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Aside from phosphodiesterase (PDE) isoenzymes,,protein kinases (cAK=cyclic AMP-binding protein kinase, CGK=cyclic GMP-binding protein kinase) have also been identified as important receptors for cyclic nucleotides. A significance of protein kinases in the control of the function of the male and female reproductive tract has been suggested; however,up until today, only a few approaches have addressed these enzymes in female genital tissues: The present study aimed to investigate by means of biochemical and immunohistochemical methods the expression of cAK and cGK. The distribution of cAK(I) and cGK(I) in relation to the vasoactive intestinal polypeptide (VIP), calcitonin gene-related peptide (CGRP) and PDE type 4 (PDE4) was also evaluated. Cytosolic supernatants prepared from specimens of vaginal wall smooth muscle or epithelium were subjected to anion exchange chromatography and the activities of cAK and cGK(I) measured. To evaluate the distribution of cAK(I) and cGK(I) in relation to VIP, CGRP and PDE4, immunohistochemistry was conducted in sections of the human vaginal wall (full-wall specimens). Activities representing cGK(I) and cAK(I) were resolved from the chromatography column. Staining specific for cAK(la) was identified in both vascular and non-vascular vaginal smooth musculature, immunoreactivity for cGK(113) was observed in the smooth muscle and endothelium of small arteries interspersing the sections. cAK(I alpha)-positive vessels were found innervated by slender varicose nerve fibers presenting the expression of VIP and CGRP. These arteries also expressed PDE4. Localization of cAK and cGK in close relation to key mediators of the cyclic AMP (PDE4, VIP) and cyclic GMP (CGRP) pathways indicate that both signaling systems may synergistically work together in human vaginal tissue.

The transient receptor potential cationic channel ankyrin 1 (TRPA1) is a channel protein assumed to act in various human tissues as mechano- and pain sensor and play a role in neurotransmission. The expression of TRPA has already been investigated in the human prostate and urethra, however, only very few studies have addressed the expression and distribution in the male and female genital tract. The present study aimed to investigate by means of immunohistochemistry (double-labeling technique, laser fluorescence microscopy) in the human clitoris and penile erectile tissue the localization of TRPA1 in relation to nNOS, the vasoactive intestinal polypeptide (VIP) and vesicular acetylcholine transporter (VAChT). In the clitoral tissue, TRPA1 was observed in basal epithelial cells and slender nNOS-positive nerve fibers transversing the subepithelial space. To a certain degree, in the clitoral epithelial cells, TRPA1 was found co-localized with vimentin. In human corpus cavernosum, immunoreactivity for TRPA1 was seen in nerves transversing the cavernous sinusoidal space and running alongside small arteries, these nerves also displayed expression of the vesicular acetylcholine transporter protein (VAChT). Varicose nerves containing nNOS or VIP were not immunoreactive for TRPA1. It seems likely that TRPA1 is involved in nitric oxide-mediated afferent sensory transmission in the clitoris while, in penile erectile tissue, a role for TRPA1 in cholinergic signaling might be assumed.

The transient receptor potential cationic channel type A1 (TRPA1), belonging to a superfamily of cationic membrane channels, has been suggested to act as mechano- and pain sensor and, thus, to play a role in neurotransmission in the human body, including the urogenital tract While the expression of TRPA1 has been investigated in a variety of tissues, up until today no Study has addressed the expression and distribution in the female genital tract. The present study aimed to investigate the expression and distribution of TRPA1 protein in human vaginal tissue, Reverse transcriptase PCR (RT-PCR) Was applied in order to identify messenger ribonuleic acid specifically encoding for TAPA/A1. The distribution of TRPA1 in relation to the neuronal nitric oxide synthase (nNOS) and the signaling peptide calcitonin gene-related peptide (CGRP) was examined by means of imnnunohistocheitical methods (double-antibody technique, laser fluorescence microscopy). RT-PCR analysis revealed the expression of mRNA encoding sequences specific for TRPA in the vaginal Wall and epithelium Immunostaining related to TRPA1 was observed in the basal epithelium and in slender Varicose nerve fibers transversing the subepithelial and stromal space of the Vaginal sections. In addition, these fibers presented immunoreactivity specific for nNOS or CGRP The Smooth:musculature of the vaginal wall, and small vessels interspersing the tissue did not present Signals related to TRPA1, The findings indicate that TRPA1 might be involved in afferent neurotransmission in the vagina and work synergistically together with the nitric oxide/cyclic guanosine monophosphate pathway.

The transient receptor potential cationic channel type A1 (TRPA1), belonging to a superfamily of cationic membrane channels, has been suggested to act as mechano- and pain sensor and, thus, to play a role in neurotransmission in the human body, including the urogenital tract While the expression of TRPA1 has been investigated in a variety of tissues, up until today no Study has addressed the expression and distribution in the female genital tract. The present study aimed to investigate the expression and distribution of TRPA1 protein in human vaginal tissue, Reverse transcriptase PCR (RT-PCR) Was applied in order to identify messenger ribonuleic acid specifically encoding for TAPA/A1. The distribution of TRPA1 in relation to the neuronal nitric oxide synthase (nNOS) and the signaling peptide calcitonin gene-related peptide (CGRP) was examined by means of imnnunohistocheitical methods (double-antibody technique, laser fluorescence microscopy). RT-PCR analysis revealed the expression of mRNA encoding sequences specific for TRPA in the vaginal Wall and epithelium Immunostaining related to TRPA1 was observed in the basal epithelium and in slender Varicose nerve fibers transversing the subepithelial and stromal space of the Vaginal sections. In addition, these fibers presented immunoreactivity specific for nNOS or CGRP The Smooth:musculature of the vaginal wall, and small vessels interspersing the tissue did not present Signals related to TRPA1, The findings indicate that TRPA1 might be involved in afferent neurotransmission in the vagina and work synergistically together with the nitric oxide/cyclic guanosine monophosphate pathway.

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Item does not contain fulltext, CONTEXT: Although an ever-increasing number of patients are being incidentally diagnosed with small renal masses, there is still a sizable portion of patients with renal cell carcinoma (RCC) who present with locally advanced or metastatic disease. Those with locally advanced disease present a challenge because they may be difficult to distinguish from those with organ-confined disease at the time of diagnosis. However, this distinction is important because they may require a different management strategy. These advanced RCC patients include those with venous tumour thrombi, extracapsular tumour extension, adjacent organ involvement, as well as nodal disease. EVIDENCE ACQUISITION: A thorough literature search of the following terms was undertaken: advanced renal cell carcinoma, renal cell carcinoma venous tumour thrombi, renal cell carcinoma extra-capsular extension, renal cell carcinoma nodal metastasis, and locally recurrent renal cell carcinoma. An international expert panel convened by the International Consultation on Urologic Diseases and the European Association of Urology reviewed these articles. EVIDENCE SYNTHESIS: Review of the available literature allowed for assessment of the level of evidence for the diagnosis, management, and therapy of locally advanced RCC with the ultimate goal of providing a synthesis of this information with a consensus statement from leaders in the field. CONCLUSIONS: Despite the advances in prognostic markers and targeted molecular therapies for RCC, currently the only curative treatment for locally advanced RCC is aggressive surgical resection.

Item does not contain fulltext, CONTEXT: Although an ever-increasing number of patients are being incidentally diagnosed with small renal masses, there is still a sizable portion of patients with renal cell carcinoma (RCC) who present with locally advanced or metastatic disease. Those with locally advanced disease present a challenge because they may be difficult to distinguish from those with organ-confined disease at the time of diagnosis. However, this distinction is important because they may require a different management strategy. These advanced RCC patients include those with venous tumour thrombi, extracapsular tumour extension, adjacent organ involvement, as well as nodal disease. EVIDENCE ACQUISITION: A thorough literature search of the following terms was undertaken: advanced renal cell carcinoma, renal cell carcinoma venous tumour thrombi, renal cell carcinoma extra-capsular extension, renal cell carcinoma nodal metastasis, and locally recurrent renal cell carcinoma. An international expert panel convened by the International Consultation on Urologic Diseases and the European Association of Urology reviewed these articles. EVIDENCE SYNTHESIS: Review of the available literature allowed for assessment of the level of evidence for the diagnosis, management, and therapy of locally advanced RCC with the ultimate goal of providing a synthesis of this information with a consensus statement from leaders in the field. CONCLUSIONS: Despite the advances in prognostic markers and targeted molecular therapies for RCC, currently the only curative treatment for locally advanced RCC is aggressive surgical resection.