No abstract

The "Japanese Clinical Guideline for Female Lower Urinary Tract Symptoms," published in Japan in November 2013, contains two algorithms (a primary and a specialized treatment algorithm) that are novel worldwide as they cover female lower urinary tract symptoms other than urinary incontinence. For primary treatment, necessary types of evaluation include querying the patient regarding symptoms and medical history, examining physical findings, and performing urinalysis. The types of evaluations that should be performed for select cases include evaluation with symptom/quality of life (QOL) questionnaires, urination records, residual urine measurement, urine cytology, urine culture, serum creatinine measurement, and ultrasonography. If the main symptoms are voiding/post-voiding, specialized treatment should be considered because multiple conditions may be involved. When storage difficulties are the main symptoms, the patient should be assessed using the primary algorithm. When conditions such as overactive bladder or stress incontinence are diagnosed and treatment is administered, but sufficient improvement is not achieved, the specialized algorithm should be considered. In case of specialized treatment, physiological re-evaluation, urinary tract/pelvic imaging evaluation, and urodynamic testing are conducted for conditions such as refractory overactive bladder and stress incontinence. There are two causes of voiding/post-voiding symptoms: lower urinary tract obstruction and detrusor underactivity. Lower urinary tract obstruction caused by pelvic organ prolapse may be improved by surgery.

No abstract

Around the onset of labor, uterine sensitivity to oxytocin (OT) increases tremendously. Although this is considered to reflect OT receptor (OTR) augmentation in myometrium, neither spatial expression of OTR nor the level of the receptor message during the course of pregnancy have been investigated at the molecular level. We examined the localization and expression of the OTR in human myometrium by means of in situ hybridization, immunohistochemistry, and Northern and Western blotting. In the term pregnant myometrium, OTR expressing smooth muscle cells are observed diffusely and heterogeneously. Some of the smooth muscle cells were expressed high levels of the receptor at the messenger RNA and protein level, and they were surrounded with cells weakly positive for the OTR or negative. The level of OTR transcripts increased according to the course of pregnancy. The receptor messenger RNA level reached over 300-fold at parturition compared with the nonpregnant myometrium. In the myometrium at 32 weeks of gestation and not in labor, a relatively large amount (about 100-fold) of the receptor message was expressed. In the nonpregnant myometrium, significant amount of the receptor protein was revealed by Western blotting. We also found that the receptor protein was augmented at term and after the onset of labor. These findings indicated that the expression of OTR changes dynamically at the transcription and protein level during pregnancy and that its expression is heterogeneous in the term myometrium.

The oxytocin receptor belongs to the G-protein-coupled seven transmembrane receptor superfamily. Its main physiological role is regulating the contraction of uterine smooth muscle at parturition and the ejection of milk from the lactating breast. Oxytocin receptor expression is observed not only in the myometrium and mammary gland but also in the endometrium, decidua, ovary, testis, epididymis, vas deferens, thymus, heart and kidney, as well as in the brain. The expression profile shows a tissue-specific as well as a stage-specific pattern. The oxytocin receptor gene is a single-copy gene consisting of four exons and three introns, localized at 3p25-3p26·2 in the human chromosome. In transfection studies using a fusion construct containing the promoter region of the oxytocin receptor gene inserted in a reporter plasmid, neither proinflammatory cytokines nor oestrogen directly activate the gene. The nuclear fractions from up-regulated (term myometrium) and down-regulated (non-pregnant myometrium) tissues show differential patterns of protein binding to the 5′-flanking region, and a human homologue of chicken MafF has been cloned as a term-myometrium-specific oxytocin receptor modulator. The oxytocin receptor gene appears to be highly methylated. Methylation around intron 1 and in intron 3 might contribute to tissue-specific suppression of the gene. The oxytocin receptor is also regulated by desensitization, whose mechanism appears to involve loss of ligand-binding activity of the protein as well as suppression of the oxytocin receptor mRNA transcription. These findings taken together indicate that the oxytocin receptor is regulated in a very complicated manner, and the transcriptional regulatory elements critical for this regulation should be investigated further.