Dual regulation by ethanol of the inhibitory effects of ketamine on spinal NMDA-induced pressor responses in rats

<p>Abstract</p> <p>Background</p> <p>Acute exposure of ethanol (alcohol) inhibits NMDA receptor function. Our previous study showed that acute ethanol inhibited the pressor responses induced by NMDA applied intrathecally; however, prolonged ethanol exposure may increase the levels of phosphorylated NMDA receptor subunits leading to changes in ethanol inhibitory potency on NMDA-induced responses. The present study was carried out to examine whether acute ethanol exposure influences the effects of ketamine, a noncompetitive NMDA receptor antagonist, on spinal NMDA-induced pressor responses.</p> <p>Methods</p> <p>The blood pressure responses induced by intrathecal injection of NMDA were recorded in urethane-anesthetized rats weighing 250-275 g. The levels of several phosphorylated residues on NMDA receptor GluN1 subunits were determined by western blot analysis.</p> <p>Results</p> <p>Intravenous injection of ethanol or ketamine inhibited spinal NMDA-induced pressor responses in a dose-dependent and reversible manner. Ketamine inhibition of NMDA-induced responses was synergistically potentiated by ethanol when ethanol was applied just before ketamine. However, ketamine inhibition was significantly reduced when applied at 10 min after ethanol administration. Western blot analysis showed that intravenous ethanol increased the levels of phosphoserine 897 on GluN1 subunits (pGluN1-serine 897), selectively phosphorylated by protein kinase A (PKA), in the lateral horn regions of spinal cord at 10 min after administration. Intrathecal administration of cAMPS-Sp, a PKA activator, at doses elevating the levels of pGluN1-serine 897, significantly blocked ketamine inhibition of spinal NMDA-induced responses.</p> <p>Conclusions</p> <p>The results suggest that ethanol may differentially regulate ketamine inhibition of spinal NMDA receptor function depending on ethanol exposure time and the resulting changes in the levels of pGluN1-serine 897.</p

Metronidazole-Induced Irreversible Optic Neuropathy

Metronidazole-induced optic neuropathy is a rare complication. Most patients have excellent visual recovery. In this study, we report a patient who presented with a sudden onset of severe visual loss after a 1-week course of metronidazole. Myelitis developed simultaneously. The vision and the accompanying neurological deficiency of the patient did not improve even after metronidazole was discontinued immediately and various treatments were given

The incidence of symptomatic venous thromboembolism following hip fractures with or without surgery in Taiwan

AbstractBackgroundInformation on the incidence of venous thromboembolism (VTE) following hip fractures in Asia is rare. This study will investigate the epidemiology of symptomatic VTE in Taiwanese patients experiencing hip fractures.Methods and resultsWe used Taiwan's National Health Insurance Research Database to retrospectively identify patients (≧45years) who experienced hip fractures from 1998 to 2007 and were followed up for 3months after the discharge. Logistic regression analysis determined the independent risk factors of symptomatic VTE after the fractures. We identified 134,034 patients (mean age: 76.2±9.7years; female: 57.8%) who experienced hip fractures, 83.2% of whom underwent hip surgery. The overall pharmacological thromboprophylaxis rate was 2.7%. The mean length of stay was 11.3±7.9days. The 3-month cumulative incidence of symptomatic VTE was 77 events per 10,000 persons. Multivariate analysis showed that previous DVT, previous PE, varicose veins, cancer, heart failure, renal insufficiency, and older age were independent risk factors of developing VTE.ConclusionsThe incidence of symptomatic VTE after hip fractures is low in Taiwan. Patients rarely received pharmacological thromboprophylaxis following hip fractures. Universal thromboprophylaxis for patients experiencing hip fractures was not necessary in Taiwan, but it should be considered in high-risk populations

Nanoscaled biphasic calcium phosphate modulates osteogenesis and attenuates LPS-induced inflammation

Micron-scale structure biphasic calcium phosphate (BCP) materials have demonstrated promising clinical outcomes in the field of bone tissue repair. However, research on biphasic calcium phosphate materials at the nanoscale level remains limited. In this study, we synthesize granular-shaped biphasic calcium phosphate nanomaterials with multiple desirable characteristics, including negatively charged surfaces, non-cytotoxicity, and the capability to penetrate cells, using a nanogrinding dispersion process with a polymeric carboxylic acid as the dispersant. Our results reveal that treating human osteoblasts with 0.5 μg/mL biphasic calcium phosphate nanomaterials results in a marked increase in alkaline phosphatase (ALP) activity and the upregulation of osteogenesis-related genes. Furthermore, these biphasic calcium phosphate nanomaterials exhibit immunomodulatory properties. Treatment of THP-1-derived macrophages with BCP nanomaterials decreases the expression of various inflammatory genes. Biphasic calcium phosphate nanomaterials also mitigate the elevated inflammatory gene expression and protein production triggered by lipopolysaccharide (LPS) exposure in THP-1-derived macrophages. Notably, we observe that biphasic calcium phosphate nanomaterials have the capacity to reverse the detrimental effects of LPS-stimulated macrophage-conditioned medium on osteoblastic activity and mineralization. These findings underscore the potential utility of biphasic calcium phosphate nanomaterials in clinical settings for the repair and regeneration of bone tissue. In conclusion, this study highlights the material properties and positive effects of biphasic calcium phosphate nanomaterials on osteogenesis and immune regulation, opening a promising avenue for further research on inflammatory osteolysis in patients undergoing clinical surgery

Mediating role of resilience in the relationships of physical activity and mindful self-awareness with peace of mind among college students

Abstract Peace of mind (PoM) is an index of mental health in Asian culture and emphasizes low arousal, happiness, harmony, and an internal state of peacefulness. While previous studies have found that mindful self-awareness can contribute to PoM, regular physical activity (PA) is also an important factor contributing to one’s PoM due to its function in promoting one's resilience. The study aims to investigate a hypothetical model that assumes PA is associated with resilience while controlling for mindful self-awareness, contributing to PoM. The PoM scale, Connor-Davidson Resilience Scale, Chinese translation of Mindful Attention Awareness Scale, and PA self-report questionnaire were used. A path analysis was applied to test the association between these variables and the mediating role of resilience. A total of 436 students from a university in Taiwan were recruited; the mean age was 20.87, with 46.3% female and 73.6% engaging in over 150 min/week of moderate PA. Gender and age negatively correlated with PA. After controlling for age and gender, there was no direct effect of physical activity on PoM; both mindful self-awareness and PA predict resilience, which in turn predicts PoM, suggesting that both cognitive (i.e., mindful self-awareness) and PA are important to cultivate resilience and thus PoM

Comparative Risk of Cardiovascular Outcomes Between Topical and Oral Nonselective NSAIDs in Taiwanese Patients With Rheumatoid Arthritis

Background: Topical NSAIDs have less systemic absorption than oral NSAIDs. We examined the risk of cardiovascular events associated with nonselective topical NSAIDs versus oral NSAIDs among patients with rheumatoid arthritis in Taiwan. Methods and Results: We conducted a retrospective cohort study that included patients with incident rheumatoid arthritis who were newly starting therapy with nonselective topical NSAIDs or oral NSAIDs. We used the Taiwan National Health Insurance Research Database (NHIRD). The first date patients received either type of NSAID was defined as the index date. NSAID exposures continued until there was a treatment gap of >30 days. The main outcome was composite cardiovascular events, including myocardial infarction, unstable angina, heart failure, stroke, or revascularization. Follow‐up was censored at treatment discontinuation, switch or addition of other NSAID category, cardiovascular outcome, death, or the end of the study. Propensity score weighted Cox regression models were used to compare the risk of cardiovascular events between topical NSAIDs and oral NSAIDs. There were 10 758 and 78 056 treatment episodes for topical and oral NSAIDs identified. After weighting by propensity score, the cohorts were well balanced over all covariates. The crude cardiovascular event rate was 1.87 per 100 person‐years for topical NSAIDs and 2.14 per 100 person‐years for oral NSAIDs. Results of propensity score weighted Cox regression found the topical NSAID group had 36% lower risk for cardiovascular events compared with the oral NSAID group (hazard ratio, 0.64; 95% confidence interval, 0.43–0.95). Conclusions: We found topical NSAID users experienced a reduced risk of cardiovascular events compared with oral NSAID users. If future studies with a larger sample size and longer follow‐up confirm these results, NSAID prescribing might change accordingly

High-level expression and molecular characterization of a recombinant prolidase from Escherichia coli NovaBlue

Long-term use of organophosphorus (OP) compounds has become an increasing global problem and a major threat to sustainability and human health. Prolidase is a proline-specific metallopeptidase that can offer an efficient option for the degradation of OP compounds. In this study, a full-length gene from Escherichia coli NovaBlue encoding a prolidase (EcPepQ) was amplified and cloned into the commercially-available vector pQE-30 to yield pQE-EcPepQ. The overexpressed enzyme was purified from the cell-free extract of isopropyl thio-β-D-galactoside IPTG-induced E. coli M15 (pQE-EcPepQ) cells by nickel-chelate chromatography. The molecular mass of EcPepQ was determined to be about 57 kDa by 12% sodium dodecyl sulfate–polyacrylamide gel electrophoresis and the result of size-exclusion chromatography demonstrated that the enzyme was mainly present in 25 mM Tris–HCl buffer (pH 8.0) as a dimeric form. The optimal conditions for EcPepQ activity were 60 °C, pH 8.0, and 0.1 mM Mn2+ ion. Kinetic analysis with Ala-Pro as the substrate showed that the Km and kcat values of EcPepQ were 8.8 mM and 926.5 ± 2.0 s−1, respectively. The thermal unfolding of EcPepQ followed a two-state process with one well-defined unfolding transition of 64.2 °C. Analysis of guanidine hydrochloride (GdnHCl)-induced denaturation by tryptophan emission fluorescence spectroscopy revealed that the enzyme had a [GdnHCl]0.5,N-U value of 1.98 M. The purified enzyme also exhibited some degree of tolerance to various water/organic co-solvents. Isopropanol and tetrahydrofuran were very detrimental to the enzymatic activity of EcPepQ; however, other more hydrophilic co-solvents, such as formamide, methanol, and ethylene glycol, were better tolerated. Eventually, the non-negative influence of some co-solvents on both catalytic activity and structural stability of EcPepQ allows to adjust the reaction conditions more suitable for EcPepQ-catalyzed bioprocess

Associations of obesity and malnutrition with cardiac remodeling and cardiovascular outcomes in Asian adults:A cohort study

BackgroundObesity, a known risk factor for cardiovascular disease and heart failure (HF), is associated with adverse cardiac remodeling in the general population. Little is known about how nutritional status modifies the relationship between obesity and outcomes. We aimed to investigate the association of obesity and nutritional status with clinical characteristics, echocardiographic changes, and clinical outcomes in the general community.Methods and findingsWe examined 5,300 consecutive asymptomatic Asian participants who were prospectively recruited in a cardiovascular health screening program (mean age 49.6 ± 11.4 years, 64.8% male) between June 2009 to December 2012. Clinical and echocardiographic characteristics were described in participants, stratified by combined subgroups of obesity and nutritional status. Obesity was indexed by body mass index (BMI) (low, ≤25 kg/m2 [lean]; high, >25 kg/m2 [obese]) (WHO-recommended Asian cutoffs). Nutritional status was defined primarily by serum albumin (SA) concentration (low, ConclusionsIn our cohort study among asymptomatic community-based adults in Taiwan, we found that obese individuals with poor nutritional status have the highest comorbidity burden, the most adverse cardiac remodeling, and the least favorable composite outcome

Anti-Photoaging Effects of Soy Isoflavone Extract (Aglycone and Acetylglucoside Form) from Soybean Cake

Soy isoflavones, found in soybean and soybean products, have been reported to possess many physiological activities such as antioxidant activity, inhibition of cancer cell proliferation, reduction of cardiovascular risk, prevention of osteoporosis and alleviation of postmenopausal syndrome. In our previous study, soy isoflavone extract ISO-1 (containing 12 soy isoflavones) from soybean cake was demonstrated to prevent skin damage caused by UVB exposure. In this study, soy isoflavone extract from soybean cake was further purified and evaluated for the protective effects on UVB-induced damage. The results revealed that Fraction 3, which contains the aglycone group (daidzein, genistein and glycitein) and acetylglucoside group (acetyldaidzin, acetylgenistin and acetylglycitin) of soy isoflavones, could inhibit UVB-induced death of human keratinocytes and reduce the level of desquamation, transepidermal water loss (TEWL), erythema and epidermal thickness in mouse skin. Furthermore, topical application of Fraction 3 increased the activity of catalase and suppressed cyclooxygenase-2 (COX-2) and proliferating cell nuclear antigen (PCNA) expression in mice exposed to UVB. In addition, in comparison with ISO-1 and genistein, the Fraction 3 possessed much greater protective effects on both UVB-induced oxidative stress and keratinocyte death than other fractions. Therefore, the soy isoflavone extract Fraction 3 from soybean cake is a desirable anti-photoaging agent for skin care