Urocortin is a novel regulator of osteoclast differentiation and function through inhibition of a canonical transient receptor potential 1-like cation channel

This study investigated the role of urocortin (UCN), a member of the corticotrophin-releasing factor (CRF) family of peptides, in osteoclast maturation and function. We found that 10(-7)?M UCN significantly (P<0.05) suppressed osteoclast differentiation from bone marrow precursor cells in culture and reduced the expression of several osteoclastic markers. Furthermore, UCN potently suppressed osteoclast bone resorption, by significantly inhibiting both the plan area of bone resorbed by osteoclasts and actin ring formation within osteoclasts at 10(-9)?M (P<0.05), with complete inhibition at 10(-7)?M (P<0.001). UCN also inhibited osteoclast motility (10(-7)?M) but had no effect on osteoclast survival. Osteoclasts expressed mRNA encoding both UCN and the CRF receptor 2β subtype. Pre-osteoclasts however, expressed CRF receptor 2β alone. Unstimulated osteoclasts contained constitutively active cation channel currents with a unitary conductance of 3-4?pS, which were inhibited by over 70% with UCN (10(-7)?M). Compounds that regulate calcium signalling and energy status of the cell, both crucial for osteoclast activity were investigated. The non-selective cation channel blockers, lanthanum (La(3)(+)) and gadolinium (Gd(3)(+)), inhibited actin ring formation in osteoclasts, whereas modulators of voltage-dependent Ca(2)(+) channels and K(ATP) channels had no effect. These findings show for the first time that UCN is a novel anti-resorptive molecule that acts through a direct effect on osteoclasts and their precursor cells.     

Entrepreneurial nurses and midwives in the United Kingdom: an integrative review

AIM: This paper is a report of an integrative literature review to investigate: (a) the extent of entrepreneurial activity by nurses, midwives and health visitors in the United Kingdom and (b) the factors that influenced these activities. BACKGROUND: Internationally, social and commercial entrepreneurial activity is regarded as important for economic growth and social cohesion. METHODS: Seventeen bibliographic databases were searched using single and combined search terms: 'entrepreneur$', 'business', 'private practice', 'self-employ$', 'intrapreneur$'social enterprise$'mutuals', 'collectives', 'co-op' and 'social capital' which were related to a second layer of terms 'Nurs$', 'Midwi$', 'Visit$'. 'Entrepreneur$' Private Midwi$, Independent Midwi$, and 'nursing workforce'. In addition, hand searches of non-indexed journals and grey literature searches were completed. The following inclusion criteria were: (a) describing nurses, midwife and/or health visitor entrepreneurship (b) undertaken in the UK, and (c) reported between January 1996 and December 2005. RESULTS: Of 154 items included only three were empirical studies; the remainder were narrative accounts. While quality of these accounts cannot be verified, they provide as complete an account as possible in this under-researched area. The numbers of nurses, midwives and health visitors acting entrepreneurially were very small and mirror international evidence. A categorization of entrepreneurial activity was inductively constructed by employment status and product offered. 'Push' and 'pull' influencing factors varied between types of entrepreneurial activity. CONCLUSION: Empirical investigation into the extent to which nurses and midwives respond to calls for greater entrepreneurialism should take account of the complex interplay of contextual factors (e.g. healthcare legislation), professional and managerial experience and demographic factors.     

Heat shock protein expression in rat skeletal muscle after repeated applications of pulsed and continuous ultrasound

Nussbaum EL, Locke M. Heat shock protein expression in rat skeletal muscle after repeated applications of pulsed and continuous ultrasound.

Objective

To determine whether repeated ultrasound treatments are capable of increasing the expression of heat shock protein (HSP) 72 and HSP 25 in rat skeletal muscles.

Design

In vivo, experimental, controlled study.

Setting

Animal laboratory.

Animals

Male Sprague-Dawley rats (n=9).

Interventions

Ultrasound (1MHz, 15min, 2.0cm² transducer) continuous at 1.0W/cm² spatial average temporal average intensity (CONTUS) or pulsed at 2.0W/cm² spatial average temporal peak intensity 50% duty cycle (PULS50) was applied on 4 consecutive days to the lower leg muscles of 1 hindlimb in each rat (n=9).

Main Outcome Measures

Twenty-four hours after the final ultrasound application, hindlimb muscles were removed, weighed, and assessed for HSP 72 and HSP 25 content by Western blotting. Bands from blots were quantified and data were assessed using t tests (α=.05).

Results

Ultrasound did not affect core or contralateral hindlimb muscle temperature. Average muscle temperatures during the final day ultrasound treatments were 38.71°±0.30°C when using PULS50 and 38.16°±0.57°C when using CONTUS. PULS50 significantly increased HSP 25 content in the plantaris and soleus muscles and HSP 72 content in the plantaris muscles. CONTUS significantly increased HSP 72 content in the white gastrocnemius muscle.

Conclusions

HSPs can be induced in skeletal muscle when ultrasound is used on a repeated basis to treat soft tissue.     

A double mobility acetabular implant for primary hip arthroplasty in patients at high risk of dislocation

IntroductionDislocation following total hip replacement continues to be a problem for which no completely satisfactory solution has been found. Several methods have been proposed to reduce the incidence of hip dislocations with varying degrees of success, including elevated rim liners, constrained liners and large diameter bearings. We present our experience with the double mobility acetabular component in patients at high risk of instability.MethodsThis was a retrospective review of 65 primary total hip arthroplasties in 55 patients (15 men, 40 women), performed between October 2005 and November 2009. The majority (80%) of patients had at least two and 26% had at least three risk factors for instability. The mean age was 76 years (range: 44–92 years). The patients were followed up for a mean duration of 60 months (range: 36–85 months).ResultsFourteen patients died and one was lost to follow-up, leaving fifty hips for final assessment. Until the final follow-up appointment, no patients had dislocation and none required revision surgery. The mean Oxford hip score improved from 45.0 to 26.5 (p<0.0001). The mean Merle d’Aubigné pain score improved from 1.4 to 4.9 (p<0.0001), the walking score from 2.3 to 3.1 (p<0.07) and the absolute hip function score from 5.4 to 10.8 (p<0.0001). There were no clinical or radiographic signs of loosening.ConclusionsThe double mobility acetabular component was successful at preventing dislocation during early to medium-term follow-up. However, as data are still lacking with regard to polyethylene wear rates at the additional bearing surface, it would be prudent to restrict the use of this implant to selected patients at high risk of instability.     

Surgical delivery of drug releasing poly(lactic-co-glycolic acid)/poly(ethylene glycol) paste with in vivo effects against glioblastoma

Introduction

The median survival of patients with glioblastoma multiforme (astrocytoma grade 4) remains less than 18 months despite radical surgery, radiotherapy and systemic chemotherapy. Surgical implantation of chemotherapy eluting wafers into the resection cavity has been shown to improve length of survival but the current licensed therapy has several drawbacks. This paper investigates in vivo efficacy of a novel drug eluting paste in glioblastoma.

Methods

Poly(lactic-co-glycolic acid)/poly(ethylene glycol) (PLGA/PEG) self-sintering paste was loaded with the chemotherapeutic agent etoposide and delivered surgically into partially resected tumours in a flank murine glioblastoma xenograft model.

Results

Surgical delivery of the paste was successful and practical, with no toxicity or surgical morbidity to the animals. The paste was retained in the tumour cavity, and preliminary results suggest a useful antitumour and antiangiogenic effect, particularly at higher doses. Bioluminescent imaging was not affected significantly by the presence of the paste in the tumour.

Conclusions

Chemotherapy loaded PLGA/PEG paste seems to be a promising technology capable of delivering active drugs into partially resected tumours. The preliminary results of this study suggest efficacy with no toxicity and will lead to larger scale efficacy studies in orthotopic glioblastoma models.     

Ultrastructural localization of human platelet thrombospondin, fibrinogen, fibronectin, and von Willebrand factor in frozen thin section

We have investigated the localization of thrombospondin (TSP), fibrinogen, fibronectin, and von Willebrand factor in human platelets by transmission electron microscopy of antibody-stained ultrathin frozen sections. In negatively stained thin sections, alpha granules were identified on the basis of their smooth, roughly spherical shape, size, single limiting electron-lucent 100 A membrane, and frequent presence of electron-dense nucleoid. In contrast, mitochondria exhibited characteristic double membranes and cristae. Sections were separately stained with affinity-purified polyclonal antibodies to these proteins as well as with three monoclonal anti-TSP antibodies. Antibody specificity was documented in radioimmunoassays, by immunofluorescent cross-blocking, and by staining of bands of appropriate mobility in Western blots of whole platelets. Bound antibody was visualized using a 5-nm colloidal gold-avidin conjugate. In resting cells, staining of virtually all alpha granules was observed for all four proteins. In contrast, consistent staining was absent from other organelles, including plasma membranes, mitochondria, and vacuolar structures that may represent the open canalicular system.     

Expression of platelet-derived growth factor and its receptors by two pre-B acute lymphocytic leukemia cell lines

Platelet-derived growth factors (PDGF) are potent regulators of cell proliferation. The three isoforms of PDGF AA, AB, and BB are encoded by two genes: PDGF A and PDGF B. The v-sis oncogene is homologous to the PDGF-B gene. v-sis can transform cells that express the appropriate PDGF receptors. Two different types of receptors, PDGF-alpha and PDGF- beta, also encoded by two genes, have been identified. We show that two cell lines. SMS-SB and NALM-6, both derived from pre-B-cell acute lymphocytic leukemias, express the PDGF-A chain gene, and one of them, SMS-SB, releases PDGF-A chains into the media. The SMS-SB cells also express the PDGF-beta receptor, whereas NALM-6 cells express the PDGF- alpha receptor and bind PDGF. This extends the possible targets for PDGF to the B-cell lineage lymphocytes.