Evaluation of beta-endorphin and naloxone on bovine uterine motility

Effects of beta-endorphin and naloxone on bovine uterine motility were tested both in vivo and in vitro. Six cyclic Holstein cows were used to study in vivo effects of beta-endorphin and naloxone on uterine motility during estrus and diestrus. Intrauterine pressure changes were recorded by a microtip pressure transducer before and after treatment. Blood samples were taken every 10 min during the recording periods for beta-endorphin assay. The results revealed that beta-endorphin anc naloxone had no effect on intrauterine pressure in vivo. The effects of beta-endorphin and naloxone on myometrial contractility were also examined in vitro. Beta-endorphin and naloxone were added to tissue baths containing estrous and diestrous uterine strips. The results showed no significant effect of beta-endorphin and naloxone on bovine myometrial contractility. The role of beta-endorphin in bovine reproductive physiology is still not clearly understood, and additional studies are needed.     

Spectral characteristics of caries autofluorescence obtained from different locations and caries severities

Dental caries usually occurs at interproximal and occlusal surfaces. The purpose of the present study was to determine if characteristic spectral factors extracted from autofluorescence (AF) spectra are informative regarding caries detection and the determination of caries stage as compared with DIAGNOdent results. AF spectra were obtained from caries lesions of different severities at two locations using a 405 nm laser. Three spectral factors, that is, spectral slope at 550 to 600 nm, spectral area under the curve at 500 to 590 nm and two‐peak ratio between 625 and 667 nm, were extracted. The values of three spectral factors linearly decreased as caries progressed. According to micro‐CT images, conventional visual and tactile inspections of lesions under or overestimated (25%‐65%) caries states, and brown or thickly stained layer on interproximal or occlusal surfaces, respectively, caused misclassifications of caries stage. Of the spectral factors examined, spectral slope and area under curve for interproximal and occlusal surfaces, respectively, were found to be significantly related to caries stage and showed least data overlap. For interproximal and occlusal surfaces, DIAGNOdent readings of different stages overlapped considerably though their mean values were significantly different regardless of stage.      

A spirochete surface protein uncouples store-operated calcium channels in fibroblasts: a novel cytotoxic mechanism

The cytotoxicity of infectious agents can be mediated by disruption of calcium signaling in target cells. Outer membrane proteins of the spirochete Treponema denticola, a periodontal pathogen, inhibit agonist-induced Ca(2+) release from internal stores in gingival fibroblasts, but the mechanism is not defined. We determined here that the major surface protein (Msp) of T. denticola perturbs calcium signaling in human fibroblasts by uncoupling store-operated channels. Msp localized in complexes on the cell surface. Ratio fluorimetry showed that in cells loaded with fura-2 or fura-C18, Msp induced cytoplasmic and near-plasma membrane Ca(2+) transients, respectively. Increased conductance was confirmed by fluorescence quenching of fura-2-loaded cells with Mn(2+) after Msp treatment. Calcium entry was blocked with anti-Msp antibodies and inhibited by chelating external Ca(2+) with EGTA. Msp pretreatment reduced the amplitude of [Ca(2+)](i) transients upon challenge with ATP or thapsigargin. In experiments using cells loaded with mag-fura-2 to report endoplasmic reticulum Ca(2+), Msp reduced Ca(2+) efflux from endoplasmic reticulum stores when ATP was used as an agonist. Msp alone did not induce Ca(2+) release from these stores. Msp inhibited store-operated influx of extracellular calcium following intracellular Ca(2+) depletion by thapsigargin and also promoted the assembly of subcortical actin filaments. This actin assembly was blocked by chelating intracellular Ca(2+) with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid acetoxymethyl ester. The reduced amplitude of agonist-induced transients and inhibition of store-operated Ca(2+) entry due to Msp were reversed by latrunculin B, an inhibitor of actin filament assembly. Thus, Msp retards Ca(2+) release from endoplasmic reticulum stores, and it inhibits subsequent Ca(2+) influx by uncoupling store-operated channels. Actin filament rearrangement coincident with conformational uncoupling of store-operated calcium fluxes is a novel mechanism by which surface proteins and toxins of pathogenic microorganisms may damage host cells.     

Higher Decorin Levels in Bone Marrow Plasma Are Associated with Superior Treatment Response to Novel Agent-Based Induction in Patients with Newly Diagnosed Myeloma - A Retrospective Study

The growth of myeloma cells depends on bone marrow (BM) stroma consisting of stromal cells, secreted cytokines and the extracellular matrix (ECM). Decorin, a small leucine-rich proteoglycan in the ECM, is a signaling ligand and native anti-tumor agent. However, the role of decorin in patients with myeloma is not clear. We evaluated the correlation between the decorin levels measured by enzyme-linked immunosorbent assay in BM plasma from 121 patients with newly diagnosed myeloma based on their clinical features and treatment response. The median decorin levels in the patients and the normal control group were 12.31 ng/mL [standard deviation (SD), 7.50 ng/mL; range, 2.45 to 44.46 ng/mL] and 10.31 ng/mL (SD, 2.42 ng/mL; range, 4.85–15.14 ng/mL), respectively (P < 0.001). Using 15.15 ng/mL as a cut-off, 46 patients (38%) exhibited higher decorin levels (H-DCN), whereas the other patients exhibited normal to lower decorin levels (NL-DCN). Except for the median age, which was significantly younger in the H-DCN than in the NL-DCN group (60.6±14.0 vs. 65.8±12.2 years, respectively; P = 0.034), there were no differences between the two groups. However, in 79 patients who had received novel agent-based induction, the overall response rate was significantly better in the H-DCN than in the NL-DCN (97 vs. 63%, respectively; P < 0.001), as was the depth of responses (P = 0.008), which were not observed in those who had received chemotherapeutic agents alone. Progression-free survival (PFS) was significantly longer in H-DCN than NL-DCN (not reached vs. 19.5 mo, respectively; P = 0.0003). Multivariate analyses indicated that H-DCN, as a significantly independent factor, was associated with better treatment response (odds ratio, 20.014; 95% CI, 2.187–183.150; P = 0.008) and longer PFS (hazard ratio, 0.135; 95% CI, 0.051–0.361; P < 0.001). These findings disclose the potential role of decorin in myeloma and provide a basis for further study on possible synergistic anti-myeloma effects between decorin and the novel agents that target BM stroma.     

Direct Medical Cost of Type 2 Diabetes in Singapore

Due to the chronic nature of diabetes along with their complications, they have been recognised as a major health issue, which results in significant economic burden. This study aims to estimate the direct medical cost associated with type 2 diabetes mellitus (T2DM) in Singapore in 2010 and to examine both the relationship between demographic and clinical state variables with the total estimated expenditure. The National Healthcare Group (NHG) Chronic Disease Management System (CDMS) database was used to identify patients with T2DM in the year 2010. DM-attributable costs estimated included hospitalisations, accident and emergency (A&E) room visits, outpatient physician visits, medications, laboratory tests and allied health services. All charges and unit costs were provided by the NHG. A total of 500 patients with DM were identified for the analyses. The mean annual direct medical cost was found to be $2,034, of which 61% was accounted for by inpatient services, 35% by outpatient services, and 4% by A&E services. Independent determinants of total costs were DM treatments such as the use of insulin only (p<0.001) and the combination of both oral medications and insulin (p=0.047) as well as having complications such as cerebrovascular disease (p<0.001), cardiovascular disease (p=0.002), peripheral vascular disease (p=0.001), and nephropathy (p=0.041). In this study, the cost of DM treatments and DM-related complications were found to be strong determinants of costs. This finding suggests an imperative need to address the economic burden associated with diabetes with urgency and to reorganise resources required to improve healthcare costs.     

Disruption of Ah Receptor Signaling during Mouse Development Leads to Abnormal Cardiac Structure and Function in the Adult

The Developmental Origins of Health and Disease (DOHaD) Theory proposes that the environment encountered during fetal life and infancy permanently shapes tissue physiology and homeostasis such that damage resulting from maternal stress, poor nutrition or exposure to environmental agents may be at the heart of adult onset disease. Interference with endogenous developmental functions of the aryl hydrocarbon receptor (AHR), either by gene ablation or by exposure in utero to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a potent AHR ligand, causes structural, molecular and functional cardiac abnormalities and altered heart physiology in mouse embryos. To test if embryonic effects progress into an adult phenotype, we investigated whether Ahr ablation or TCDD exposure in utero resulted in cardiac abnormalities in adult mice long after removal of the agent. Ten-months old adult Ahr^-/- and in utero TCDD-exposed Ahr^+/+ mice showed sexually dimorphic abnormal cardiovascular phenotypes characterized by echocardiographic findings of hypertrophy, ventricular dilation and increased heart weight, resting heart rate and systolic and mean blood pressure, and decreased exercise tolerance. Underlying these effects, genes in signaling networks related to cardiac hypertrophy and mitochondrial function were differentially expressed. Cardiac dysfunction in mouse embryos resulting from AHR signaling disruption seems to progress into abnormal cardiac structure and function that predispose adults to cardiac disease, but while embryonic dysfunction is equally robust in males and females, the adult abnormalities are more prevalent in females, with the highest severity in Ahr^-/- females. The findings reported here underscore the conclusion that AHR signaling in the developing heart is one potential target of environmental factors associated with cardiovascular disease.     

Knock-down of human MutY homolog (hMYH) decreases phosphorylation of checkpoint kinase 1 (Chk1) induced by hydroxyurea and UV treatment

The effect of human MutY homolog (hMYH) on the activation of checkpoint proteins in response to hydroxyurea (HU) and ultraviolet (UV) treatment was investigated in hMYH-disrupted HEK293 cells. hMYH-disrupted cells decreased the phosphorylation of Chk1 upon HU or UV treatment and increased the phosphorylation of Cdk2 and the amount of Cdc25A, but not Cdc25C. In siMYH-transfected cells, the increased rate of phosphorylated Chk1 upon HU or UV treatment was lower than that in siGFP-transfected cells, meaning that hMYH was involved in the activation mechanism of Chk1 upon DNA damage. The phosphorylation of ataxia telangiectasia and Rad3- related protein (ATR) upon HU or UV treatment was decreased in hMYH-disrupted HEK293 and HaCaT cells. Co-immunoprecipitation experiments showed that hMYH was immunoprecipitated by anti-ATR. These results suggest that hMYH may interact with ATR and function as a mediator of Chk1 phosphorylation in response to DNA damage.     

Potential Risk Factors of Persistent Low Back Pain Developing from Mild Low Back Pain in Urban Japanese Workers

Study Design

Two-year, prospective cohort data from the Japan epidemiological research of occupation-related back pain study in urban settings were used for this analysis.

Objective

To examine the association between aggravated low back pain and psychosocial factors among Japanese workers with mild low back pain.

Summary of Background Data

Although psychosocial factors are strongly indicated as yellow flags of low back pain (LBP) leading to disability, the association between aggravated LBP and psychosocial factors has not been well assessed in Japanese workers.

Methods

At baseline, 5,310 participants responded to a self-administered questionnaire including questions about individual characteristics, ergonomic work demands, and work-related psychosocial factors (response rate: 86.5%), with 3,811 respondents completing the 1-year follow-up questionnaire. The target outcome was aggravation of mild LBP into persistent LBP during the follow-up period. Incidence was calculated for the participants with mild LBP during the past year at baseline. Logistic regression was used to explore risk factors associated with persistent LBP.

Results

Of 1,675 participants who had mild LBP during the preceding year, 43 (2.6%) developed persistent LBP during the follow-up year. Multivariate analyses adjusted for individual factors and an ergonomic factor found statistically significant or almost significant associations of the following psychosocial factors with persistent LBP: interpersonal stress at work [adjusted odds ratio (OR): 1.96 and 95% confidence interval (95%CI): 1.00–3.82], job satisfaction (OR: 2.34, 95%CI: 1.21–4.54), depression (OR: 1.92, 95%CI: 1.00–3.69), somatic symptoms (OR: 2.78, 95%CI: 1.44–5.40), support from supervisors (OR: 2.01, 95%CI: 1.05–3.85), previous sick-leave due to LBP (OR: 1.94, 95%CI: 0.98–3.86) and family history of LBP with disability (OR: 1.98, 95%CI: 1.04–3.78).

Conclusions

Psychosocial factors are important risk factors for persistent LBP in urban Japanese workers. It may be necessary to take psychosocial factors into account, along with physical work demands, to reduce LBP related disability.