Winai Wananukul

Effects of dynorphin A(1-13) on opiate withdrawal in humans.

Abstract The objectives of the current study were to determine 1) the effects of various doses of dynorphin A (1–13) on opiate withdrawal in humans and 2) the safety of dynorphin at these doses. Opiate dependent subjects who had been stabilized on morphine received a single IV dose of placebo, 150, 500 or 1000μg/kg dynorphin after exhibiting spontaneous withdrawal using a randomized, double-blinded, between-subjects study design. Observer Withdrawal Scores were lower in the 150 and 1000μg/kg groups as compared to placebo (P<0.05) but no significant differences were observed on the observer-rated Wang or Sickness Scales. Significant decreases were also found for self-reported symptoms of nervousness, runny nose, sneezing, and painful joints in the 500μg/kg group. Significant increases in serum prolactin levels were seen after all dynorphin doses; however, these were not dose-related. Dynorphin A (1–13) was well tolerated and safe, with no changes in physiologic parameters. We conclude that dynorphin A (1–13) has a modest effect in reducing mild opiate withdrawal in humans and is well tolerated at doses up to 1000μg/kg.

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.

Pharmacokinetics of mitragynine in man

Background Kratom, known botanically as Mitragyna speciosa (Korth.), is an indigenous tree in Southeast Asia. Kratom is currently easily available worldwide via special shops and the Internet to use as a drug of abuse, opioid alternative, or pain killer. So far, the pharmacokinetics of this plant has been studied only in animals, and there is no such study in humans. The major abundant active alkaloid in Kratom, mitragynine, is one of the promising new chemical substances to be developed as a new drug. The aim of this study was to examine the pharmacokinetics of mitragynine and assess the linearity in pharmacokinetics in chronic users. Methods Since Kratom is illegal in Thailand, studies in healthy subjects would be unethical. We therefore conducted a prospective study by enrolling ten chronic, regular, healthy users. We adjusted the steady state in each subject by giving a known amount of Kratom tea for 7 days before commencement of the experiment. We admitted and gave different oral doses to subjects to confirm linearity in pharmacokinetics. The mitragynine blood concentrations at 17 times points and the urine concentrations during the 24-hour period were collected and measured by liquid chromatography-tandem mass spectrometry method. Results Ten male subjects completed the study without adverse reactions. The median duration of abuse was 1.75 years. We analyzed one subject separately due to the abnormal behavior of blood concentration. From data of nine subjects, the pharmacokinetic parameters established were time to reach the maximum plasma concentration (0.83±0.35 hour), terminal half-life (23.24±16.07 hours), and the apparent volume of distribution (38.04±24.32 L/kg). The urine excretion of unchanged form was 0.14%. The pharmacokinetics were observed to be oral two-compartment model. Conclusion This was the first pharmacokinetic study in humans, which demonstrated linearity and was consistent with the oral two-compartment model with a terminal half-life of about 1 day. The pharmacokinetic linearity and parameters reported are necessary pharmacological information of Kratom, and there is a possibility for it to be developed medically as a pain killer or better opioid substitute in the future.

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.

Survival analysis for respiratory failure in patients with food-borne botulism.

Introduction. Botulism is a rare presynaptic neuromuscular junction disorder caused by potent toxins produced by the anaerobic, spore-forming, Gram-positive bacterium Clostridium botulinum. Food-borne botulism is caused by the ingestion of foods contaminated with botulinum toxin. In March 2006, there was a large outbreak of food-borne botulism associated with the ingestion of home-canned bamboo shoots in Thailand. The survival analyses for respiratory failure in these patients were studied and are reported here. Methods. A prospective observational cohort study was conducted on this outbreak. The primary outcome of interest was the time to respiratory failure. The secondary outcome was the time to weaning off ventilator. The prognostic factors associated with respiratory failure and weaning off ventilator are presented. Results. A total of 91 in-patients with baseline clinical characteristics were included. Most cases first presented with gastrointestinal symptoms followed by neurological symptoms, the most striking of which being difficulty in swallowing. Common clinical features included ptosis, ophthalmoplegia, proximal muscle weakness, pupillary abnormality, and respiratory failure. Forty-two patients developed respiratory failure requiring mechanical ventilation and the median duration on ventilator was 14 days. The median length of hospital stay for all patients was 13.5 days. Difficulty in breathing, moderate to severe ptosis, and dilated and fixed pupils were associated with respiratory failure. Among patients who were on ventilators, a short incubation period and pupillary abnormality were associated with a longer period of mechanical ventilation. All patients had antitoxin injection and there was no mortality in this outbreak. Conclusion. The history of difficult breathing and the findings of moderate to severe ptosis and pupillary abnormality were associated with severe illness and respiratory failure. A long incubation time was associated with a better prognosis. Although botulism is a potentially fatal disease, there was no mortality in this outbreak. All patients had antitoxin injection and good intensive care that resulted in good clinical outcomes.

A mass cyanide poisoning from pickling bamboo shoots

Context. Bamboo shoots contain cyanogenic glycosides named taxiphyllin. Cyanide poisoning from cyanogenic glycosides commonly occurs following ingestion. However, toxicity caused by inhalation of hydrogen cyanide gas (HCN) produced from pickled shoots has never been reported. Objective. To describe cyanide poisoning in eight victims who were exposed to HCN produced in a well containing pickling bamboo shoots. Materials and methods. Due to a series of botched rescue attempts, a total of eight patients entered into a 27 m3 well containing pickled bamboo shoots and immediately lost consciousness. After rescue, two patients developed cardiac arrest, metabolic acidosis and died. Four other patients suffered metabolic acidosis, but recovered after supportive care. The remaining two regained consciousness and recovered soon after the event. Ambient air study and cyanide content of bamboo shoots helped confirm the diagnosis. Results. All patients had high anion gap metabolic acidosis with normal oxygenation. Blood cyanide levels ranged from 2.66 to 3.30 mcg/ml (taken after about 18 h of incident). Ambient air study (21 h after incident) revealed oxygen 20.9%, and sulfur dioxide 19.4 ppm. The instrument was unfortunately not equipped to detect HCN. A simulation study revealed HCN and sulfur dioxide in the ambient air at 10 ppm and 7.5 ppm, respectively. Cyanide content in the bamboo shoots ranged from 39 to 434 mg/kg in the wet shoots. Discussion. This series of patients developed sudden onset of alteration of consciousness and metabolic acidosis upon exposure, and cyanide was confirmed in all victims. The simulation study confirmed the presence of HCN in the ambient air of the well containing bamboo shoots. Conclusion. We have reported mass acute cyanide poisoning with two fatalities. The source of HCN was unusual as it was produced from pickling bamboo shoot.

Metal doped keratin film standard for LA-ICP-MS determination of lead in hair samples

Lead doped keratin film standard was introduced as a new calibration standard for LA-ICP-MS determination of Pb along hair strands. The Pb doped keratin film standard was prepared by precipitation of hair protein solution casting in Pb standard solutions in the presence of trichloroacetic acid as a denaturant solution. Sulfur, which is a major matrix element in hair, was used as an internal standard element to normalize Pb intensity and to correct for variations in ablation efficiency and plasma condition. The method was applied to quantitatively determine Pb distribution along a single human hair strand obtained from workers in a battery manufacturing factory in Thailand who faced risk of Pb exposure. Single hair strands were analyzed along their length by LA-ICP-MS with a fixed spot size of 50 μm. The position of an analyzed hair sample on a strand was converted into time (hair closer to the scalp is newer) on the basis of an average hair growth rate of 0.33 mm per day. The patterns of Pb distribution of each worker in the same battery factory were different suggesting that these workers might either not be involved in the same activities or not work in the same room. This study demonstrated the applicability of LA-ICP-MS for rapid acquisition and tracking Pb concentrations along a single hair strand.

High coverage and safety of influenza A (H1N1) 2009 monovalent vaccination among health care personnel in Thailand

We aimed to report the coverage and safety of the influenza A (H1N1) 2009 monovalent vaccination (Panenza; Sanofi Pasteur, Val de Reuil Cedex, France) among health care personnel (HCP) in a university hospital setting in Thailand. The hospital set up a system to vaccinate HCP and did surveillance of the adverse effects (AEs). During a 4-week period, 6,210 (78.7%) HCP were vaccinated. There were 82 reported nonserious AEs among 32 HCP. The most common AE was fatigue/uncomfortable feeling (24%).

Increasing carbonmonoxide blood levels in Bangkok bus drivers

Abstract In order to study the effects of air pollution in Bangkok, 31 bus drivers were examined and blood was drawn for measurement of carboxyhemoglobin (COHb) prior to and after work. The COHb level before work was 2.19±2.46% (range 0–7.18). It had increased after work to 5.26±2.52% (range 0–10.4) (p