Antioxidant Sol-Gel Improves Cutaneous Wound Healing in Streptozotocin-Induced Diabetic Rats

We examined the effects of vitamin C in Pluronic F127 on diabetic wound healing. Full-thickness excision skin wounds were made in normal and diabetic Wistar rats to evaluate the effect of saline, saline plus vitamin C (antioxidant sol), Pluronic F127, or Pluronic F127 plus vitamin C (antioxidant sol-gel). The rate of wound contraction, the levels of epidermal and dermal maturation, collagen synthesis, and apoptosis production in the wound tissue were determined. In vitro data showed that after 6 hours of air exposure, the order of the scavenging abilities for HOCl, H2O2, and O2 - was antioxidant sol-gel > antioxidant saline > Pluronic F127 = saline. After 7 and 14 days of wound injury, the antioxidant sol-gel improved wound healing significantly by accelerated epidermal and dermal maturation, an increase in collagen content, and a decrease in apoptosis formation. However, the wounds of all treatments healed mostly at 3 weeks. Vitamin C in Pluronic F127 hastened cutaneous wound healing by its antioxidant and antiapoptotic mechanisms through a good drug delivery system. This study showed that Pluronic F127 plus vitamin C could potentially be employed as a novel wound-healing enhancer

Antinociceptive actions of honokiol and magnolol on glutamatergic and inflammatory pain

The antinociceptive effects of honokiol and magnolol, two major bioactive constituents of the bark of Magnolia officinalis, were investigated on animal paw licking responses and thermal hyperalgesia induced by glutamate receptor agonists including glutamate, N-methyl-D-aspartate (NMDA), and metabotropic glutamate 5 receptor (mGluR5) activator (RS)-2-chloro-5-hydroxyphenylglycine (CHPG), as well as inflammatory mediators such as substance P and prostaglandin E2 (PGE2) in mice. The actions of honokiol and magnolol on glutamate-induced c-Fos expression in the spinal cord dorsal horn were also examined. Our data showed that honokiol and magnolol blocked glutamate-, substance P- and PGE2-induced inflammatory pain with similar potency and efficacy. Consistently, honokiol and magnolol significantly decreased glutamate-induced c-Fos protein expression in superficial (I-II) laminae of the L4-L5 lumbar dorsal horn. However, honokiol was more selective than magnolol for inhibition of NMDA-induced licking behavioral and thermal hyperalgesia. In contrast, magnolol was more potent to block CHPG-mediated thermal hyperalgesia. These results demonstrate that honokiol and magnolol effectively decreased the inflammatory pain. Furthermore, their different potency on inhibition of nociception provoked by NMDA receptor and mGluR5 activation should be considered

Therapeutic Effect of C-Phycocyanin Extracted from Blue Green Algae in a Rat Model of Acute Lung Injury Induced by Lipopolysaccharide

C-Phycocyanin (CPC), extracted from blue green algae, is a dietary nutritional supplement due to its several beneficial pharmacological effects. This study was conducted to evaluate whether CPC protects against lipopolysaccharide- (LPS-) induced acute lung injury (ALI) in rats. Rats were challenged with LPS (5 mg/kg body weight) intratracheally to induce ALI. After 3 h LPS instillation, rats were administrated with CPC (50 mg/kg body weight, i.p.) for another 3 h. Our results showed that posttreatment with CPC significantly inhibited LPS-induced elevation of protein concentration, nitrite/nitrate level, release of proinflammatory cytokines, the number of total polymorphonuclear cells in bronchoalveolar lavage fluid, and lung edema evidenced by decrease of lung wet/dry weight ratio accompanied by a remarkable improvement of lung histopathological alterations. Furthermore, CPC significantly attenuated LPS-induced myeloperoxidase activity, O2− formation, expression of inducible nitric oxide synthase, and cyclooxygenase-2 as well as nuclear factor-kappa B (NF-κB) activation in lungs. Additionally, CPC significantly downregulated proapoptotic proteins such as caspase-3 and Bax, but upregulated antiapoptotic proteins such as Bcl-2 and Bcl-XL in lungs exposed to LPS. These findings indicate that CPC could be potentially useful for treatment of LPS-related ALI by inhibiting inflammatory responses and apoptosis in lung tissues

Nondiabetic older adults with untreated hypertension in Taiwan: Treatment implication in elderly hypertension

AbstractBackgroundHypertension is common and often left undiagnosed in the elderly. The main purpose of this study was to evaluate the clinical characteristics of nondiabetic hypertensive older adults.MethodsCommunity-living older adults in Taipei City participating in annual health examinations were invited for study. Subjects with diabetes mellitus, whether treated or newly diagnosed, were excluded for further analysis. All participants were classified into three groups: normotension, untreated hypertension (UH), and treated hypertension (TH).ResultsIn total, 3244 subjects (mean age: 73.4±5.4 years, 56.2% males) were enrolled. The prevalence of hypertension, chronic kidney disease (CKD), and left ventricular hypertrophy (LVH) was 52.9% (36.1% TH and 16.8% UH), 20.9%, and 6.2%, respectively. Compared with the normotension group, UH subjects were older (73.8±5.5 years vs. 72.9±5.6 years, p=0.003); having higher body mass index (24.2±3.4kg/m2 vs. 23.6±3.4kg/m2, p=0.001), fasting glucose (101.7±9.1mg/dL vs. 100.5±9.0mg/dL, p=0.007), total cholesterol (TC) (205.0±37.8mg/dL vs. 196.5±36.4mg/dL, p<0.001), triglyceride (TG) (134.5±84.9mg/dL vs. 119.4±77.0mg/dL, p<0.001); and higher prevalence of overt proteinuria (19.3% vs. 13.5%, p=0.001), CKD (21.1% vs. 16.6%, p=0.025), and LVH (8.1% vs. 3.8%, p<0.001). However, the prevalence of overt proteinuria (19.3% vs. 21.1%, p=0.378) and LVH (8.1% vs. 8.5%, p=0.79) between UH and TH groups was similar. Adjusted for age, TC, TG, fasting plasma glucose, and the incidence of LVH, both UH [odds ratio (OR)=1.30, 95% confidence interval (CI)=1.01–1.66, p=0.040] and TH (OR=1.69, 95% CI=1.39–2.05, p<0.001) were significant risk factor for CKD. In addition, independent risk factors for CKD included age (OR=1.07, 95% CI=1.05–1.09, p<0.001), body mass index (OR=1.07, 95% CI=1.04–1.10, p<0.001), TC (OR=1.003, 95% CI=1.001–1.005, p=0.021), TG (OR=1.002, 95% CI=1.001–1.003, p<0.001), and hypertension (TH or UH) (OR=1.44, 95% CI=1.20–1.72, p<0.001).ConclusionIn conclusion, risk of CKD existing along with blood pressure rises among nondiabetic older hypertensive adults, and hypertension (TH or UH) carries a significant risk of CKD after adjustment of other cardiovascular risk factors. Renal protection should be highlighted in the antihypertensive treatment strategy in older hypertensive patients

THE USE OF MANDAMUS TO COMPEL EDUCATIONAL INSTITUTIONS TO CONFER DEGREES

Hispolon is an active phenolic compound of <i>Phellinus igniarius</i>, a mushroom that was recently shown to have antioxidant and anticancer activities in various solid tumors. Here, the molecular mechanisms by which hispolon exerts anticancer effects in acute myeloid leukemia (AML) cells was investigated. The results showed that hispolon suppressed cell proliferation in the various AML cell lines. Furthermore, hispolon effectively induced apoptosis of HL-60 AML cells through caspases-8, -9, and -3 activations and PARP cleavage. Moreover, treatment of HL-60 cells with hispolon induced sustained activation of JNK1/2, and inhibition of JNK by JNK1/2 inhibitor or JNK1/2-specific siRNA significantly abolished the hispolon-induced activation of the caspase-8/-9/-3. In vivo, hispolon significantly reduced tumor growth in mice with HL-60 tumor xenografts. In hispolon-treated tumors, activation of caspase-3 and a decrease in Ki67-positive cells were observed. Our results indicated that hispolon may have the potential to serve as a therapeutic tool to treat AML

Undiagnosed diabetes mellitus among residents in Taiwanese long-term care facilities: A comparison of fasting glucose, postprandial plasma glucose, and hemoglobin A1c

AbstractBackgroundThe prevalence of diabetes mellitus (DM) is escalating with an aging population, and the chances of diabetic older patients admitted to long-term care facilities (LTCFs) are increased because of DM-related complications. However, undiagnosed DM among LTCF residents is a recognized hidden problem in this setting and may result in adverse outcomes.MethodsIn May 2011, 10 private LTCFs in northern Taipei participated in this study. Trained research nurses reviewed the medical records and performed physical examinations and blood sampling for all participants. Diabetes mellitus was diagnosed, based on the levels of fasting glucose, 2-hour postprandial plasma glucose, and hemoglobin A1c (HbA1c). Patients were categorized as having DM if they met the diagnostic cut-offs of the aforementioned criteria.ResultsOne hundred and ninety-nine residents (mean age, 79.6 ± 10.5 years; 52.3% males) participated in this study. They were all moderately/severely disabled (Karnofsky Performance Scale mean score was 50 ± 13). Forty-six (23.1%) residents were diabetic, based on their medical records, or were current users of antidiabetic agents. The prevalence was 29.6% after testing with a mean HbA1c level of 6.9% ± 0.9%. The overall undiagnosed DM rate was 4%, 3.5%, and 4.5%, based on fasting glucose, 2-hour postprandial plasma glucose, and HbA1c criteria, respectively. Diabetic patients had significantly higher serum levels of prealbumin, compared to nondiabetic patients (220.8 ± 45.9 vs. 201.1 ± 62.2 mg/L; p = 0.03), but there were no differences in the levels of hemoglobin, serum albumin, or total cholesterol. Diabetic patients had a significantly higher serum triglyceride level, compared to the nondiabetic patients (1.6 ± 0.7 vs. 1.1 ± 0.5 mmol/L; p < 0.01) and a lower high-density lipoprotein level (1.0 ± 0.3 vs. 1.2 ± 0.3 mmol/L; p < 0.01). Among 43 pharmacologically treated diabetic patients, 65.1% (28/43) of patients were using oral antidiabetic agents and 41.9% (18/43) of patients had been prescribed insulin, whereas 32.6% of the patients were managed by combination therapy.ConclusionThe prevalence of DM among LTCF residents in Taipei was 29.6%, and the undiagnosed rate was no more than 5%, based on fasting glucose, 2-hour postprandial plasma glucose, or HbA1c. Further study is needed for the optimal treatment strategy of DM in LTCFs

Hesperetin-7,3'-O-dimethylether selectively inhibits phosphodiesterase 4 and effectively suppresses ovalbumin-induced airway hyperresponsiveness with a high therapeutic ratio

<p>Abstract</p> <p>Background</p> <p>Hesperetin was reported to selectively inhibit phosphodiesterase 4 (PDE4). While hesperetin-7,3'-<it>O</it>-dimethylether (HDME) is a synthetic liposoluble hesperetin. Therefore, we were interested in investigating its selectivity on PDE4 and binding ability on high-affinity rolipram-binding sites (HARBs) <it>in vitro</it>, and its effects on ovalbumin-induced airway hyperresponsiveness <it>in vivo</it>, and clarifying its potential for treating asthma and chronic obstructive pulmonary disease (COPD).</p> <p>Methods</p> <p>PDE1~5 activities were measured using a two-step procedure. The binding of HDME on high-affinity rolipram-binding sites was determined by replacing 2 nM [³<it>H</it>]-rolipram. AHR was assessed using the FlexiVent system and barometric plethysmography. Inflammatory cells were counted using a hemocytometer. Cytokines were determined using mouse T helper (Th)1/Th2 cytokine CBA kits, and total immunoglobulin (Ig)E or IgG_2alevels were done using ELISA method. Xylazine (10 mg/kg)/ketamine (70 mg/kg)-induced anesthesia was performed.</p> <p>Results</p> <p>HDME revealed selective phosphodiesterase 4 (PDE4) inhibition with a therapeutic (PDE4_H/PDE4_L) ratio of 35.5 <it>in vitro</it>. <it>In vivo</it>, HDME (3~30 μmol/kg, orally (p.o.)) dose-dependently and significantly attenuated the airway resistance (R_L) and increased lung dynamic compliance (C_dyn), and decreased enhanced pause (P_enh) values induced by methacholine in sensitized and challenged mice. It also significantly suppressed the increases in the numbers of total inflammatory cells, macrophages, lymphocytes, neutrophils, and eosinophils, and levels of cytokines, including interleukin (IL)-2, IL-4, IL-5, interferon-γ, and tumor necrosis factor-α in bronchoalveolar lavage fluid (BALF) of these mice. In addition, HDME (3~30 μmol/kg, p.o.) dose-dependently and significantly suppressed total and ovalbumin-specific immunoglobulin (Ig)E levels in the BALF and serum, and enhanced IgG_2alevel in the serum of these mice.</p> <p>Conclusions</p> <p>HDME exerted anti-inflammatory effects, including suppression of AHR, and reduced expressions of inflammatory cells and cytokines in this murine model, which appears to be suitable for studying the effects of drugs on atypical asthma and COPD, and for screening those on typical asthma. However, HDME did not influnce xylazine/ketamine-induced anesthesia. Thus HDME may have the potential for use in treating typical and atypical asthma, and COPD.</p