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1.
BMC Endocr Disord ; 24(1): 17, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38297286

RESUMO

BACKGROUND: Hyperuricemia has placed an immense burden on the global healthcare system. Studies have discovered a close correlation between serum uric acid (SUA) and insulin resistance (IR). The objective of this investigation is to examine the association between the triglyceride-glucose (TyG) index, a simple surrogate for IR, and the presence of hyperuricemia. METHODS: Between 2017 and 2021, an epidemiologic study was conducted on Royal Thai Army (RTA) personnel aged 35-60 years, involving a total of 231,286 participants. In the study, hyperuricemia was defined as a SUA level of 7 mg/dL and 6 mg/dL among male and female participants, respectively. Using linear regression analysis and logistic regression analysis, the association between the TyG index and SUA was determined. RESULTS: A positive relationship was demonstrated between the TyG index and the SUA. Overall, SUA increased by 0.32 per unit of TyG index growth (95% CI: 0.31-0.32). In comparison with the first quartile, employees in the fourth TyG quartile had a greater likelihood of having hyperuricemia [adjusted odds ratio (AOR): 2.45, 95% CI: 2.38-2.52]. Effect modification by obesity on the association between the TyG index and SUA was observed (P-interaction < 0.001). Among individuals with obesity, compared with the first TyG index quartile, the AOR for hyperuricemia was 2.15 (95% CI: 2.06-2.25) and 2.14 (95% CI: 1.81-2.53) for the fourth quartile of the TyG index for males and females, respectively. However, for nonobese personnel, in comparison to the top quartile of the TyG index, the AOR for hyperuricemia was 2.73 (95% CI:2.61-2.84) and 5.03 (95% CI: 4.03-6.29) for the fourth quartile of the TyG index for males and females, respectively. Personnel in the fourth TyG index quartile revealed that the prevalence of hyperuricemia reached 44.2%. CONCLUSION: A robust positive association between the TyG index and SUA was illustrated among active-duty RTA personnel. Obesity was identified as a modifier influencing this relationship. Furthermore, individuals in the fourth quarter of the TyG index, regardless of their obesity status, could be considered appropriate candidates for screening SUA levels.


Assuntos
Hiperuricemia , Resistência à Insulina , Militares , Humanos , Masculino , Feminino , Glucose , Hiperuricemia/diagnóstico , Hiperuricemia/epidemiologia , Triglicerídeos , Ácido Úrico , Tailândia/epidemiologia , Estudos Transversais , Obesidade , Fatores de Risco , Glicemia/análise , Biomarcadores
2.
Malar J ; 22(1): 105, 2023 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-36959593

RESUMO

BACKGROUND: New anti-malarial drugs are needed urgently to address the increasing challenges of drug-resistant falciparum malaria. Two rhinacanthin analogues containing a naphthoquinone moiety resembling atovaquone showed promising in-vitro activity against a P. falciparum laboratory reference strain (K1). The anti-malarial activity of these 2 compounds was further evaluated for P. falciparum field isolates from an area of multi-drug resistance in Northeast Thailand. METHODS: Using a pLDH enzyme-linked immunosorbent assay, four P. falciparum isolates from Northeast Thailand in 2018 were tested for in vitro sensitivity to the two synthetic rhinacanthin analogues 1 and 2 as well as established anti-malarials. Mutations in the P. falciparum cytochrome b gene, a marker for atovaquone (ATQ) resistance, were genotyped in all four field isolates as well as 100 other clinical isolates from the same area using PCR-artificial Restriction Fragment Length Polymorphisms. Pfkelch13 mutations, a marker for artemisinin (ART) resistance, were also examined in all isolates. RESULTS: The 50% inhibitory concentrations (IC50) of P. falciparum field isolates for rhinacanthin analogue 1 was 321.9-791.1 nM (median = 403.1 nM). Parasites were more sensitive to analogue 2: IC50 48.6-63.3 nM (median = 52.2 nM). Similar results were obtained against P. falciparum reference laboratory strains 3D7 and W2. The ART-resistant IPC-5202 laboratory strain was more sensitive to these compounds with a median IC50 45.9 and 3.3 nM for rhinacanthin analogues 1 and 2, respectively. The ATQ-resistant C2B laboratory strain showed high-grade resistance towards both compounds (IC50 > 15,000 nM), and there was a strong positive correlation between the IC50 values for these compounds and ATQ (r = 0.83-0.97, P < 0.001). There were no P. falciparum cytochrome b mutations observed in the field isolates, indicating that P. falciparum isolates from this area remained ATQ-sensitive. Pfkelch13 mutations and the ring-stage survival assay confirmed that most isolates were resistant to ART. CONCLUSIONS: Two rhinacanthin analogues showed parasiticidal activity against multi-drug resistant P. falciparum isolates, although less potent than ATQ. Rhinacanthin analogue 2 was more potent than analogue 1, and can be a lead compound for further optimization as an anti-malarial in areas with multidrug resistance.


Assuntos
Antimaláricos , Malária Falciparum , Humanos , Antimaláricos/farmacologia , Antimaláricos/uso terapêutico , Plasmodium falciparum , Atovaquona/uso terapêutico , Tailândia , Citocromos b/genética , Malária Falciparum/parasitologia , Resistência a Medicamentos
3.
BMC Cardiovasc Disord ; 23(1): 183, 2023 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-37020277

RESUMO

BACKGROUND: Cardiovascular diseases (CVD) are the leading causes of death globally, including Thailand. Approximately one-tenth of Thai adults have type 2 diabetes (T2D), a significantly increasing CVD. Our study aimed to determine the trends of predicted 10-year CVD risk among patients with T2D. METHODS: A series of hospital-based cross-sectional studies were conducted in 2014, 2015 and 2018. We included Thai patients with T2D aged 30-74-year-old without a history of CVD. The predicted 10-year risk for CVD was calculated based on Framingham Heart Study equations both with simple office-based nonlaboratory and laboratory-based. Age- and sex-adjusted means and proportions of predicted 10-year risk for CVD were calculated. RESULTS: A total of 84,602 patients with T2D were included in the present study. The average SBP among study participants was 129.3 ± 15.7 mmHg in 2014 and rose to 132.6 ± 14.9 mmHg in 2018. Likewise, the average body mass index was 25.7 ± 4.5 kg/m2 in 2014 and elevated to 26.0 ± 4.8 kg/m2 in 2018. The age- and sex-adjusted mean of the predicted 10-year CVD risk (simple office-based) was 26.2% (95% CI: 26.1-26.3%) in 2014 and rose to 27.3% (95% CI: 27.2-27.4%) in 2018 (p-for trend < 0.001). While the age- and sex-adjusted mean of the predicted 10-year CVD risk (laboratory-based) ranged from 22.4-22.9% from 2014 to 2018 (p-for trend < 0.001). The age- and sex-adjusted prevalence of the high predicted 10-year CVD risk (simple office-based) was 67.2% (95% CI: 66.5-68.0%) in 2014 and significantly rose to 73.1% (95% CI: 72.4-73.7%) in 2018 (p-for trend < 0.001). Nevertheless, the age- and sex-adjusted prevalence of the high predicted 10-year CVD risk (laboratory-based) ranged from 46.0-47.4% from 2014 to 2018 (p-for trend = 0.405). However, among patients with available laboratory results, a significantly positive correlation was noted between predicted 10-year CVD risk, simple office-based and laboratory-based (r = 0.8765, p-value < 0.001). CONCLUSION: Our study demonstrated significant rising trends in the predicated 10-year CVD risk among Thai patients with T2D. In addition, the results empowered further improved modifiable CVD risks, especially regarding high BMI and high blood pressure.


Assuntos
Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Adulto , Humanos , Pessoa de Meia-Idade , Idoso , Diabetes Mellitus Tipo 2/complicações , Doenças Cardiovasculares/epidemiologia , Fatores de Risco , Estudos Transversais , Tailândia
4.
BMC Cardiovasc Disord ; 23(1): 361, 2023 07 18.
Artigo em Inglês | MEDLINE | ID: mdl-37464282

RESUMO

BACKGROUND: Elevated pulse pressure (PP) is a robust independent predictor of cardiovascular diseases. The relationship between PP and body mass index (BMI) was presented in a few studies. However, the findings were inconsistent. Therefore, the aim of the present study is to identify the association between elevated PP and BMI using a large sample of active-duty Royal Thai Army (RTA) personnel. METHODS: A cross-sectional study was conducted through the use of the dataset obtained from the annual health examination database of RTA personnel in Thailand in 2022. BMI 25.0-29.9 kg/m2 was classified as obesity I, whereas BMI ≥ 30.0 kg/m2 was classified as obesity II. Elevated PP was defined as PP ≥ 50 mmHg. Multivariable linear regression and log-binomial regression models were utilized for determining the association between elevated PP and BMI. RESULTS: A total of 62,113 active-duty RTA personnel were included in the study. The average BMI was 25.4 ± 3.8 kg/m2, while the average PP was 50.1 ± 11.2 mmHg. Compared to individuals with normal weight, the [Formula: see text] coefficients of PP and BMI were 1.38 (95% CI: 1.15-1.60) and 2.57 (95% CI: 2.25-2.88) in individuals with obesity I and obesity II, respectively. Effect modification by high blood pressure (BP) on the association between elevated PP and BMI was observed. Among participants with normal BP, in comparison with BMI of 18.5-22.9 kg/m2, the adjusted prevalence ratio (PR) for elevated PP was 1.23 (95% CI: 1.19-1.28) and 1.41 (95% CI: 1.35-1.48) in those with obesity I and obesity II, respectively. Meanwhile, among individuals with high BP, the adjusted PR for elevated PP was 1.05 (95% CI: 1.01-1.08) and 1.09 (95% CI: 1.06-1.13) in those with obesity I and obesity II, respectively. CONCLUSION: PP was positively associated with BMI in active-duty RTA personnel. High BP was the modifier of the association between PP and BMI. A weaker association between elevated PP and BMI was observed among RTA personnel with high BP.


Assuntos
Hipertensão , Militares , Humanos , Índice de Massa Corporal , Pressão Sanguínea/fisiologia , Tailândia/epidemiologia , Estudos Transversais , População do Sudeste Asiático , Obesidade/diagnóstico , Obesidade/epidemiologia , Hipertensão/diagnóstico , Hipertensão/epidemiologia
5.
BMC Cardiovasc Disord ; 23(1): 143, 2023 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-36944947

RESUMO

BACKGROUND: The relationship between hypertension (HT) and serum liver enzymes was reported in a few studies, but the findings were inconsistent. Therefore, the present study aimed to identify the association between elevated serum liver enzymes and raised BP through the use of a large sample of Royal Thai Army (RTA) personnel. METHODS: The dataset obtained from the annual health examination database of RTA personnel in Thailand was utilized. A total of 244,281 RTA personnel aged 35-60 were included in the current study. Elevated serum liver enzymes were defined as aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≥ 40 U/L in males and ≥ 35 U/L in females. HT was defined as systolic BP ≥ 140 or diastolic BP ≥ 90 mmHg. A multivariable linear regression model was used to estimate the coefficient and 95% confidence intervals (CI), whereas a multivariable logistic regression model was applied to estimate adjusted odds ratios (AORs) and 95% CI for the association between raised BP and serum liver enzymes. RESULTS: Compared to individuals with SBP < 120 and DBP < 80 mmHg, the ß coefficients of log-transformed AST and ALT were 0.13 (95% CI: 0.12-0.13) and 0.11 (95% CI: 0.11-0.12) in males with HT. Meanwhile, the ß  coefficients of log-transformed AST and ALT were 0.03 (95% CI: 0.02-0.04) and 0.07 (95% CI: 0.05-0.08) in females with HT. In males, HT was associated with elevated AST (AOR: 1.92; 95% CI: 1.85-2.01) and elevated ALT (AOR: 1.43; 95% CI: 1.38-1.48). On the other hand, in females, HT was associated with elevated AST (AOR: 1.42; 95% CI: 1.21-1.66) and elevated ALT (AOR: 1.38; 95% CI: 1.21-1.57). CONCLUSION: Raised BP was positively correlated with elevated AST and ALT in active-duty RTA personnel. Moreover, HT was independently attributed to higher odds of elevated AST and ALT in comparison to optimal BP in both males and females. Furthermore, the relationship between serum liver enzymes and BP was modified by sex.


Assuntos
Hipertensão , Hepatopatias , Militares , Masculino , Feminino , Humanos , Fígado , Pressão Sanguínea , Tailândia/epidemiologia , População do Sudeste Asiático , Hipertensão/diagnóstico , Alanina Transaminase , Aspartato Aminotransferases
6.
Lipids Health Dis ; 22(1): 47, 2023 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-37013603

RESUMO

BACKGROUND: Insulin resistance (IR) is a major pathogenesis of nonalcoholic fatty liver disease (NAFLD). The triglyceride-glucose (TyG) index has recently gained popularity to assess IR and NAFLD due to its simplicity and low cost. The aim of the current study was to evaluate the relationship between the TyG index and aminotransferase. METHODS: A serial cross-sectional study was conducted among 232,235 Royal Thai Army (RTA) personnel aged 35-60 years from 2017-2021. Elevated aminotransferase was defined as ≥ 40 U/L and ≥ 35 U/L among males and females, respectively. A linear regression analysis between the TyG index and log-transformed aminotransferase was performed. High- and low-TyG index groups were divided according to Youden's index cut point for predicting elevated aminotransferase. Multivariable logistic analysis was also utilized to investigate the association between the TyG index and elevated aminotransferase. RESULTS: The TyG index revealed a dose‒response relationship with log-transformed aminotransferase in both sexes and all age groups. The TyG index was positively associated with the prevalence of elevated aminotransferases. In comparison with the first TyG quartile (< 8.37), participants in the fourth quartile (> 9.23) had a higher chance for elevated ALT (AOR: 2.81, 95% CI: 2.71-2.90 for males and AOR: 4.01, 95% CI: 3.50-4.60 for females, P < 0.001 for both). In the fourth TyG quartile, the prevalence of elevated ALT was 47.8% and 40.2% in the participants aged 35-44 and male participants, respectively. CONCLUSION: A high TyG index is a novel risk factor for elevated aminotransferase among RTA personnel. Those with a high TyG index should be screened for elevated aminotransferase, particularly males aged 35-44 years.


Assuntos
Resistência à Insulina , Militares , Hepatopatia Gordurosa não Alcoólica , Feminino , Humanos , Masculino , Biomarcadores , Glicemia , Estudos Transversais , Glucose , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Fatores de Risco , População do Sudeste Asiático , Transaminases , Triglicerídeos , Adulto , Pessoa de Meia-Idade
7.
BMC Public Health ; 23(1): 448, 2023 03 08.
Artigo em Inglês | MEDLINE | ID: mdl-36882723

RESUMO

BACKGROUND: Helminth infection is a global health issue that not only causes acute helminthiasis but long-term infection may lead to complicated symptoms as well as severe complications. The World Health Organization cooperated with the Ministry of Public Health in many countries, particularly where high prevalence, spending a lot of resources for limiting the infection. In Thailand, the incidence of parasitic helminth infections was continuously declined in the last few decades according to several campaigns for parasitic elimination. However, the rural community in the northeast of Thailand where the highest prevalence of the country still needs to be monitored. This present study aims to report the current prevalence of parasitic helminth infections in Nakhon Ratchasima and Chaiyaphum provinces where sharing a huge area of the northeastern region of Thailand but only a few studies have been published. METHODS: The stool specimens were collected from 11,196 volunteers and processed by modified Kato-Katz thick smear, PBS-ethyl acetate concentration techniques, and PCR. The epidemiological data were collected, analyzed, and used for generating of parasitic hotspots. RESULTS: The results indicated that O. viverrini remains the major parasite in this area with a total prevalence of 5.05% followed by Taenia spp., Hookworms, T. trichiura, and Echinostoma spp., respectively. Mueang district of Chaiyaphum province has the highest prevalence especially O. viverrini with a prevalence of 7.15% that higher than the latest national surveillance. Interestingly, the prevalence of O. viverrini was hugely reported (more than 10%) in five subdistricts. The geographic localization of O. viverrini infections revealed that a lot of water reservoirs such as the lakes or branches of the river in the two-most prevalent subdistricts. Our finding indicated that gender and age were insignificantly different. CONCLUSION: This finding suggested that the parasitic helminth infection in the rural areas of northeast of Thailand remains high and the housing location is a major contributing factor for the parasitic infection.


Assuntos
Helmintíase , Parasitos , Humanos , Animais , Prevalência , População Rural , Tailândia/epidemiologia , Helmintíase/epidemiologia
8.
Exp Parasitol ; 238: 108281, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35594932

RESUMO

Copro-microscopic diagnostic methods are the most common approach for screening patients with parasitic infections. However, expertise is required to identify helminthic eggs from fecal specimens. Consequently, new methods are required to support accurate species identification. Novel technologies have recently been developed for the classification of organisms, including geometric morphometric (GM) approaches. In this study, the outline-based GM approach was used to distinguish the eggs of 12 common human parasite species, including Ascaris lumbricoides, Trichuris trichiura, Enterobius vermicularis, hookworm, Capillaria philippinensis, Opisthorchis spp., Fasciola spp., Paragonimus spp., Schistosoma mekongi, Taenia spp., Hymenolepis diminuta and Hymenolepis nana. The GM analysis revealed that the size cannot be used as the main variable in the identification of parasite species at the egg stage, producing only 30.18% overall accuracy. However, comparisons of shape based on the Mahalanobis distances between pairs of parasite species showed significant differences in all pairs (p < 0.05). The shape analysis produced 84.29% overall accuracy. This is the first time that outline-based GM has been preliminarily confirmed as a valuable approach to support copro-microscopic analysis, in order to effectively screen helminth eggs. However, further studies with a larger set of helminth eggs and artefacts should be carried out to increase confidence in the identification of parasite species in the absence of local experts.


Assuntos
Helmintos , Parasitos , Taenia , Animais , Fezes/parasitologia , Humanos , Contagem de Ovos de Parasitas , Trichuris
9.
Exp Parasitol ; 243: 108384, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36154837

RESUMO

Protein-ligand (GOLD) docking of the NCI compounds into the ligand-binding site of Plasmodium falciparum adenosine deaminase (PfADA) identified three most active azo compounds containing 4-[(4-hydroxy-2-oxo-1H-quinolin-3-yl) moiety. These compounds showed IC50 of 3.7-15.4 µM against PfADA, as well as inhibited the growth of P. falciparum strains 3D7 (chloroquine (CQ)-sensitive) and K1 (CQ-resistant) with IC50 of 1.8-3.1 and 1.7-3.6 µM, respectively. The identified compounds have structures similar to the backbone structure (4-N-(7-chloroquinolin-4-yl)) in CQ, and NSC45545 could mimic CQ by inhibiting the bioformation of hemozoin in parasitic food vacuole. The amount of in situ hemozoin in the ring-stage parasite was determined using a combination of synchrotron transmission Fourier transform infrared microspectroscopy and Principal Component Analysis. Stretching of the C-O bond of hemozoin propionate group measured at 1220-1210 cm-1 in untreated intraerythrocytic P. falciparum strains 3D7 and K1 was disappeared following treatment with 1.85 and 1.74 µM NSC45545, similar to those treated with 0.02 and 0.13 µM CQ, respectively. These findings indicate a novel dual function of 4-[(4-hydroxy-2-oxo-1H-quinolin-3-yl) azo compounds in inhibiting both PfADA and in situ hemozoin biocrystallization. These lead compounds hold promise for further development of new antimalarial therapeutics that could delay the onset of parasitic drug resistance.


Assuntos
Inibidores de Adenosina Desaminase , Antimaláricos , Compostos Azo , Plasmodium falciparum , Adenosina Desaminase , Antimaláricos/farmacologia , Compostos Azo/farmacologia , Biomineralização , Cloroquina/farmacologia , Resistência a Medicamentos , Ligantes , Plasmodium falciparum/efeitos dos fármacos , Inibidores de Adenosina Desaminase/farmacologia
10.
BMC Public Health ; 22(1): 1569, 2022 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-35978422

RESUMO

BACKGROUND: Hypertriglyceridemia is a common health problem independently associated with an increased risk of atherosclerosis cardiovascular diseases (ASCVD), including ischemic heart disease and stroke. This study aims to determine the prevalence of hypertriglyceridemia among Royal Thai Army (RTA) personnel and its behavioral and cardiometabolic risk factors using the RTA personnel database of the physical health examination from 2017 to 2021. METHODS: A serial cross-sectional study was conducted from 2017 to 2021. A total of 257,683 active-duty RTA personnel aged 35-60 years were included in the study. We defined hypertriglyceridemia as fasting triglyceride ≥150 mg/dL. Moreover, we performed a multivariable logistic regression analysis to investigate behavioral and cardiometabolic risk factors for the prevalence of hypertriglyceridemia. The magnitude of the association was presented as an adjusted odds ratio (AOR) with a 95% confidence interval (CI). RESULTS: The hypertriglyceridemia prevalence among RTA personnel was 43.4% (95% CI: 42.9-43.8%) in 2017. It then continuously decreased to 40.3% (95% CI: 39.9-40.7%) in 2020 and slightly rose to 41.0% (95% CI: 40.6-41.4%) in 2021 (p for trend < 0.001). The prevalence of hypertriglyceridemia was higher for males than females (AOR 2.15; 95% CI: 2.07-2.23); RTA personnel aged 40-44 years compared with those aged 35-39 years (AOR 1.05; 95% CI: 1.02-1.08); and RTA personnel residing in the northeast (AOR; 1.15 95% CI: 1.11-1.18) and the north (AOR 1.05; 95% CI: 1.02-1.08) compared with those residing in Bangkok. The independent behavioral factors associated with hypertriglyceridemia included alcohol consumption, smoking, and sedentary behavior. Moreover, cardiometabolic risk factors, including higher body mass index, high fasting plasma glucose (≥ 100 mg/dL), high blood pressure (≥ 140/90 mmHg), and hypercholesterolemia (≥ 200 mg/dL), were significantly related to hypertriglyceridemia. CONCLUSION: Our data demonstrated that hypertriglyceridemia is a frequent health issue, especially among males, participants aged 40-44 years, and RTA personnel residing in the northeast and the north. The prevalence of hypertriglyceridemia in this population was greatly influenced by alcohol consumption, cigarette smoking, and sedentary behavior. Both behavioral and cardiometabolic risk factors are potential targets for intervention to enhance the primary prevention of sequelae of hypertriglyceridemia, including ASCVD.


Assuntos
Hiperlipidemias , Hipertrigliceridemia , Militares , Fatores de Risco Cardiometabólico , Estudos Transversais , Feminino , Humanos , Hipertrigliceridemia/epidemiologia , Masculino , Prevalência , Fatores de Risco , Tailândia/epidemiologia
11.
Analyst ; 145(24): 8077-8086, 2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33078771

RESUMO

The highly sensitive and selective determination of Escherichia coli (E. coli) in urine was achieved using a SYBR™ safe loop-mediated isothermal amplification (LAMP) method with a distance-based paper device. New primers set specific to multi-copy the 16s rRNA gene of E. coli were designed and used in this study. The detection sensitivity of these primers was higher than in related work and they could be incorporated with a low-cost paper-based device to quantify E. coli in urine at a concentration lower than 101 CFU mL-1. Regarding standard artificial urine, a linear range of a 10-fold dilution of E. coli concentration (105-100 CFU mL-1) with an R-square value (R2) = 0.9823 was observed directly using a fluorescent migratory distance of the 4 µL reaction mixture in the detection zone under blue light without the need for postreaction staining process. Based on the device, E. coli infection could be significantly categorized into 3 groups; none, light, and heavy levels, which is beneficial for UTI diagnosis. Hence, this paper-based device is suitable for use with the SYBR™ Safe-LAMP assay to semi-quantify E. coli, especially in resource-limited settings due to advantages of low cost, simple fabrication and operation, and no requirement for sophisticated instruments, as well as its disposability and portability.


Assuntos
Escherichia coli , Técnicas de Amplificação de Ácido Nucleico , Escherichia coli/genética , Técnicas de Diagnóstico Molecular , RNA Ribossômico 16S/genética , Sensibilidade e Especificidade
12.
Molecules ; 26(14)2021 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-34299634

RESUMO

The method for the determination of primaquine (PQ) and 5,6-orthoquinone primaquine (5,6-PQ), the representative marker for PQ active metabolites, via CYP2D6 in human plasma and urine has been validated. All samples were extracted using acetonitrile for protein precipitation and analyzed using the ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) system. Chromatography separation was carried out using a Hypersil GOLDTM aQ C18 column (100 × 2.1 mm, particle size 1.9 µm) with a C18 guard column (4 × 3 mm) flowed with an isocratic mode of methanol, water, and acetonitrile in an optimal ratio at 0.4 mL/min. The retention times of 5,6-PQ and PQ in plasma and urine were 0.8 and 1.6 min, respectively. The method was validated according to the guideline. The linearity of the analytes was in the range of 25-1500 ng/mL. The matrix effect of PQ and 5,6-PQ ranged from 100% to 116% and from 87% to 104% for plasma, and from 87% to 89% and from 86% to 87% for urine, respectively. The recovery of PQ and 5,6-PQ ranged from 78% to 95% and form 80% to 98% for plasma, and from 102% to from 112% to 97% to 109% for urine, respectively. The accuracy and precision of PQ and 5,6-PQ in plasma and urine were within the acceptance criteria. The samples should be kept in the freezer (-80 °C) and analyzed within 7 days due to the metabolite stability. This validated UHPLC-MS/MS method was beneficial for a pharmacokinetic study in subjects receiving PQ.


Assuntos
Primaquina/análise , Primaquina/química , Primaquina/farmacocinética , Cromatografia Líquida de Alta Pressão , Humanos
13.
Bioorg Chem ; 98: 103732, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32171989

RESUMO

This study reported the discovery of novel compounds containing five-membered ring fused quinoline core structures as anticancer and antimalarial agents. Two libraries containing these core structures, neocryptolepines and carbocycle-fused quinolines, were prepared and evaluated. Compound 3h was found to be much more potent than other analogs against cancer cell lines with high selectivity. Meanwhile, carbocycle-fused quinolines 5h and 5s showed moderate anticancer properties but much less cytotoxicity to normal cell than doxorubicin. In addition, compound 3h also showed much lower cytotoxic against human normal kidney cell line compared to doxorubicin standard. However, only compounds 3s and 3p provided acceptable results for antimalarial activities.


Assuntos
Alcaloides/farmacologia , Antimaláricos/farmacologia , Antineoplásicos/farmacologia , Plasmodium falciparum/efeitos dos fármacos , Quinolinas/farmacologia , Alcaloides/síntese química , Alcaloides/química , Antimaláricos/síntese química , Antimaláricos/química , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Estrutura Molecular , Testes de Sensibilidade Parasitária , Quinolinas/síntese química , Quinolinas/química , Relação Estrutura-Atividade
14.
BMC Public Health ; 20(1): 850, 2020 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-32493314

RESUMO

BACKGROUND: Obesity is one principle risk factor increasing the risk of noncommunicable diseases including diabetes, hypertension and atherosclerosis. In Thailand, a 2014 study reported obesity (BMI ≥25 kg/m2) in a Thai population aged ≥15 years was 37.5, 32.9 and 41.8% overall and among males and females, respectively. The study aimed to determine trends in the prevalence of obesity among adults residing in a Thai rural community between 2012 and 2018 and investigate the associations between obesity and behavioral factors. METHODS: Serial cross-sectional studies were conducted in 2012 and 2018 among adults in Na-Ngam rural community. In 2012 and 2018, all 635 and 627 individuals, respectively, were interviewed using structured questionnaires related to demographics, risk behaviors, comorbidities and arthrometric measurement. Spot urine was collected by participants and obesity was defined as BMI ≥25 kg/m2. The risk factors for obesity were analyzed in the 2018 survey. RESULTS: A total of 1262 adults in Na-Ngam rural community were included in the study. The prevalence of obesity was 33.9% in 2012 and 44.8% in 2018 (P < 0.001). The average BMI increased from 23.9 ± 4.2 kg/m2 in 2012 to 25.0 ± 4.52 kg/m2 in 2018 (P < 0.001). Obesity was associated with higher age (AOR 0.99; 95%CI 0.97-0.99), smoking (AOR 0.52; 95%CI 0.28-0.94), instant coffee-mix consumption > 1 cup/week (AOR 1.44; 95%CI 1.02-2.04), higher number of chronic diseases (≥1 disease AOR 1.82; 95%CI 1.01-2.68, > 2 diseases AOR 2.15; 95%CI 1.32-3.50), and higher spot urine sodium level (AOR 1.002; 95%CI 0.99-1.01). CONCLUSION: Our data emphasized that obesity constituted a serious problem among adults residing in a rural community. A trend in significant increase was found regarding the prevalence of obesity and average BMI in the rural community over 6 years. Effective public health interventions should be provided at the community level to reduce BMI. Moreover, modifiable risk factors for obesity should be attenuated to inhibit the progression of metabolic syndrome, noncommunicable diseases and their complications.


Assuntos
Aterosclerose/epidemiologia , Diabetes Mellitus Tipo 2/epidemiologia , Hipertensão/epidemiologia , Doenças não Transmissíveis/epidemiologia , Obesidade/epidemiologia , Adolescente , Adulto , Idoso , Aterosclerose/etiologia , Índice de Massa Corporal , Doença Crônica , Estudos Transversais , Diabetes Mellitus Tipo 2/etiologia , Feminino , Humanos , Hipertensão/etiologia , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Prevalência , Fatores de Risco , População Rural/estatística & dados numéricos , Fumar/efeitos adversos , Fumar/epidemiologia , Inquéritos e Questionários , Tailândia/epidemiologia , Adulto Jovem
15.
Korean J Parasitol ; 57(5): 499-504, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31715690

RESUMO

Head-lice infestation, pediculosis capitis, remains a public-health burden in many countries. The widely used first-line pediculicides and alternative treatments are often too costly for use in poor socio-economic settings. Ivermectin has been considered an alternate treatment for field practice. This study was composed of 2 parts, a cross-sectional survey and an intervention study. The main objectives were to determine the prevalence and potential factors associated with head-lice infestation, and to evaluate the effectiveness and safety of oral ivermectin administration. A community-based cross-sectional survey was conducted among 890 villagers in rural areas along Thai-Myanmar border. Females with infestations were eligible for the intervention study, and 181 participated in the intervention study. A post-treatment survey was conducted to assess acceptance of ivermectin as a treatment choice. Data analysis used descriptive statistics and a generalized-estimation-equation model adjusted for cluster effect. The study revealed the prevalence of head-lice infestation was 50% among females and only 3% among males. Age stratification showed a high prevalence among females aged <20 years, and among 50% of female school-children. The prevalence was persistent among those with a history of infestation. The major risk factors were residing in a setting with other infected cases, and sharing a hair comb. The study also confirmed that ivermectin was safe and effective for field-based practice. It was considered a preferable treatment option. In conclusion, behavior-change communication should be implemented to reduce the observed high prevalence of headlice infestation. Ivermectin may be an alternative choice for head-lice treatment, especially in remote areas.


Assuntos
Inseticidas/administração & dosagem , Ivermectina/administração & dosagem , Infestações por Piolhos/tratamento farmacológico , Pediculus/efeitos dos fármacos , Administração Oral , Adolescente , Adulto , Animais , Criança , Feminino , Humanos , Infestações por Piolhos/epidemiologia , Infestações por Piolhos/parasitologia , Masculino , Pessoa de Meia-Idade , Pediculus/fisiologia , População Rural , Tailândia/epidemiologia , Resultado do Tratamento , Adulto Jovem
16.
Malar J ; 17(1): 197, 2018 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-29764451

RESUMO

BACKGROUND: In Thailand, artemisinin-based combination therapy (ACT) has been used to treat uncomplicated falciparum malaria since 1995. Unfortunately, artemisinin resistance has been reported from Thailand and other Southeast Asian countries since 2003. Malarone®, a combination of atovaquone-proguanil (ATQ-PG), has been used to cease artemisinin pressure in some areas along Thai-Cambodia border, as part of an artemisinin resistance containment project since 2009. This study aimed to determine genotypes and phenotypes of Plasmodium falciparum isolates collected from the Thai-Cambodia border after the artemisinin resistance containment project compared with those collected before. RESULTS: One hundred and nine of P. falciparum isolates collected from Thai-Cambodia border from Chanthaburi and Trat provinces during 1988-2016 were used in this study. Of these, 58 isolates were collected after the containment. These parasite isolates were characterized for in vitro antimalarial sensitivities including chloroquine (CQ), quinine (QN), mefloquine (MQ), piperaquine (PPQ), artesunate (AS), dihydroartemisinin (DHA), ATQ and PG and genetic markers for drug resistance including the Kelch13 (k13), Plasmodium falciparum chloroquine resistance transporter (pfcrt), P. falciparum multidrug resistance 1 (pfmdr1) and cytochrome b (cytb) genes. Mean CQ, QN, MQ, PPQ and AS IC50s of the parasite isolates collected from 2009 to 2016 exhibited significantly higher than those of parasites collected before 2009. Approximately 57% exhibited in vitro MQ resistance. Approximately 94% of the isolates collected from 2009 to 2016 contained the pfmdr1 184F allele. Mutations of the k13 gene were detected in approximately 90% of the parasites collected from 2009 to 2016 which were significantly higher than the parasite isolates collected before. No ATQ-resistant genotype and phenotype of P. falciparum were found among the isolates collected after the containment project. CONCLUSIONS: Although the containment project had been implemented in this area, the expansion of artemisinin-resistant parasites did not decline. In addition, reduced sensitivity of the partner drugs of ACT including MQ and PPQ were identified.


Assuntos
Antimaláricos/farmacologia , Artemisininas/farmacologia , Resistência a Medicamentos/genética , Plasmodium falciparum/efeitos dos fármacos , Plasmodium falciparum/genética , Genótipo , Fenótipo , Plasmodium falciparum/fisiologia , Tailândia
17.
Malar J ; 16(1): 131, 2017 03 27.
Artigo em Inglês | MEDLINE | ID: mdl-28347310

RESUMO

BACKGROUND: To date, human peripheral blood mononuclear cells (PBMCs) have been used mainly in immune stimulation assays and the interpretation of data can be influenced by the previous immunological history of donors and cross reactivity with other infectious agents. Resolving these limitations requires an alternative in vitro model to uncover the primary response profiles. METHODS: A novel in vitro model of mononuclear cells (MNCs) generated from haematopoietic stem cells (HSCs) was developed and these cells were then co-cultured with various antigens from Plasmodium falciparum and Plasmodium vivax to investigate the response of naïve immune cells to malaria antigens by flow cytometry. RESULTS: In vitro stimulation of naïve lymphocytes showed that CD4+ and CD8+ T lymphocytes were significantly reduced (P < 0.01) by exposure to lysates of infected erythrocytes or intact erythrocytes infected with P. falciparum. The depletion was associated with the expression of CD95 (Fas receptor) on the surface of T lymphocytes. Maturation of T lymphocytes was affected differently, showing elevated CD3+CD4+CD8+ and CD3+CD4-CD8- T lymphocytes after stimulation with cell lysates of P. falciparum and P. vivax, respectively. In addition, antigen presenting monocytes and dendritic cells derived from haematopoietic stem cells showed impaired HLA-DR expression as a consequence of exposure to different species of malaria parasites. CONCLUSION: These results suggest that naïve mononuclear cells differentiated in vitro from HSCs could provide a valid model for the assessment of immunity. P. falciparum and P. vivax malaria parasites could modulate various populations of immune cells starting from newly differentiated mononuclear cells.


Assuntos
Imunidade Celular , Leucócitos Mononucleares/imunologia , Malária Falciparum/imunologia , Malária Vivax/imunologia , Plasmodium falciparum/imunologia , Plasmodium vivax/imunologia , Células-Tronco Hematopoéticas/fisiologia , Humanos , Malária Falciparum/parasitologia , Malária Vivax/parasitologia
18.
J Eukaryot Microbiol ; 64(6): 820-828, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28370779

RESUMO

Leishmania martiniquensis, a zoonotic hemoflagellate, is a causative agent of cutaneous (CL) and visceral leishmaniasis (VL) among humans and animals. This organism, first reported in Martinique Island, now has become an emerging infectious agent in Thailand. Symptomatic cases of L. martiniquensis infection among humans have continuously increased. In the meantime, asymptomatic infection of this novel species has seriously created national public health awareness and concern to prevent and control disease transmission. The unsuccessful serological test using the commercial rK39 dipstick based on antigen from Leishmania donovani to detect the antibodies against VL among infected Thai patients has encouraged us to further explore a new sensitive and specific antigenic epitope. In this study, we determined the sequences and expressed recombinant proteins of kinesin 39 (k39), heat shock protein 70 (hsp70), heat shock protein 83 (hsp83), and glycoprotein 63 (gp63) of L. martiniquensis to evaluate the diagnostic efficiency to detect antibodies against L. martiniquensis in patient sera. The preliminary results from western blot analysis have suggested that K39 is the most sensitive recombinant protein to detect L. martiniquensis. Moreover, this recombinant protein reacts with antibodies against L. donovani and Leishmania infantum, making it a promising antigen for further development of a universal rapid diagnostic tool for VL.


Assuntos
Anticorpos Antiprotozoários/sangue , Antígenos de Protozoários/imunologia , Western Blotting/métodos , Testes Diagnósticos de Rotina/métodos , Leishmaniose/diagnóstico , Proteínas Recombinantes/imunologia , Humanos , Sensibilidade e Especificidade , Tailândia
20.
Artigo em Inglês | MEDLINE | ID: mdl-27405118

RESUMO

Primaquine (PQ), an 8-aminoquinoline, is considered a tissue schizonticide drug for radical cure in vivax and ovale malaria, with minimal impact on asexual erythrocytic stages at therapeutic concentrations. Tafenoquine (TQ), a new 8-aminoquinoline analog of PQ, is active against both malaria parasite tissue and blood stages and is being promoted as a drug candidate for antimalarial chemotherapy and chemoprophylaxis and potential transmission blocking against Plasmodium vivax and P. falciparum. This study compared in vitro sensitivity of Thai P. falciparum isolates against three 8-aminoquinolines, PQ, TQ and sitamaquine (SQ), a related 8-aminoquinoline and assessed the importance of pfmdr1 polymorphism on the in vitro response. Seventy-eight laboratory adapted Thai P. falciparum isolates were evaluated for in vitro sensitivity to the three 8-aminoquinolines using a radioisotopic assay, and pfmdr1 polymorphisms were determined using PCR-based methods. All three drugs have weak antiplasmodial activity against asexual erythrocytic stage with SQ being the most potent by almost 10 folds. Cross susceptibility was observed in all three 8-aminoquinolines. Parasites containing pfmdr1 86Y, 184Y or 1034S allele exhibit significantly higher PQ IC50. TQ sensitivity was reduced in those parasites containing pfmdr1 86Y, 1034S or 1042N allele. However, there was no significant influence of pfmdr1 alleles on SQ sensitivity. The data highlight unique differences among three representative 8-aminoquinoline drugs that may be useful in understanding their potential utility in antimalarial development.


Assuntos
Aminoquinolinas/farmacologia , Antimaláricos/farmacologia , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Plasmodium falciparum , Primaquina/farmacologia , Humanos , Malária Falciparum/parasitologia , Plasmodium falciparum/efeitos dos fármacos , Plasmodium falciparum/genética , Tailândia
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