Profile development of noncommunicable chronic diseases in a Brazilian rural town.

OBJECTIVE: To assess the relationship between socioeconomic and anthropometric data, frequency of food consumption, and the development of noncommunicable diseases (NCDs) in patients from a small rural town in northeastern Brazil. METHODS: A cross-sectional questionnaire study was performed on patients from the Lagarto City Hospital (n = 50) and from family health units (n = 370). RESULTS: The 420 patients in the study had one or more NCDs such as hypertension, type 2 diabetes mellitus, and dyslipidemia. The mean age was 63.1 ± 8.7 years for both sexes. The typical patient was of mixed or black descent (66%), a farmer, and of low socioeconomic status and education; 100% of men and 84% of women were illiterate or had less than 4 years of schooling. Approximately 50% of women and 89% of men were married and most had never used tobacco or were ex-smokers. The body mass index (BMI) of the study population was 29.4 ± 5.5 kg/m(2), where 70% of the patients were type 2 diabetic with waist circumferences of 99.8 ± 21.2 cm for men and 98.1 ± 13.9 cm for women. The correlation between BMI and waist circumference was r = 0.88. Even with the use of medication, total cholesterol levels of above 240 mg/dL were recorded in 10% of women and about 5% of men. Likewise, 10% of women and 100% of men had triglyceride levels above 200 mg/dL; glucose levels were 133.6 ± 47.4 mg/dL in men and 110.8 ± 38.8 mg/dL in women. Blood pressure values were high, even in patients using one or more antihypertensive drugs for at least 2 years (systolic pressure = 128.5 ± 18.2; diastolic pressure = 86.3 ± 8.9 mmHg). Indices considered above the limit recommended by the World Health Organization (WHO) were obtained for 60% of women and 100% of men. Our research revealed that this population is characterized by a relatively low intake of fats and oils. Nevertheless, 100% of patients consumed meat every day, 57.6% never consumed processed foods such as candy or soft drinks, and 89% consumed coffee daily. Furthermore, the consumption of fruits was very low: 46.6% of respondents never ate fruit and 7.8% rarely consumed fruit. Likewise, 68.2% reported never eating milk and dairy products. Vegetables were consumed by only 51.4% of the population and 38.5% rarely or never consumed green vegetables. Products made from wheat, maize, cassava, beans, and rice were often consumed by 59.2% of the population. CONCLUSIONS: Our results indicate that the studied population is affected by nutritional transition, in which the greater access to carbohydrates and animal proteins is associated with high BMI, with the vast majority overweight and suffering from uncontrolled hypertension despite the use of medications. The high consumption of carbohydrates and animal protein, rapid urbanization, and sedentary lifestyle are the main factors responsible for the epidemic of noncommunicable diseases, especially among people with low income and education. Men are particularly affected, with increased visceral fat characterized by an increased waist circumference.

Bioanalytical method for in vitro metabolism study of repaglinide using 96-blade thin-film solid-phase microextraction and LC-MS/MS.

BACKGROUND: A high-throughput bioanalytical method using 96-blade thin film microextraction (TFME) and LC-MS/MS for the analysis of repaglinide (RPG) and two of its main metabolites was developed and used for an in vitro metabolism study. RESULTS: The target analytes were extracted from human microsomal medium by a 96-blade-TFME system employing the low-cost prototype 'SPME multi-sampler' using C18 coating. Method validation showed recoveries around 90% for all analytes and was linear over the concentration range of 2-1000 ng ml(-1) for RPG and of 2-500 ng ml(-1) for each RPG metabolite. CONCLUSION: The method was applied to an in vitro metabolism study of RPG employing human liver microsomes and proved to be very useful for this purpose.

Enantioselective analysis of ranolazine and desmethyl ranolazine in microsomal medium using dispersive liquid-liquid microextraction and LC-MS/MS.

BACKGROUND: An enantioselective bioanalytical method using dispersive liquid-liquid microextraction (DLLME) and LC-MS/MS was developed for the chiral analysis of ranolazine (RNZ) and one of its metabolites (desmethyl ranolazine [DRNZ]). RESULTS: The analytes were extracted from microsomal medium by DLLME, using chloroform as extractor solvent and acetone as dispersive solvent. The enantiomers of RNZ and DRNZ were analyzed simultaneously for the first time using a Chiralcel OD-H(®). Method validation showed recoveries in the order of 55 and 45%, and LLOQ of 25 and 10 ng ml(-1) for the enantiomers of RNZ and DRNZ, respectively. Linearity was established in the concentration range of 10 to 1000 and 25 to 2500 ng ml(-1) for each DRNZ and RNZ enantiomer, respectively. CONCLUSION: The unprecedented use of DLLME was demonstrated to be very useful for sample preparation of microsomal matrix. Furthermore, the in vitro metabolism of RNZ was enantioselective.

In vitro metabolism study of the promising anticancer agent the lignan (-)-grandisin.

The lignan (-)-grandisin has shown important pharmacological activities, such as citotoxicity and antiangiogenic, antibacterial and trypanocidal activities. So, it has been considered as a potential drug candidate. In the early drug development process, drug metabolism is one of the main parameters that should be evaluated; therefore, the biotransformation of this lignan by rat liver microsomes was investigated for the first time. In order to perform the biotransformation study and to determine the kinetic parameters, a simple, sensitive and selective HPLC method was developed and fully validated. After method validation, the biotransformation study was accomplished and the kinetic parameters were determined. The biotransformation study obeyed the Michaelis-Menten kinetics. The V(max) and K(m) were 1.46 ± 0.034 µmol/mg protein/h and 8.99 ± 0.488 µM, respectively. In addition, the formation of dihydro-grandisin, characterized by GC-MS, by mammalian systems indicated the involvement of a CYP450 enzyme type.

Solid phase microextraction and LC-MS/MS for the determination of paliperidone after stereoselective fungal biotransformation of risperidone.

The present work describes for the first time the use of SPME coupled to LC-MS/MS employing the polar organic mode in a stereoselective fungal biotransformation study to investigate the fungi ability to biotransform the drug risperidone into its chiral and active metabolite 9-hydroxyrisperidone (9-RispOH). The chromatographic separation was performed on a Chiralcel OJ-H column using methanol:ethanol (50:50, v/v) plus 0.2% triethylamine as the mobile phase at a flow rate of 0.8 mL min(-1). The SPME process was performed using a C18 fiber, 30 min of extraction time and 5 min of desorption time in the mobile phase. The method was completely validated and all parameters were in agreement with the literature recommendations. The Cunninghamella echinulata fungus was able to biotransform risperidone into the active metabolite, (+)-9-RispOH, resulting in 100% of enantiomeric excess. The Cunninghamella elegans fungus was also able to stereoselectively biotransform risperidone into (+)- and (-)-9-RispOH enantiomers at different rates.

Hollow fiber-based liquid-phase microextraction (HF-LPME) of isradipine and its main metabolite followed by chiral HPLC analysis: application to an in vitro biotransformation study.

An enantioselective liquid chromatographic method using two-phase hollow fiber liquid-phase microextraction (HF-LPME-HPLC) was developed for the determination of isradipine (ISR) enantiomers and its main metabolite (pyridine derivative of isradipine, PDI) in microsomal fractions isolated from rat liver. The analytes were extracted from 1 mL of microsomal medium using a two-phase HF-LPME procedure with hexyl acetate as the acceptor phase, 30 min of extraction, and sample agitation at 1,500 rpm. For the first time, ISR enantiomers and PDI were resolved. For this separation, a Chiralpak(®) AD column with hexane/2-propanol/ethanol (94:04:02, v/v/v) as the mobile phase at a flow rate of 1.5 mL min(-1) was used. The column was kept at 23 ± 2 °C. The drug and metabolite detection was performed at 325 nm and the internal standard oxybutynin was detected at 225 nm. The recoveries were 23% for PDI and 19% for each ISR enantiomer. The method presented quantification limits (LOQ) of 50 ng mL(-1) and was linear over the concentration range of 50-5,000 and 50-2,500 ng mL(-1) for PDI and each ISR enantiomer, respectively. The validated method was employed to an in vitro biotransformation study of ISR using rat liver microsomal fraction showing that (+)-(S)-ISR is preferentially biotransformed.