, with five specimens collected monthly. Blood samples were submitted to serum hormone measurements and the prostates were morphologically, morphometrically, and immunohistochemically analyzed. The results indicated that the two prostatic regions (ventral and dorsal) of A. lituratus had different morphology, as well as different physiology and regulation. Annual fluctuations in abiotic factors seemed to influence the dorsal region more than the ventral region. Conversely, variations on testicular factors, such as testosterone and estradiol, influenced the ventral region more than the dorsal region. Despite these differences, both prostatic regions were strongly synchronized to the main reproductive peak of the species in September. The holocrine pattern of the ventral prostate was not directly affected by abiotic factors or by factors released by the testes., (© 2021 Wiley Periodicals LLC.)

Background: The male and female prostates are controlled by steroid hormones, suffering important morphological and physiological changes after castration. Prolactin is involved in the regulation of the male prostate, having already been identified in the tissue, acting through its receptor PRLR. In the Mongolian gerbil, in addition to the male prostate, the female prostate is also well developed and active in its secretion processes. The aim of the present study was to evaluate the effects of exposure to exogenous prolactin in the prostate of both intact and castrated male and female gerbils in order to establish if prolactin administration can sustain prostate cell activity in conditions of sexual hormone deprivation., Methods: The morphological analyses were performed by biometric analysis, lesion histological analysis and morphometric-stereological aspects. In addition, immune-cytochemical tests were performed for prolactin and its receptor, as well as for the receptors of androgen and oestrogen and serum prolactin dosage. All data were submitted to ANOVA or Kruskal-Wallis tests for comparison between groups. P < 0.05 was considered to be statistically significant., Results: The results showed a strong influence of prolactin on the morphology of the prostate, with the development of important epithelial alterations, after only 3 days of administration, and an expressive epithelial cell discard process after 30 days of administration. Prolactin acts in synergy with testosterone in males and mainly with oestrogens in females, establishing different steroid hormonal receptor immunoreactivity according to sex. It was also demonstrated that prolactin can assist in the recovery from some atrophic effects caused in the gland after castration, without causing additional tissue damage., Conclusions: The prolactin and its receptor are involved in the maintenance of the homeostasis of male and female gerbils, and also cause distinct histological alterations after exogenous exposure for 3 and 30 days. The effects of prolactin are related to its joint action on androgens and oestrogens and it can also assist in the recovery from the atrophic effects of castration.

Myotis nigricans is a species of bat from the Vespertilionidae family that is endemic of the Neotropical region. Its insectivorous feeding habit plus its large range of prey species, great geographical dispersion, wide colonies, and anthropomorphized behavior make this species an important ecological agent that acts in the control of nocturnal insects. Reproductively, M. nigricans presents geographic variations, having different patterns of reproduction according to its geographical location. Despite these extremely interesting characteristics, no more detailed study of the hormonal control of the reproduction of this species has been conducted. Therefore, the aim of the present study was to evaluate the variations in serum hormone concentrations and in uterine hormonal control of this bat during its different reproductive phases. Twenty adult females were collected, divided into four (4) sample groups, according to the reproductive status (nonreproductive, initial, and advanced pregnancy and lactating), and submitted to hormone dosage and immunohistochemical analyses. The results demonstrated that the uterus of M. nigricans is strongly regulated by the interaction/cross-talk between serum concentrations of estradiol (E2) and progesterone with their respective hormone receptors. Significant increases in the concentration of E2 and progesterone are needed to regulate the early pregnancy. The persistence of the corpus luteum throughout pregnancy is necessary, since its placenta does not express aromatase. The expressions of ERα and PR appear to be synchronized in order to coordinate a large portion of the processes that occur inside the uterus of M. nigricans during pregnancy and lactation.

The endocrine disruptive effects caused by bisphenol A (BPA) are well known. Despite this, to date, evaluation of its long term effects is limited, meaning that there is still much to be unveiled in terms of alterations caused by perinatal exposure to BPA. Our aim was to determine if perinatal exposure to two different doses of BPA causes long term morphological and molecular alteration effects in the mammary gland (MG). We evaluated MG from Mongolian gerbil offspring exposed perinatally (during gestation and lactation) to 50 or 5000 μg/kg/day BPA. At 90 days of age the animals were subjected to a single dose of N-nitroso-N-methylurea in order to mimic a carcinogenic environment. At 6 months of age, animals in estrous were euthanized for morphological evaluation of the MGs. The MG architecture presented considerable changes in terms of detached epithelial cells, inflammation, glandular hyperplasia, and collagen fiber deposition. Furthermore, a higher index of epithelial cell proliferation was detected in comparison to the intact control group. In addition, we verified a higher molecular expression of EZH2 in the vehicle treated group, indicating that corn oil applied alone can alter the expression of this epigenetic biomarker. In conclusion, BPA perinatal exposure promotes significant changes in glandular cytoarchitecture and increases glandular epithelium proliferation rate, leading to the retention of stem-like properties. This event could compromise the fate and differentiation potential of mammary epithelium., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Artibeus lituratus is a frugivorous bat that directly assists in the restoration of degraded habitats through the effective dispersion of seeds and fruits. Given its great importance, this work aimed to evaluate the uterine hormonal control of A. lituratus during its different reproductive phases. The uteri of 30 sexually mature adult females, five specimens for each of the six sample groups (NON, nonreproductive; P1, initial pregnancy; P2, intermediate pregnancy; P3, advanced pregnancy; LAC, lactating; P + LAC, pregnant-lactating), were submitted to analyses of serum estradiol and progesterone concentrations, in addition to immunohistochemical analyses. Both estradiol and progesterone, gradually increased during pregnancy, with a marked significant increase in P3 females. Both returned to low levels in LAC-females; however, estradiol levels decreased further in P + LAC-females, while progesterone increased in the same group. In general, signs indicative of aromatase expression were observed in the endometrium of all analyzed groups and in the placenta of bats in the gestation groups. Similarly, ERα and PR were expressed in the myometrium, endometrium and placenta at varying levels of intensity. The results indicate that the uterine microenvironment of A. lituratus is directly regulated by serum concentrations of estradiol and progesterone, and fluctuations in these concentrations control morphological and physiological changes of this organ during different phases of the reproductive cycle. RESEARCH HIGHLIGHTS: Increases in serum concentrations of estradiol and progesterone coordinate the gestational period of A. lituratus. Estradiol activates ERα, stimulating cell proliferation in the uterus, in addition to activating the expression of PR, which trigger the quiescence of the myometrium and stimulation of the secretion and differentiation of the endometrium. Results showed several similarities to humans, indicating the use of A. lituratus as an animal model in reproductive studies., (© 2020 Wiley Periodicals, Inc.)

Hormonal regulation controls mammary gland (MG) development. Therefore some hormone-related factors can disrupt the early phases of MGs development, making the gland more susceptible to long term modifications in its response to circulating hormones. Endocrine disruptors, such as bisphenol A (BPA), are able to cause alterations in hormone receptor expression, leading to changes in the cell proliferation index, which may expose the tissue to neoplastic alterations. Thus, we evaluated the variations in hormone receptor expression in the MG of 6-month old Mongolian gerbils exposed to BPA and 17β estradiol during the perinatal period. Receptors for estrogen alpha (ERα), beta (ERβ), progesterone (PGR), prolactin (PRL-R), and co-localization of connexin 43 (Cx43) and ERα in gerbils were analyzed, and serum concentrations of estradiol and progesterone were assessed. No alterations in body, liver, and ovary-uterus complex weights were observed. However, there was an increase in epithelial ERα expression in the 17β estradiol (E2) group and in PGR in the BPA group. Although immunohistochemistry did not show alterations in ERβ expression, western blotting revealed a decrease in this protein in the BPA group. PRL-R was more present in epithelial cells in the vehicle control (VC), E2, and BPA groups in comparison to the intact control group. Cx43 was more frequent in E2 and BPA groups, suggesting a protective response from the gland against possible malignancy. Serum concentration of estradiol reduced in VC, E2, and BPA groups, confirming that alterations also impacts steroid levels. Consequently, perinatal exposure to BPA and the reference endogenous estrogen, 17β estradiol, are able to increase the tendency of endocrine disruption in MG in a long term manner, since repercussions are observed even 6 months after exposure., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Vegetable oils are frequently used as a vehicle in the administration of lipophilic drugs in animal tests. However, the composition of these oils may interfere with the results. One alternative to reduce this potential bias is the use of mineral oil, which is not supposed to interfere in the physiology of experimental models, since this oil is considered to be innocous. The present study shows for the first time the effects of the oral administration of corn and mineral on the prostate, demonstrating their interference in homeostasis and revealing their potential to act as endocrine disruptors. Mineral oil treatment increased the expression of AR and ERα and serum estradiol concentrations, while corn oil increased the expression of positive cells for both types of estrogen receptors. The variation in the expression of these hormone receptors resulted in morphological changes in the prostate., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Finasteride is a drug that is widely used in the treatment of benign prostatic hyperplasia, hair loss and even as a chemotherapeutic agent in the treatment of prostatic adenocarcinoma. However, its use is known to cause several side effects in adults and it can also cause changes in the embryonic development of the male prostate, which is a cause for concern given the possibility of the accumulation of finasteride in the environment. Nevertheless, no studies have investigated the effects of finasteride on the development of the prostate in females, which occurs in several species of mammals. To evaluate the effects of intrauterine exposure to finasteride (500μgkg-1 day-1) on postnatal prostate development in the Mongolian gerbil in the present study, we used immunohistochemistry, immunofluorescence, serological analysis and three-dimensional reconstruction techniques. Differences were observed in the effects of finasteride on periductal smooth muscle and cell proliferation between the sexes, as well as intersex differences in the presence of the androgen receptor, which was elevated in males, and the oestrogen receptor ERα, which was increased in females. Together, the data indicate that the female prostate has its own hormone dynamics and that there are sex-specific differences in the way in which the female prostate reacts to prenatal exposure to finasteride.

Prostate cancer development has been associated with changes in mitochondrial activity and reactive oxygen species (ROS) production. Melatonin (MLT) and docosahexaenoic acid (DHA) have properties to modulate both, but their protective role, mainly at early stages of prostate cancer, remains unclear. In this study, the effects of MLT and DHA, combined or not, on PNT1A cells with regard to mitochondria bioenergetics, ROS production, and proliferation-related pathways were examined. Based on dose response and lipid accumulation assays, DHA at 100  μ M and MLT at 1  μ M for 48 h were chosen. DHA doubled and MLT reduced (40%) superoxide anion production, but coincubation (DM) did not normalize to control. Hydrogen peroxide production decreased after MLT incubation only ( p < 0.01). These alterations affected the area and perimeter of mitochondria, since DHA increased whereas MLT decreased, but such hormone has no effect on coincubation. DHA isolated did not change the oxidative phosphorylation rate (OXPHOS), but decreased ( p < 0.001) the mitochondrial bioenergetic reserve capacity (MBRC) which is closely related to cell responsiveness to stress conditions. MLT, regardless of DHA, ameliorated OXPHOS and recovered MBRC after coincubation. All incubations decreased AKT phosphorylation; however, only MLT alone inhibited p-mTOR. MLT increased p-ERK1/2 and, when combined to DHA, increased GSTP1 expression ( p < 0.01). DHA did not change the testosterone levels in the medium, whereas MLT alone or coincubated decreased by about 20%; however, any incubation affected AR expression. Moreover, incubation with luzindole revealed that MLT effects were MTR1/2-independent. In conclusion, DHA increased ROS production and impaired mitochondrial function which was probably related to AKT inactivation; MLT improved OXPHOS and decreased ROS which was related to AKT/mTOR dephosphorylation, and when coincubated, the antiproliferative action was related to mitochondrial bioenergetic modulation associated to AKT and ERK1/2 regulation. Together, these findings point to the potential application of DHA and MLT towards the prevention of proliferative prostate diseases.

Objective: The purpose of this study was to estimate the need for population-level services for alcohol and other drug abuse in support of local planning., Method: Data were drawn from a subsample of 2,942 interviewees from the São Paulo Megacity Study, which evaluated mental health in the general population (18 years and older) of residents in the São Paulo metropolitan area. This population was classified into five hierarchical categories of severity, making it possible to obtain estimates of need for services, combining evaluation criteria regarding drug and alcohol use and general and mental health comorbidities over the last 12 months. For the at-risk groups in this population, estimates from the Potential Demand for the Use of Services survey interviews over the last year were generated., Results: Concerning the need for services, 86.5% of the population (Tier 1) had no problems related to drug and alcohol use, 8.9% (Tier 2) used heavily, 3.5% (Tiers 3, 4, and 5) met criteria for substance abuse disorders, among whom 1.3% (Tiers 4 and 5) require more specialized and intensive treatment and support. The following estimates for the Potential Demand for the Use of Services were found: 25.5% (Tier 3) and 51.1% (Tier 4), indicating that a significant number of individuals met criteria for substance abuse disorders but did not perceive any need for professional help or neglected the help available., Conclusions: In São Paulo there exists a large sector of the population that requires prevention strategies regarding the risks and harm resulting from alcohol and drug use, followed by a group requiring more specialized care. But a large number of substance users requiring specialized support did not use services and did not believe that they needed professional help.