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J Urol. 2000 Dec;164(6):2006-9.
Outcome results of transurethral collagen injection for female stress incontinence: assessment by urinary incontinence score.

Groutz A, Blaivas JG, Kesler SS, Weiss JP, Chaikin DC.

Weill Medical College, Cornell University, New York, New York, USA.

PURPOSE: We assessed the results of collagen injection for female sphincteric incontinence using strict subjective and objective criteria. MATERIALS AND METHODS: We evaluated 63 consecutive women with sphincteric incontinence who underwent a total of 131 transurethral collagen injections. Sphincteric incontinence was confirmed by urodynamics. All patients were treated with 1 to 5 transurethral collagen injections and treatment outcome was classified according to a new outcome score. Cure was defined as no urinary loss due to urge or stress incontinence documented by a 24-hour diary and pad test, and patient assessment that cure was achieved. Failure was defined as poor objective results and patient assessment that treatment failed. Cases that did not fulfill these cure and failure criteria were considered improved and further classified as a good, fair or poor response. RESULTS: Mean patient age plus or minus standard deviation was 67.7 +/- 12.8 years. All women had a long history of severe stress urinary incontinence, 18 (29%) underwent previous anti-incontinence surgery, and 41% had combined stress and urge incontinence. Preoperatively diary and pad tests revealed a mean of 7.5 +/- 4.6 incontinence episodes and 152 +/- 172 gm. of urine lost per 24 hours. Overall 1 to 5 injections were given in 26, 17, 13, 3 and 4 patients, respectively. Mean interval between injections was 4.4 +/- 5.7 months, mean followup was 12 +/- 9.6 months, and mean interval between the final injection and outcome assessment was 6.4 +/- 4.9 months. There was a statistically significant decrease in the total number of incontinence episodes per 24-hour voiding diary after each injection session. Although there was a clear trend toward decreased urinary loss per 24-hour pad test, statistical significance was not established. Using the strict criteria of our outcome score overall 13% of procedures were classified as cure, 10%, 17% and 42% as good, fair and poor, respectively, and 18% as failure. CONCLUSIONS: As defined by strict subjective and objective criteria, we noted a low short-term cure rate after collagen injection in women with severe sphincteric incontinence. It remains to be determined how patients with less severe incontinence would fare using our outcome assessment instruments.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11061903&dopt=Abstract

J Cell Sci. 2000 Dec;113 Pt 23:4319-30.
Sustained ERK phosphorylation is necessary but not sufficient for MMP-9 regulation in endothelial cells: involvement of Ras-dependent and -independent pathways.

Genersch E, Hayess K, Neuenfeld Y, Haller H.

Franz Volhard Clinic at the Max Delbruck Center for Molecular Medicine, Medical Faculty of the Charite, Humboldt University of Berlin, Wiltberg Strasse 50, Germany. elke.generscedkem.lu.se

Endothelial expression of matrix metalloproteinase-9 (MMP-9), which degrades native type IV collagen, was implicated as a prerequisite for angiogenesis. Therefore, the aim of this study was to determine signaling requirements that regulate MMP-9 expression in endothelial cells. Both, primary and permanent human umbilical vein endothelial cells (HUVEC and ECV304, respectively) were stimulated with phorbol 12-myristate 13-acetate (PMA) and the cytokine tumor necrosis factor-(alpha) (TNF(alpha)) to induce MMP-9 expression. While both cell types responded to PMA at the protein, mRNA and promoter level by induction of MMP-9, TNF(alpha) caused this response only in ECV304. Inhibitors specific for mitogen-activated protein/ERK kinase 1/2 (MEK1/2), protein kinase C (PKC), and Ras and co-transfections of wild-type and mutant Raf were used to elucidate the signaling cascades involved. Thus, we could show that the Raf/MEK/ERK cascade is mainly responsible for MMP-9 induction in endothelial cells and that this cascade is regulated independently of PKC and Ras subsequent to TNF(alpha) stimulation and in a PKC-dependent manner as a result of PMA treatment. In addition, PMA triggers a Ras-dependent signal transduction pathway bypassing the phosphorylation of ERK. Finally, we provide evidence that sustained phosphorylation of ERK1/2 is necessary but not sufficient for expression of MMP-9.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11069776&dopt=Abstract

Arch Biochem Biophys. 2000 Oct 15;382(2):182-8.
Effects of dioxin and estrogen on collagenase-3 in UMR 106-01 osteosarcoma cells.

Partridge NC, Fiacco GJ, Walling HW, Barmina OY, Jeffrey JJ, Ruh MF.

Department of Pharmacological and Physiological Science, Saint Louis University School of Medicine, Missouri 63104, USA. partrinmdnj.edu

Since estrogen is important in preventing osteoporosis in postmenopausal women and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is an estrogen antagonist in reproductive tissues, we investigated the effects of 17beta-estradiol (E2) and TCDD on collagenase-3 secretion using parathyroid hormone (PTH)-stimulated UMR 106-01 cells, a rat osteoblastic osteosarcoma cell line. Whereas E2 or TCDD had no effect on UMR cells in the absence of PTH, cells grown in the presence of 10(-7) M PTH, which induces a dramatic 30-fold increase in collagenase-3 secretion, surprisingly demonstrated a further stimulation of collagenase-3 secretion in the presence of TCDD or E2. However, the potentiating response was biphasic; i.e., at higher concentrations of E2 or TCDD, there was no enhancement of the PTH effect. PTH induces multiple effects on UMR cells, including inducing collagenase-3 mRNA transcription and regulating its extracellular abundance through a specific receptor and endocytosis. Thus, we investigated the ability of TCDD or E2 to stimulate the induction of collagenase-3 mRNA using Northern analysis. As previously reported, PTH dose dependently induced collagenase-3 mRNA after 4 h of treatment. There was little effect of TCDD or E2 on PTH-induced levels of collagenase-3 mRNA. These data could not account for the final effects on secreted collagenase-3. We postulated that low concentrations of E2 and TCDD may downregulate the collagenase-3 endocytotic two-step receptor-mediated process that includes the LDL-receptor-related protein to enhance the effects of PTH. However, this was not the case. Therefore, we conclude that low concentrations of TCDD and estrogen alter translation or secretion of PTH-stimulated collagenase-3.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11068867&dopt=Abstract

Osteoarthritis Cartilage. 2000 Nov;8(6):464-73.
The acute structural changes of loaded articular cartilage following meniscectomy or ACL-transection.

Kaab MJ, Ito K, Clark JM, Notzli HP.

AO/ASIF Research Institute, Davos, Switzerland. max.kaeaeharite.de

OBJECTIVE: Meniscectomy and anterior cruciate ligament (ACL) rupture have been identified as precursors of osteoarthrosis (OA) in clinical reviews and animal experiments. In this study, the acute effects of these injuries on articular cartilage matrix deformation, preserved in a loaded state using a cryopreservation technique, were studied by scanning electron microscopy (SEM). METHOD: Whole knee joints from adult White New Zealand rabbits (N=87) were loaded ex vivo, using a simulated quadriceps pull under static and cyclic loading conditions, following medial meniscectomy or transection of the ACL. Specimens were plunge-frozen while under load, or following a recovery period, and prepared for SEM by cryofixation. Using SEM and photographic images, the medial tibial plateau cartilage was assessed both qualitatively and quantitatively. RESULTS: After meniscectomy, significantly increased bending and crimping of radial collagen fibers occurred with static loading. Compared to intact knees, the area of tibial cartilage showing an indentation was increased by 80% (P< 0.05), the articular cartilage thickness was significantly more reduced when under load (for high force long duration static loading, intact joints had 53%+/-3 reduction in cartilage thickness compared to 39%+/-4 after meniscectomy, P< 0.05), and it took nearly twice as long for the cartilage thickness to recover following loading. These post-meniscectomy differences were either not present or were minimal when the joint was allowed to extend when loaded. ACL-transection slightly increased collagen deformation in the deeper zones, but only with cyclic loading. CONCLUSION: The findings indicate that, with static loading, significantly increased deformation of articular cartilage collagen structure can occur following meniscectomy, but is minimized by joint motion. This increased deformation may be relevant to the etiology and progression of joint degeneration. 2000 OsteoArthritis Research Society International.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11069731&dopt=Abstract

Connect Tissue Res. 1998;38(1-4):149-57; discussion 201-5.
General principle of ordered apatitic crystal formation in enamel and collagen rich hard tissues.

Plate U, Arnold S, Stratmann U, Wiesmann HP, Hohling HJ.

Institute of Medical Physics and Biophysics, University Muenster, Germany. plateni-muenster.de

The biomineralization processes in different hard tissues like enamel, circumpulpal dentine, epiphyseal growth plates were analyzed morphologically and ultrastructurally by an energy filtering transmission electron microscope. In the primary stage of crystal formation Ca- and phosphate-ions accumulate at charged sites, "active sites", along the fiber matrix-molecules of the extracellular matrix. After exceeding the critical radius for nucleation, crystal nuclei appear that develop to "chains" of stable nanometer-sized paracrystalline particles. In the latest studies of small area electron diffraction it was found that in the earliest stage of crystal formation these mineral chains show a parallel orientation in the direction of the c-axis of apatite. This was supported by a texture of the 002 reflection in the corresponding diffraction patterns. Since apatite is bipolar in this direction crystal growth would be in like manner in both directions. Thus the center-to-center distances between nucleating sites along the matrix macromolecules show with the chains of nanometer islands the same process of biomineralization in the different mineralizing hard tissue systems. This way of crystal formation might be a general principle of apatitic biomineralization.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11063023&dopt=Abstract

Hair loss is a problem in modern soceity. Examining the factors of hair growth may shed light on how hair loss might occur. How long can hair grow before it stops growing eventually if it does? Given that the hair growth rate is quite uniform and constant, somewhere between 0.3-0.5 millimeters per day, it's believed that the length of anagen, the growth phase, differs among individuals, and this is the major determinant to the maximum hair length. For some individuals, anagen may last ten years. Of course the length of the anagen is governed by genes, and the genetic background of the individuals. Non-genetic factors such as nutritional condition, weather, seasonal changes (hair may grow a bit faster during winter), taking medications, health condition may of course influence the rate of hair growth as well as The shape of the hair, straight or curly, is dependent on the shape of the follicle. A circular or round hair follicle would generate straight hair, while the follicle with oval or elliptical shapes (in its cross-section) would produce a curly hair.

DHEA has been suggested to provide numerous potential benefits. DHEA (or dehydroepiandrosterone) is converted into androgens (male hormones) or estrogens (female hormones) in the cells.

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