Risk factors predicting intractability in focal epilepsy in children under 3 years of age: A cohort study.

BACKGROUND: Focal onset epilepsy carries a higher risk of intractability than generalized onset epilepsy. Knowledge of the risk factors of intractability will help guide the treatment of children with focal epilepsy. In addition to risk factors present at initial diagnosis, the evolution of clinical and electroencephalographic features may also play a role in predicting intractability. METHODS: A prospective cohort study was done on children aged one month to three years with newly diagnosed focal epilepsy. Initial treatment of carbamazepine was given according to a standard protocol after assessment of clinical manifestations, neurologic and developmental status, EEG, and brain MRI. Depending on response to therapy, subjects may also receive valproic acid or phenobarbitone following the protocol. Follow-up was done in the second week and every month thereafter. At the end of the study period, seizure type was re-assessed and a repeat neurological and developmental examination and EEG was obtained to evaluate the role of clinical and EEG evolution in predicting intractability. RESULTS: Out of 71 subjects, 21 (29.6%) had intractable epilepsy at the end of the study period. Age of onset (p = 0.216) and neurological status (p = 0.052) were not associated with intractable epilepsy. On logistic regression analysis, evolution of seizure type (p < 0.001; RR 56.45; 95%CI 6.56 to 485.85) and evolution of background EEG rhythm (p < 0.001; RR 56.51; 95%CI 2.77 to 1152.16) were significantly associated with intractable epilepsy. CONCLUSIONS: Changes in seizure type and baseline EEG rhythm may predict intractability in children one month to three years of age with focal epilepsy.

Safety and Efficacy of NC120 for Improving Lipid Profile: A Double Blind Randomized Controlled Trial.

BACKGROUND: the use of statin to lower blood cholesterol is often associated with bothersome adverse effects such as myopathy and liver dysfunction. NC120 is herbal lipid lowering drug containing red yeast rice (RYR) extract, guggulipid, and chromium picolinate, and expected to have better safety profile. The aim of this study was to evaluate the efficacy and safety profiles of NC120 in lowering blood lipid. METHODS: this was a double blind randomized clinical trial comparing NC120 with placebo in subjects with hypercholesterolemia. Two capsules of NC120 or placebo were administered twice a day for 28 days. Blood total-cholesterol, LDL-cholesterol, and triglyceride were measured on day-0, day-7, and day-28. Unpaired t-test was used to compare study parameter between groups, and one-way ANOVA was used to compare within group. RESULTS: 25 subjects received NC120 and 24 subjects received placebo. Significant decrease of total cholesterol and LDL-cholesterol were observed since day-7 in NC120 group, while the changes in placebo group were not significant at all time of observation. No significant decrease of triglyceride was observed in NC120 group and in placebo group. Side effects were minor and comparable between the two groups. CONCLUSION: NC120 is effective in reducing total cholesterol and LDL-cholesterol, but not triglyceride. This drug shows a good safety profile, and thus can be considered for patients who can not tolerate statin drugs.

Differential expression of several drug transporter genes in HepG2 and Huh-7 cell lines.

BACKGROUND: Cell culture techniques have many advantages for investigation of drug transport to target organ like liver. HepG2 and Huh-7 are two cell lines available from hepatoma that can be used as a model for hepatic drug transport. The present study is aimed to analyze the expression level of several drug transporter genes in two hepatoma cell lines, HepG2 and Huh-7 and their response to inhibitors. MATERIALS AND METHODS: This is an in vitro study using HepG2 and Huh-7 cells. The expression level of the following drug transporter genes was quantified: P-glycoprotein/multidrug resistance protein 1, Organic Anionic Transporter Protein 1B1 (OATP1B1) and Organic Cationic Transporter-1 (OCT1). Ribonucleic acid was extracted from the cells using Tripure isolation reagent, then gene expression level of the transporters is quantified using Applied Biosystems quantitative reverse transcriptase polymerase chain reaction. Verapamil (P-glycoprotein inhibitor), nelfinavir (OATP1B1 inhibitor), quinidine (OCT1 inhibitor) were used to differentiate the inhibitory properties of these agents to the transporter expressions in HepG2 and Huh-7 cells. RESULTS: Huh-7 shows a higher level of P-glycoprotein, OATP1B1 and OCT1 expressions compared with those of HepG2. Verapamil reduces the expressions of P-glycoprotein in HepG2 and Huh-7; nelfinavir reduces the expression of OATP1B1 in HepG2 and Huh-7; while quinidine reduces the OCT1 gene expressions in HepG2, but not in Huh-7 cells. CONCLUSION: This study indicates that HepG2 might be a more suitable in vitro model than Huh-7 to study drug transport in hepatocytes involving drug transporters.

Effects of Curcumin on Parameters of Myocardial Oxidative Stress and of Mitochondrial Glutathione Turnover in Reoxygenation after 60 Minutes of Hypoxia in Isolated Perfused Working Guinea Pig Hearts.

In cardiovascular surgery ischemia-reperfusion injury is a challenging problem, which needs medical intervention. We investigated the effects of curcumin on cardiac, myocardial, and mitochondrial parameters in perfused isolated working Guinea pig hearts. After preliminary experiments to establish the model, normoxia was set at 30 minutes, hypoxia was set at 60, and subsequent reoxygenation was set at 30 minutes. Curcumin was applied in the perfusion buffer at 0.25 and 0.5 µM concentrations. Cardiac parameters measured were afterload, coronary and aortic flows, and systolic and diastolic pressure. In the myocardium histopathology and AST in the perfusate indicated cell damage after hypoxia and malondialdehyde (MDA) levels increased to 232.5% of controls during reoxygenation. Curcumin protected partially against reoxygenation injury without statistically significant differences between the two dosages. Mitochondrial MDA was also increased in reoxygenation (165% of controls), whereas glutathione was diminished (35.2%) as well as glutathione reductase (29.3%), which was significantly increased again to 62.0% by 0.05 µM curcumin. Glutathione peroxidase (GPx) was strongly increased in hypoxia and even more in reoxygenation (255% of controls). Curcumin partly counteracted this increase and attenuated GPx activity independently in hypoxia and in reoxygenation, 0.25 µM concentration to 150% and 0.5 µM concentration to 200% of normoxic activity.

Co-administration of ritonavir and primaquine decreases plasma concentration of primaquine: single- and multiple-dose study in the rats.

AIM: to explore the effects of ritonavir and primaquine combination given as a single-dose or multiple-dose compared to ritonavir alone on ritonavir plasma concentration in the rats. METHODS: in single-dose study, 30 male Spraque Dawley rats were randomly allocated to receive primaquine 12.5 mg/kgBW or primaquine 12.5 mg/kgBW + ritonavir 10 mg/kgBW or primaquine 12.5 mg/kgBW + ketokonazole 10 mg/kgBW. Ketokonazole was used as positive control for inhibitor of primaquine metabolism. In the multiple-dose study, thirty Spraque Dawley male rats were randomly allocated to receive primaquine 12.5 mg/kgBW/day or primaquine 12.5 mg/kgBW/day + ritonavir 10 mg/kgBW/day or primaquine 12.5 mg/kgBW/day + rifampicin 100 mg/kgBW/day. Rifampicin was used as a positive control for inducer of primaquine metabolism. RESULTS: in the single-dose study, ketokonazole increases the area under the plasma concentration (AUC) of primaquine (h45.8%, p<0.000), while the ritonavir decreases the AUC of primaquine (i64.6%, p<0.000). Multiple-dose study shows that both rifampicin and ritonavir decreases the AUC of primaquine by 60.2% (p<0.000) and 67.7% (p<0.000), respectively. CONCLUSION: concomitant administration of primaquine and ritonavir decreases the AUC of ritonavir. This effect could result in the insufficient concentration of primaquine as anti-relapse therapy in malaria caused by Plasmodium vivax, which might lead to treatment failure with primaquine.

The effect of curcumin on lipid level in patients with acute coronary syndrome.

AIM: to evaluate the effects of curcumin on total cholesterol, LDL cholesterol, HDL cholesterol, and triglyceride in acute coronary syndrome patients. METHODS: this study were conducted at Dr. Cipto Mangunkusumo General Hospital (RSUPN-CM), Persahabatan Hospital, MMC Hospital and Medistra Hospital, Jakarta. The study started from 1 May 2005 to 5 May 2006. Study Design was an interventional study which was a randomized double blind controlled trial to evaluate the effects of curcumin administration at escalating doses (low dose 3 times 15 mg/day, moderate dose 3 times 30 mg/day, and high dose 3 times 60 mg/day) on total cholesterol level, LDL cholesterol level, HDL cholesterol level, and triglyceride level in ACS patients. RESULTS: a 75 ACS patients undergoing randomization participated in randomized controlled trial (RCT). Of the 75 ACS patients participating in that RCT, 67 received care at RSCM, 6 at Persahabatan Hospital, and 2 at MMC Hospital. As many as 63 patients were able to participate in the RCT up to its conclusion. There was no significant difference in age, sex, risk factor of dyslipidemia, DM, smoking, hypertension, CHD history in family, height, body weight and body mass index, waist circumference, systolic blood pressure, diastolic blood pressure in the four groups of patients. This showed that the randomization performed was reasonably good. There was no significant difference in laboratory parameters, such as total cholesterol, LDL cholesterol, HDL cholesterol, and triglyceride, fasting blood glucose, blood glucose 2 hours PP, glyco Hb, triglyceride, Hb, Ht, leukocyte, thrombocyte, ureum, creatinine, SGOT, SGPT, in the four groups. There was no significant difference in types of ACS and locations of ACS in the four groups as well. There was no significant difference in statin medicatios (simvastatin), aspirin ACE inhibitor, and DM medications in the four groups. No patient used tiazolidindion. No significant difference was found in the percentage of compliance in the four groups of patients. The effects of curcumin on total cholesterol level and LDL cholesterol level, there was a trend that the lower the dose of curcumin, the higher the effect of reduction. For HDL cholesterol level, there was also a trend that the lower the dose of curcumin, the higher the effect of increase in HDL cholesterol level. However, for triglyceride the pattern was not the same, and the group of moderate-dose curcumin shoed the minimal effect of increase, followed by the low-dose curcumin and finally the high-dose curcumin that showed the highest effect of increase. CONCLUSION: the administration of low-dose curcumin showed a trend of reduction in total cholesterol level and LDL cholesterol level in ACS patients.