Curcumin-Loaded Hydrophobic Surface-Modified Hydroxyapatite as an Antioxidant for Sarcopenia Prevention.

Oxidative stress and later-induced chronic inflammation have been reported to play an important role on the progression of sarcopenia. Current treatments for sarcopenia are mainly administered to patients whom sarcopenia already developed. However, there has been no promising results shown in therapy. Therefore, the development of therapeutic and preventive strategies against sarcopenia would be necessary. Curcumin is a traditional medicine that possesses anti-inflammatory and antioxidative properties. In the present study, hydroxyapatite was subjected to hydrophobic surface modifications for curcumin loading (Cur-SHAP). It was, subsequently, utilized for delivery to the patient's body via intramuscular injection in order to achieve constant release for more than 2 weeks, preventing the progression of the sarcopenia or even leading to recovery from the early stage of the illness. According to the results of WST-1, LIVE/DEAD, DCFDA, and gene expression assays, Cur-SHAP exhibited good biocompatibility and showed great antioxidant/anti-inflammatory effects through the endocytic pathway. The results of the animal studies showed that the muscle endurance, grip strength, and fat/lean mass ratio were all improved in Cur-SHAP-treated rats from LPS-induced sarcopenia. In summary, we successfully synthesized hydrophobic surface modification hydroxyapatite for curcumin loading (Cur-SHAP) and drug delivery via the IM route. The LPS-induced sarcopenia rats were able to recover from disease after the Cur-SHAP treatment.

The Gopen-Yang Superior Semicircular Canal Dehiscence Questionnaire: development and validation of a clinical questionnaire to assess subjective symptoms in patients undergoing surgical repair of superior semicircular canal dehiscence.

OBJECTIVE: To characterise subjective symptoms in patients undergoing surgical repair of superior semicircular canal dehiscence. METHODS: Questionnaires assessing symptom severity and impact on function and quality of life were administered to patients before superior semicircular canal dehiscence surgery, between June 2011 and March 2016. Questionnaire sections included general quality of life, internal amplified sounds, dizziness and tinnitus, with scores of 0-100 points. RESULTS: Twenty-three patients completed the questionnaire before surgery. Section scores (mean±standard deviation) were: 38.2 ± 25.2 for general quality of life, 52.5 ± 23.9 for internal amplified sounds, 35.1 ± 28.8 for dizziness, 33.3 ± 30.7 for tinnitus, and 39.8 ± 22.2 for the composite score. Cronbach's α statistic averaged 0.93 (range, 0.84-0.97) across section scores, and 0.83 for the composite score. CONCLUSION: The Gopen-Yang Superior Semicircular Canal Dehiscence Questionnaire provides a holistic, patient-centred characterisation of superior semicircular canal dehiscence symptoms. Internal consistency analysis validated the questionnaire and provided a quantitative framework for further optimisation in the clinical setting.

Decreased peritherapeutic VEGF expression could be a predictor of responsiveness to first-line FOLFIRI plus bevacizumab in mCRC patients.

OBJECTIVE: Bevacizumab is the only anti-angiogenic agent approved in first-line therapy for metastatic colorectal cancer (mCRC). Although chemotherapy plus bevacizumab has led to improve outcomes for mCRC patients and is a common choice for first-line treatment of mCRC, previous research has established no prominent biomarker that can help to select patients who may benefit from bevacizumab in order to improve cost-effectiveness and therapeutic outcomes. The aim of this study was to compare pre- and post-therapeutic VEGF immunohistochemical (IHC) expression in mCRC patients treated with FOLFIRI plus bevacizumab to identify its potential role as a predictive biomarker. METHODS: A total of 57 mCRC patients who underwent FOLFIRI combined with bevacizumab chemotherapy as a first-line neoadjuvant regimen were enrolled and clinical outcome data analyzed. RESULTS: Low post-therapeutic VEGF expression (P < 0.001) and decreased peri-therapeutic VEGF expression (P < 0.001) were significantly predictive factors of responders. Furthermore, the 6-month progression-free survival (PFS) rate in mCRC patients with decreased peri-therapeutic VEGF expression was significantly better than the rate for those patients with no peri-therapeutic VEGF expression alterations (P = 0.033). CONCLUSIONS: Decreased peri-therapeutic VEGF expression in mCRC patients could probably be used to predict responsiveness to bevacizumab and subsequent PFS in clinical practice.

Integration of independent component analysis with near-infrared spectroscopy for analysis of bioactive components in the medicinal plant Gentiana scabra Bunge.

Independent component (IC) analysis was applied to near-infrared spectroscopy for analysis of gentiopicroside and swertiamarin; the two bioactive components of Gentiana scabra Bunge. ICs that are highly correlated with the two bioactive components were selected for the analysis of tissue cultures, shoots and roots, which were found to distribute in three different positions within the domain [two-dimensional (2D) and 3D] constructed by the ICs. This setup could be used for quantitative determination of respective contents of gentiopicroside and swertiamarin within the plants. For gentiopicroside, the spectral calibration model based on the second derivative spectra produced the best effect in the wavelength ranges of 600-700 nm, 1600-1700 nm, and 2000-2300 nm (correlation coefficient of calibration = 0.847, standard error of calibration = 0.865%, and standard error of validation = 0.909%). For swertiamarin, a spectral calibration model based on the first derivative spectra produced the best effect in the wavelength ranges of 600-800 nm and 2200-2300 nm (correlation coefficient of calibration = 0.948, standard error of calibration = 0.168%, and standard error of validation = 0.216%). Both models showed a satisfactory predictability. This study successfully established qualitative and quantitative correlations for gentiopicroside and swertiamarin with near-infrared spectra, enabling rapid and accurate inspection on the bioactive components of G. scabra Bunge at different growth stages.

Effect of citral, eugenol, nerolidol and alpha-terpineol on the ultrastructural changes of Trichophyton mentagrophytes.

The antifungal effects of citral, eugenol, nerolidol and alpha-terpineol on Trichophyton mentagrophytes were investigated. Citral over 0.1 mg/ml strongly inhibited the hyphal growth of T. mentagrophytes, and the antifungal activity of alpha-terpineol was less effective. The morphological changes of the fungus exposed to the terpenes were observed by electron microscopy. The hyphae were distorted and collapsed at 0.2, 0.4 and 1 mg/ml of eugenol, nerolidol and alpha-terpineol respectively, and cell membrane and organelles were irreversibly damaged at 0.2 mg/ml citral. These suggested that four terpenes possess antifungal activity against T. mentagrophytes, and the activity might lead to irreversible cellular disruption.

Dry deposition study by using dry deposition plate and water surface sampler in Shalu, central Taiwan.

This study presents the chemical composition of dry deposition by using dry deposition plate and water surfaces sampler during daytime and nighttime sampling periods at a near highway traffic sampling site. In addition, the characterization for mass and water soluble species of total suspended particulate (TSP), PM2.5 and PM10 were also studied at this sampling site during August 22 to October 31 of 2006 around central Taiwan. The samples collected were analyzed by using Ion Chromatography (DIONEX 100) for the ionic species analysis. Results of the particulate dry deposition fluxes are higher in the water surfaces sampler than that of the dry deposition plate. In other words, the results also indicated that water surface can absorb more ambient dry deposition inorganic pollutants than that of dry deposition plate in this study. The results obtained in this study indicated that the ionic species of Cl(-), NO3(-) and SO4(2-) occupied about average 60-70% downward flux out of total ionic species for either dry deposition plate or water surfaces sampler during August to October of 2006 at this near highway traffic sampling site.

Stilbazulenyl nitrone decreases oxidative stress and reduces lung injury after hemorrhagic shock/resuscitation and LPS.

Multiorgan failure is a major cause of late morbidity and mortality after trauma. Reactive oxygen species generated during shock/resuscitation contribute to tissue injury by priming the immune system for an exaggerated response to subsequent inflammatory stimuli such as LPS. Stilbazulenyl nitrone (STAZN) is a novel second-generation azulenyl nitrone that has been shown to have potent antioxidant properties in a rat model of brain ischemia. We hypothesized that STAZN may confer protection against lung injury after shock/resuscitation and LPS by reducing oxidative stress and lowering the production of NF-kappaB-dependent pro-inflammatory cytokines. Sprague-Dawley rats were submitted to a two-hit model of lung injury involving hemorrhagic shock/resuscitation and subsequent intratracheal LPS injection, with and without intraperitoneal injections of STAZN. STAZN reduced overall lung injury in response to LPS alone and also after shock/resuscitation plus LPS. STAZN also reduced plasma levels of 8-isoprostane, a proxy measure of oxidative stress, indicating its antioxidant activity in vivo. The effect of STAZN was, at least in part, related to its effect on nuclear translocation of NF-kappaB and generation of the pro-inflammatory cytokine TNF-alpha. Azulenyl nitrones such as STAZN represent a promising novel class of antioxidants for treating organ injury.

Ultrasonographic observation of intestinal mobility of dogs after acupunctural stimulation on acupoints ST-36 and BL-27.

objectives of this study were to observe normal peristalsis and mixing (or segmental movements) and to evaluate an acupuncture stimulation (ST-36 and BL-27) on the intestinal (duodenum) motility in normal dogs using duplex Doppler sonography. Fifteen healthy Beagle dogs were used for this experiment after the administration of warm saline and pellet feeding. The duodenal motility was examined using duplex Doppler sonography. Six hours after the pellet feeding, an electroacupuncture stimulation at ST-36 and BL-27 was applied and the duodenal motility was examined using duplex Doppler sonography pre-stimulation, during the stimulation and post-stimulation. After saline and pellet administration, the duplex Doppler sonograms showed 3 types of peristalsis and a mixing type (or segmental movement) of duodenum motility. In the peristalsis types, most yielded high-amplitude signals which had one high peak (type-1), two high peaks (type-2), and three high peaks (type-3) and lasted more than 1.3 seconds. Mixing type of duodenum motility had weak signals and were lasted more than 1.5 seconds. Among the peristalsis types, the type 1 and type 2 were predominant and the type 3 was rarely observed. The frequency of intestinal motility stimulated by ST-36 acupoint was increased during the acupuncture stimulation (20% increase compared to the basal value) and decreased (7% decrease compared to the basal value) after stimulation. The frequency of intestinal motility stimulated by BL-27 acupoint was decreased during the acupuncture stimulation (31% decrease compared to the basal value) and increased (18% increase compared to the basal value) after stimulation. There was a significant increase between the value found in during and the post-stimulation tests. We conclude that duplex Doppler studies permit a graphic visualization of intestinal movements which can be qualitatively and quantitatively analyzed using this technique, it is possible to evaluate the gastrointestinal motility after an acupuncture

Probing the interaction between inactivation gating and Dd-sotalol block of HERG.

Potassium channels encoded by HERG underlie I:(Kr), a sensitive target for most class III antiarrhythmic drugs, including methanesulfonanilides such as Dd-sotalol. Recently it was shown that these drugs are trapped in the channel as it closes during hyperpolarization. At the same time, HERG channels rapidly open and inactivate when depolarized, and methanesulfonanilide block is known to develop in a use-dependent manner, suggesting a potential role for inactivation in drug binding. However, the role of HERG inactivation in class III drug action is uncertain: pore mutations that remove inactivation reduce block, yet many of these mutations also modify the channel permeation properties and could alter drug affinity through gating-independent mechanisms. In the present study, we identify a definitive role for inactivation gating in Dd-sotalol block of HERG, using interventions complementary to mutagenesis. These interventions (addition of extracellular Cd(2+), removal of extracellular Na(+)) modify the voltage dependence of inactivation but not activation. In normal extracellular solutions, block of HERG current by 300 micromol/L Dd-sotalol reached 80% after a 10-minute period of repetitive depolarization to +20 mV. Maneuvers that impeded steady-state inactivation also reduced Dd-sotalol block of HERG: 100 micromol/L Cd(2+) reduced steady-state block to 55% at +20 mV (P:<0.05); removing extracellular Na(+) reduced block to 44% (P:<0.05). An inactivation-disabling mutation (G628C-S631C) reduced Dd-sotalol block to only 11% (P:<0.05 versus wild type). However, increasing the rate of channel inactivation by depolarizing to +60 mV reduced Dd-sotalol block to 49% (P:<0.05 versus +20 mV), suggesting that the drug does not primarily bind to the inactivated state. Coexpression of MiRP1 with HERG had no effect on inactivation gating and did not modify Dd-sotalol block. We postulate that Dd-sotalol accesses its receptor in the open pore, and the drug-receptor interaction is then stabilized by inactivation. Whereas deactivation traps the bound methanesulfonanilide during hyperpolarization, we propose that HERG inactivation stabilizes the drug-receptor interaction during membrane depolarization.

Medical nutrition therapy lowers serum cholesterol and saves medication costs in men with hypercholesterolemia.

This study was designed to evaluate whether medical nutrition therapy administered by registered dietitians could lead to a beneficial clinical and cost outcome in men with hypercholesterolemia. Ninety-five subjects participating in a cholesterol-lowering drug study took part in an 8-week nutrition intervention program before initiating treatment with a cholesterol-lowering medication, Patient records were reviewed via a retrospective chart review to determine plasma lipid levels at the beginning and end of the program and the number and length of sessions with a dietitian. Complete information was available for 74 subjects aged 60.8 n+/- 9.8 years (mean +/- SD). Medical nutrition therapy lowered total serum cholesterol levels 13% (P < .001), low-density lipoprotein cholesterol (LDL-C) 15% (P < .0001), triglyceride 11% (P < .05), and high-density lipoprotein-cholesterol (HDL-C) 4% (P < .05). Total dietitian intervention time was 144 +/- 21 minutes (range = 120 to 180 minutes) in 2.8 +/- 0.7 sessions (range = 2 to 4) during 6.81 +/- 0.7 weeks of medical nutrition therapy (range = 6 to 8 weeks). Analysis of covariance was conducted to examine whether mean change in LDL-C differed by number of dietitian visits. Results showed a marginal difference between the number of dietitian visits and change in LDL-C (f = 2.6, P < .084). However, the magnitude of LDL-C reduction was significantly higher with 4 dietitian visits (180 minutes) than with 2 visits (120 minutes) (21.9% vs 12.1%; P = .027). Lipid drug eligibility was obviated in 34 of 67 (51%) subjects per the National Cholesterol Treatment Program guidelines algorithm. The estimated annualized cost savings from the avoidance of lipid medications was $60,561.68. Therefore, we conclude that 3 or 4 individualized dietitian visits of 50 minutes each over 7 weeks are associated with a significant serum cholesterol reduction and a savings of health care dollars.

Genistein potentiates wild-type and delta F508-CFTR channel activity.

Effects of genistein on wild-type (wt) and delta F508-cystic fibrosis transmembrane conductance regulator (CFTR) were studied in NIH/3T3 cells stably transfected with wt or mutant CFTR cDNA. As measured by I- efflux, half-maximal concentration of agonist (K1/2) for forskolin-dependent activation was greater for delta F508-CFTR than wt-CFTR. Genistein decreased the K1/2 for both forms of the channel and increased the maximal activity of delta F508-CFTR by 3.7-fold. In cell-attached patches, 10 microM forskolin induced minimal delta F508-CFTR activity with characteristic prolonged closed times (estimated time constant, > 30 s). Genistein increased the forskolin-induced macroscopic currents of wt-CFTR and delta F508-CFTR by 3- and 19-fold, respectively. Variance analysis suggested that in the presence of forskolin and genistein the open probabilities (Po) of wt- and delta F508-CFTR were identical. In single-channel studies, at maximal adenosine 3',5'-cyclic monophosphate (cAMP) stimulation, genistein increased the Po of wt-CFTR by prolonging the open time, but, at submaximal cAMP stimulation, the Po was increased by prolonging the open time and shortening the closed time. In excised patches with CFTR channels preactivated in the cell-attached mode, genistein increased ATP-dependent wt- and delta F508-CFTR current about twofold by prolonging the open time. Our results thus suggest that phosphorylation-dependent activation of delta F508-CFTR is defective and that genistein corrects this defect at least in part by binding to the CFTR protein.

Growth hormone response to the hypothalamic somatostatinergic activity in acromegalic patients.

Oral glucose administration suppresses the TRH-induced TSH response by enhancing the hypothalamic somatostatinergic activity (HSA). We assessed the HSA in 13 acromegalic patients by measuring glucose-induced suppression of TRH-stimulated TSH secretion. The HSA showed wide variation with up to 64% suppression. The mean HSA of the patients (25 +/- 6%) did not differ from that in normal young men (19 +/- 4%) in our previous study. Six patients had normal or low HSA, and the other 7 patients had high HSA. The mean TRH-stimulated TSH levels of the patients with normal or low HSA was significantly lower than that of the patients with high HSA (5.13 +/- 0.10 vs. 11.30 +/- 2.80 mU/L). The HSA did not relate to sex, age, tumor size, basal GH levels, the paradoxical responses to TRH and GnRH, octreotide response, or the gsp oncogene. In the combined glucose-TRH test, glucose pretreatment completely suppressed the paradoxical increase in GH level at 30 min in 4 patients. However, it could suppress the paradoxical GH response by only 6-51% in the other 5 patients who also showed the paradoxical response in TRH test. The tumor diameter of patients with good response to the HSA was significantly larger than that of the patients with poor response (31 +/- 5 vs. 14 +/- 2 mm) as was the tumor grade (3.3 +/- 0.3 vs. 1.7 +/- 0.2). This study supports the idea that a reduction of HSA is not a primary cause of acromegaly, and the HSA seems to increase to suppress the autonomous secretion of GH from the pituitary adenomas. HSA as well as the response of tumors to HSA do not determine tumor growth.

Suppression of TRH-stimulated TSH secretion by glucose-induced hypothalamic somatostatin release.

To determine whether the combined glucose-thyrotropin-releasing hormone (TRH) test can be a useful method for the evaluation of the hypothalamic somatostatinergic activity, we investigated whether TRH-induced thyroid stimulating hormone (TSH) secretion can be suppressed by the oral glucose administration that stimulates the hypothalamic somatostatin (SRIH) secretion. Six tests were performed in ten healthy young men. Test 1: 1 ml of normal saline was intravenously administered at 0 min. Test 2: TRH was administered intravenously at 0 min. Test 3: Glucose, 75 g, was administered orally at -60 min. Test 4: Glucose and TRH were administered as above. Test 5: Pyridostigmine (PST), 120 mg, was given orally at -90 min followed by the administration of GH and TRH as above. Basal TSH levels were suppressed slightly, but significantly. In Test 3 compared to those observed in Test 1. The oral glucose administration also significantly suppressed TRH-stimulated TSH response by 27-35% between 40 min and 80 min in Test 4. In contrast, the pretreatment with PST completely reverted the suppressive effect of glucose on TRH-stimulated TSH response in Test 5. These data suggest that the increased hypothalamic SRIH secretion induced by oral glucose administration can suppress TRH-stimulated TSH response in normal men, and the combined glucose-TRH test can be a useful method to evaluate the hypothalamic somatostatinergic activity.

Combined pyridostigmine-thyrotrophin-releasing hormone test for the evaluation of hypothalamic somatostatinergic activity in healthy normal men.

Pyridostigmine (PST), a cholinesterase inhibitor, induces a clear growth hormone (GH) release in man by suppression of hypothalamic somatostatin (SRIH). Somatostatin suppresses thyrotrophin (TSH) release in rats and men. Earlier studies showed that the thryotrophin-releasing hormone (TRH)-induced TSH response was not altered by 60-120 mg of PST. We studied whether a larger dose (180 mg) of PST can increase the TSH response to TRH. Six healthy young men were studied with the following six tests: (Test 1) 200 micrograms of TRH i.v.; (Test 2) 180 mg of PST po; (Test 3) three different doses of PST (60, 120, 180 mg) + TRH; (Test 4) 100 micrograms of octreotide (SMS) i.v.; (Test 5) SMS + TRH; (Test 6) PST + SMS + TRH. A large dose of PST (180 mg) significantly augmented GH, TSH and prolactin responses to TRH, while smaller doses of PST (60 and 120 mg) did not significantly increase the responses of GH and TSH. While the increased TRH-induced prolactin response by PST was not suppressed by SMS, the increased responses of GH and TSH were suppressed remarkably by SMS. Most of the subjects noticed a mild to moderate abdominal pain, nausea and muscular fasciculation after the administration of a large dose of PST administration. These data suggest that suppression of hypothalamic SRIH secretion by 180 mg of PST can augment the TSH response to TRH. However, the considerable side effects should be minimized before clinical application of the combined PST-TRH test.

Treatment of infections due to multiresistant Neisseria gonorrhoeae with sulbactam/ampicillin.

Between January and April 1984, 229 of 448 male patients with urethritis at the Choong-Ku Venereal Disease Clinic in Seoul had positive urethral cultures: 66 for penicillinase-producing Neisseria gonorrhoeae (PPNG) and 163 for non-penicillinase-producing N. gonorrhoeae (non-PPNG). Forty-five men with PPNG urethritis were enrolled in a study of the efficacy of treatment with sulbactam/ampicillin plus probenecid. Diagnosis and evaluation of cure were based on culture results. The agar-plate dilution method was used for susceptibility testing, and the chromogenic cephalosporin test was used for detection of beta-lactamases. MICs of various antibiotics for the isolates were high. MICs of sulbactam/ampicillin were 0.25-4 micrograms/ml, with an MIC90 of 4 micrograms/ml, a value 16-fold lower than that for ampicillin alone (MIC90 greater than 32 micrograms/ml). Patients were treated with 1 g of probenecid orally and either one vial of sodium sulbactam/ampicillin or two vials intramuscularly. Each vial contained 0.5 g of sodium sulbactam and 1 g of sodium ampicillin. Patients were followed up for three to five days. All patients but one were cured, and no remarkable adverse reactions were noted. The two regimens of sulbactam/ampicillin were equally effective in the treatment of uncomplicated PPNG in men.