Gut microbiome: a novel preventive and therapeutic target for prostatic disease.

The human gut microbiome (GM) impacts various physiological processes and can lead to pathological conditions and even carcinogenesis if homeostasis is disrupted. Recent studies have indicated a connection between the GM and prostatic disease. However, the underlying mechanisms are still unclear. This review aims to provide a summary of the existing information regarding the connection between the GM and various prostatic conditions such as chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), benign prostatic hyperplasia (BPH), and prostate cancer (PCa). Furthermore, the review aims to identify possible pathogenic mechanisms and suggest potential ways of targeting GM to prevent and treat prostatic disease. Due to the complexity of the mechanism between GM and prostatic diseases, additional research is required to comprehend the association between the two. This will lead to more effective treatment options for prostatic disease.

Fosfomycin-trometamol (FT) or fluoroquinolone (FQ) as single-dose prophylaxis for transrectal ultrasound-guided prostate biopsy (TRUS-PB): A prospective cohort study.

OBJECTIVES: The increasing incidence of fluoroquinolones (FQ) resistance may lower its efficacy in preventing UTI following transrectal ultrasound-guided prostate biopsy (TRUS-PB). We assessed the efficacy and safety of FQ and fosfomycin-trometamol (FT) in patients undergoing TRUS-PB. METHODS: A prospective observational study was conducted between April 2017 and June 2019 and enrolled men undergoing TRUS-PB and receiving a single-dose of FQ (FQ-arm) or FT (FT-arm) for UTI prophylaxis per physician's choice. The primary efficacy endpoint was self-reported TRUS-PB UTI. We assessed baseline factors associated with UTI with logistic regression. RESULTS: A total of 222 men were enrolled, 141/222 (64%) received FQ, and 81/222 (36%) FT. The median age was 67.6 years [IQR, 61.4-72.1] and the Charlson score was 3 [IQR, 3-5]. The overall incidence of self-reported TRUS-PB UTI was 12% (24/197, (95%CI, 8%-17%)): 15% (17/116, (95% CI, 10%-17%)) in FQ-arm, versus 9% (7/81, 95% CI (5%-13%)) in FT-arm (RR = 0.55 (95% CI, 0.22-1.40), p-value = 0.209). No baseline characteristic was significantly associated with TRUS-PB UTI. Safety was similar between the arms: the rate of the reported adverse event was 31% (36/116, (95% CI, 25%-37%) in the FQ-arm versus 36% (28/81, (95% CI, 28%-41%)) in the FT-arm (RR = 1.17 (95% CI, 0.64-2.15), p = 0.602). CONCLUSIONS: TRUS-PB UTI prophylaxis with FT and FQ has similar efficacy and safety. A randomized comparison of these two antibiotics is warranted.

Effect of Gloriosa superba linn (EEGS) on mPT and monosodium glutamate-induced proliferative disorder using rat model.

ETHNOPHARMACOLOGICAL RELEVANCE: Hyperplasia, Tumors and cancers are various forms of proliferative disorders affecting humans. Surgery is the main treatment approach while other options are also associated with adverse effects. There is therefore a need for the development of better alternative therapy that is cost effective and readily available with little or no adverse effect. Some bioactive agents in medicinal plants exhibit their anti-proliferative potential by induction of mitochondrial permeability transition pore (mPT) opening. Gloriosa superba, a medicinal plant, is folklorically used in the treatment of tumors and cancers. AIM OF THE STUDY: This study therefore aimed at investigating the effect of ethanol leaf extract of Gloriosa superba (EEGS) on mPT and monosodium glutamate-induced proliferative disorder in some specific tissues using rat model. MATERIALS AND METHODS: Isolated rat liver mitochondria were exposed to different concentrations (10, 30, 50, 70 and 90 µg/ml) of EEGS. The mPT pore opening, cytochrome c release, mitochondrial ATPase activity and lipid peroxidation were assessed spectrophotometrically. Caspases 9 and 3 activities were carried out using ELISA technique. Histological assessment of the liver, prostate and uterus of normal and monosodium glutamate (MSG)-treated rats were carried out. RESULTS: The results showed significant induction of mPT pore opening, release of cytochrome c, enhancement of mitochondrial ATPase activity, inhibition of lipid peroxidation and activation of caspases 9 and 3 activities by EEGS. The histological assessment revealed the presence of MSG-induced hepato-cellular damage, benign prostate hyperplasia and uterine hyperplasia which were ameliorated by EEGS co-administration. CONCLUSIONS: These findings suggest that EEGS contains putative agents that can induce apoptosis via induction of mPT pore opening and as well protect against MSG-induced hepato-cellular damage and proliferative disorder in prostate and uterus.

Effectiveness of a Very Low Calorie Ketogenic Diet on Testicular Function in Overweight/Obese Men.

BACKGROUND: Obesity has become an increasingly worrisome reality. A very-low-calorie ketogenic diet (VLCKD) represents a promising option by which to achieve significant weight loss. This study sought to evaluate the effectiveness of VLCKD on metabolic parameters and hormonal profiles of obese male patients. METHODS: We enrolled 40 overweight/obese men who consumed VLCKD for at least eight weeks. Body weight, waist circumference, fasting glucose, insulin, total cholesterol, high-density lipoprotein, triglycerides, creatinine, uric acid, aspartate aminotransferase, alanine aminotransferase, vitamin D, luteinizing hormone (LH), total testosterone (TT), and prostate-specific antigen (PSA) were calculated before and after VLCKD consumption. We additionally determined the homeostasis model assessment index and low-density lipoprotein (LDL) values. RESULTS: After VLCKD (13.5 ± 0.83 weeks), the mean body weight loss was 21.05 ± 1.44 kg; the glucose homeostasis and lipid profile were improved significantly; serum vitamin D, LH, and TT levels were increased and the PSA levels were decreased significantly as compared with pretreatment values. These results are of interest since obesity can lead to hypogonadism and in turn, testosterone deficiency is associated with impaired glucose homeostasis, metabolic syndrome, and diabetes mellitus. Moreover, a close relationship between obesity, insulin resistance, and/or hyperinsulinemia and increased prostate volume has been reported, with a consequent greater risk of developing lower urinary tract symptoms. CONCLUSIONS: VLCKD is an effective tool against obesity and could be a noninvasive, rapid, and valid means to treat obese patients with metabolic hypogonadism and lower urinary tract symptoms.

Effects of adjuvant-induced arthritis on the ventral prostate of rats treated with angiotensin AT1 receptor blocker.

AIMS: To analyze the prostatic compartments, extracellular matrix, microvascularization, transforming growth factor-beta (TGF-ß) and angiotensin II receptors type 1 (AT1) levels, and histopathology of the ventral prostate in a rat model for rheumatoid arthritis, and to evaluate the effect of angiotensin II AT1 receptor blocker (ARB) in the disease. MAIN METHODS: Fifteen male rats (90 days old) were divided into three groups (n = 5/group): control, adjuvant-induced arthritis without (AIA) or with AT1 receptor blocker (AIA + ARB). Animals were euthanized 60 days after immunization. The ventral prostate was collected, weighed, and processed for histological and immunohistochemical analysis. KEY FINDINGS: Our results show that AIA increases production of the prostatic epithelium and extracellular matrix, accompanied by a reduction in the number of tissue capillaries. ARB treatment promotes decreased production of extracellular matrix and increased TGF-ß and AT1 receptor immunostaining. SIGNIFICANCE: AIA may activate specific mechanisms that modify the prostatic environment; the use of ARB attenuates some altered prostate parameters in a rat model for arthritis.

Selenium Supplementation and Prostate Health in a New Zealand Cohort.

BACKGROUND: There is variable reporting on the benefits of a 200 µg/d selenium supplementation towards reducing prostate cancer impacts. The current analysis is to understand whether stratified groups receive supplementation benefits on prostate health. METHODS: 572 men were supplemented with 200 µg/d selenium as selinized yeast for six months, and 481 completed the protocol. Selenium and prostate-specific antigen (PSA) levels were measured in serum at pre- and post-supplementation. Changes in selenium and PSA levels subsequent to supplementation were assessed with and without demographic, lifestyle, genetic and dietary stratifications. RESULTS: The post-supplementation selenium (p = 0.002) and the gain in selenium (p < 0.0001) by supplementation were significantly dependent on the baseline selenium level. Overall, there was no significant correlation between changes in PSA and changes in selenium levels by supplementation. However, stratified analyses showed a significant inverse correlation between changes in PSA and changes in selenium in men below the median age (p = 0.048), never-smokers (p = 0.031), men carrying the GPX1 rs1050450 T allele (CT, p = 0.022 and TT, p = 0.011), dietary intakes above the recommended daily intake (RDI) for zinc (p < 0.05), and below the RDI for vitamin B12 (p < 0.001). CONCLUSIONS: The current analysis shows the influence of life factors on prostate health benefits of supplemental selenium.

The Polyphenols as Potential Agents in Prevention and Therapy of Prostate Diseases.

In recent years, the progress of science and medicine greatly has influenced human life span and health. However, lifestyle habits, like physical activity, smoking cessation, moderate alcohol consumption, diet, and maintaining a normal body weight represent measures that greatly reduce the risk of various diseases. The type of diet is very important for disease development. Numerous epidemiological clinical data confirm that longevity is linked to predominantly plant-based diets and it is related to a long life; whereas the western diet, rich in red meat and fats, increases the risk of oxidative stress and thus the risk of developing various diseases and pre-aging. This review is focused on the bioavailability of polyphenols and the use of polyphenols for the prevention of prostate diseases. Special focus in this paper is placed on the isoflavonoids and flavan-3-ols, subgroups of polyphenols, and their protective effects against the development of prostate diseases.

[Testosterone therapy]. / Testosterontherapie.

Hormone replacement therapy with testosterone has become well-established over the course of time. The initial substantial concerns with respect to complications and potential adverse events, particularly in older patients, were proven to be unfounded over time. Testosterone therapy has therefore gradually become a regular treatment modality in urological practice. It has also been shown to represent a valuable tool as supportive treatment for patients with erectile dysfunction and hypogonadism. A variety of testosterone preparations are available for treatment. Recent pharmaceutical developments have greatly improved the practicability and ease of administration for patients. Several guidelines have been developed that provide clearly formulated standards and instructions for indications, contraindications, application, risk factors and monitoring of testosterone therapy. Adverse events affecting the cardiovascular system and especially diseases of the prostate gland are of great importance, thus making the urologist the primary partner in the treatment of patients with testosterone deficiency.

Clinical effectiveness and safety of tazobactam/piperacillin 4.5 g for the prevention of febrile infectious complication after prostate biopsy.

We investigated the clinical effectiveness and safety of tazobactam/piperacillin (TAZ/PIPC) in a 1:8 ratio, a ß-lactamase inhibitor with penicillin antibiotic, for the prevention of febrile infectious complication after prostate biopsy. Each patient received a single dose of TAZ/PIPC 4.5 g, 30 min before the biopsy in Group 1 or TAZ/PIPC 4.5 g twice, once 30 min before and once after the biopsy (just before discharge or 5 h after the biopsy), in Group 2. Estimation of efficacy was performed within 1-month after prostate biopsy. Clinical diagnosis of febrile infectious complication was based on a body temperature elevation greater than 38 °C. Infectious complication after prostate biopsy was detected in 2.5% (4/160 patients) in Group 1 and in 0.45% (2/442 patients) in Group 2. All of the patients with febrile infectious complication had risk factors: 5 patients had voiding disturbance, 2 patients had diabetes mellitus and 1 patient had steroid dosing. In group 1, 88 patients had at least one risk factor and 72 patients had no risk factors. Of the patients with a risk factor, 4 had febrile infectious complication after prostate biopsy, but there was no significant difference between the two groups. In group 2, 87 patients had at least one risk factor and 255 patients had no risk factors. The patients with a risk factor had febrile infectious complication significantly more frequently than did patients without a risk factor (P = 0.038). Therefore, TAZ/PIPC appears to be effective as preoperative prophylaxis against the occurrence of febrile infectious complication after prostate biopsy.

Control of infective complications of transrectal prostate biopsy.

BACKGROUND: To describe a preparatory protocol for prostate biopsy consisting of prophylaxis based on a third-generation cephalosporin and suppository-type povidone-iodine. METHODS: From January 2004 to May 2012 we reviewed infective complications in 1,684 patients who underwent transrectal ultrasound (TRUS)-guided prostate biopsy. All of the patients received prophylactic antibiotics through a single intravenous injection of a third-generation cephalosporin and cefixime at 100 mg PO for 5 d, with this regimen begun before biopsy, and were also given gynobetadine in a dose of 200 mg just before biopsy. Infectious complications were classified as sepsis, fever (>38°C) without sepsis, and other clinical manifestations of infection. To evaluate the bactericidal effects of gynobetadine, we counted bacterial colonies prospectively in cultures of rectal swab specimens from 150 patients who underwent TRUS-guided prostate biopsy. RESULTS: Complications occurred in 46 of the patients (2.73%), including infective complications in 11 (0.65%) patients and non-infective complications in 35 (2.08%) patients. Of the patients with infective complications, two had fever without sepsis, none had clinical urinary tract infections without fever, and none had sepsis. In prospective in vitro investigations, the mean bacterial colony count before rectal preparation with an enema or rectal insertion of povidone-iodine suppository was 2.38×10(6), whereas the colony count after a povidone-iodine rectal enema and subsequent biopsy was 1.81×10(3) and the colony count after rectal preparation with povidone-iodine suppository and subsequent biopsy was 8.1×10(2) (all p<0.001). CONCLUSIONS: The administration of cephalosporin-based prophylactic antibiotics and the simple use of suppository-type povidone-iodine provided an excellent protocol for reducing infective complications of TRUS-guided prostate biopsy. The simplicity of use and cost effectiveness of gynobetadine were noteworthy.

Protective effects of different antioxidants against cadmium induced oxidative damage in rat testis and prostate tissues.

The present study was performed to determine the effects of different antioxidants on testicular histopathology and oxidative damage induced by cadmium (Cd) in rat testis and prostate. Twenty five rats were equally divided into five groups (n = 5/group). The control group was injected subcutaneously with saline while the Cd alone treated group received a subcutaneous injection of 0.2 mg/kg CdCl(2). Other groups were treated with sulphoraphane (25 µg/rat), vitamin E (75 mg/kg), and Ficus Religiosa plant extract (100 mg/kg) orally along with subcutaneous injections of 0.2 mg/kg CdCl(2) for fifteen days. Oxidative damage in the testicular and prostate tissues were assessed by the estimation of catalase (CAT), peroxidase (POD), superoxide dismutase (SOD), and glutathione reductase (GSR) activity. Lipid peroxidation (TBARS), protein estimation, and histomorphology were also assessed. Cadmium exposure caused a significant decrease in antioxidant enzymes like CAT, POD, SOD, GSR, protein concentrations, and a marked increase in TBARS activity in rat testis and prostate. Histological examination of adult male rat testes showed a disruption in the arrangement of seminiferous tubules along with a reduction in the number of germ cells, Leydig cells, tunica albuginea thickness, diameter of seminiferous tubules, and height of germinal epithelium. Co-treatment with vitamin E, sulphoraphane, and Ficus religiosa were found to be effective in reversing Cd induced toxicity, representing potential therapeutic options to protect the reproductive tissues from the detrimental effects of Cd toxicity.

The meaning of touch the prostate for man: the nurse in health promotion / O significado do toque da próstata para o homem: enfermeiro na promoção da saúde / El sentido del tacto de la próstata para el hombre: enfermero en la promoción de la salud

Objetivos: Identificar o significado para os homens sobre o exame clínico de toque digital da próstata para detecção precoce de câncer, caracterizar a causa do déficit na procura de exame preventivos e serviços de saúde pelos homens e discutir atuação do enfermeiro na promoção da saúde dos homens. Método: Estudo qualitativo descritivo com pesquisa de campo norteada por formulário semi-estruturado. Resultados: Os significados atribuídos ao toque digital da próstata foram constrangimento, desconforto, estigma e importante. A informação e o acesso estão condicionados aos fatores socioeconômicos dos participantes. Conclusão: Enfermeiros devem assistir na educação em saúde e na saúde integral, uniformizando as informações para diferentes grupos socioeconômicos, minimizando o estigma e o constrangimento, ressaltando a importância do autocuidado para o homem, visando melhorar a busca pelos serviços de saúde, exames de rastreamento e prevenção.

Objectives: To identify the meaning for the men on the clinical examination of digital touch Prostate cancer early detection, to characterize the cause of the deficit in the search for preventive examination and health services by men and discuss the nurse's role in promoting men's health. Method: Qualitative descriptive study with field research guided by semi-structured form. Results: The meanings attributed to the digital touch of the prostate were embarrassment, discomfort, stigma and important. The information and access are tied to socioeconomic factors of the participants. Conclusion: Nurses should assist in health education and comprehensive health care by standardizing the information for different socioeconomic groups, minimizing the stigma and embarrassments, highlighting the importance of self care for man, to improve the search for health services, screening exams and prevention.

Objetivos: Identificar el significado de los hombres en el tacto digital de detección de cáncer de próstata, caracterizar la causa del déficit en la búsqueda de examen y los servicios preventivos de salud por los hombres y discutir el papel de la enfermera en la promoción de la salud masculina. Método: investigación cualitativa descriptiva de campo guiada por formulario séme-estructurado. Resultados: Los significados atribuidos al tacto digital de la próstata son vergüenza, incomodidad, estigma y importante. La información y acceso están condicionados a factores socioeconómicos de los participantes. Conclusión: Enfermeras deben asistir en la educación en salud y la salud integral, mediante la estandarización de la información para los diferentes grupos socioeconómicos, minimizando el estigma y la vergüenza, resaltando la importancia del auto cuidado para el hombre, para mejorar la búsqueda de los servicios de salud, exámenes de rastreo y prevención.

Protective effect of γ-tocopherol-enriched diet on N-methyl-N-nitrosourea-induced epithelial dysplasia in rat ventral prostate.

Despite recent advances in understanding the biological basis of prostate cancer (PCa), the management of this disease remains a challenge. Chemoprotective agents have been used to protect against or eradicate prostate malignancies. Here, we investigated the protective effect of γ-tocopherol on N-methyl-N-nitrosourea (MNU)-induced epithelial dysplasia in the rat ventral prostate (VP). Thirty-two male Wistar rats were divided into four groups (n = 8): control (CT): healthy control animals fed a standard diet; control+γ-tocopherol (CT+γT): healthy control animals without intervention fed a γ-tocopherol-enriched diet (20 mg/kg); N-methyl-N-nitrosourea (MNU): rats that received a single dose of MNU (30 mg/kg) plus testosterone propionate (100 mg/kg) and were fed a standard diet; and MNU+γ-tocopherol (MNU+γT): rats that received the same treatment of MNU plus testosterone and were fed with a γ-tocopherol-enriched diet (20 mg/kg). After 4 months, the VPs were excised to evaluate morphology, cell proliferation and apoptosis, as well as cyclooxygenase-2 (Cox-2), glutathione-S-transferase-pi (GST-pi) and androgen receptor (AR) protein expression, and matrix metalloproteinase-9 (MMP-9) activity. An increase in the incidence of epithelial dysplasias, such as stratified epithelial hyperplasia and squamous metaplasia, in the MNU group was accompanied by augmented cell proliferation, GST-pi and Cox-2 immunoexpression and pro-MMP-9 activity. Stromal thickening and inflammatory foci were also observed. The administration of a γ-tocopherol-enriched diet significantly attenuated the adverse effects of MNU in the VP. The incidence of epithelial dysplasia decreased, along with the cell proliferation index, GST-pi and Cox-2 immunoexpression. The gelatinolytic activity of pro-MMP-9 returned to the levels observed for the CT group. These results suggest that γ-tocopherol acts as a protective agent against MNU-induced prostatic disorders in the rat ventral prostate.

Heteropterys tomentosa (A. Juss.) infusion counteracts Cyclosporin a side effects on the ventral prostate.

BACKGROUND: Cyclosporin A (CsA) is an immunosuppressive drug widely used in treatment of auto-immune diseases or after organ transplants. However, several side effects are commonly associated with CsA long term intake, some regarding to loss of reproductive organ function due to oxidative damage. Considering that phytotherapy is an important tool often used against oxidative stress, we would like to describe the beneficial effects of Heteropterys tomentosa intake to minimize the damage caused by CsA to the ventral prostate tissue of Wistar rats under laboratorial conditions. METHODS: Thirty adult Wistar rats (Rattus norvegicus albinus) were divided into: control group (water); CsA group (Cyclosporin A); Ht group (H. tomentosa infusion) and CsA + Ht group (CsA and H. tomentosa infusion). Plasmic levels of hepatotoxicity markers, triglycerides, cholesterol and glucose were quantified. The ventral prostate tissue was analyzed under light microscopy, using stereological, morphometrical and immunohistochemical techniques. RESULTS: H. tomentosa did not cause any alterations either of the plasmic parameters or of the ventral prostate structure. CsA caused alterations of GOT, total and indirect bilirubin, cholesterol, triglycerides and glucose levels in the plasma; CsA-treated rats showed alterations of the ventral prostate tissue. There were no alterations regarding the plasma levels of GOT, triglycerides and glucose of CsA + Ht animals. The same group also showed normalization of most of the parameters analyzed on the ventral prostate tissue when compared to the CsA group. The treatments did not alter the pattern of AR expression or the apoptotic index of the ventral prostate epithelium. CONCLUSIONS: The results suggest a protective action of the H. tomentosa infusion against the side effects of CsA on the ventral prostate tissue, which could also be observed with plasmic biochemical parameters.

[Calculus formation in the prostatic cavity after transurethral resection of the prostate: causes, treatment and prevention].

OBJECTIVE: To study the causes, clinical manifestations, treatment and prevention of calculus that develops in the prostatic cavity after transurethral resection of the prostate. METHODS: We reported 11 cases of calculus that developed in the prostatic cavity after transurethral resection or transurethral plasmakinetic resection of prostate. The patients complained of repeated symptoms of frequent micturition, urgent micturition and urodynia after operation, accompanied with urinary tract infection and some with urinary obstruction, which failed to respond to anti-infective therapies. Cystoscopy revealed calculi in the prostatic cavity, with eschar, sphacelus, uneven wound surface and small diverticula in some cases. After diagnosis, 1 case was treated by holmium laser lithotripsy and a second transurethral resection of the prostate, while the other 10 had the calculi removed under the cystoscope, followed by 1 -2 weeks of anti-infective therapy. RESULTS: After treatment, all the 11 cases showed normal results of routine urinalysis, and no more symptoms of frequent micturition, urgent micturition and urodynia. Three- to six-month follow-up found no bladder irritation symptoms and urinary tract infection. CONCLUSION: Repeated symptoms of frequent micturition, urgent micturition, urodynia and urinary tract infection after transurethral resection of the prostate should be considered as the indicators of calculus in the prostatic cavity, which can be confirmed by cystoscopy. It can be treated by lithotripsy or removal of the calculus under the cystoscope, or even a second transurethral resection of the prostate. For its prevention, excessive electric coagulation and uneven wound surface should be avoided and anti-infection treatment is needed.

Diet, obesity, and prostate health: are we missing the link?

Prostate problems, such as benign prostatic hyperplasia, prostatic intra-epithelial neoplasia, prostatitis, and prostate cancer have been recognized as problems largely related to androgens and genetic factors. They affect a large fraction of the elderly population, contributing significantly to morbidity and mortality. Estrogen has also now been recognized as one of the important regulators of prostate growth. Diet, general health, and obesity were disregarded as the causative or complicating factors until very recently. Increasing episodes of prostate problems, complications in overweight/obese individuals, or both have attracted attention toward these contemporary risk factors. Prostate problems are reportedly less frequent or less severe in areas in which a plant-based diet is predominant. Consumption of certain fatty acids, particularly of animal origin, has been correlated with increased prostate problems. As adipose tissue is increasingly being regarded as hormonally active tissue, high body fat and obesity need in-depth exploration to understand the associated risk of prostate problems. Adipose tissue is now known to affect circulating levels of several bioactive messengers and therefore could affect the risk of developing prostate problems in addition to several other well-recognized health problems. Nevertheless, increased plasma volume, excess tissue growth, and fat deposition could affect resection and number of biopsies required, thus adding further complications because of a delayed diagnosis. In short, evidence is gathering to support the influence of diet and obesity on prostate health. In this review article, we have tried to make this connection more apparent using supporting published data.

Dietary patterns and prostatic diseases.

Dietary patterns play a role on prostatic diseases in association with genetic, behavioral, occupational and environmental ones. Data from reviewed literature provide evidences of a possible relationship between dietary habits and the incidence of prostate disorders, even if it is not enough to justify a widespread adoption of new dietary habits. In this review the role of dietary patterns, including the use of supplements, in the prevention and treatment of the most frequent and known prostatic diseases, benign prostatic hyperplasia (BPH) and prostate cancer (PC) was analyzed. A limited number of well designed trials were identified in which diet and dietary supplement intervention appeared to slow disease progression. Although conclusive evidences are limited, the current data suggest that a diet low in total calories and fat, high in vegetables and fruits and that body weight control could be possibly effective in preventing prostatic diseases. On the other hand care must be taken to ensure that over-consumption of dietary supplements does not occur because it may be harmful.

Establishment of a rescue program for anorectal malformations induced by retinoic acid in mice.

AIMS OF STUDY: Retinoid-mediated signal transduction plays a crucial role in the embryogenesis of various organs. We previously reported the successful induction of anorectal malformations in mice using retinoic acid (RA). Retinoic acid controls the expression of essential target genes for cell differentiation, morphogenesis, and apoptosis through a complicated interaction in which RA receptors form heterodimers with retinoid X receptors. In the present study, we investigated whether the retinoid antagonist, LE135, could prevent the induction of anorectal malformations (ARMs) in mice. METHODS: Retinoic acid was intraperitoneally administered as 100 mg/kg of all-trans RA on E9; and then the retinoid antagonist, LE135, was intraperitoneally administered to pregnant ICR strain mice on the eighth gestational day (E8), 1 day before administration of RA (group B) or on E9, simultaneously (group C) with RA administration. All of the embryos were obtained from the uteri on E18. Frozen sections were evaluated for concentric layers around the endodermal epithelium by hematoxylin and eosin staining. RESULTS: In group A, all of the embryos demonstrated ARM with rectoprostatic urethral fistula, or rectocloacal fistula, and all of the embryos showed the absence of a tail. In group B, 36% of the embryos could be rescued from ARM. However, all of the rescued embryos had a short tail that was shorter than their hind limb. The ARM rescue rates in group B were significantly improved compared to those in group A (P < .01). In group C, 45% of the embryos were rescued from ARM, but all of the rescued embryos had short tail. The ARM rescue rate in group C was significantly improved compared to that in group A (P < .01). However, there was no significant difference in the ARM rescue rate between group B and Group C. CONCLUSION: The present study provides evidence that in the hindgut region, RAR selective retinoid antagonist, LE135, could rescue embryos from ARM. However, the disturbance of all-trans RA acid was limited to the caudal region. Further study to establish an appropriate rescue program for ARM in a mouse model might suggest a step toward protection against human ARM in the future.