Sming Kaojarern

Association between Inflammatory Marker, Environmental Lead Exposure, and Glutathione S-Transferase Gene

A number of studies suggested that lead is related to the induction of oxidative stress, and alteration of immune response. In addition, modifying these toxic effects varied partly by GST polymorphism. The objectives of this study were to assess the association between the lead-induced alteration in serum hs-CRP, with GSTM1, GSTT1, and GSTP1 Val105Ile genetic variations and the health consequence from environmental lead exposure. The 924 blood samples were analyzed for blood lead, CRP, and genotyping of three genes with real-time PCR. Means of blood lead and serum hs-CRP were 5.45 μg/dL and 2.07 mg/L. Both CRP and systolic blood pressure levels were significantly higher for individuals with blood lead in quartile 4 (6.48–24.63 μg/dL) compared with those in quartile 1 (1.23–3.47 μg/dL, P < 0.01). In particular, in men with blood lead >6.47 μg/dL the adjusted odds ratio (OR) of CRP levels for individuals with GSTP1 variants allele, GSTM1 null, GSTT1 null, double-null GSTM1, and GSTT1 compared with wild-type allele was 1.46 (95% CI; 1.05–2.20), 1.32 (95% CI; 1.03–1.69), 1.65 (95% CI; 1.17–2.35), and 1.98 (95% CI; 1.47–2.55), respectively. Our findings suggested that lead exposure is associated with adverse changes in inflammatory marker and SBP. GST polymorphisms are among the genetic determinants related to lead-induced inflammatory response.

The influence of metabolic gene polymorphisms on urinary 1-hydroxypyrene concentration in Thai bus drivers.

Polycyclic aromatic hydrocarbons (PAHs) are associated with an increased cancer risk. CYP1A1 and GSTs enzymes are important in metabolism of PAHs. Genetic polymorphisms of these enzymes are responsible for enzyme activity and concentration variation. The objectives of this study were to evaluate association of 1-OHP concentration with genetic polymorphisms of CYP1A1 and GSTs in Thai bus drivers. The results showed that 1-OHP levels in bus drivers were significantly higher than that in the control group. Significant difference in 1-OHP was found between smokers and non-smokers, in only bus drivers. Significantly increasing of 1-OHP levels were observed in bus drivers with CYP1A1 MspI and exon 7 variants. Whereas, bus drivers with GSTP1 Val and GSTM1 null genotypes showed decreasing in excretion of 1-OHP. No association between 1-OHP and polymorphisms of GSTT1 was found. This study indicated that 1-OHP concentrations were associated with exposure to air pollution, cigarette smoking and polymorphisms of CYP1A1, GSTM1 and GSTP1 genes.

Non-occupational Lead and Cadmium Exposure and Blood Pressure in Thai Men

In this study, the effects of low level exposure to lead and cadmium on blood pressure among 212 men have been examined. The mean age was 41 years (range 34-53). The means of systolic and diastolic blood pressure were 126 (range 94-159) and 78 (range 58-117) mmHg, respectively. Blood lead concentration ranged from 144.31 to 779.34 ηmol/L with a geometric mean (GM) of 363.11 ηmol/L. Blood cadmium levels ranged from 1.33-37.81ηmol/L with GM of 8.09 ηmol/L. For stepwise regression analysis, an increase in systolic blood pressure was significantly predictive by an increasing blood lead (p<0.001) whereas blood cadmium showed no significant correlation with blood pressure. Body mass index and alcohol consumption also contributed to both systolic and diastolic blood pressure. These findings also supported our proposal concerning the association between blood lead and blood pressure. Asia Pac J Public Health 2004; 16(2): 133-137.

Kratom abuse in Ramathibodi Poison Center, Thailand: a five-year experience.

Abstract Kratom (Mitragyna speciosa Korth), a native tree in Southeast Asia, is misused as an abuse drug and becomes legally widespread to several countries. Currently, it is available through the online market or by some shops. The clinical manifestations of Kratoms effects are not well-defined and the clinical studies are limited. This study was designed to identify the characteristics of Kratom poisoning and withdrawal cases from Kratom exposure cases in Ramathibodi Poison Center (RPC), Thailand, during a five-year period. We used a retrospective review of Kratom exposure cases from the RPC toxic surveillance system. A total of 52 Kratom exposure cases were identified. The trend of case consultations has been increasing. There were Kratom poisoning cases (76.9%) and withdrawal cases (23.1%). Common presenting symptoms in the poisoning group were palpitation (22.5%), followed by seizure (17.5%). For the withdrawal group, the common presenting symptoms were myalgia (33.3%), insomnia (16.67%), fatigue (16.67%), and chest discomfort (16.67%). There was a baby with withdrawal symptoms who was delivered from a chronic Kratom-abusing mother, suggesting possible exposure via the transplacental route. There were no deaths in either group. Kratom abuse can cause either poisoning or withdrawal. Most cases in both groups had good prognostic outcome.

Single oral loading dose of phenytoin: a pharmacokinetics study

In order to determine the optimal single oral loading dose of phenytoin in patients with seizures, a two part study of phenytoin pharmacokinetics was conducted. In the first part, 15 mg/kg of phenytoin was given orally as a single dose to 19 normal medical volunteers with informed consent. Serum concentrations of phenytoin reached the therapeutic level (10 micrograms/ml) with an average of 2.62 +/- 1.25 h. The peak concentrations at 7.26 +/- 4.77 h was 11.95 +/- 2.8 micrograms/ml. The oral loading doses, calculated from a model incorporating a first order of absorption and Michaelis-Menten elimination kinetics to yield the target phenytoin serum concentration of 15 micrograms/ml were 18.7 mg/kg in males and 24.8 mg/kg in females. The larger dose for females is probably required due to the higher total apparent volume of distribution in females than in males. In the second part, seven male and seven female patients with seizures with informed consent received these calculated dosage regimens. For these patients, a single oral loading dose of phenytoin rapidly produced therapeutic concentration (10 micrograms/ml) within an average of 2.04 +/- 0.44 h in males and 2.35 +/- 1.6 h in females with minimal side-effects. For males, the peak concentration at 9.71 +/- 5.94 h was 23.89 +/- 5.46 micrograms/ml and that for females was 21.46 +/- 5.08 micrograms/ml at 7.71 +/- 3.73 h, respectively. Oral loading dose of phenytoin is safe, effective and can be considered in patients who need prompt control of seizures within a few hours, particularly in those areas where medical facilities are limited. It may also replace the intravenous route of phenytoin when the intravenous route is contraindicated.

Comparative Bioavailability of Praziquantel Tablets

Six different brands of 600 mg praziquantel tablets were evaluated. In vitro studies demonstrated that all but one of the products met the British Pharmacopoeia 1980 disintegration time specifications. The comparative bioavailability of four of the internationally available brands of praziquantel tablets were then studied in eight healthy volunteers using a crossover design. Serum praziquantel levels were determined by high-performance liquid chromatography. Individual serum profiles were analyzed for pharmacokinetic parameters such as maximum serum concentration, time to reach maximum, and area under the curve. Following administration of praziquantel 40 mg/kg po, the mean peak serum concentrations and the time to reach the peak ranged from 1.007 to 1.625 μg/ml and from 1.72 to 2.81 hours, respectively. The elimination half-life of praziquantel was 1.15 (0.94–1.25) hours. Differences greater than 20 percent (p < 0.05) were noted for these parameters between the original brand and the generic formulations. The relative bioavailabilities of the generic praziquantel formulations, with respect to the original brand, were 91.25, 80.95, and 69.86 percent. This is due to the failure of disintegration and subsequently poor dissolution. The effect of 30 percent reduction of bioavailability may lead to unacceptably high rates of treatment failure.

Environmental Lead Exposure, Catalase Gene, and Markers of Antioxidant and Oxidative Stress Relation to Hypertension: An Analysis Based on the EGAT Study

Lead has been linked to the development of hypertension via oxidative stress. Catalase plays an important role in the disposal of hydrogen peroxide in erythrocyte and its activity was determined by CAT gene. The aims of this study were to investigate (1) the association between blood levels of antioxidant markers such as catalase, superoxide dismutase, glutathione, glutathione peroxidase, oxidative stress-marker (malondialdehyde), and blood lead level and (2) the influence of genetic polymorphism of CAT gene (rs769217) on change in blood pressure in general population of EGAT study project. This is a cross-sectional study of 332 normotensive, 432 prehypertensive, and 222 hypertensive male subjects. Hypertensive subjects had significantly higher blood lead level (5.28 μg/dL) compared to normotensive (4.41 μg/dL) and prehypertensive (4.55 μg/dL) subjects (P < 0.05). These significant findings are also found in MDA levels. Moreover, individuals with TT genotype in hypertensive group had significantly higher blood lead and MDA levels (6.06 μg/dL and 9.67 μmol/L) than those with CC genotype (5.32 μg/dL and 8.31 μmol/L, P < 0.05). Our findings suggested that decreased blood catalase activity in this polymorphism together with low level lead exposure induced lipid peroxidation may be responsible for hypertension.

Genetic Variations of Glutathione S-Transferase Influence on Blood Cadmium Concentration

The glutathione S-transferases (GSTs) are involved in biotransformation and detoxification of cadmium (Cd). Genetic polymorphisms in these genes may lead to interindividual variation in Cd susceptibility. The objective of this study was to assess the association of GSTs (GSTT1, GSTM1, and GSTP1 Val105Ile) polymorphisms with blood Cd concentrations in a nonoccupationally exposed population. The 370 blood samples were analyzed for Cd concentration and polymorphisms in GSTs genes. Geometric mean of blood Cd among this population was 0.46 ± 0.02 μg/L (with 95% CI; 0.43–0.49 μg/L). Blood Cd concentrations in subjects carrying GSTP1 Val/Val genotype were significantly higher than those with Ile/Ile and Ile/Val genotypes. No significant differences in blood Cd concentrations among individual with gene deletions of GSTT1 and GSTM1 were observed. GSTP1/GSTT1 and GSTP1/GSTM1 combinations showed significantly associated with increase in blood Cd levels. This study indicated that polymorphisms of GSTP1 combined with GSTT1 and/or GSTM1 deletion are likely to influence on individual susceptibility to cadmium toxicity.

Biochemical, Environmental, and Genetic Factors Associated with Paraoxonase (PON1) Activity

Paraoxonase (PON1, EC 3.1.8.1) is tightly linked to high-density lipoprotein (HDL) and shows significant correlation with apo AI concentrations. It plays an important role in functions such as protection against vascular disease (e.g., atherosclerosis) through its inhibition of low-density lipoprotein (LDL) oxidation and detoxification of organophosphorus compounds by hydrolyzing the bioactive oxons (Mackness et al. 1991). The activity of PON1 is modulated by genetic and environmental factors. Two coding region polymorphisms of the PON1 gene result in amino acid substitutions at position 192 (PON1 Q192R, glutamine to arginine) and at position 55 (PON1 L55 M, leucine to methionine). PON1 Q192R has been reported to account for 73–76% of the variation in hydrolysis activity of paraoxon (paraoxonase activity) and 12–25% of the variation in activity for the hydrolysis of diazoxon (diazonase activity) in vitro (Jarvik et al. 2000). The L55 M polymorphism also contributes to PON1 protein stability and activity (Leviev et al. 2001). PON1 polymorphisms have been studied in many populations of the world; the frequency of the low-activity

Gentamicin Removal during Intermittent Peritoneal Dialysis

Gentamicin removal during intermittent peritoneal dialysis was studied in 13 uremic patients. The peak serum level after 80 mg of gentamicin intravenous drip was 6.00 +/- 1.3 micrograms/ml with a serum half-life of 13.6 +/- 4.07 h. The gentamicin dialysate level did not correlate with the corresponding serum concentration. The peritoneal gentamicin clearance (10.0 +/- 3.65 ml/min) correlated with the rate of protein loss, but not with the peritoneal clearances of urea and creatinine. When 4% glucose dialysate was used, the clearance of the drug increased considerably along with the ultrafiltration rate. Adding gentamicin (5 micrograms/ml) to the dialysate resulted in a sustained serum drug level. The mechanism of gentamicin transport through the peritoneal membrane is discussed. The study demonstrated significant removal of gentamicin during intermittent peritoneal dialysis.