CT and US findings of a rare case of amoebic liver abscess rupturing into the pericardial cavity

A rare case of amoebic liver abscess that ruptured into the pericardial cavity is reported. This is the first case in the world in which CT scan and ultrasonography were performed in conjunction with each other in demonstrating the fistulous tract. CT scan, ultrasonographic and echocardiographic findings were described in detail. Pericardectomy with surgical drainage and supportive measures led to complete recovery after 37 days of hospitalization.     

Normal Values of High-Resolution Manometry in Supine and Upright Positions in a Thai Population

Digestive Diseases and Sciences - Although cut-off values used in high-resolution manometry (HRM) to diagnose esophageal motility disorders are based on representative samples of the US population...     

Pharmacokinetics and Pharmacodynamics of (+)-Primaquine and (?)-Primaquine Enantiomers in Rhesus Macaques (Macaca mulatta)

Primaquine (PQ) remains the sole available drug to prevent relapse of Plasmodium vivax malaria more than 60 years after licensure. While this drug was administered as a racemic mixture, prior studies suggested a pharmacodynamic advantage based on differential antirelapse activity and/or toxicities of its enantiomers. Oral primaquine enantiomers prepared using a novel, easily scalable method were given for 7 days to healthy rhesus macaques in a dose-rising fashion to evaluate their effects on the blood, liver, and kidneys. The enantiomers were then administered to Plasmodium cynomolgi-infected rhesus macaques at doses of 1.3 and 0.6 mg/kg of body weight/day in combination with chloroquine. The (−)-PQ enantiomer had higher clearance and apparent volume of distribution than did (+)-PQ and was more extensively converted to the carboxy metabolite. There is evidence for differential oxidative stress with a concentration-dependent rise in methemoglobin (MetHgb) with increasing doses of (+)-PQ greater than that seen for (−)-PQ. There was a marked, reversible hepatotoxicity in 2 of 3 animals dosed with (−)-PQ at 4.5 mg/kg. (−)-PQ in combination with chloroquine was successful in preventing P. cynomolgi disease relapse at doses of 0.6 and 1.3 mg/kg/day, while 1 of 2 animals receiving (+)-PQ at 0.6 mg/kg/day relapsed. While (−)-PQ was also associated with hepatotoxicity at higher doses as seen previously, this has not been identified as a clinical concern in humans during >60 years of use. Limited evidence for increased MetHgb generation with the (+) form in the rhesus macaque model suggests that it may be possible to improve the therapeutic window for hematologic toxicity in the clinic by separating primaquine into its enantiomers.     

Fruit and Vegetables Consumption: A Pointer for Cholangiocarcinoma Prevention in Northeast Thailand,the Highest Incidence Area in the World

Cholangiocarcinoma (CCA) caused by opisthorchiasis is a specific public health problem in the Greater Mekong subregional countries. The Northeast Thailand is considered a world's prime area of CCA. Many epidemiological studies found the association between fruit and vegetables consumption and CCA, but their results were inconclusive. Therefore, this meta-analysis aimed to investigate the relationship between fruit and vegetables consumption and CCA prevention in the Northeast Thailand. The authors conducted a comprehensive search of scholarships on MEDLINE, EMBASE, and SCOPUS published during 1990 and 2015. Selected studies about fruit and vegetables consumption and CCA were analyzed. The fixed-effect model was used to estimate pool odds ratios for the consumption vs. nonconsumption. Based on a meta-analysis, consumption of mixed fruit [odds ratio (OR) = 0.79; 95% confidence interval (CI): 0.65–0.96], mixed vegetables (OR = 0.61; 95% CI: 0.50–0.75), and combined fruit and vegetables (OR = 0.68; 95% CI: 0.57–0.80) was associated with the reduction of CCA risk statistically. These findings support that fruit and vegetables consumption is associated with CCA risk reduction. If implemented in a larger geographical area, the study will shed light on possibilities to future reduction of CCA. Educators can replicate the study to solve CCA or other types of cancer and discover the best practice.     

Antibacterial Activity of a Cardanol from Thai Apis mellifera Propolis

Background: Propolis is a sticky, dark brown resinous residue made by bees that is derived from plant resins. It is used to construct and repair the nest, and in addition possesses several diverse bioactivities. Here, propolis from Apis mellifera from Nan province, Thailand, was tested for antibacterial activity against Gram^+ve (Staphylococcus aureus and Paenibacillus larvae) and Gram^-ve (Escherichia coli) bacteria.Materials and methods: The three bacterial isolates were confirmed for species designation by Gram staining and analysis of the partial sequence of 16S rDNA. Propolis was sequentially extracted by methanol, dichloromethane and hexane. The antibacterial activity was determined by agar well diffusion and microbroth dilution assays using streptomycin as a positive control. The most active crude extract was further purified by quick column and adsorption chromatography. The apparent purity of each bioactive fraction was tested by thin layer chromatography. The chemical structure of the isolated bioactive compound was analyzed by nuclear magnetic resonance (NMR).Results: Crude methanol extract of propolis showed the best antibacterial activity with a minimum inhibition concentration (MIC) value of 5 mg/mL for S. aureus and E. coli and 6.25 mg/mL for P. larvae. After quick column chromatography, only three active fractions were inhibitory to the growth of S. aureus and E. coli with MIC values of 6.25 and 31.3 µg/mL, respectively. Further adsorption chromatography yielded one pure bioactive fraction (A1A) with an IC₅₀ value of 0.175 µg/mL for E. coli and 0.683 µg/mL for P. larvae, and was determined to be cardanol by NMR analysis. Scanning and transmission electron microscopy analysis revealed unusual shaped (especially in dividing cells), damaged and dead cells in cardanol-treated E. coli.Conclusion: Thai propolis contains a promising antibacterial agent.     

Topical cream-based oxyresveratrol in the treatment of cutaneous HSV-1 infection in mice

Anti-herpes simplex virus (HSV) activities of oxyresveratrol in vitro and topical administration in cutaneous HSV-1 infection in mice were examined. The inhibitory concentrations for 50% plaque formation (IC₅₀) of oxyresveratrol against HSV-1 clinical isolates and HSV-2 clinical isolates were 20.9-29.5 and 22.2-27.5 μg/ml, respectively. In topical administration in cutaneous HSV-1 infection in mice, 2.5%, 5%, 10% and 20% oxyresveratrol in cream vehicle applied three times daily for 7 days after infection were evaluated and 10% and 20% oxyresveratrol cream were significantly effective in delaying the development of skin lesions and protection from death (P < 0.01). The concentration of 10% oxyresveratrol in cream was significantly more effective than that of 30% oxyresveratrol in vaseline applied three times daily (P < 0.01). Oxyresveratrol cream at 20% was as effective as 5% ACV cream applied three times daily (P < 0.01). Both 10% and 20% oxyresveratrol cream were as effective as that of 5% ACV cream applied two times daily (P > 0.05). Therapeutic efficacy of oxyresveratrol in cream vehicle was dose-dependent and the maximum efficacy observed on day 6 after infection was shown at 10% oxyresveratrol in cream applied three times daily. The frequency of application of 10% oxyresveratrol cream at three, four and five times daily was as effective as that of 5% ACV cream applied five times daily (P > 0.05). These results demonstrated that topical administration of oxyresveratrol in novel cream vehicle reduced the concentration of oxyresveratrol to 10% and was suitable for cutaneous HSV infection.     

Hepatic SEL1L-HRD1 ER-associated degradation regulates systemic iron homeostasis via ceruloplasmin

Iron homeostasis is critical for cellular and organismal function and is tightly regulated to prevent toxicity or anemia due to iron excess or deficiency, respectively. However, subcellular regulatory mechanisms of iron remain largely unexplored. Here, we report that SEL1L-HRD1 protein complex of endoplasmic reticulum (ER)-associated degradation (ERAD) in hepatocytes controls systemic iron homeostasis in a ceruloplasmin (CP)-dependent, and ER stress-independent, manner. Mice with hepatocyte-specific Sel1L deficiency exhibit altered basal iron homeostasis and are sensitized to iron deficiency while resistant to iron overload. Proteomics screening for a factor linking ERAD deficiency to altered iron homeostasis identifies CP, a key ferroxidase involved in systemic iron distribution by catalyzing iron oxidation and efflux from tissues. Indeed, CP is highly unstable and a bona fide substrate of SEL1L-HRD1 ERAD. In the absence of ERAD, CP protein accumulates in the ER and is shunted to refolding, leading to elevated secretion. Providing clinical relevance of these findings, SEL1L-HRD1 ERAD is responsible for the degradation of a subset of disease-causing CP mutants, thereby attenuating their pathogenicity. Together, this study uncovers the role of SEL1L-HRD1 ERAD in systemic iron homeostasis and provides insights into protein misfolding-associated proteotoxicity.

Systemic iron metabolism is tightly regulated for cellular and organismal function. Iron is stored in the hepatocytes and distributed to the peripheral tissues through an intricate process: Ferrous iron (Fe²⁺) is exported from hepatocytes via the iron exporter ferroportin (FPN1) and subsequently oxidized at the plasma membrane by a ferroxidase known as ceruloplasmin (CP) to ferric iron (Fe³⁺) prior to be loaded onto transferrin (TF) in the circulation (1–4). Iron-loaded TF can then be endocytosed by cells via TF receptor 1 (TFR1), while TF receptor 2 (TFR2) on hepatocytes senses blood iron levels to modulate the expression of a key iron-regulating hormone, hepcidin (2, 3). Gain- or loss-of-function of any of the aforementioned factors such as FPN1, CP, TF, hepcidin, and TFR1/2 alters systemic iron metabolism, leading to either toxicity or anemia due to iron excess or deficiency, respectively, in mice and humans (2, 5–7). However, while most of these factors are synthesized in the endoplasmic reticulum (ER) as either membrane or secreted proteins, molecular details underlying their biogenesis in the ER remained largely unexplored.ER-associated degradation (ERAD) is a principal ER quality-control mechanism that targets misfolded ER proteins for cytosolic proteasomal degradation (8, 9). The SEL1L-HRD1 protein complex represents the most evolutionarily conserved ERAD (10–17). Using conditional and cell type-specific Sel1L-deficient mice, we showed that SEL1L is an obligatory cofactor for the E3 ligase HRD1 (18). Subsequent studies from several laboratories have collectively demonstrated a critical physiological and pathological importance of this ERAD complex in various cell types in energy metabolism, food intake, immunity, gut and kidney homeostasis, cartilage development, and quiescence of hematopoietic stem cells (19–33). However, the significance of SEL1L-HRD1 ERAD in iron metabolism remains unknown.In this study, we report the role of hepatocyte-specific SEL1L-HRD1 ERAD in systemic iron homeostasis by regulating the maturation and turnover of CP in the ER. Mice with hepatocyte-specific Sel1L deficiency have altered basal iron homeostasis and altered response to iron deficiency and overload. Mechanistically, SEL1L-HRD1 ERAD mediates the proteasomal degradation of both endogenous and disease mutants of CP proteins, thereby regulating its abundance in the circulation and limiting their pathogenicity, respectively.     

Randomized,Double-Blind,Placebo-Controlled Clinical Trial of a Two-Day Regimen of Dihydroartemisinin-Piperaquine for Malaria Prevention Halted for Concern over Prolonged Corrected QT Interval

Dihydroartemisinin-piperaquine, the current first-line drug for uncomplicated malaria caused by Plasmodium falciparum and Plasmodium vivax in Cambodia, was previously shown to be of benefit as malaria chemoprophylaxis when administered as a monthly 3-day regimen. We sought to evaluate the protective efficacy of a compressed monthly 2-day treatment course in the Royal Cambodian Armed Forces. The safety and efficacy of a monthly 2-day dosing regimen of dihydroartemisinin-piperaquine were evaluated in a two-arm, randomized, double-blind, placebo-controlled cohort study with 2:1 treatment allocation. Healthy military volunteers in areas along the Thai-Cambodian border where there is a high risk of malaria were administered two consecutive daily doses of 180 mg dihydroartemisinin and 1,440 mg piperaquine within 30 min to 3 h of a meal once per month for a planned 4-month period with periodic electrocardiographic and pharmacokinetic assessment. The study was halted after only 6 weeks (69 of 231 projected volunteers enrolled) when four volunteers met a prespecified cardiac safety endpoint of QTcF (Fridericia''s formula for correct QT interval) prolongation of >500 ms. The pharmacodynamic effect on the surface electrocardiogram (ECG) peaked approximately 4 h after piperaquine dosing and lasted 4 to 8 h. Unblinded review by the data safety monitoring board revealed mean QTcF prolongation of 46 ms over placebo at the maximum concentration of drug in serum (C_max) on day 2. Given that dihydroartemisinin-piperaquine is one of the few remaining effective antimalarial agents in Cambodia, compressed 2-day treatment courses of dihydroartemisinin-piperaquine are best avoided until the clinical significance of these findings are more thoroughly evaluated. Because ECG monitoring is often unavailable in areas where malaria is endemic, repolarization risk could be mitigated by using conventional 3-day regimens, fasting, and avoidance of repeated dosing or coadministration with other QT-prolonging medications. (This study has been registered at ClinicalTrials.gov under registration no. {"type":"clinical-trial","attrs":{"text":"NCT01624337","term_id":"NCT01624337"}}NCT01624337.)     

Prevention of renal crystal deposition by an extract of <Emphasis Type="Italic">Ammi visnaga</Emphasis> L. and its constituents khellin and visnagin in hyperoxaluric rats

In Egypt, teas prepared from the fruits of Ammi visnaga L. (syn. “Khella”) are traditionally used by patients with urolithiasis. The aim of this study was to evaluate whether oral administration of an aqueous extract prepared from the fruits of A. visnaga as well as two major constituents khellin and visnagin could prevent crystal deposition in stone-forming rats. Hyperoxaluria was induced in male Sprague-Dawley rats by giving 0.75% ethylene glycol and 1% ammonium chloride via the drinking water. The Khella extract (KE; 125, 250 or 500 mg/kg) was orally administered for 14 days. The histopathological examination of the kidneys revealed that KE significantly reduced the incidence of calcium oxalate (CaOx) crystal deposition. In addition, KE significantly increased urinary excretion of citrate along with a decrease of oxalate excretion. Comparable to the extract, khellin and visnagin significantly reduced the incidence of CaOx deposition in the kidneys. However, both compounds did not affect urinary citrate or oxalate excretion indicating a mechanism of action that differs from that of the extract. For KE, a reasonably good correlation was observed between the incidence of crystal deposition, the increase in citrate excretion and urine pH suggesting a mechanisms that may interfere with citrate reabsorption. In conclusion, our data suggest that KE and its compounds, khellin and visnagin, may be beneficial in the management of kidney stone disease caused by hyperoxaluria but that it is likely that different mechanism of action are involved in mediating these effects.     

Estimated dietary sodium intake in Thailand: A nationwide population survey with 24‐hour urine collections

Thailand has committed to reducing population sodium intake by 30% by 2025. However, reliable nationally representative data are unavailable for monitoring progress toward the goal. We estimated dietary sodium consumption using 24‐hour urinary analyses in a nationally representative, cross‐sectional population‐based survey. We selected 2388 adults (aged ≥ 18 years) from the North, South, North‐east, Central Regions, and Bangkok, using multi‐stage cluster sampling. Mean sodium excretion was inflated by 10% to adjust for non‐urinary sources. Multivariate logistic regression was performed to assess factors associated with sodium consumption ≥ 2000 mg. Among 1599 (67%) who completed urine collection, mean age was 43 years, 53% were female, and 30% had hypertension. Mean dietary sodium intake (mg/day) was 3636 (±1722), highest in South (4108 ± 1677), and lowest in North‐east (3316 ± 1608). Higher sodium consumption was independently associated with younger age (Adjusted Odds Ratio (AOR) 2.81; 95% Confidence interval (CI): 1.53‐5.17; p = .001); higher education (AOR 1.79; 95% CI: 1.19‐2.67; p = .005), BMI ≥ 25 (AOR 1.55; 95% CI: 1.09‐2.21; p=.016), and hypertension (AOR 1.58; 95% CI: 1.02‐2.44; p = .038). Urine potassium excretion was 1221 mg/day with little variation across Regions. Estimated dietary sodium consumption in Thai adults is nearly twice as high as recommended levels. These data provide a benchmark for future monitoring.