Lipid Levels: A Link Between Cardiovascular Disease and Osteoporosis?

Epidemiological observations support a positive relationship between cardiovascular diseases (CVD) and osteoporosis, where cholesterol has been indicated to be a possible link. Only a few studies have investigated the relation between lipids and BMD, but the association remains unclear. We studied the relationship between serum lipids and BMD of the calcaneus. A cross‐sectional population‐based study was performed, based on data from the Longitudinal Aging Study Amsterdam, including 620 men and 635 women, 65–88 yr of age. BMD was measured by quantitative ultrasound (QUS), velocity of sound (VOS; m/s), and broadband ultrasound attenuation (BUA; dB/MHz). Models were adjusted for age, body mass index, physical activity, smoking, alcohol, diabetes mellitus, hypertension, testosterone, and 25‐hydroxyvitamin D. No association was found between total cholesterol (TC) and QUS. Men and women in the highest quartile of high‐density lipoprotein cholesterol (HDL‐c) had a significantly lower QUS (men—VOS: β = ?20.8, p = 0.00; BUA: β = ?5.2, p = 0.02; women—VOS: β = ?18.6, p = 0.00) compared with men and women in the lowest quartile. An even stronger positive association was seen between TC/HDL‐c ratio and QUS (men—VOS: β = 21.8, p = 0.00; BUA: β = 5.5, p = 0.01; women—VOS: β = 19.2, p = 0.00; BUA: β = 3.6, p = 0.05). Our analysis shows that the lipid profile that is favorable in the prevention of CVD (i.e., high levels of HDL‐c and low TC/HDL‐c ratio) is unfavorable for QUS. These results indicate that HDL‐c levels do not explain the association between osteoporosis and CVD.     

Heme oxygenase-1 attenuates ischemia/reperfusion-induced apoptosis and improves survival in rat renal allografts

BACKGROUND: Kidneys can be preserved only for a limited time without jeopardizing graft function and survival. Induction of heat shock proteins (HSPs) can protect against ischemia/reperfusion (I/R) injury. Therefore, we investigated whether the induction of the HSP, heme oxygenase-1 (HO-1), improves outcome following isotransplantation after an extended period of cold storage. METHODS: Rats were subjected to heat preconditioning (HP; 42 degrees C for 20 minutes). Kidneys harvested after 24 hours, were preserved in cold University of Wisconsin (UW) solution at 4 degrees C for 45 hours and transplanted into bilateral nephrectomized rats. Cobalt protoporphyrin (CoPP) was administered in another group of animals in order to induce HO-1 pharmacologically, while other groups of animals received the HO-1 inhibitor, tin protophorphyrine (SnPP), following HP or CoPP. RESULTS: Cold ischemia caused a complete attenuation of graft function within 3 days following transplantation and subsequent death of all animals, whereas HP protected graft function and five of nine rats survived for 3 weeks. HP inhibited the induction of osteopontin and induced the expression of HO-1, HSP 70 and 90, and the antiapoptotic factor Bcl-XL. Grafts exposed to HP were protected against structural I/R injuries as revealed by histologic assessment using a semiquantitative score. Furthermore, induction of apoptosis was attenuated and activation of caspase-3 was inhibited. Comparable results were observed after administration of CoPP, whereas SnPP inhibited the effects of HP and CoPP. CONCLUSION: HP or administration of CoPP induced both HO-1, preserved kidney graft function, and prevented postreperfusion apoptosis after cold preservation.     

Auricular Acupressure as a Treatment for Anxiety in Prehospital Transport Settings

Background: Auricular acupuncture at the relaxation point has been previously shown to be an effective treatment for anxiety in the preoperative setting. The purpose of this prospective, randomized, blinded study was to determine whether auricular acupressure can reduce stress and anxiety during ambulance transport.

Methods: Patients who required ambulance transport secondary to medical conditions were randomized to receive auricular acupressure at the relaxation point (n = 17) or at a sham point (n = 19). A visual analog scale was used to assess state anxiety as well as patient anticipation of hospital medical treatment (estimated waiting period for treatment, anticipated pain during treatment, attitude toward the physicians, and treatment outcomes). These variables were assessed at baseline and on arrival to the hospital.

Results: Patients in the relaxation group reported significantly less anxiety than patients in the sham group on arrival to the hospital (visual analog scale mean +/- SD: 37.6 +/- 20.6 to 12.4 +/- 7.8 mm vs. 42.5 +/- 29.9 to 46.7 +/- 25.9 mm, respectively;P = 0.002). Similarly, patient perception of pain during treatment (mean visual analog scale +/- SD: 32.7 +/- 27.7 to 14.5 +/- 8.1 mm vs. 17.2 +/- 26.1 to 28.8 +/- 21.9 mm, respectively;P = 0.006) and treatment outcomes of their illnesses (mean visual analog scale +/- SD: 46.7 +/- 29.4 to 19.1 +/- 10.4 mm vs. 35.0 +/- 25.7 to 31.5 +/- 20.5 mm, respectively;P = 0.014) were significantly more positive in the relaxation group than in the sham group. No differences were found in the other variables assessed.     

Eine neue arthroskopische Klassifikation der artikularseitigen Rotatorenmanschettenpartialruptur

Zusammenfassung   Die Klassifikationen der RM-Partialrupturen nach Ellman sowie Snyder beschreiben die betroffene Sehnenfl?che sowie die L?sionstiefe ohne die ?tiopathomorphologie der Rupturentstehung an der Sehneninsertion zu berücksichtigen. Ziel unserer prospektiven Studie war eine rationelle reproduzierbare Beschreibung zur Quantifizierung der artikularseitigen Rotatorenmanschettenpartialruptur (RMPR) zu entwickeln. 56 konsekutive Patienten mit klinischer und mittels MRT nachgewiesener artikularseitiger RMPR wurden standardisiert diagnostisch arthroskopiert. Die RMPR wurde intraoperativ nach Ellman und Snyder klassifiziert. Zus?tzlich wurde das Ausma? der RMPR zweidimensional gemessen. Die londitudinale Rupturausdehnung wurde anhand der L?nge des freiliegenden kn?chernen Footprints in der paracoronaren Ebene bestimmt. Die sagittale Rupturausdehnung in der transversalen Ebene wurde definiert als Ruptur des lateralen Pulley-Systems am medialen Supraspinatussehnenrand und / oder als Ruptur im Bereich der Crescent-Zone. Arthroskopisch wiesen 71,4 % eine isolierte artikularseitige SSP-Ruptur und 28,6 % wiesen eine kombinierte artikularseitige SSP- und SCP-Ruptur auf. 62,5 % der Patienten mit artikularseitiger SSP-Ruptur hatten ein positives Cable-Sign. In der transversalen Ebene wiesen Patienten mit artikularseitiger SSP-Ruptur in 26,8 % eine Ruptur des LCH, die sich in die SSP-Sehne fortsetzte (Zone A) auf. Bei 23,2 % fand sich eine artikularseitige SSP-Ruptur in der Crescent-Zone bei intaktem Rotatorenintervall (Zone B) und 50 % wiesen eine artikularseitige SSP-Ruptur mit Ausdehnung in Zone A und B auf. In der paracoronaren Ebene fand sich bei 48,2 % eine Ausdehnung der artikularseitigen SSPRuptur in die übergangszone von Knorpel zu Knochen (Typ 1), in 37,5 % eine Rupturausdehnung bis zur Mitte des Footprints (Typ 2) und in 14,2 % bis zum Tuberculum majus (Typ 3). Statistisch wurde eine hohe Korrelation (Spearman's rho r = 0.920; p < 0.0001) zwischen der Klassifikation nach Ellman und nach Snyder beobachtet. Eine geringe Korrelation bestand (r = 0.342; p = 0.007) zwischen der Klassifikation nach Snyder und der Rupturausdehnung in der übergangszone sowie zwischen der Klassifikation nach Ellman und der Rupturausdehnung and der übergangszone (r = 0.376; p = 0.003). Zwischen SSP-Rupturausdehnung bis zur Mitte des Footprints und der Klassifikation nach Ellman (r = 0.380; p = 0.003) sowie der Klassifikation nach Snyder (r = 0.326; p = 0.011) besteht ebenfalls nur eine geringe Korrelation. Die Klasifikationen der artikularseitigen Supraspinatussehnenrupturen nach Snyder und nach Ellman reproduzieren nicht die Ausdehnung der Rotatorenmanschettenpartialruptur in der transversalen und in der coronaren Ebene ausgehend von der Sehneninsertion. * Diese Arbeit wurde mit dem Best-Paper-Preis der DVSE ausgezeichnet.     

Circulating alloreactive T cells correlate with graft function in longstanding renal transplant recipients

Monitoring for alloreactive memory T cells after organ transplantation may allow individualization of immunosuppression. Two pathways of T cell allorecognition have been implicated in chronic graft dysfunction: Direct (recipient T cells respond to donor peptides presented by donor antigen-presenting cells) and indirect (donor peptides are processed and presented by recipient antigen-presenting cells). Previous studies have assessed these alloresponses only during the first 2 yr after kidney transplantation,so this study correlated the presence of circulating donor-reactive memory/effector T cells, primed by both pathways, in 34 longstanding living-donor renal transplant recipients using the highly sensitive IFN-gamma Elispot assay. Remarkably, 59% of patients had directly primed donor-reactive T cells, and their presence correlated directly with serum creatinine (P = 0.001) and inversely with estimated GFR (P = 0.042). Multivariate analysis revealed that hyporesponsiveness of direct, donor-specific T cells was the only variable that significantly correlated with graft function and that antidonor indirect alloreactivity was the only variable that significantly correlated with proteinuria. Interestingly, when both allorecognition pathways were considered together, patients with undetectable direct alloreactivity had better longterm graft function, independent of allosensitization by the indirect pathway. In conclusion, circulating donor-specific alloreactive T cells primed by both pathways are detectable long after transplantation and are associated with graft injury. Assessment of alloreactive memory/effector T cells might be helpful to tailor individual immunosuppression regimens for transplant recipients in the future.     

Brain death induces inflammation in the donor intestine

BACKGROUND: Brain death donors are frequently used for transplantation. Previous studies showed that brain death (BD) negatively affects the immunological and inflammatory status of both liver and kidney. Because the intestine is increasingly used as a donor organ and no information on effects of BD on small intestine is available we performed this study. METHODS: We studied the inflammatory and apoptotic changes in donor intestine after BD induction. Brain death was induced in rats by inflation of a balloon catheter. Three groups (n=6) were compared: 1-hr BD, 4-hr BD, and sham-operated controls. RESULTS: An increased polymorphonuclear cell influx in ileum, as a measure of inflammation, was observed in 1- and 4-hr BD group compared with controls. Jejunum showed a significant increase at the 4-hr BD group compared with the control group. Intercellular adhesion molecule-1, vascular cell adhesion molecule-1, E-selectin, and interleukin-6 were upregulated after 1- and 4-hr BD. Caspase-3 positive cells were found in jejunum and ileum after 4-hr BD on the top of the villi. Serum interleukin-6 was severely elevated in the 1- and 4-hr brain dead rats. CONCLUSION: These data show the early occurrence of intestinal inflammation and apoptosis after BD induction. These events may ultimately have a negative influence on the outcome of intestinal transplantation.     

Thyroid-stimulating hormone restores bone volume, microarchitecture, and strength in aged ovariectomized rats.

We show the systemic administration of low levels of TSH increases bone volume and improves bone microarchitecture and strength in aged OVX rats. TSH's actions are mediated by its inhibitory effects on RANKL-induced osteoclast formation and bone resorption coupled with stimulatory effects on osteoblast differentiation and bone formation, suggesting TSH directly affects bone remodeling in vivo. INTRODUCTION: Thyroid-stimulating hormone (TSH) receptor haploinsufficient mice with normal circulating thyroid hormone levels have reduced bone mass, suggesting that TSH directly affects bone remodeling. We examined whether systemic TSH administration restored bone volume in aged ovariectomized (OVX) rats and influenced osteoclast formation and osteoblast differentiation in vitro. MATERIALS AND METHODS: Sprague-Dawley rats were OVX at 6 months, and TSH therapy was started immediately after surgery (prevention mode; n = 80) or 7 mo later (restoration mode; n = 152). Hind limbs and lumbar spine BMD was measured at 2- or 4-wk intervals in vivo and ex vivo on termination at 8-16 wk. Long bones were subjected to microCT, histomorphometric, and biomechanical analyses. The direct effect of TSH was examined in osteoclast and osteoblast progenitor cultures and established rat osteosarcoma-derived osteoblastic cells. Data were analyzed by ANOVA Dunnett test. RESULTS: In the prevention mode, low doses (0.1 and 0.3 microg) of native rat TSH prevented the progressive bone loss, and importantly, did not increase serum triiodothyroxine (T3) and thyroxine (T4) levels in aged OVX rats. In restoration mode, animals receiving 0.1 and 0.3 microg TSH had increased BMD (10-11%), trabecular bone volume (100-130%), trabecular number (25-40%), trabecular thickness (45-60%), cortical thickness (5-16%), mineral apposition and bone formation rate (200-300%), and enhanced mechanical strength of the femur (51-60%) compared with control OVX rats. In vitro studies suggest that TSH's action is mediated by its inhibitory effects on RANKL-induced osteoclast formation, as shown in hematopoietic stem cells cultivated from TSH-treated OVX rats. TSH also stimulates osteoblast differentiation, as shown by effects on alkaline phosphatase activity, osteocalcin expression, and mineralization rate. CONCLUSIONS: These results show for the first time that systemically administered TSH prevents bone loss and restores bone mass in aged OVX rats through both antiresorptive and anabolic effects on bone remodeling.     

Psychosocial Functioning following Bariatric Surgery

Morbid obesity is associated with an increased risk of morbidity and mortality as well as psychosocial problems and poor quality of life. The ultimate goal of bariatric surgery is not only reduced weight and reduction of co-morbidities, but also improved psychosocial functioning and quality of life. However, not all patients are successful. A systematic literature search of recent articles identified relevant variables reflecting postoperative psychosocial functioning. Most studies showed that bariatric surgery does not only lead to substantial weight reduction, but also to improvement or cure of physical as well as psychological co-morbidities. Although most studies are optimistic and report broad psychosocial improvement, a significant minority of patients do not benefit psychologically from surgery. Although there are mixed results, the overall improvements in psychosocial functioning provide additional justification for surgical treatment of morbid obesity.     

Altered bone matrix mineralization in a patient with Rett syndrome

Rett syndrome (RTT) is a common X-linked neurodevelopmental disorder caused by mutations in the coding region of methyl-CpG-binding 2 (MECP2) gene. Patients with RTT have a low bone mineral density and increased risk of fracture. However, very little is known if bone matrix mineralization is altered in RTT. A 17-year-old girl with a classical form of RTT with a heterozygous nonsense mutation in exon 3 in the MECP2-gene was treated in our hospital. Her femoral neck BMD is 43.3% below the 3rd percentile when compared to age and sex-matched controls. She underwent surgery for correction of her scoliosis, which provided a unique opportunity to obtain bone tissue to study bone matrix mineralization (Bone Mineralization Density Distribution—BMDD) using quantitative backscattered electron imaging (qBEI) and histomorphometry. BMDD outcomes were compared to recently published normative reference data for young individuals. qBEI analysis showed a significant shift to lower matrix mineralization despite histomorphometric indices indicate a low bone turnover. There was a reduction in CaMean (? 7.92%) and CaPeak (? 3.97%), which describe the degree of mineralization. Furthermore the fraction of low mineralized matrix (CaLow: + 261.84%) was dramatically increased, which was accompanied with an increase in the heterogeneity of mineralization (CaWidth: + 86.34%).Our findings show a significantly altered bone matrix mineralization of a typical patient with RTT. This may partly explain the low bone density seen in these patients. These results also warrant further studies on the molecular role of MECP2 in bone matrix mineralization.