Healthcare burden and factors of type 2 diabetes mellitus with Schizophrenia.

This study investigated healthcare utilization and expenditure for patients with type 2 diabetes mellitus and schizophrenia and associated factors. Healthcare utilization (outpatient visits and hospitalization) and expenditure (outpatient, inpatient, and total medical expenditure) between 2002 and 2013 of patients with T2DM with schizophrenia (case group) and without (control group) were examined using the Taiwan National Health Insurance Research Database. (1) The average total numbers of outpatient visits and hospital admissions of the case group were 35.14 outpatient visits and 1.09 hospital admissions significantly higher than those of the control group in the whole study period (based on every 3-year period). Nonpsychiatric outpatient visits and nonpsychiatric hospital admissions were significantly more numerous for the case group. (2) The total outpatient expenditure, total inpatient expenditure, and total medical expenditure of the case group were NT$65,000, NT$170,000, and NT$235,000 significantly higher than those of the control group, respectively. Nonpsychiatric outpatient expenditure was significantly lower for the case group, but the inpatient and total nonpsychiatric medical expenditure were similar between groups. (3) Patients who were elder of low income, with complications, and high diabetes mellitus complication severity index had higher total numbers of outpatient visits and hospitalizations and medical expenditure. (4) Women had a higher number of outpatient visits but a lower number of hospitalization and medical expenditure. Lower non-psychiatric outpatient expenditure despite more visits indicated non-psychiatrist may not understand schizophrenia patients and cannot communicate well with them, leading to neglect of medical evaluation and treatment that should be carried out.

Djulis (Chenopodium formosanum) and Its Bioactive Compounds Protect Human Lung Epithelial A549 Cells from Oxidative Injury Induced by Particulate Matter via Nrf2 Signaling Pathway.

The protective effects of water extracts of djulis (Chenopodium formosanum) (WECF) and their bioactive compounds on particulate matter (PM)-induced oxidative injury in A549 cells via the nuclear factor-erythroid 2-related factor 2 (Nrf2) signaling were investigated. WECF at 50-300 µg/mL protected A549 cells from PM-induced cytotoxicity. The cytoprotection of WECF was associated with decreases in reactive oxygen species (ROS) generation, thiobarbituric acid reactive substances (TBARS) formation, and increases in superoxide dismutase (SOD) activity and glutathione (GSH) contents. WECF increased Nrf2 and heme oxygenase-1 (HO-1) expression in A549 cells exposed to PM. SP600125 (a JNK inhibitor) and U0126 (an ERK inhibitor) attenuated the WECF-induced Nrf2 and HO-1 expression. According to the HPLC-MS/MS analysis, rutin (2219.7 µg/g) and quercetin derivatives (2648.2 µg/g) were the most abundant bioactive compounds present in WECF. Rutin and quercetin ameliorated PM-induced oxidative stress in the cells. Collectively, the bioactive compounds present in WECF can protect A549 cells from PM-induced oxidative injury by upregulating Nrf2 and HO-1 via activation of the ERK and JUN signaling pathways.

The Inhibitory Effects of Djulis (Chenopodium formosanum) and Its Bioactive Compounds on Adipogenesis in 3T3-L1 Adipocytes.

The aim of this study was to provide new insights into the role of the ethanolic extracts of Djulis (Chenopodium formosanum, EECF) and its bioactive compounds in preventing adipogenesis in 3T3-L1 adipocytes. The results demonstrated EECF significantly inhibited oil red O-stained material (OROSM), triglyceride levels and glycerol-3-phosphate dehydrogenase (GPDH) activity in 3T3-L1 adipocytes. The expression of the critical molecules involved in lipid synthesis such as PPARγ, C/EBPα and SREBP-1c was attenuated in EECF-treated cells. According to HPLC-DAD and HPLC-MS/MS analysis, rutin, kaempferol, betanin and another nine compounds were present in EECF. The suppression of lipid accumulation by rutin, kaempferol and betanin occurred by decreasing the gene expression of PPARγ, C/EBPα and SREBP-1c. Taken together, these findings suggest the presence of bioactive compounds in EECF may partly account for the anti-adipogenesis of EECF and EECF is therefore a potentially lipid lowering functional food.

Rimantadine and 2-adamantanamine elicit local anesthesia to cutaneous nociceptive stimuli in a rat model.

The aim of this study was to investigate infiltrative cutaneous anesthesia of 2-adamantanamine and rimantadine. After subcutaneous injections of drugs in rats, the blockade of cutaneous trunci muscle reflex by 2-adamantanamine and rimantadine was evaluated. Lidocaine, a common local anesthetic, was used as control. We showed that rimantadine and 2-adamantanamine as well as the local anesthetic lidocaine produced infiltrative anesthesia of skin in a dose-dependent fashion. Saline (vehicle) group displayed no cutaneous anesthesia. The relative potency of these drugs was rimantadine [23.8 (21.1-26.8)] = lidocaine [26.4 (22.7-30.6)] > 2-adamantanamine [64.6 (55.0-75.9)] (P < 0.01). On an equianesthetic basis [25% effective dose (ED25 ), ED50 , and ED75 ], rimantadine and 2-adamantanamine had longer duration of action than lidocaine (P < 0.05). Neither local injection of saline nor intraperitoneal administration of a large dose of drugs elicited cutaneous anesthesia (data not shown). These data demonstrated for the first time that rimantadine had a similar potent and longer duration of skin infiltrative anesthesia than did lidocaine, whereas 2-adamantanamine had a less potency but longer duration of cutaneous anesthesia than did lidocaine.

Protective effects of sweet orange (Citrus sinensis) peel and their bioactive compounds on oxidative stress.

Protective effects of sweet orange (Citrus sinensis) peel and their bioactive compounds on oxidative stress were investigated. According to HPLC-DAD and HPLC-MS/MS analysis, hesperidin (HD), hesperetin (HT), nobiletin (NT), and tangeretin (TT) were present in water extracts of sweet orange peel (WESP). The cytotoxic effect in 0.2mM t-BHP-induced HepG2 cells was inhibited by WESP and their bioactive compounds. The protective effect of WESP and their bioactive compounds in 0.2mM t-BHP-induced HepG2 cells may be associated with positive regulation of GSH levels and antioxidant enzymes, decrease in ROS formation and TBARS generation, increase in the mitochondria membrane potential and Bcl-2/Bax ratio, as well as decrease in caspase-3 activation. Overall, WESP displayed a significant cytoprotective effect against oxidative stress, which may be most likely because of the phenolics-related bioactive compounds in WESP, leading to maintenance of the normal redox status of cells.

Retinal artery occlusion and the 3-year risk of stroke in Taiwan: a nationwide population-based study.

PURPOSE: To verify the association between retinal artery occlusion (RAO) and stroke with a large-scale nationwide study. DESIGN: Retrospective nationwide population-based administrative database study. METHODS: Data were collected from the Longitudinal Health Insurance Database 2000 (LHID2000), which contains claim data from 1 million randomly selected beneficiaries among Taiwan's 23 million residents. The study cohort consisted of all patients with a diagnosis of RAO from January 1999 through December 2006 (n = 464). The control group consisted of randomly selected patients (n = 2748) matched with the study group by age, sex, date of index medical care, and comorbid hypertension. Patients were tracked from their index date for 3 years. The Kaplan-Meier method was used to compute the stroke-free survival rate. Cox proportional hazard regressions were used to compute the adjusted stroke-free survival rate after adjusting for possible confounding factors. RESULTS: Ninety-one RAO patients (19.61%) and 280 controls (10.05%) had a stroke (P < .0001) during the 3-year follow-up period. Compared with the controls, the incidence rate ratios of stroke in RAO patients were 9.46 at 0-1 month, 5.57 at 1-6 months, and 2.16 at 0-3 years after RAO (P < .0001). After adjusting for age, sex, and selected comorbid disorders, the hazard ratio of having a stroke for RAO patients was still 2.07 times higher than that of controls and 3.34 times higher in the ≤60-year-old subgroup. CONCLUSIONS: RAO increases the risk for subsequent stroke. Early neurologic evaluation and secondary prevention for stroke are recommended for RAO patients.

Spinal anesthesia with diphenhydramine and pheniramine in rats.

The aim of this study was to evaluate the local anesthetic effects of pheniramine and diphenhydramine, two histamine H1 receptor antagonists, on spinal anesthesia and their comparison with lidocaine, a commonly used local anesthetic. After rats were injected intrathecally with diphenhydramine and pheniramine, the dose-response curves were obtained. The potency and duration of diphenhydramine and pheniramine on spinal anesthesia were compared with lidocaine. We showed that diphenhydramine and pheniramine produced dose-dependent spinal blockades in motor function, proprioception, and nociception. On a 50% effective dose (ED50) basis, the rank of potency of drugs was diphenhydramine=pheniramine>lidocaine (p<0.05 for the differences). In equianesthetic doses (ED25, ED50, and ED75), the block duration caused by diphenhydramine was longer than that caused by pheniramine or lidocaine (p<0.01 for the differences). Diphenhydramine, but not pheniramine or lidocaine, elicited longer duration of sensory block than that of motor block at the same dose of 1.75 µmol. These preclinical data reported that diphenhydramine with a more sensory-selective action over motor blockade demonstrated more potent and longer-lasting spinal blockades, compared with pheniramine or lidocaine.

Nutrient deficiencies as a risk factor in Taiwanese patients with postherpetic neuralgia.

Postherpetic neuralgia (PHN) is the most common complication of herpes zoster (HZ). The aim of the present study was to compare the nutritional status of PHN patients with that of healthy controls, and then to identify risk factors for PHN using multivariate multiple logistic regressions. In the present cross-sectional study, we prospectively enrolled fifty PHN patients for at least 3 months and fifty healthy controls. We selected nine circulating nutrients including ionised Ca, Zn, retinol, folic acid, vitamin B12, vitamin C, α-tocopherol, γ-tocopherol and lycopene associated with both immunity and the modulation of neuropathic pain, and measured their concentrations in plasma/serum. Concentrations of ionised Ca, Zn, vitamin C and vitamin B12 were significantly lower in PHN patients than in controls after excluding those patients receiving supplements since the outbreak of HZ. The prevalence of either mild/marginal or severe deficiencies for any of the nine selected circulating nutrients in PHN patients (92 %) was much higher than that in controls (46 %) (P < 0·001). Lower concentrations of vitamin C ( ≤ 45·0 µmol/l), ionised Ca ( ≤ 1·05 mmol/l) and Zn ( ≤ 0·91 g/l) were found to increase independently the risk of PHN using binary variable (dichotomy) analyses with both PHN patients and controls in a multivariate logistic regression analysis. No significant correlations existed between the risks of PHN and the concentrations of retinol, folic acid, vitamin B12, lycopene or α:γ-tocopherol ratios. Thus, lower concentrations of circulating nutrients, namely vitamin C, ionised Ca or Zn, are probably a risk factor in Taiwanese patients with PHN.

Epinephrine, phenylephrine, and methoxamine induce infiltrative anesthesia via alpha1-adrenoceptors in rats.

AIM: To assess whether epinephrine, phenylephrine, and methoxamine act via certain subtypes of adrenoceptors to exert their local anesthetic activity. METHODS: We investigated cutaneous anesthesia from adrenoceptor agonists and/or antagonists in conscious, unanesthetized Sprague-Dawley male rats (weight 200-250 g). Cutaneous anesthesia was evidenced by a block of the cutaneous trunci muscle reflex, which is characterized by reflex movement of the skin over the back produced by twitches of lateral thoracispinal muscles in response to local dorsal cutaneous noxious pinprick. RESULTS: Local infiltration of epinephrine, L-phenylephrine, or methoxamine alone induces cutaneous anesthesia in rats in a dose-dependent way. Epinephrine is found to be 19 and 29 times more potent than those of methoxamine and L-phenylephrine, respectively. The cutaneous anesthesia induced by epinephrine, phenylephrine, or methoxamine can be significantly reduced by alpha(1)-adrenoceptor antagonists (eg, prazosin), alpha1, alpha2-adrenoceptor antagonist, alpha(1A)-adrenoceptor antagonist (eg, 5-methylurapdil), alpha(1B)-adrenoceptor antagonist (eg, chloroethylclonidine), or alpha(1D)-adrenoceptor antagonist (eg, BMY7873). CONCLUSION: Our results indicate that epinephrine, phenylephrine and methoxamine all act mainly via mixed subtypes of alpha(1)-adrenoceptors to induce cutaneous anesthesia in the rat.

Shiunko and acetylshikonin promote reepithelialization, angiogenesis, and granulation tissue formation in wounded skin.

Shiunko is a traditional botanic formula (ointment) used clinically for treating wounded skin. The aim of the present study was to compare the effects of Shiunko and acetylshikonin, and its active ingredient, with those of gentamicin and silver sulfadiazine ointments, two disinfectants for wound healing. Wounds were cut in the backs of Sprague-Dawley rats. Different bacterial inoculations (Pseudomonas aeruginosa and Staphylococcus aureus) and treatments (Shiunko, acetylshikonin, gentamicin, silver sulfadiazine, and vehicle ointments) were used to treat these wounds. We found that rats treated with Shiunko and acetylshikonin on both the sterilized and infected wounds showed higher rates of reepithelialization than those treated with the other ointments (p < 0.05) during a 7-day observation. In the histological study, rats treated with Shiunko and acetylshikonin on both the sterilized and infected wounds showed greater reepithelialization, angiogenesis, and granulation tissue formation than rats treated with the other ointments (p < 0.05) on day 5 after the wounds had been sutured. Differences between rats treated with Shiunko and acetylshikonin ointments were not statistically significant. In conclusion, topically applying Shiunko and acetylshikonin on wounded skin promoted wound healing. Both ointments were effective on sterilized and infected wounds.

The antinociceptive and anti-inflammatory effects of five depot formulations of ketorolac propyl ester in rats.

BACKGROUND: Ketorolac is a potent nonsteroidal anti-inflammatory drug. Recently, a ketorolac prodrug, ketorolac propyl ester, was synthesized in our laboratory. The aim of the study was to evaluate the antinociceptive and anti-inflammatory effects of ketorolac propyl ester in five depot formulations. The vehicles used in these formulations were injectable vegetable oils, i.e., sesame oil, peanut oil, soybean oil, castor oil, and cottonseed oil. The traditional therapentic form of ketorolac tromethamine in saline was used as control. METHODS: Six studies were carried out to test the antinociceptive and anti-inflammatory effects of intramuscular ketorolac tromethamine (in saline) and its propyl ester (in five depot formulations) 240 micromol/kg on Sprague-Dawley rats treated with intraplantar carrageenin. RESULTS: Ketorolac tromethamine (in saline) produced an 8 h duration of action on both antinociception and anti-inflammation, whereas ketorolac propyl ester in five oily vehicles produced 54- to 78-h durations of actions in both antinociception and anti-inflammation. Ketorolac propyl ester in cottonseed oil produced a duration of action of 78h in both antinociception and anti-inflammation. CONCLUSIONS: All five depot formulations of ketorolac propyl ester produced longer durations of antinociceptive and anti-inflammatory effects.