Poisoning from Ingestion of Fungus-Infected Cicada Nymphs: Characteristics and Clinical Outcomes of Patients in Thailand.

The current data regarding poisoning associated with ingestion of fungus-infected cicada nymphs are limited. We performed a retrospective cohort study of patients who ingested fungus-infected cicada nymphs and were referred to the Ramathibodi Poison Center for consultation from June 2010 to June 2022. Thirty-nine patients were included for analysis. Most were men (53.8%). Mean age was 40.2 ± 15.0 years. All nymphs were ingested as a health/food supplement. Thirty-one patients (79.5%) reported gastrointestinal symptoms. Median time from ingestion to symptom onset was 5 h. Twenty-nine patients (74.4%) reported neurological symptoms, including tremor, myoclonus, muscle rigidity, nystagmus/ocular clonus, drowsiness, dysarthria, seizure, and confusion. Some complained of dizziness, urinary retention, and jaw stiffness. Most patients (94.9%) were admitted to the hospital. Median hospital stay was 3 days. Ibotenic acid was detected in the blood and urine samples of one patient. All received supportive care. Four patients developed infectious complications. No deaths occurred. Consuming fungus-infected cicada nymphs may cause poisoning in humans. Gastrointestinal and neurological symptoms were common. Ibotenic acid might be the underlying cause. The main treatment is supportive care and appropriate management of complications. Education of the general public is advocated to prevent the incidence of this type of poisoning.

Lowering of lysophosphatidylcholines in ovariectomized rats by Curcuma comosa.

Decline of ovarian function in menopausal women increases metabolic disease risk. Curcuma comosa extract and its major compound, (3R)-1,7-diphenyl-(4E,6E)-4,6-heptadien-3-ol (DPHD), improved estrogen-deficient ovariectomized (OVX) rat metabolic disturbances. However, information on their effects on metabolites is limited. Here, we investigated the impacts of C. comosa ethanol extract and DPHD on 12-week-old OVX rat metabolic disturbances, emphasizing the less hydrophobic metabolites. Metabolomics analysis of OVX rat serum showed a marked increase compared to sham-operated rat (SHAM) in levels of lysophosphatidylcholines (lysoPCs), particularly lysoPC (18:0) and lysoPC (16:0), and of arachidonic acid (AA), metabolites associated with inflammation. OVX rat elevated lysoPCs and AA levels reverted to SHAM levels following treatments with C. comosa ethanol extract and DPHD. Overall, our studies demonstrate the effect of C. comosa extract in ameliorating the metabolic disturbances caused by ovariectomy, and the elevated levels of bioactive lipid metabolites, lysoPCs and AA, may serve as potential biomarkers of menopausal metabolic disturbances.

Clinical outcomes of empirical high-dose meropenem in critically ill patients with sepsis and septic shock: a randomized controlled trial.

BACKGROUND: Appropriate antimicrobial dosing is challenging because of changes in pharmacokinetics (PK) parameters and an increase in multidrug-resistant (MDR) organisms in critically ill patients. This study aimed to evaluate the effects of an empirical therapy of high-dose versus standard-dose meropenem in sepsis and septic shock patients. METHODS: We performed a prospective randomized open-label study to compare the changes of modified sequential organ failure assessment (mSOFA) score and other clinical outcomes of the high-dose meropenem (2-g infusion over 3 h every 8 h) versus the standard-dose meropenem (1-g infusion over 3 h every 8 h) in sepsis and septic shock patients. Patients' characteristics, clinical and microbiological outcomes, 14 and 28-day mortality, vasopressor- and ventilator-free days, intensive care unit (ICU) and hospital-free days, percent of the time of antibiotic concentrations above the minimum inhibitory concentration (%T>MIC), and safety were assessed. RESULTS: Seventy-eight patients were enrolled. Median delta mSOFA was comparable between two groups (- 1 in the high-dose group vs. - 1 in the standard-dose group; P value = 0.75). There was no difference between the two groups regarding clinical and microbiological cure, 14- and 28-day mortality, vasopressor- and ventilator-free days, and ICU- and hospital-free days. In patients admitted from the emergency department (ED) with a mSOFA score ≥ 7, the high-dose group demonstrated significantly better microbiological cure compared with the standard-dose group (75% (9/12 patients) vs. 20% (2/10 patients); P value = 0.03). Likewise, the high-dose group presented higher microbiological cure rate in patients admitted from ED who had either APACHE II score > 20 (83.3% (10/12) vs. 28.6% (2/7); P value = 0.045) or on mechanical ventilator (87.5% (7/8) vs. 23.1% (3/13); P value = 0.008) than the standard-dose group. Adverse events were comparable between the two groups. CONCLUSIONS: Empirical therapy with the high-dose meropenem presented comparable clinical outcomes to the standard-dose meropenem in sepsis and septic shock patients. Besides, subgroup analysis manifested superior microbiological cure rate in sepsis or septic shock patients admitted from ED. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03344627, registered on November 17, 2017.

Curcuma comosa reduces visceral adipose tissue and improves dyslipidemia in ovariectomized rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Curcuma comosa Roxb. (C. comosa) or Wan chak motluk Zingiberaceae family, is widely used in Thai traditional medicine for treatment of gynecological problems as well as relief of postmenopausal symptoms. Since C. comosa contains phytoestrogen and causes lipid lowering effect by an unknown mechanism, we investigated its effect on adiposity and lipid metabolism in estrogen-deprived rats. MATERIALS AND METHODS: Adult female rats were ovariectomized (OVX) and received daily doses of either a phytoestrogen from C. comosa [(3R)-1,7-diphenyl-(4E,6E)-4,6-heptadien-3-ol; DPHD], C. comosa extract, or estrogen (17ß-estradiol; E2) for 12 weeks. Adipose tissue mass, serum levels of lipids and adipokines were determined. In addition, genes and proteins involved in lipid synthesis and fatty acid oxidation in visceral adipose tissue were analyzed. RESULTS: Ovariectomy for 12 weeks elevated level of serum lipids and increased visceral fat mass and adipocyte size. These alterations were accompanied with the up-regulation of lipogenic mRNA and protein expressions including LXR-α, SREBP1c and their downstream targets. OVX rats showed decrease in proteins involved in fatty acid oxidation including AMPK-α and PPAR-α in adipose tissue, as well as alteration of adipokines; leptin and adiponectin. Treatments with E2, DPHD or C. comosa extract in OVX rats prevented an increase in adiposity, down-regulated lipogenic genes and proteins with marked increases in the protein levels of AMPK-α and PPAR-α. These findings indicated that their lipid lowering effects were mediated via the suppression of lipid synthesis in concert with an increase in fatty acid oxidation. CONCLUSIONS: C. comosa exerts a lipid lowering effect in the estrogen deficient rats through the modulations of lipid synthesis and AMPK-α activity in adipose tissues, supporting the use of this plant for health promotion in the post-menopausal women.

Use of Xylazine in Drug-Facilitated Crimes.

Human xylazine poisoning is uncommon. This report describes the use of xylazine for intentional poisoning with criminal intent. Two incidents occurred within 3 weeks: the first involved one victim, and the second involved two victims. The clinical presentations were brief coma, bradycardia, hypotension, and hyperglycemia. The victims recalled having been given a drink from a stranger in a hospital waiting room before loss of consciousness. In the first case, general drug screening by gas chromatography/mass spectrometry (MS) revealed xylazine in the gastric contents, but liquid chromatography-tandem MS (LC-MS/MS) of serum did not. In the second incident, LC-MS/MS screening of both victims' urine and serum samples revealed an unknown peak in the total ion chromatograms, which a molecular mass database identified as morantel or xylazine. The latter was confirmed by comparison with a xylazine standard. Based on this report, we suggest that xylazine should be classified as a controlled drug.

Serum lipidomics analysis of ovariectomized rats under Curcuma comosa treatment.

ETHNOPHARMACOLOGICAL RELEVANCE: Curcuma comosa Roxb. (C. comosa) or Wan Chak Motluk, Zingiberaceae family, has been used in Thai traditional medicine for the treatment of gynecological problems and inflammation. AIM OF THE STUDY: This study aimed to investigate the therapeutic potential of C. comosa by determining the changes in the lipid profiles in the ovariectomized rats, as a model of estrogen-deficiency-induced hyperlipidemia, after treatment with different components of C. comosa using an untargeted lipidomics approach. MATERIALS AND METHODS: Lipids were extracted from the serum of adult female rats subjected to a sham operation (SHAM; control), ovariectomy (OVX), or OVX with 12-week daily doses of estrogen (17ß-estradiol; E2), (3R)-1,7-diphenyl-(4E,6E)-4,6-heptadien-3-ol (DPHD; a phytoestrogen from C. comosa), powdered C. comosa rhizomes or its crude ethanol extract. They were then analyzed by liquid chromatography-mass spectrometry, characterized, and subjected to the orthogonal projections to latent structures discriminant analysis statistical model to identify tentative biomarkers. RESULTS: Levels of five classes of lipids (ceramide, ceramide-1-phosphate, sphingomyelin, 1-O-alkenyl-lysophosphatidylethanolamine and lysophosphatidylethanolamine) were elevated in the OVX rats compared to those in the SHAM rats, while the monoacylglycerols and triacylglycerols were decreased. The E2 treatment only reversed the levels of ceramides, whereas treatments with DPHD, C. comosa extract or powder returned the levels of all upregulated lipids back to those in the SHAM control rats. CONCLUSIONS: The findings suggest the potential beneficial effects of C. comosa on preventing the increased ceramide levels in OVX rats, a possible cause of metabolic disturbance under estrogen deficiency. Overall, the results demonstrated the power of untargeted lipidomics in discovering disease-relevant biomarkers, as well as evaluating the effectiveness of treatment by C. comosa components (DPHD, extract or powder) as utilized in Thai traditional medicine, and also providing scientific support for its folklore use.

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.