The anabolic action of intermittent parathyroid hormone on cortical bone depends partly on its ability to induce nitric oxide-mediated vasorelaxation in BALB/c mice

There is strong evidence that vasodilatory nitric oxide (NO) donors have anabolic effects on bone in humans. Parathyroid hormone (PTH), the only osteoanabolic drug currently approved, is also a vasodilator. We investigated whether the NO synthase inhibitor L-NAME might alter the effect of PTH on bone by blocking its vasodilatory effect. BALB/c mice received 28 daily injections of PTH[1-34] (80 µg/kg/day) or L-NAME (30 mg/kg/day), alone or in combination. Hindlimb blood perfusion was measured by laser Doppler imaging. Bone architecture, turnover and mechanical properties in the femur were analysed respectively by micro-CT, histomorphometry and three-point bending. PTH increased hindlimb blood flow by >30% within 10 min of injection (P < 0.001). Co-treatment with L-NAME blocked the action of PTH on blood flow, whereas L-NAME alone had no effect. PTH treatment increased femoral cortical bone volume and formation rate by 20% and 110%, respectively (P < 0.001). PTH had no effect on trabecular bone volume in the femoral metaphysis although trabecular thickness and number were increased and decreased by 25%, respectively. Co-treatment with L-NAME restricted the PTH-stimulated increase in cortical bone formation but had no clear-cut effects in trabecular bone. Co-treatment with L-NAME did not affect the mechanical strength in femurs induced by iPTH. These results suggest that NO-mediated vasorelaxation plays partly a role in the anabolic action of PTH on cortical bone

Theophylline Increases the Uptake of Radioiodine by Mouse Thyroid

Diagnostic and therapeutic use of radioiodine in the management of thyroid disorders depends on the ability of thyroid cells to concentrate radioiodine, a process that is regulated by the intracellular increase in cAMP. We hypothesized that theophylline, a drug known to increase intracellular cAMP via inhibition of phosphodiesterase, could increase thyroidal radioiodine uptake. We tested this effect in vivo, using C57BL/6j mice, and in vitro, using Fisher rat thyroid (FRTL-5) cells. One mouse received 2.5mg theophylline i.p., whereas a control mouse received only saline. Twenty-hours after theophylline, mice were injected with 10 µCi Na125I in 0.1 mL saline through the tail vein. Mean thyroidal 125I activity was 3.3-fold higher in theophylline-treated mice than in their respective controls. Radioiodine uptake and intracellular cAMP production of FRTL-5 cells were increased by a relatively low concentration of theophylline (1 µM). Intracellular cAMP increased up to 30 min and then declined in response to 1 µM theophylline. Sera from theophylline-treated mice stimulated 125I uptake and intracellular cAMP production by FRTL-5 cells. These findings show that theophylline can enhance radioiodine uptake by thyrocytes in vivo and in vitro. The in vitro effects of theophylline on both radioiodine uptake and cAMP production in a dose-dependent manner are consistent with an action mediated by phosphodiesterase inhibition

The dental implications of bisphosphonates and bone disease

The document attached has been archived with permission from the Australian Dental Association. An external link to the publisher’s copy is included.In 2002/2003 a number of patients presented to the South Australian Oral and Maxillofacial Surgery Unit with unusual non-healing extraction wounds of the jaws. All were middle-aged to elderly, medically compromised and on bisphosphonates for bone pathology. Review of the literature showed similar cases being reported in the North American oral and maxillofacial surgery literature. This paper reviews the role of bisphosphonates in the management of bone disease. There were 2.3 million prescriptions for bisphosphonates in Australia in 2003. This group of drugs is very useful in controlling bone pain and preventing pathologic fractures. However, in a small number of patients on bisphosphonates, intractable, painful, non-healing exposed bone occurs following dental extractions or denture irritation. Affected patients are usually, but not always, over 55 years, medically compromised and on the potent nitrogen containing bisphosphonates, pamidronate (Aredia/Pamisol), alendronate (Fosamax) and zolendronate (Zometa) for nonosteoporotic bone disease. Currently, there is no simple, effective treatment and the painful exposed bone may persist for years. The main complications are marked weight loss from difficulty in eating and severe jaw and neck infections. Possible preventive and therapeutic strategies are presented although at this time there is no evidence of their effectiveness. Dentists must ask about bisphosphonate usage for bone disease when recording medical histories and take appropriate actions to avoid the development of this debilitating condition in their patients

Bisphosphonates antagonise bone growth factors' effects on human breast cancer cells survival

Bone tissue constitutes a fertile 'soil' for metastatic tumours, notably breast cancer. High concentrations of growth factors in bone matrix favour cancer cell proliferation and survival, and a vicious cycle settles between bone matrix, osteoclasts and cancer cells. Classically, bisphosphonates interrupt this vicious cycle by inhibiting osteoclast-mediated bone resorption. We and others recently reported that bisphosphonates can also induce human breast cancer cell death in vitro, which could contribute to their beneficial clinical effects. We hypothesised that bisphosphonates could inhibit the favourable effects of 'bone-derived' growth factors, and indeed found that bisphosphonates reduced or abolished the stimulatory effects of growth factors (IGFs, FGF-2) on MCF-7 and T47D cell proliferation and inhibited their protective effects on apoptotic cell death in vitro under serum-free conditions. This could happen through an interaction with growth factors' intracellular phosphorylation transduction pathways, such as ERK1/2-MAPK. In conclusion, we report that bisphosphonates antagonised the stimulatory effects of growth factors on human breast cancer cell survival and reduced their protective effects against apoptotic cell death. Bisphosphonates and growth factors thus appear to be concurrent compounds for tumour cell growth and survival in bone tissue. This could represent a new mechanism of action of bisphosphonates in their protective effects against breast cancer-induced osteolysis.Journal ArticleResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe

Erlendir reiðhjólaferðamenn á Íslandi

Reiðhjólaferðamenn verða sífellt meira áberandi á Íslandi á milli ára. Þeir ferðast um hringveginn og virðast bera það með sér að fljóta yfir landið án þess að skilja mikið eftir sig. Í þessari rannsókn var þessi hópur ferðamanna skoðaður. Gerð var könnun á meðal ferðamannanna á lýðfræðilegri stöðu þeirra, ferðavenjum og þáttum er lúta að ferðalaginu þeirra um Ísland. Markmiðið var að skoða þann hóp ferðamanna sem skilgreindur er sem reiðhjólaferðamenn. Draga upp greinagóða mynd af þessum markhópi þannig að íslensk ferðaþjónusta öðlist betri möguleika til þess að koma til móts við óskir hans og þarfir. Ferðahegðun þessa hóps var svo borin saman við ferðahegðun hins almenna erlenda ferðamanns á Íslandi. Niðurstöðurnar sýna að þessi hópur virðist vera samsettur af vel menntuðu fólki, með meðaltekjur, mikinn áhuga á náttúrunni, dvelja lengur og hafa yngri meðalaldur en hin almenni ferðamaður.Every year we seem to see more and more bicycle tourists in Iceland. They are travellers that cycle the main ring road around Iceland and seem to go through without leaving much behind. In this research, this group of travellers were studied. A survey was done among them with the intension of trying to draw a good picture of this market group, so that the tourism industry in Iceland could better meet their needs. In general, this tourist group seemed to be, well educated people, with an average income, high interest in nature, stay longer and to be younger than the average foreign traveller in Iceland

Að fá heila þjóð með sér: Ferli upplýsingafunda almannavarna og þjónandi leiðtogar á tímum Covid-19

Markmið rannsóknarinnar er að greina upplýsingaferli almannavarna vegna Covid-19 allt frá formlegum fundum á meðan á óvissustigi stóð yfir í það tímabil þegar neyðarstigi var lýst yfir með tilheyrandi samkomubanni. Þegar þessari rannsókn lauk 4. maí 2020 var verið að aflétta samkomubanni í litlum skrefum. Kenningarammi rannsóknarinnar sem er eigindleg er breytingastjórnun og þjónandi forysta. Fjallað er um þau atriði sem eru vænleg til árangurs í breytingastjórnun og farið yfir helstu ástæður fyrir því að breytingaferli mistakast. Farið er í gegnum hvað þjónandi forysta stendur fyrir og hver helstu einkenni þjónandi leiðtoga eru. Ferli upplýsingafunda almannavarna er rakið frá janúar – maí 2020. Á fordæmalausum tímum samkomubanns var ekki í boði að taka viðtöl við hlutaðeigandi og því rýndi ég og skoðaði stöðuskýrslur sem birtar eru á heimasíðu almannavarnadeildar ríkislögreglustjóra og horfði á daglega upplýsingafundi á meðan á samkomubanni stóð með það í huga að skoða hvernig upplýsingaferlið samræmdist breytingastjórnun. Ég rýndi í framsetningu upplýsinga, viðmót og framkomu hjá stjórnendum upplýsingafunda almannavarna til að skoða hvernig þeir samræmast þjónandi leiðtogum. Niðurstöður rannsóknarinnar leiddu í ljós að innleiðing upplýsinga og áframhaldandi ferli er hliðstætt ferlum breytingastjórnar sem bornir voru saman við aðgerðir þeirra. Niðurstöður sýna einnig að framkoma og viðmót á upplýsingafundum speglar þá þætti sem einkenna þjónandi leiðtoga. Niðurstöður þessarar rannsóknar eru því þær að það eru greinileg líkindi með upplýsingaferli almannavarna og viðurkenndum breytingaferlum. Því til viðbótar eru færð rök fyrir því að stjórnendur upplýsingafundanna komu fram sem þjónandi leiðtogar. Þetta tvennt hafði þau áhrif að þjóðin hreifst með og sýndi samstöðu sem skilaði mjög góðum árangri á heimsvísu.Winning Over a Nation The Information Process of the Department of Civil Protection and Emergency Management and Servant Leaders During the Period of Covid-19 The objective of this study is to analyze the information process of the Department of Civil Protection and Emergency Management for Covid-19, ranging from formal meetings during the uncertainty phase to the period when the emergency phase was declared and assembly ban established. When this study was completed on May 4th, 2020, the assembly ban was incrementally being lifted. The theoretical framework of this qualitative study is based on theories of change management and servant leadership. The issues that are promising for success in change management are discussed as well as the main reasons why change processes fail. Servant leadership is explained and the main characteristics of servant leaders listed. The process of the Department of Civil Protection and Emergency Management briefings is traced from January – May 2020. During the unprecedented times of assembly ban it was not possible to interview the persons concerned, therefore I looked at and reviewed status reports published on the website of the Department of Civil Protection and Emergency Management and watched daily briefings during the assembly ban to examine how the information process complied with change management. I reviewed the presentation of information as well as the manner and conduct of the leaders of the briefings to see how they accord with serving leaders. The findings of the study showed that the introduction of information and the ongoing process are similar to the processes of change management that were compared with their actions. Furthermore, the findings show that the manner and conduct at the briefings reflect the factors that characterize servant leaders. The findings of this study are therefore that there are clear similarities with the information process of the Department of Civil Protection and Emergency Management and recognized change processes. In addition it is argued that the managers of the briefings acted as servant leaders. The combination of these factors had the effect that the nation was unified and showed solidarity that yielded very good results on a global scale

Að fá heila þjóð með sér: Fyrstu 100 dagarnir, ferli upplýsingafunda almannavarna og þjónandi leiðtogar á tímum Covid-19

Rannsóknin miðar að því að greina upplýsingaferli Almannavarna fyrstu 100 daga Covid-19 á Íslandi, allt frá formlegum fundum á meðan á óvissustigi stóð, yfir í það tímabil þegar neyðarstigi var lýst yfir með tilheyrandi samkomubanni. Þegar þessari rannsókn lauk 4. maí 2020 var verið að aflétta samkomubanni í litlum skrefum. Kenningarammi rannsóknarinnar sem er eigindleg er breytingastjórnun, krísustjórnun og þjónandi forysta. Fjallað er um þau atriði sem eru vænleg til árangurs í breytinga- og krísustjórnun og farið yfir helstu ástæður fyrir því að ferli mistakast. Farið er í gegnum hvað þjónandi forysta stendur fyrir og hver helstu einkenni þjónandi leiðtoga eru. Markmið rannsóknarinnar er að sýna fram á að aðferðir breytinga- og krísustjórnunar ásamt þjónandi forystu voru lykilþáttur í mikilli samstöðu meðal þjóðarinnar. Ferli upplýsingafunda Almannavarna er rakið frá janúar – maí 2020. Á fordæmalausum tímum samkomubanns var ekki í boði að taka viðtöl við hlutaðeigandi og því rýndi höfundur og skoðaði stöðuskýrslur sem birtar eru á heimasíðu Almannavarnadeildar ríkislögreglustjóra og horfði á daglega upplýsingafundi á meðan á samkomubanni stóð með það í huga að skoða hvernig upplýsingaferlið samræmdist breytinga- og krísustjórnun. Höfundur rýndi í framsetningu upplýsinga, viðmót og framkomu hjá stjórnendum upplýsingafunda Almannavarna til að skoða hvernig þeir samræmast þjónandi leiðtogum. Rannsóknin leiddi í ljós að innleiðing upplýsinga og áframhaldandi ferli er hliðstætt ferlum breytinga- og krísustjórnunar sem bornir voru saman við aðgerðir þeirra. Einnig endurspeglar framkoma og viðmót á upplýsingafundum þá þætti sem einkenna þjónandi leiðtoga. Niðurstöður þessarar rannsóknar eru því þær að það eru greinileg líkindi með upplýsingaferli Almannavarna og viðurkenndum breytinga- og krísuferlum. Því til viðbótar eru færð rök fyrir því að stjórnendur upplýsingafundanna komu fram sem þjónandi leiðtogar. Þetta hafði þau áhrif að þjóðin hreifst með og sýndi samstöðu sem skilaði fyrirmyndarárangri