Comparison of elderly patients with and without intertrochanteric fractures and the factors affecting fracture severity

BackgroundIntertrochanteric fractures in elderly patients are common and normally caused by low-energy injuries, such as falls. The favored treatment method is closed reduction with internal fixation using plate or nail systems. In general, the severity of an intertrochanteric fracture is one of key factors that affects the success rate of fixation. However, the factors that affect the severity of intertrochanteric fractures in elderly patients are rarely reported in the literature. In this prospective study, several possible factors were investigated.MethodsThe bone mineral densities (BMD) of 48 elderly patients (≥ 65 years) with intertrochanteric fractures due to low-energy injuries were compared with the BMDs of 48 elderly persons without hip fractures. Both groups were composed of people of similar ages and male-to-female ratios. Furthermore, in the patients with fractures, BMD, body mass index (BMI), body weight, and body height were compared between patients with nonsevere (intact lesser trochanter; 14 patients) and severe (displaced lesser trochanter or reverse obliquity fractures; 34 patients) intertrochanteric fractures.ResultsPatients with intertrochanteric fractures had significantly lower BMDs compared with persons without hip fractures to the lesser trochanter, total hip area, femoral neck, or greater trochanter (p = 0.001, <0.001, <0.001, and <0.001, respectively). There was no statistical difference in terms of BMD, BMI, body weight, or body height between patients with nonsevere and severe fractures.ConclusionElderly patients with intertrochanteric fractures have lower BMDs than persons without hip fractures. However, the severity of intertrochanteric fractures cannot be predicted by local BMD, BMI, body weight, or body height.     

Food Frequency Questionnaires and Overnight Urines Are Valid Indicators of Daidzein and Genistein Intake in U.S. Women Relative to Multiple 24-h Urine Samples

Data regarding convenient, valid methods for measuring U.S. isoflavone intake are limited. We evaluated a soy food questionnaire (SFQ), the Willett food frequency questionnaire (FFQ), and overnight urine samples relative to excretion in 24-h urine samples. We also described intake among women in a high-risk program for breast or ovarian cancer. Between April 2002 and June 2003, 451 women aged 30 to 50 yr with a family history of breast or ovarian cancer completed the SFQ and FFQ. Of them, 27 provided four 24-h and overnight urine specimens. In these women, 24-h sample measures were correlated with SFQ estimates of daidzein (Spearman r = .48) and genistein (r = .54) intake, moderately correlated with the Willett FFQ (daidzein r = .38, genistein r = .33), and strongly correlated with overnight urine excretion (daidzein r = .84, genistein r = 0.93). Among all 451 SFQ respondents, mean (median) daidzein and genistein intakes were 2.8 (0.24) and 3.9 (0.30) mg/day. Primary sources of both were soymilk, soy nuts, and tofu. We conclude that targeted soy food questionnaires, comprehensive FFQs, and multiple overnight urines are all reasonable options for assessing isoflavone intake in epidemiologic studies.     

Detection of chymase activity using a specific peptide probe conjugated onto gold nanoparticles

Gold nanoparticles (AuNPs) can be applied in biosensors using fluorescence resonance energy transfer (FRET) technique. Based on this technique, we have established a sensitive and efficient biosensing method by modifying a peptide-probe onto AuNPs to detect proteinase enzyme activity in this study. This biosensing method was designed for chymase activity detection and applied in kidney disease diagnosis. In this study, 16 nm-AuNPs were used to construct the AuNPs-based fluorescence peptide probe (named AuNPs-peptide probe) for chymase activity determination. The peptide sequence is FITC-Acp-DRVYIHPFHLDDDDDC, which comprises a fluorophore at the N-terminal end, an enzyme (chymase) substrate (DRVYIHPFHL), a spacer (DDDDD) and cysteine (C) to conjugate to AuNPs surface. When the enzyme catalyzes the substrate sequence, the fluorophore drifts away from AuNPs and the fluorescence emitting signal can be excited at 495 nm and detected at 515 nm. The results indicate that the time required for the AuNPs-peptide probe for activity detection of chymase was only 15 min, and a linear correlation from 10 to 100 ng mL⁻¹ of chymase was acquired. The chymase reaction would be significantly inhibited by addition of specific chymase inhibitor chymostatin. The AuNPs-peptide probe was tested for the detection of high concentrations of trypsin and chymotrypsin, but only minor emitted fluorescence intensity was detected. According to these results, sensitivity and specificity of the AuNPs-peptide probe for chymase detection have been confirmed. AuNPs-peptide probe was successfully used for the detection of renal chymase activity; and the results indicate the pathogenically increased chymase activity in kidney tissue of nephropathic mice from aristolochic acid I treatment.

The gold nanoparticles (AuNPs) peptide probe functionalized with specific peptide sequences was developed for the sensitive and efficient detection of chymase activity.     

GPCR dimerization in brainstem nuclei contributes to the development of hypertension

Background and Purpose

μ-Opioid receptors, pro-opiomelanocortin and pro-enkephalin are highly expressed in the nucleus tractus solitarii (NTS) and μ receptor agonists given to the NTS dose-dependently increased BP. However, the molecular mechanisms of this process remain unclear. In vitro, μ receptors heterodimerize with α_2A-adrenoceptors. We hypothesized that α_2A-adrenoceptor agonists would lose their depressor effects when their receptors heterodimerize in the NTS with μ receptors.

Experimental Approach

We microinjected μ-opioid agonists and antagonists into the NTS of rats and measured changes in BP. Formation of μ receptor/α_2A-adrenoceptor heterodimers was assessed with immunofluorescence and co-immunoprecipitation methods, along with proximity ligation assays.

Key Results

Immunofluorescence staining revealed colocalization of α_2A-adrenoceptors and μ receptors in NTS neurons. Co-immunoprecipitation revealed interactions between α_2A-adrenoceptors and μ receptors. In situ proximity ligation assays confirmed the presence of μ receptor/α_2A-adrenoceptor heterodimers in the NTS. Higher levels of endogenous endomorphin-1 and μ receptor/α_2A-adrenoceptor heterodimers were found in the NTS of hypertensive rats, than in normotensive rats. Microinjection of the μ receptor agonist [D-Ala², MePhe⁴, Gly⁵-ol]-enkephalin (DAMGO), but not that of the α_2A-adrenoceptor agonist guanfacine, into the NTS of normotensive rats increased μ receptor/α_2A-adrenoceptor heterodimer formation and BP elevation. The NO-dependent BP-lowering effect of α_2A-adrenoceptor agonists was blunted following increased formation of μ receptor/α_2A-adrenoceptor heterodimers in the NTS of hypertensive rats and DAMGO-treated normotensive rats.

Conclusions and Implications

Increases in endogenous μ receptor agonists in the NTS induced μ receptor/α_2A-adrenoceptor heterodimer formation and reduced the NO-dependent depressor effect of α_2A-adrenoceptor agonists. This process could contribute to the pathogenesis of hypertension.     

Activating mitochondrial function and haemoglobin expression with EH-201, an inducer of erythropoietin in neuronal cells,reverses memory impairment

Background and Purpose

Memory impairment can be progressive in neurodegenerative diseases, and physiological ageing or brain injury, mitochondrial dysfunction and oxidative stress are critical components of these issues. An early clinical study has demonstrated cognitive improvement during erythropoietin treatment in patients with chronic renal failure. As erythropoietin cannot freely cross the blood–brain barrier, we tested EH-201 (2,3,5,4′-tetrahydroxystilbene-2-O-β-d-glucoside, also known as TSG), a low MW inducer of erythropoietin, for its therapeutic effects on memory impairment in models of neurodegenerative diseases, physiological ageing or brain injury.

Experimental Approach

The effects of EH-201 were investigated in astrocytes and PC12 neuronal-like cells. In vivo, we used sleep-deprived (SD) mice as a stress model, amyloid-β (Aβ)-injected mice as a physiological ageing model and kainic acid (KA)-injected mice as a brain damage model to assess the therapeutic effects of EH-201.

Key Results

EH-201 induced expression of erythropoietin, PPAR-γ coactivator 1α (PGC-1α) and haemoglobin in astrocytes and PC12 neuronal-like cells. In vivo, EH-201 treatment restored memory impairment, as assessed by the passive avoidance test, in SD, Aβ and KA mouse models. In the hippocampus of mice given EH-201 in their diet, levels of erythropoietin, PGC-1α and haemoglobin were increased

Conclusions and Implications

The induction of endogenous erythropoietin in neuronal cells by inducers such as EH-201 might be a therapeutic strategy for memory impairment in neurodegenerative disease, physiological ageing or traumatic brain injury.     

Betulinic acid exerts anti-hepatitis C virus activity via the suppression of NF-κB- and MAPK-ERK1/2-mediated COX-2 expression

Background and Purpose

This study was designed to evaluate the effect of betulinic acid (BA), extracted from Avicennia marina, on the replication of hepatitis C virus (HCV) and to investigate the mechanism of this BA-mediated anti-HCV activity.

Experimental Approach

HCV replicon and infectious systems were used to evaluate the anti-HCV activity of BA. Exogenous COX-2 or knock-down of COX-2 expression was used to investigate the role of COX-2 in the anti-HCV activity of BA. The effects of BA on the phosphorylation of NF-κB and on kinases in the MAPK signalling pathway were determined. The anti-HCV activity of BA in combination with other HCV inhibitors was also determined to assess its use as an anti-HCV supplement.

Key Results

BA inhibited HCV replication in both Ava5 replicon cells and in a cell culture-derived infectious HCV particle system. Treatment with a combination of BA and IFN-α, the protease inhibitor telaprevir or the NS5B polymerase inhibitor sofosbuvir resulted in the synergistic suppression of HCV RNA replication. Exogenous overexpression of COX-2 gradually attenuated the inhibitory effect of BA on HCV replication, suggesting that BA reduces HCV replication by suppressing the expression of COX-2. In particular, BA down-regulated HCV-induced COX-2 expression by reducing the phosphorylation of NF-κB and ERK1/2 of the MAPK signalling pathway.

Conclusions and Implications

BA inhibits HCV replication by suppressing the NF-κB- and ERK1/2-mediated COX-2 pathway and may serve as a promising compound for drug development or as a potential supplement for use in the treatment of HCV-infected patients.