Bone remodeling during the development of osteoporosis in paraplegia

Summary Osteoporosis developing during the first weeks after the onset of traumatic paraplegia was studied with cortical and cancellous samples of iliac crest and tibia of 14 patients, and compared to normals. We used a procedure of bone particle fractionation (according to degree of mineralization) that allowed us to establish a profile reflecting the metabolic remodeling of bone and to analyze the organic matrix of the newly synthesized tissue. In paraplegics, we observed a large increase in the proportion of little calcified bone in the cortical as well as in the cancellous bone. Based on amino acid analyses, we found a decreased number of hydroxyproline residues in the newly synthesized organic matrix from paraplegia bone resulting either from an alteration of the prolyl hydroxylation or from the presence of an excess of noncollagen polypeptides. These results, together with previously published data reporting increased urinary hydroxylproline and calcium kinetic parameters, suggest an enhanced rate of skeletal remodeling in acute paraplegia. When investigated 2 years after injury, the patterns of distribution approach that of normal subjects.     

F-19 MR imaging of glucose metabolism in the rabbit

Noninvasive metabolic magnetic resonance (MR) imaging reflecting glucose metabolism in the aldose-reductase-sorbitol (ARS) pathway was performed in the rabbit head; after administration of the fluorinated glucose analogue 3-fluoro-3-deoxy-D-glucose (3FD-glucose), fluorine-19 images were generated. Images of 3FD-glucose showed significant 3FD-glucose uptake by adipose tissue, indicating its buffering effects in case of excess loads of glucose. Images of 3-fluoro-3-deoxy-D-sorbitol (3FD-sorbitol) demonstrated the spatial distribution of aldose reductase activities and significant sorbitol accumulation in the lens. Images of 3-fluoro-3-deoxy-D-fructose (3FD-fructose) showed preferential uptake of fructose by muscle tissue. The extremely low toxicity of 3FD-glucose indicates promise for its clinical application in metabolic imaging.     

Histological and transcriptional study of angiogenesis and lymphangiogenesis in uninvolved skin,acute pinpoint lesions and established psoriasis plaques: An approach of vascular development chronology in psoriasis

BackgroundDysregulation of angiogenesis and lymphangiogenesis could participate in psoriasis pathogenesis. Analysis of nascent psoriasis lesions should help at identifying early vascular anomalies.ObjectiveTo analyse vascular development, angiogenesis and lymphangiogenesis markers expression in uninvolved skin in psoriatic patients (N), early psoriasis lesions or pinpoints (PP) and psoriasis plaques (PSO).MethodsSkin biopsies were taken in 17 patients in N and in PSO and/or PP. The mRNA steady-state level of angiogenesis and lymphangiogenesis markers was measured by RT-PCR. Immunohistochemistry was performed for von Willebrand factor, podoplanin, Ki-67 and VEGFR3. Blood (BV) and lymphatic (LV) vessels expansion was measured by computer-assisted morphometry.ResultsClinical and epidermal aspects indicated that PP are intermediate between N and PSO. While total BV area was already increased in PP similarly to PSO as compared to N, LV area in PP was intermediate between N and PSO. Mean LV size was identical in N and PP and increased in PSO, mean BV size in PP being intermediate between N and PSO. VEGF-A 189 variant was increased in PP as compared to N and PSO. As compared to N, angiogenesis markers (VEGF-A isoforms, PlGF, VEGFR2, NRP-1), VEGF-C and NRP-2 were similarly increased in PP and PSO. Keratin 16 and the lymphangiogenesis markers (VEGFR3, prox-1) were intermediate in PP.ConclusionThese data suggest that the expansion of lymphatic vessels occurs after blood vascular development in psoriasis. Expansion of BV in PP could be followed by vessel enlargement during progression to PSO, in parallel with a decreased VEGF-A 189/VEGF-A 121 balance in plaques.     

Histology of the vaginal wall in women with pelvic organ prolapse: a literature review

Introduction and hypothesis

The pathophysiology of pelvic organ prolapse (POP) is incompletely understood. The purpose of this study is to describe the current knowledge about histology of the vaginal wall and its possible involvement in the pathogenesis of pelvic organ prolapse.

Methods

Eligible studies were selected through a MEDLINE search covering January 1986 to December 2012. The research was limited to English-language publications.

Results

Investigations of changes in the vaginal tissue that occur in women with genital prolapse are currently still limited and produced contrary results. The heterogeneity of the patients and the control groups in terms of age, parity and hormonal status, of the localization of biopsies and the histological methods as well as the lack of validation of the quantification procedures do not allow clear and definitive conclusions to be drawn.

Conclusions

This review shows that current knowledge of the histological changes observed in women with POP are inconclusive and relatively limited. More studies are needed in this specific field to better understand the mechanisms that lead to POP.     

Elastin density: Link between histological and biomechanical properties of vaginal tissue in women with pelvic organ prolapse?

Introduction and hypothesis

The aim of the study was to correlate histological and biomechanical characteristics of the vaginal wall in women with pelvic organ prolapse (POP).

Methods

Tissue samples were collected from the anterior [point Ba; POP Questionnaire (POP-Q)] and/or posterior (point Bp; POP-Q) vaginal wall of 15 women who underwent vaginal surgery for POP. Both histological and biomechanical assessments were performed from the same tissue samples in 14 of 15 patients. For histological assessment, the density of collagen and elastin fibers was determined by combining high-resolution virtual imaging and computer-assisted digital image analysis. For biomechanical testing, uniaxial tension tests were performed to evaluate vaginal tissue stiffness at low (C₀) and high (C₁) deformation rates.

Results

Biomechanical testing highlights the hyperelastic behavior of the vaginal wall. At low strains (C₀), vaginal tissue appeared stiffer when elastin density was low. We found a statistically significant inverse relationship between C₀ and the elastin/collagen ratio (p?=?0.048) in the lamina propria. However, at large strain levels (C₁), no clear relationship was observed between elastin density or elastin/collagen ratio and stiffness, likely reflecting the large dispersion of the mechanical behavior of the tissue samples.

Conclusion

Histological and biomechanical properties of the vaginal wall vary from patient to patient. This study suggests that elastin density deserves consideration as a relevant factor of vaginal stiffness in women with POP.

     

Factors linked to bacterial vaginosis in nonpregnant women

OBJECTIVES: The purposes of this study were to test the hypothesis that vaginal douching is linked to bacterial vaginosis in both symptomatic and asymptomatic women and to identify other demographic, reproductive, and lifestyle factors associated with bacterial vaginosis. METHODS: In this cross-sectional study involving 3 clinic sites, 496 nonpregnant women completed a self-administered questionnaire. Their vaginal smears were assessed and cross-validated for bacterial vaginosis. RESULTS: The prevalence of bacterial vaginosis across clinics ranged from 15% to 30%. In analyses restricted to site 1, adjusted odds ratios (ORs) for bacterial vaginosis remained significant for African American women with 13 or fewer years of education (OR = 5.5, 95% confidence interval [CI] = 2.1, 14.5), hormone use within the past 6 months (OR = 0.5, 95% CI = 0.2, 0.8), and vaginal douching within the past 2 months (OR = 2.9, 95% CI = 1.5, 5.6). CONCLUSIONS: Two lifestyle factors emerge as strongly associated with bacterial vaginosis: systemic contraceptives appear protective, whereas douching is linked to an increase in prevalence. The temporal relationship between douching and bacterial vaginosis needs further clarification.     

Invasion of reconstituted basement membrane matrix is not correlated to the malignant metastatic cell phenotype

Interactions between tumor cells and basement membranes represent a critical step in the progression of neoplasia and in the metastatic process. Reconstituted basement membrane matrix, matrigel, has been recently used with the aim of developing an in vitro assay of tumor cell invasiveness. We have extended these studies by comparing the invasiveness of a large series of normal and malignant epithelial and mesenchymal cells of human and animal origin cultured on matrigel. Normal cells (fibroblasts, glomerular mesangial cells, keratinocytes), human fibrosarcoma cells (HT1080), and reticular sarcoma cells (M5076) clearly established invasive capabilities in the matrix. However, all the other tested cell lines, malignant or virally transformed cells invasive in vivo (MCF7, T47D, SA52, SW613, MO4, A431, BeWo), as well as normal nontransformed cells (MOH22) were incapable of penetration. The morphological features of matrigel invasion by normal fibroblasts and HT1080 cells are described at the light and electron microscope levels. The extent of degradation of a radiolabeled matrigel is minimal and similar in several cell lines reported to be noninvasive or invasive in vivo. Our data suggest that matrigel does not provide a universal model to correlate the invasiveness of cells in vivo and in vitro.     

Digital beam attenuator technique for compensated chest radiography

The feasibility of producing patient-specific beam attenuators for chest radiography has been investigated using an anthropomorphic phantom and a human volunteer. A low-dose test exposure is digitized, processed, and used to print a small cerium filter, which is placed in the x-ray beam near the collimator. The final radiograph is recorded on film. The technique results in relatively uniform film exposure, so that structures in all regions of the chest are simultaneously displayed with optimal film contrast. The equalized exposure improves image quality in the normally underpenetrated regions and reduces the role of cross-scatter from the lungs. The image is analogous to optical or computer-processed unsharp masking techniques, but the processing is accomplished in the x-ray beam and results in an improved exposure distribution, giving advantages that cannot be achieved with image processing techniques alone.     

In vitro tubulogenesis of endothelial cells by relaxation of the coupling extracellular matrix-cytoskeleton

OBJECTIVE: This investigation aimed at determining the importance of the rigidity of the adhesive support and the participation of the cytoskeleton in tubulogenesis of endothelial cells in vitro. METHODS: The morphotype, biosynthetic phenotype and cytoskeleton organization of human umbilical vein endothelial cells (HUVEC) were analyzed on supports of variable mechanical resistance. RESULTS: Western blot analysis revealed a strong reduction of the expression of actin and focal-adhesion plaque (FAP) proteins in HUVEC organized in tube-like structures (TLS) on soft matrigel or on matrigel co-polymerized with heat-denatured collagen as compared to HUVEC remaining in a monolayer pattern on rigid matrigel-coat or on matrigel co-polymerized with type I collagen. Human skin fibroblasts morphotype was not altered in these culture conditions and the pattern of FAP proteins and actin was not modulated. By using polyacrylamide gels polymerized with various concentrations of bis-acrylamide to modulate the mechanical resistance of the support and cross-linked to a constant amount of gelatin to provide an equal density of attachment sites, it was shown that the less rigid the support, the more endothelial cells switched to a tube-like pattern. Collagen type I-induced tubulogenesis was accompanied by a profound and reversible remodeling of the actin-FAP complex suggesting a weakening of the bridging between extracellular matrix (ECM) and the cytoskeleton. Human skin fibroblasts and smooth muscle cells, used as control cells, adhered strongly to the collagen, did not form TLS and their network of actin stress fibers was not remodeled. The inhibition of collagen type I-induced tubulogenesis by agents altering the actin cytoskeleton-FAP complex including calpain type I inhibitor, orthovanadate, KT5720 and jasplakinolide, further supports the determinant role of mechanical coupling between the cells and the matrix in tubulogenesis. CONCLUSIONS: A reduced tension between the endothelial cells and the extracellular matrix, originating in the support or within the cells is sufficient to trigger an intracellular signaling cascade leading to tubulogenesis, an event mimicking one of the last steps of angiogenesis.     

A full-UV spectrum absorbing daily use cream protects human skin against biological changes occurring in photoaging

BACKGROUND: There is overwhelming evidence that exposure of human skin to ultraviolet radiations (UVR) leads to the development of cutaneous photoaging and eventually to neoplasia. This study was designed to evaluate in humans the protection afforded by a daily use cream containing a photostable combination of UVB and UVA absorbers (Uvinul N539, Parsol 1789 and Mexoryl SX) providing a continuous absorption through the entire UV spectrum, against damages induced by repeated daily exposure to solar simulated radiation (SSR). METHODS: Buttock skin of 12 healthy volunteers was exposed 5 days per week for 6 weeks to one minimal erythema dose of solar simulated radiation per exposure. The following parameters in treated and untreated skin were evaluated: erythema, pigmentation, skin hydration, skin microtopography, histology and immunochemistry, and collagen and metalloproteinase (MMP) mRNA levels. RESULTS: In SSR exposed unprotected skin sites, we observed melanization and changes in the skin hydration and microtopography. The epidermis revealed a significant increase in stratum corneum and stratum granulosum thickness. In the dermis, an enhanced expression of tenascin and a reduced expression of type I pro-collagen were evidenced just below the dermal epidermal junction. Although we were unable to visualize any change in elastic fibers in exposed buttock skin, a slightly increased deposition of lysozyme and alpha 1 antitrypsin on these fibers was observed using immunofluorescence techniques. Furthermore, types I and III collagen mRNA were slightly increased and a significant enhancement (up to 2.8-fold) of MMP-2 mRNA level was observed. The daily use cream was shown to prevent all these biological changes. CONCLUSION: Our results show in vivo that an appropriate full-UV spectrum product significantly reduces the solar-UV-induced skin damage, demonstrating the benefit of daily photoprotection.