Contractile changes of the clitoral cavernous smooth muscle in female rabbits with experimentally induced overactive bladder

INTRODUCTION: Recently, growing clinical evidence has suggested that sexual dysfunction is more prevalent in women with overactive bladder (OAB). Aims. However, there has been no basic research to clarify the relationship between OAB and female sexual dysfunction. Therefore, we investigated this issue using a rabbit model of OAB. METHODS: Twenty-seven New Zealand white female rabbits were randomly divided into the OAB and control groups. MAIN OUTCOME MEASURES: The contractile responses of clitoral cavernous strips to K(+), phenylephrine (PE), Bay K 8644, and endothelin (ET)-1, and the relaxation responses of acetylcholine (ACh), sodium nitroprusside (SNP), and Y-27632 to PE-induced contraction by measuring isometric tension. Results. The contractile responses to K(+), PE, Bay K 8644, and ET-1 were significantly more increased in the OAB group in a dose-dependant manner than in the control group (P < 0.05), and the responses to ET-1 were more prominent than those to the remaining substances (P < 0.01). The increased contractile responses to ET-1 were blocked by BQ123 (ET(A) receptor antagonist) but not by BQ788 (ET(B) receptor antagonist). Clitoral cavernosal strips from the OAB group were more difficult to relax than those from the control group in terms of ACh- and SNP-induced relaxation (P < 0.05). The Y-27632-induced relaxant responses to PE- and ET-1-induced contraction were less prominent in the OAB group than in the control group. CONCLUSIONS; The results of this study provide evidence that female OAB may deteriorate clitoral engorgement, which is associated with a greater force generation by increased calcium sensitization and subsequently decreased of relaxation. The activation of ET and Rho-kinase system may be crucial to negatively effect the clitoral smooth muscle relaxation in experimentally induced OAB animal model. But whether these vasomotor effects are revived in human clitoris is still debatable.     

Phenolic constituents of Amorpha fruticosa that inhibit NF-kappaB activation and related gene expression

NF-kappaB is known to play a crucial role in the regulation of genes controlling the immune system, apoptosis, tumor cell growth, and tissue differentiation. Bioassay-guided fractionation of the n-hexane-soluble fraction of a methanol extract of Amorpha fruticosa afforded four new compounds, 5, 7, 8, and 9, and eight known compounds. Their structures were elucidated by spectroscopic methods. All compounds inhibited NF-kappaB activity, and tephrosin (1), 11-hydroxytephrosin (2), and deguelin (3) were the most active, with IC50 values of 0.11, 0.19, and 0.22 microM, respectively, in TNF-alpha-stimulated HeLa cell-based reporter gene assays. Further investigations showed that compounds 1, 5, and 6 blocked NF-kappaB/DNA binding activity and suppressed the expression of NF-kappaB target genes.     

Triterpenoids from the leaves of Diospyros kaki (persimmon) and their inhibitory effects on protein tyrosine phosphatase 1B

Phytochemical study on a methanol-soluble extract of the leaves of persimmon (Diospyros kaki) resulted in the isolation of two new ursane-type triterpenoids, 3alpha,19alpha-dihydroxyurs-12,20(30)-dien-24,28-dioic acid (1) and 3alpha,19alpha-dihydroxyurs-12-en-24,28-dioic acid (2), together with 12 known ursane- and oleanane-type triterpenoids (3-14). Triterpenoids with a 3beta-hydroxy group were found to inhibit protein tyrosine phosphatase 1B (PTP1B) activity, with IC50 values ranging from 3.1+/-0.2 to 18.8+/-1.3 microM, whereas those with a 3alpha-hydroxy moiety were not active.     

Interleukin-1alpha polymorphism -889C/T related to obesity in Korean Taeumin women

Interleukin-1 (IL-1), a cytokine produced predominantly by cells from the macrophage lineage, can affect multiple neuroendocrine and metabolic functions. IL-1alpha production by cultured peripheral blood mononuclear cells from an obese group was significantly elevated in comparison to a control group. The aim of this study was to investigate whether the IL-1alpha polymorphism and Sasang constitution, a major branch in Korean traditional medicine, were related to obesity. Genotyping was done in 182 healthy females with a marked variation in body mass index (BMI) by a PCR-restriction fragment length polymorphism assay. The T allele was associated with decreased BMI (p = 0.020). In a subgroup with BMI values ranging from 27 approximately 29 kg/m(2), the frequency of the T allele was significantly decreased (p = 0.004, odds ratio, OR = 0.141 compared to a subgroup with a BMI values less than 25 Kg/m(2)). In addition, in Taeumin female subjects, the frequency of the IL-1alpha T allele was markedly decreased in a subgroup with BMI values in the range of 27 approximately 29 kg/m(2) compared to a lean group with BMI values less than 25 kg/m(2) (p = 0.004, OR = 0.139). In Korean women, an association was found between -889C/T polymorphism in the regulatory region of the IL-1alpha gene and BMI values. In addition, an association was found among IL-1alpha polymorphism, obesity, and the Sasang constitution.     

Anti-atherogenic effects of the aqueous extract of rhubarb in rats fed an atherogenic diet

The present study was designed to investigate whether the aqueous extract of rhubarb (AR) could prevent the development of atherosclerosis through regulating vascular inflammatory processes in rats fed with an atherogenic diet. AR significantly reduced plasma low-density lipoprotein-cholesterol, and increased plasma high-density lipoprotein-cholesterol in rats fed with an atherogenic diet. AR inhibited vascular expressions of endothelin-1 (ET-1) and endothelin-converting enzyme (ECE) induced in rats with an atherogenic diet. On the other hand, AR augmented the vascular expression of endothelial nitric oxide synthase (ecNOS) and restored vascular nitric oxide (NO) production. Furthermore, AR suppressed the elevated expression of vascular nuclear factor-kappaB (NF-kappaB) p65 as well as adhesion molecules, including intracellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin in rats fed with an atherogenic diet. Also, AR decreased endothelial expression of ICAM-1 and ET-1 in aorta. These results suggest that AR suppresses the development of atherosclerosis in the atherogenic-diet rat model through inhibiting vascular expressions of proinflammatory and adhesion molecules via the regulation of nitric oxide and endothelin system.