Intranasal nerve growth factor bypasses the blood-brain barrier and affects spinal cord neurons in spinal cord injur y

The purpose of this work was to investigate whether, by intranasal administration, the nerve growth factor bypasses the blood-brain barrier and turns over the spinal cord neurons and if such therapeutic approach could be of value in the treatment of spinal cord injury. Adult Sprague-Dawley rats with intact and injured spinal cord received daily intranasal nerve growth factor administration in both nostrils for 1 day or for 3 consecutive weeks. We found an in-creased content of nerve growth factor and enhanced expression of nerve growth factor receptor in the spinal cord 24 hours after a single intranasal administration of nerve growth factor in healthy rats, while daily treatment for 3 weeks in a model of spinal cord injury improved the deifcits in locomotor behaviour and increased spinal content of both nerve growth factor and nerve growth factor receptors. These outcomes suggest that the intranasal nerve growth factor bypasses blood-brain barrier and affects spinal cord neurons in spinal cord injury. They also suggest exploiting the possible therapeutic role of intranasally delivered nerve growth factor for the neuroprotection of damaged spinal nerve cells.     

Caesarean section is protective against stress urinary incontinence: an analysis of women with multiple deliveries

All women who had three elective caesarean sections were selected from a database of 40,000 women delivering between 1977 and 1998, and age-matched with women having three vaginal births. They all completed a (validated) urinary and bowel symptom questionnaire. Women who had vaginal births had a significantly higher prevalence of stress incontinence but not other urinary or faecal symptoms compared with those delivered by caesarean section. The prevalence of faecal incontinence was lower than the prevalence of urinary incontinence. Although the prevalence of faecal incontinence was lower after caesarean delivery, this was not statistically different. These data have shown that caesarean section was associated with a lower risk of urinary incontinence, although a protective effect on development of faecal symptoms was not seen.     

Angiogenesis in myelodysplastic syndromes

It is now well established that solid tumour growth depends on angiogenesis. However, less is known about the generation of new vessels in haematological malignancies and, in particular, in preleukaemic-myelodysplastic syndromes (MDS). In this study, bone marrow microvessel density (MVD) was assessed by immunohistochemistry and compared in trephine biopsies from 14 controls, five infectious disease (ID), 82 MDS, 15 acute myeloid leukaemia (AML) and 14 myeloproliferative disorder (MPD) patients. Statistical analysis (P < 0.001) demonstrated that MDS MVD was higher than in controls and ID (21 +/- 9 vs 6 +/- 2 and 10 +/- 8 respectively) but lower than AML (30 +/- 12) and MPD (40 +/- 12). Among MDS-FAB subtypes, MVD was significantly higher in RAEB-t, CMML and fibrosis subsets compared to RA, RARS and RAEB subsets (P= 0.008). To further investigate angiogenesis machinery, the expression of vascular endothelial growth factor (VEGF) was evaluated by means of immunohistochemistry in control, MDS, AML and MPD biopsies. Even though VEGF mRNA expression was reported in the past in AML cell cultures and cell lines, in our samples VEGF expression was found to be particularly strong in most of the megakaryocytes but significantly less prominent in other cell populations including blasts. Since our findings suggest a correlation between angiogenesis and progression to leukaemia, additional work is now warranted to determine what regulates the generation of new vessels in MDS and leukaemia.     

bcl-2 proto-oncogene expression in normal and neoplastic human myeloid cells.

The present study provides immunobiochemical and molecular data on the differentiation-linked expression of the bcl-2 proto-oncogene in normal and neoplastic myeloid cells. Using a recently developed monoclonal antibody (MoAb) to the bcl-2 molecule, staining of normal bone marrow myeloblasts, promyelocytes, and myelocytes, but neither monocytes nor most polymorphonuclear cells, was demonstrated. By two-color flow cytometric analysis, bcl-2 was evidenced in CD33+ and CD33+/CD34+ myeloid cells as well as in the more primitive CD33-/CD34+ population. The leukemic cell lines HL-60, KG1, GM-1, and K562 were bcl-2 positive together with 11 of 14 acute myeloid leukemias (AML) and three of three chronic myeloid leukemias (CML) in blast crises; six of seven CML were negative. Among myelodysplastic cases, augmentation of the bcl-2 positive myeloblastic compartment was found in refractory anemia with excess of blasts (RAEB) and in transformation (RAEB-t). Western blots of myeloid leukemias and control lymphocytes extracts evidenced an anti-bcl-2 immunoreactive band of the expected size (26 Kd). Moreover, the HL-60 and KG1 cell lines, both positive for the bcl-2 protein, exhibited the appropriate size bcl-2 mRNA (7.5 Kb). These findings clearly indicate that the bcl-2 gene is operative in myeloid cells and that the anti-bcl-2 MoAb identifies its product and not a cross-reactive epitope. Induction of HL-60 differentiation toward the monocytic and granulocytic pathways was accompanied by a marked decrease in bcl-2 mRNA and protein levels; bivariate flow cytometric analysis showed that the fraction becoming bcl-2 negative was in the G1 phase of the cell cycle. These data establish that the bcl-2 proto-oncogene is expressed on myeloid cells and their progenitors and is regulated in a differentiation-linked manner.     

Female Urinary Incontinence at Orgasm: A Possible Marker of a More Severe Form of Detrusor Overactivity. Can Ultrasound Measurement of Bladder Wall Thickness Explain It?

IntroductionCoital incontinence (CI) during orgasm is a form of urinary incontinence possibly because of detrusor overactivity (DO), as the underlying pathophysiological condition. Women with this symptom usually show a pharmacological lower cure rate than those with DO alone. The ultrasound measurement of the bladder wall thickness (BWT) allows an indirect evaluation of detrusor muscle thickness, giving a potential index of detrusor activity.AimWe wanted to understand if CI at orgasm could be a marker of severity of DO by comparing BWT in women with both DO and CI at orgasm vs. women with DO alone. In addition we aimed to confirm if CI during orgasm is related to antimuscarinics treatment failure.MethodsThis is a prospective cohort study performed in two tertiary urogynecological referral departments, recruiting consecutive patients seeking treatment for symptomatic DO.Main Outcome MeasuresAll patients were thoroughly assessed including physical examination, urodynamic evaluation, and BWT measurement according to the International Continence Society/International Urogynecological Association and ICI recommendations. Solifenacine 5 mg once daily was then prescribed and follow-up was scheduled to evaluate treatment. Multiple logistic regression (MLR) was performed to identify risk factors for treatment failure.ResultsBetween September 2007 and March 2010, 31 (22.6%) and 106 (77.4%) women with DO with and without CI at orgasm were enrolled. Women complaining of CI at orgasm had significantly higher BWT than the control group (5.8 ± 0.6 mm vs. 5.2 ± 1.2 mm [P = 0.007]). In patients with CI at orgasm, the nonresponder rate to antimuscarinics was significantly higher than controls (P = 0.01). After MLR, CI at orgasm was the only independent predictor decreasing antimuscarinics efficacy (odds ratio [OR] 3.16 [95% CI 1.22–8.18], P = 0.02).ConclusionsWomen with DO and CI at orgasm showed a significantly higher BWT values and worse cure rates than women with DO alone. CI at orgasm could be a marker of a more severe form of DO. Serati M, Salvatore S, Cattoni E, Siesto G, Soligo M, Braga A, Sorice P, Cromi A, Ghezzi F, Cardozo L, and Bolis P. Female urinary incontinence at orgasm: A possible marker of a more severe form of detrusor overactivity. Can ultrasound measurement of bladder wall thickness explain it?.     

CD34 immunohistochemistry of bone marrow biopsies: Prognostic significance in primary myelodysplastic syndromes

Bone marrow (BM) biopsies from 58 patients with primary myelodysplastic syndrome (MDS) were studied using QBEND10, a monocional antibody that recognizes the human progenitor CD34 antigen in routine aldehyde-fixed paraffin-embedded samples. FAB subtypes were RA (5 patients), RARS (9 patients), RAEB (20 patients), RAEBt (11 patients), CMML (3 patients). In addition, 10 MDS patients whose BM biopsies revealed heavy reticulum fibrosis were included. Neither the percentage of CD34⁺ cells nor the number of CD34⁺ aggregates (defined as clusters of 3 or more cells) correlated with the presence and morphology of abnormal localizations of immature precursors (ALIP). When all patients were considered, median survival was 69 months in those with less, and 25 months in patients with more than 1% CD34⁺ cells (P < 0.05). Median survival was 15 months in patients with CD34⁺ aggregates and 41 months in those without aggregates (P = 0.0017). When RAEB patients were considered median survival was 41 months in those with less than 1%, and 29 months in those with more than 1% CD34⁺ cells; the 4-year survival chance was 45% in the former and 18.3% in the latter group. Therefore, CD34 positivity of more than 1% identifies a subset of RAEB patients with shorter life expectancy. In addition, leukemic transformation was observed in 11 of 35 patients (31%) with no CD34 aggregates, but in 14 of 23 patients (60%) with aggregates (P < 0.05). CD34 immunostaining, which can be easily performed on routinely prepared BM biopsies, was found to be a powerful prognostic tool for predicting survival and outcome in MDS. © 1994 Wiley-Liss, Inc.     

CD34 expression is regulated reciprocally with adhesion molecules in vascular endothelial cells in vitro

Freshly cultured vascular endothelial cells express the CD34 antigen in a diffuse cell surface pattern with some concentration on microvilli. Expression is downregulated with proliferation in continuous culture and undetectable after nine population doublings but can be maintained by restraining cell proliferation and promoting cell contact. Expression of CD34 at the antigen and mRNA levels on early passage cells is rapidly downregulated by interleukin-1 beta (IL-1 beta), interferon-gamma (INF-gamma), and tumor necrosis factor-alpha (TNF- alpha) under conditions in which these ligands upregulate the adhesion molecules: endothelial leukocyte adhesion molecule 1 (ELAM-1) and intracellular adhesion molecule 1 (ICAM-1). This reciprocal pattern of expression and the topographic distribution of CD34 molecules on the lumenal interdigitated microprocesses of adjacent endothelial cells in vivo suggest that CD34 might have a negative modulating role on adhesion functions of endothelia.