Altered detrusor contractility and voiding patterns in mice lacking the mechanosensitive TREK-1 channel.

Background: Previously published results from our laboratory identified a mechano-gated two-pore domain potassium channel, TREK-1, as a main mechanosensor in the smooth muscle of the human urinary bladder. One of the limitations of in vitro experiments on isolated human detrusor included inability to evaluate in vivo effects of TREK-1 on voiding function, as the channel is also expressed in the nervous system, and may modulate micturition via neural pathways. Therefore, in the present study, we aimed to assess the role of TREK-1 channel in bladder function and voiding patterns in vivo by using TREK-1 knockout (KO) mice.

The Expression of Transcription Factors Mecp2 and CREB Is Modulated in Inflammatory Pelvic Pain.

Early activation of transcription factors is one of the epigenetic mechanisms contributing to the induction and maintenance of chronic pain states. Previous studies identified the changes in a number of nociception-related genes, such as calcitonin gene-related peptide (CGRP), substance P (SP), and brain-derived neurotropic factor (BDNF) in the pelvic organs after transient colonic inflammation. The gene and protein expression of these neuropeptides could be modulated by transcription factors Methyl-CpG-binding protein 2 (Mecp2) and cAMP response element-binding protein (CREB).

Transurethral Instillation Procedure in Adult Male Mouse.

Transurethral instillation can be used to deliver different solutions with active ingredients (e.g., drugs, chemicals, bacteria, and viruses) locally into the urinary bladder to either induce animal models of bladder pathologies or evaluate the effectiveness of intravesical treatments.

Impact of Regular Cannabis Use on Biomarkers of Lower Urinary Tract Function.

Objective: To evaluate the differences in the composition and quantities of urine peptides in regular cannabis users and nonusers by liquid chromatography tandem mass spectrometry analysis.

Materials And Methods: Urine specimens from healthy control subjects and cannabis users were utilized to identify the differences in the number and quantity of urine proteins by liquid chromatography tandem mass spectrometry analysis. Significantly altered proteins were determined by a permutation testing statistical method.

Altered expression and modulation of the two-pore-domain (K) mechanogated potassium channel TREK-1 in overactive human detrusor.

Detrusor overactivity (DO) is the abnormal response of the urinary bladder to physiological stretch during the filling phase of the micturition cycle. The mechanisms of bladder smooth muscle compliance upon the wall stretch are poorly understood. We previously reported that the function of normal detrusor is regulated by TREK-1, a member of the mechanogated subfamily of two-pore-domain potassium (K) channels.

Fertility Preservation Options for Men and Women With Cancer.

Approximately 0.2% of Americans aged 20 to 39 years are childhood cancer survivors. Advances in cancer detection and therapy have greatly improved survival rates for young cancer patients; however, treatment of childhood cancers can adversely impact reproductive function.

Clomiphene citrate in the management of male infertility.

Clomiphene citrate, a selective estrogen receptor modulator, has been used to treat infertility in women and men for 50 years. In men, clomiphene citrate has been employed in the management of unexplained infertility, oligo and asthenospermia, hypogonadism, and nonobstructive azoospermia. The available evidence reveals mixed results and suggests that clomiphene citrate may be appropriate for the management of male infertility in specific clinical scenarios.

Effects of testosterone and progressive resistance exercise in healthy, highly functioning older men with low-normal testosterone levels.

Context: Aging in men is associated with reduced testosterone (T) levels and physiological changes leading to frailty, but the benefits of T supplementation are inconclusive.

Objective: We studied the effects of T supplementation with and without progressive resistance training (PRT) on functional performance, strength, and body composition.

Design, Setting, And Participants: We recruited 167 generally healthy community-dwelling older men (66 ± 5 years) with low-normal baseline total T levels (200-350 ng/dL).

The use of in vitro fertilization in the management of male infertility: what the urologist needs to know.

Infertility affects approximately 10% to 20% of reproductive-age couples, many of whom may present initially to a urologist. Some couples may be treated medically to increase spontaneous conception rates; however, many will require more aggressive management with in vitro fertilization (IVF) and/or intracytoplasmic sperm injection (ICSI). IVF involves ovarian stimulation, oocyte retrieval, and fertilization outside of the body; ICSI involves injecting one sperm into the oocyte to promote fertilization.

Genome wide analysis of differentially expressed genes in HK-2 cells, a line of human kidney epithelial cells in response to oxalate.

Nephrolithiasis is a multi-factorial disease which, in the majority of cases, involves the renal deposition of calcium oxalate. Oxalate is a metabolic end product excreted primarily by the kidney. Previous studies have shown that elevated levels of oxalate are detrimental to the renal epithelial cells; however, oxalate renal epithelial cell interactions are not completely understood.

The antioxidant, MnTE-2-PyP, prevents side-effects incurred by prostate cancer irradiation.

Prostate cancer is the most commonly diagnosed cancer, with an estimated 240,000 new cases reported annually in the United States. Due to early detection and advances in therapies, more than 90% of patients will survive 10 years post diagnosis and treatment. Radiation is a treatment option often used to treat localized disease; however, while radiation is very effective at killing tumor cells, normal tissues are damaged as well.

Kidney injury molecule-1 is up-regulated in renal epithelial cells in response to oxalate in vitro and in renal tissues in response to hyperoxaluria in vivo.

Oxalate is a metabolic end product excreted by the kidney. Mild increases in urinary oxalate are most commonly associated with Nephrolithiasis. Chronically high levels of urinary oxalate, as seen in patients with primary hyperoxaluria, are driving factor for recurrent renal stones, and ultimately lead to renal failure, calcification of soft tissue and premature death.

The transcription factor SPDEF suppresses prostate tumor metastasis.

Emerging evidence suggests that the SAM pointed domain containing ETS transcription factor (SPDEF) plays a significant role in tumorigenesis in prostate, breast, colon, and ovarian cancer. However, there are no in vivo studies with respect to the role of SPDEF in tumor metastasis. The present study examined the effects of SPDEF on tumor cell metastasis using prostate tumor cells as a model.

Potentiation of mitomycin C tumoricidal activity for transitional cell carcinoma by histone deacetylase inhibitors in vitro.

Purpose: Histone deacetylase inhibitors represent promising cancer treatments since they offer improved access to target DNA/protein complexes by cytotoxic agents. We hypothesized that histone deacetylase inhibitors would be most effective when combined with DNA damaging agents such as mitomycin C. Valproic acid is a safe, affordable histone deacetylase inhibitor.

Molecular aspects of renal cell carcinoma: a review.

Renal cell carcinoma (RCC) is a disease in which cancer cells form in the tubules of the kidney. RCC, the incidence of which is increasing annually, represents five percent of adult epithelial cancers. Clear cell carcinoma represents the most frequent histological subtype.

The computerized rounding report: implementation of a model system to support transitions of care.

Objectives: In response to ACGME work-hour restrictions, residency programs that require continuous inpatient clinical care for educational objectives will be forced to increase the proportion of junior resident experience involved in shift work. Maintaining the balance of education over service at these levels will be a challenge, where a considerable amount of time must be spent gathering data for morning rounds and signing out patients at shift change. Patient safety is an issue with this new paradigm.

Loss of PDEF, a prostate-derived Ets factor is associated with aggressive phenotype of prostate cancer: regulation of MMP 9 by PDEF.

Background: Prostate-derived Ets factor (PDEF) is expressed in tissues of high epithelial content including prostate, although its precise function has not been fully established. Conventional therapies produce a high rate of cure for patients with localized prostate cancer, but there is, at present, no effective treatment for intervention in metastatic prostate cancer. These facts underline the need to develop new approaches for early diagnosis of aggressive prostate cancer patients, and mechanism based anti-metastasis therapies that will improve the outlook for hormone-refractory prostate cancer.

p38 mitogen-activated protein kinase-driven MAPKAPK2 regulates invasion of bladder cancer by modulation of MMP-2 and MMP-9 activity.

In transitional cell carcinoma, the most common form of bladder cancer, overexpression of the matrix metalloproteinases MMP-2 and MMP-9 offers prognostic value as markers of disease-specific survival. These molecules have been implicated in metastasis of bladder cancer, but the underlying mechanisms through which they are controlled are poorly defined. In this study, we investigated a role of p38 mitogen-activated protein kinase (MAPK) in this process, using bladder cancer cell lines HTB9 and HTB5 that were derived from different tumor stages.

Testosterone and the prostate: implications for the treatment of hypogonadal men.

Late-onset hypogonadism (LOH) and testosterone replacement therapy (TRT) are subjects of much recent research. Because aging men are at risk for benign prostatic hyperplasia (BPH) and prostate cancer, elucidating the relationship between testosterone and these diseases is crucial to ensure its safe administration. It is known that testosterone supplementation may worsen active prostate cancer and that its blockade or removal slows the disease's progression.

Focal adhesion kinase controls aggressive phenotype of androgen-independent prostate cancer.

Overexpression of focal adhesion kinase (FAK) has been well correlated with tumor development and/or the maintenance of tumor phenotype. In addition, inappropriate activation of the extracellular regulated kinase (ERK) signaling pathway is common to many human cancers. In the present study, we investigated the interplay between FAK and ERK in androgen-independent prostate cancer cells (PC3 and DU145 cells).

Primary culture and characterization of human renal inner medullary collecting duct epithelial cells.

Purpose: Our understanding of physiological and pathophysiological events associated with inner medullary collecting duct epithelium is based on studies in cells isolated from mice and rats. We established primary cultures of hIMCD (human papillary collecting duct epithelial) cells.

Materials And Methods: Normal papillary tissues were dissected from the surgical waste of consenting patients undergoing renal surgery.