Chuthamanee Suthisisang

Andrographis paniculata in the symptomatic treatment of uncomplicated upper respiratory tract infection: systematic review of randomized controlled trials.

Objective:  To assess the efficacy of Andrographis paniculata in the symptomatic treatment of uncomplicated upper respiratory tract infection.

Study of anti-inflammatory activities of the pure compounds from Andrographis paniculata (burm.f.) Nees and their effects on gene expression.

In inflammation, the responses to noxious stimuli are controlled by the highly modulated interactions between various immune cells and chemical mediators. The purpose of this study is to evaluate and compare the anti-inflammatory effect of diterpenoids isolated from Andrographis paniculata, including dehydroandrographolide (AP1), andrographolide (AP2) and neoandrographolide (AP3), on the production of inflammatory cytokines and COX activities. Furthermore, the alteration of gene expression involved in this activity was investigated in the most potent compound to elucidate the other possible molecular mechanisms. AP1 (30.1 μM; 10 μg/ml) and AP2 (28.5 μM; 10 μg/ml) markedly inhibited COX-1 in ionophore A23187-induced human platelets. AP2 (28.5 μM) and AP3 (20.8 μM; 10 μg/ml) strongly suppressed the LPS-stimulated COX-2 activity in human blood. In addition, AP2 modulated the level of LPS-induced TNF-α, IL-6, IL-1β and IL-10 secretion in human blood in a concentration-dependent manner. The results revealed that AP2 exhibited the highest efficacy. Therefore, changes in the levels of mRNA transcripts by AP2 were further measured using human cDNA microarrays. The molecular response to AP2 was complex and mediated by various processes. Among the altered gene expressions, the genes involved in immune and inflammation processes were selectively down-regulated, such as cytokines and cytokine receptors (TNFSF14, TNF, TNFRSF6, and IL1A), chemokines (CCL8 and CXCL11), JAK/STAT signaling (JAK3 and STAT5A), TLRs family (TLR4 and TLR8) and NF-κB (NFKB1). Expression of some genes was validated using RT-PCR. The results demonstrated that AP1, AP2 and AP3 exhibited the anti-inflammatory effect by interfering COX and inflammatory cytokines and the underlying mechanisms of AP2 may be related to down-expression of genes involved in inflammatory cascade.

Meta-analysis of the effect of herbal supplement on glycemic control in type 2 diabetes

ETHNOPHARMACOLOGICAL RELEVANCE A variety of herbs has been used in traditional medicine for the treatment of diabetes. However, evidence is limited regarding the efficacy of individual herbs for glycemic control. We performed a systematic review and meta-analysis to evaluate the effect of herbal supplement on glycemic control in type 2 diabetes. MATERIALS AND METHODS Randomized controlled trials were identified through electronic searches (MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials) up until February 2011, historical searches of relevant articles and personal contact with experts in the area. Studies were included in the meta-analysis if they were (1) randomized placebo-controlled trial of single herb aimed at assessing glycemic control in type 2 diabetes, (2) of at least 8 weeks duration, and (3) reporting HbA(1c). Treatment effect was estimated with mean difference in the final value of HbA(1c) and FBG between the treatment and the placebo groups. RESULTS Nine randomized, placebo-controlled trials (n = 487 patients) were identified. Ipomoea batatas, Silybum marianum and Trigonella foenum-graecum significantly improved glycemic control, whereas Cinnamomum cassia did not. The pooled mean differences in HbA(1c) were -0.30% (95% CI -0.04% to -0.57%; P = 0.02), -1.92% (95% CI -0.51% to -3.32%; P = 0.008), and -1.13% (95% CI -0.11% to -2.14%; P = 0.03), respectively, for Ipomoea batatas, Silybum marianum, and Trigonella foenum-graecum. The corresponding values for FBG were -10.20mg/dL (95% CI -5.32 mg/dL to -15.08 mg/dL; P<0.0001) and -38.05 mg/dL (95% CI -9.54 mg/dL to -66.57 mg/dL; P = 0.009), respectively, for Ipomoea batatas and Silybum marianum. CONCLUSIONS The current evidence suggests that supplementation with Ipomoea batatas, Silybum marianum, and Trigonella foenum-graecum may improve glycemic control in type 2 diabetes. Such effect was not observed with Cinnamomum cassia. Given the limitations of the available studies and high heterogeneity of the study results for milk thistle and fenugreek, further high quality, large controlled trials using standardized preparation are warranted to better elucidate the effects of these herbs on glycemic control in type 2 diabetes patients.

Meta-analysis of the efficacy and safety of naproxen sodium in the acute treatment of migraine

(Headache 2010;50:808‐818)

Alternative therapies and medical science: designing clinical trials of alternative/complementary medicines--is evidence-based traditional Chinese medicine attainable?

Evidence‐based traditional Chinese medicine is attainable. With good planning and a positive attitude, the remedies used in traditional Chinese medicine (TCM) and Chinese proprietary medicines can be studied at a standard acceptable to modern science. The identification of an active principal should not delay the search for effective remedies from the TCM pharmacopoeia. Herbal mixtures can be validly tested to establish their efficacy. Problems with potential batch‐to‐batch variation can be circumvented by appropriate randomization. Subsequent independent screening and randomization to treatment and placebo arms can allow for the individualization of treatments by TCM practitioners. However, clearly defined treatments are required and should be recorded in a manner that enables other suitably trained researchers to reproduce them reliably (e.g., using prescriptions in Chinese). Quality control of TCM is a prerequisite of credible clinical trials. Correct natural ingredients must be used without adulteration or erroneous substitution. Evidence of safety in man is essential, and in lieu of data from formal toxicity studies, clear, convincing, and impartial evidence of safety is needed based on their long‐term use in mainstream TCM practice backed up by publications in the Chinese medical/scientific literature.

Paraoxonase 1 status in the Thai population

AbstractHuman serum paraoxonase 1 (PON1), a high-density lipoprotein (HDL)-associated enzyme, has been shown to reduce the oxidation of low-density lipoprotein (LDL) and HDL by degrading lipid peroxides. This property of PON1 accounts for its ability to protect against atherosclerosis. In this study, we identified four polymorphisms in both the coding (L55M and Q192R) and regulatory regions (T-108C and G-909C) of the human PON1 gene in 202 healthy Thai individuals and investigated the influence of these polymorphisms on serum PON1 activity towards three substrates, namely, paraoxon, phenylacetate and diazoxon. The PON1 L55M, Q192R and G-909C polymorphisms significantly affected the variation in serum PON1 activity towards paraoxon. Serum PON1 activity towards paraoxon was significantly different among the genotype groups, as follows: 55LL > 55LM/55MM, 192RR > 192QR > 192QQ and −909CC > −909CG > −909GG. The PON1 Q192R and G-909C polymorphisms also influenced the variation in serum PON1 activity towards diazoxon but in the opposite direction to the activity towards paraoxon. Only the PON1 L55M polymorphism was associated with significant variation in serum PON1 activity towards phenylacetate while the PON1 T-108C polymorphism had no significant effect on serum PON1 activity towards any substrate. We also found linkage disequilibrium among the polymorphic sites, including Q192R versus L55M, Q192R versus T-108C and Q192R versus G-909C. Serum PON1 activity towards both paraoxon and phenylacetate, but not diazoxon, was positively correlated with HDL cholesterol (HDL-C) and apo AI concentrations. None of the PON1 polymorphisms significantly affected serum lipid, lipoprotein or apolipoprotein concentrations. Our findings suggest that the physiological relevance of the PON1 polymorphisms is that they are associated with significant differences in serum PON1 activity, and the impact of PON1 polymorphisms on this activity is substrate-dependent.

Efficacy of Low-Dose Ibuprofen in Acute Migraine Treatment: Systematic Review and Meta-Analysis

Background: Nonsteroidal antiinflammatory drugs such as aspirin and ibuprofen have been shown to be effective in treating migraine. Objective: To evaluate the efficacy of low-dose ibuprofen for treatment of acute migraine attack. Methods: Clinical trials were identified through electronic searches (MEDLINE, EMBASE, EBM review, and the Cochrane Library) up to November 2006 and historical searches of relevant articles. Studies were included if they (1) were double-blind, randomized, placebo-controlled trials that evaluated ibuprofen tablets in moderate or severe migraine attacks in patients greater than 16 years of age, (2) evaluated at least one migraine attack, and (3) reported headache relief, pain-free, sustained pain-free, or relief of other migraine-associated symptoms at 2 hours. The MeSH search terms used were migraine disorders, headache, vascular headache, ibuprofen, adult, and clinical trial. This was followed by a key word search using migraine, cephalalgia, and cephalgia as key words. The reference lists of relevant articles were also scanned to identify possible published trials. There was no language restriction. Two authors extracted data independently. Disagreements were resolved through discussion. Results: Ibuprofen 200 and 400 mg were more effective than placebo in reducing pain intensity and eliminating pain (pain-free) within 2 hours in adults with moderate or severe migraine attacks. For the 200 mg dose, the number needed to treat was 8 (95% CI 5 to 20) for headache relief and 13 (95% CI 8 to 50) for pain-free. The risk ratios for headache relief and pain-free were 1.89 (95% CI 1.45 to 2.46: p < 0.0001) and 2.15 (95% Cl 1.24 to 3.73; p = 0.0063), respectively, for ibuprofen 400 mg. The 24-hour sustained pain-free outcome with ibuprofen was no better than with placebo. Ibuprofen 400 mg increased the chance of relief in photophobia and phonophobia by 30% (95% CI 8 to 57; p < 0.01) and 49% (95% CI 23 to 81; p < 0.0001), respectively. Conclusions: The available evidence suggests that ibuprofen 200 and 400 mg are effective in reducing headache intensity and rendering patients pain-free at 2 hours. Photophobia and phonophobia improved with 400 mg dosing. Due to the limited data and the shortcomings of the available evidence, further studies are needed

The Glucuronidation of R- and S-Lorazepam: Human Liver Microsomal Kinetics, UDP-Glucuronosyltransferase Enzyme Selectivity, and Inhibition by Drugs

The widely used hypnosedative-anxiolytic agent R,S-lorazepam is cleared predominantly by conjugation with glucuronic acid in humans, but the enantioselective glucuronidation of lorazepam has received little attention. The present study characterized the kinetics of the separate R and S enantiomers of lorazepam by human liver microsomes (HLMs) and by a panel of recombinant human UDP-glucuronosyltransferase (UGT) enzymes. Respective mean Km and Vmax values for R- and S-lorazepam glucuronidation by HLM were 29 ± 8.9 and 36 ± 10 µM, and 7.4 ± 1.9 and 10 ± 3.8 pmol/min ⋅ mg. Microsomal intrinsic clearances were not significantly different, suggesting the in vivo clearances of R- and S-lorazepam are likely to be similar. Both R- and S-lorazepam were glucuronidated by UGT2B4, 2B7, and 2B15, whereas R-lorazepam was additionally metabolized by the extrahepatic enzymes UGT1A7 and 1A10. Based on in vitro clearances and consideration of available in vivo and in vitro data, UGT2B15 is likely to play an important role in the glucuronidation of R- and S-lorazepam. However, the possible contribution of other enzymes and the low activities observed in vitro indicate that the lorazepam enantiomers are of limited use as substrate probes for UGT2B15. To identify potential drug-drug interactions, codeine, fluconazole, ketamine, ketoconazole, methadone, morphine, valproic acid, and zidovudine were screened as inhibitors of R- and S-lorazepam glucuronidation by HLM. In vitro–in vivo extrapolation suggested that, of these drugs, only ketoconazole had the potential to inhibit lorazepam clearance to a clinically significant extent.

Efficacy and Safety of Mirtazapine in Fibromyalgia Syndrome Patients: A Randomized Placebo-Controlled Pilot Study

BACKGROUND Data from an open-label trial suggest that mirtazapine might prove useful in treatment of fibromyalgia syndrome (FMS). OBJECTIVE To obtain preliminary efficacy data of mirtazapine for estimation of sample size requirements for a Phase 2 clinical trial in FMS. METHODS This 13-week randomized controlled trial compared the effects of mirtazapine 15 mg/day, mirtazapine 30 mg/day, and placebo in 40 patients with FMS. The primary outcomes were change in Pain Visual Analog Scale (PVAS) and proportion of pain responders (≥30% PVAS reduction). Secondary outcomes included scores from the Jenkins Sleep Scale (JSS), Patient Global Impression of Change (PGIC), Fibromyalgia Impact Questionnaire (FIQ), Hamilton Depression Rating Scale (HAM-D), Patient Global Assessment, and self-reported adverse events. RESULTS Significant within-group PVAS reductions from baseline were observed in all 3 groups, with the greatest improvement in the mirtazapine 30-mg group (p < 0.005); between-group difference was not significant. The proportion of pain responders did not meet significance criteria (66.67% for mirtazapine 30 mg, 50% for mirtazapine 15 mg, 41.67% for placebo). Significant within-group improvement in JSS scores was seen for mirtazapine 30 mg (p < 0.01) and mirtazapine 15 mg (p < 0.05). Between-group comparison achieved significance for JSS item 3, waking several times per night (p < 0.05). On the PGIC, 72.73% felt better with both mirtazapine dosages compared with 50% for placebo. Within-group FIQ responses indicated improvement in only mirtazapine-treated groups, whereas within-group improvement for HAM-D and Patient Global Assessment was observed in all groups. Based on our findings, the sample size requirement (80% power, 5% type I error) should be 83 per group to detect PVAS change difference between mirtazapine 30 mg and placebo. Common mirtazapine-related adverse events were increased appetite and weight gain. CONCLUSIONS Patients with FMS taking mirtazapine exhibited within-group significant improvement in most of the measured outcomes. Between-group analysis was predictably compromised by the small sample size. Mirtazapine was well tolerated. Further study with a larger sample size is likely to be useful.

Beyond symptomatic effects: potential of donepezil as a neuroprotective agent and disease modifier in Alzheimer's disease

Alzheimers disease (AD) is associated with neurodegenerative changes resulting clinically in progressive cognitive and functional deficits. The only therapies are the cholinesterase inhibitors donepezil, galantamine and rivastigmine and the N‐methyl‐D‐aspartate‐receptor antagonist memantine. Donepezil acts primarily on the cholinergic system as a symptomatic treatment, but it also has potential for disease modification and may reduce the rate of progression of AD. This review explores the potential for disease modifying effects of donepezil. Several neuroprotective mechanisms that are independent of cholinesterase inhibition, are suggested. Donepezil has demonstrated a range of effects, including protecting against amyloid β, ischaemia and glutamate toxicity; slowing of progression of hippocampal atrophy; and up‐regulation of nicotinic acetylcholine receptors. Clinically, early and continuous treatment with donepezil is considered to preserve cognitive function more effectively than delayed treatment. The possible neuroprotective effects of donepezil and the potential for disease pathway modification highlight the importance of early diagnosis and treatment initiation in AD.