Chemometric analysis of NMR and GC datasets for chemotype characterization of essential oils from different species of Ocimum.

The genus Ocimum (Labiatae) comprises 30 species found in tropical and subtropical regions of the planet, of which species O. basilicum L. and O. gratissimum are widely used in food and traditional medicine. Phytochemical studies on Ocimum have revealed a number of essential oil chemotypes, for example, eugenol, methyl chavicol, linalool, and methyl cinnamate. Since essential oils are commercially assessed according to their content, the aim of this study was to develop a simple and precise method for their qualitative and quantitative analysis using NMR spectroscopy combined with chemometrics. Seven essential oils from different species of Ocimum, an unknown sample, and a commercial sample were evaluated and the results compared to those from established and precise GC-MS and GC-FID methods. Chemometric evaluation from both 1H NMR and GC-MS data revealed three chemotypes: eugenol for O. gratissimum, O. micranthum, and O. tenuiflorum; estragole for O. basilicum, O. basilicum var. purpuracens, and O. selloi; and methyl cinnamate for O. americanum. The unknown and commercial species were classified as cinnamate and eugenol chemotypes, respectively. Despite the corroborating results, the chemometric analysis revealed the higher robustness (better adjustment) of the 1H NMR model compared to the GC-MS method in terms of certain statistical parameters. The 1H NMR method allows for the detection and quantification of organic compounds in a complex mixture without the need for certified standard compounds. Although GC-MS and GC-FID were able to detect five compounds not observed by NMR spectroscopy, the four most important metabolites (eugenol, estragole, methyl cinnamate, and eucalyptol) were more readily detected and quantified by 1H NMR.

Constituintes químicos voláteis e não-voláteis de Moringa oleifera Lam., Moringaceae / Volatile and non-volatile chemical constituents of Moringa oleifera Lam., Moringaceae

O estudo fitoquímico do extrato etanólico das folhas de Moringa oleifera Lam., Moringaceae, resultou no isolamento dos derivados benzilnitrilas niazirina, niazirinina e 4-hidroxifenil-acetonitrila, enquanto que das cascas dos frutos somente o octacosano foi obtido. Os óleos essenciais das folhas, flores e frutos foram analisados por cromatografia gasosa acoplada a espectrometria de massa. Os constituintes principais identificados foram: fitol (21,6 por cento) e timol (9,6 por cento) nas folhas, octadecano (27,4 por cento) e ácido hexadecanóico (18,4 por cento) nas flores e docosano (32,7 por cento) e tetracosano (24,0 por cento) nos frutos. As estruturas dos compostos isolados foram identificadas a partir de técnicas espectroscópicas (RMN, IV e EM). A 4-hidroxifenil-acetonitrila está sendo citada pela primeira vez para o gênero Moringa e os óleos essenciais das flores e frutos estão sendo citados pela primeira vez para a espécie M. oleifera.

Phytochemical analysis of the ethanol extract from leaves of Moringa oleifera Lam., Moringaceae, yield the benzylnitriles: niazirine, niazirinine and 4-hydroxyphenylacetonitrile, while of fruit shells only octacosane was isolated. The essential oils from leaves, flowers and fruits were examined by gas chromatography-mass spectrometry. The major constituents identified were: phytol (21.6 percent) and thymol (9.6 percent) in the leaves oil, octadecane (27.4 percent) and hexadecanoic acid (18.4 percent) in the flowers oil, docosane (32.7 percent) and tetracosane (24.0 percent) in the fruits oil. The structures of all compounds were identified by spectroscopic analyses (NMR, IR and MS). 4-hydroxyphenylacetonitrile is reported for the first time to the Moringa genus and the essential oils of flowers and fruits are reported for the first time to the species M. oleifera.

Role of health care providers in educational training of patients with diabetes.

Diabetes mellitus is a high prevalence chronic disease, in which several health care providers are involved in the treatment of patients. Multifaceted professional and organizational interventions that facilitate structured and regular review of patients are effective in improving the process of care. Moreover, patient education and enhancement of role of nurses improve clinical outcomes and process of care. As diabetic management requires strict commitment of the patients, their educational therapy is mandatory. Therapeutic Patient Education (TPE) is a continous process, integrated in health care; it is a permanent care process, patient-centred, that must be adapted to the evolution of illness and to the patient's lifestyle; TPE must be structured and organized and it should receive benefits from the appropriate pedagogic means. Since the publication of DCCT data it was clear that intensive insulin therapy had been successfully applied only in centers where a diabetologist, a specialized nurse, a dietician, a psycologist and a motivated patient worked all together, i.e. where there was a "team". The team has to follow a pedagogic, multidisciplinary and patient-centred methodology of care. Well structured integration between health care providers may help to avoid the burn-out syndrome.

Assessing resting heart rate in adolescents: determinants and correlates.

The aim of this study was to evaluate the distribution of resting heart rate and its biological and environmental determinants in adolescents. The study was cross- sectional and the population consisted of 2230 children and adolescents, age range 12-18 years, enrolled randomly from state schools in Turin, Italy. In all participants the following parameters were evaluated: heart rate, blood pressure (BP), weight, height, degree of sexual development, physical activity, parental socio-cultural level. Heart rate and BP were measured after 5, 10 and 15 min in a sitting position. Furthermore, to obtain regression equations to define heart rate as a function of the other variables available, a multiple regression analysis was performed. In both sexes BP, but not heart rate, declined significantly from the first to the last determination. Heart rate was positively and significantly correlated to BP level in both sexes; heart rate was higher in girls (3 bpm) and followed a progressive decreasing trend with age in both sexes, that was opposite to BP values. Age, sexual maturation, height, physical activity and parental socio-cultural level were independent determinants of resting heart rate. In conclusion, resting heart rate in adolescents is related to several methodological, constitutional and environmental factors that have to be taken into account when assessing heart rate values and constructing tables of normal values.

Assessment of N-methylformamide (NMF) administered orally on a three times weekly schedule: a phase I study.

This phase I study was conducted to reevaluate the dose-limiting toxicities, maximum tolerated (MTD) and recommended phase II doses of oral NMF administered on a three times weekly schedule for 4 out of every 6 weeks. This schedule was based on the observation that prolonged administration of NMF was associated with the most efficacious antitumor activity in preclinical studies. Phase II trials that employed a starting dose of 800 mg/m2, determined in a previous phase I trial, were suspended because of frequent and severe toxicities. In the current study, a symptom complex characterized by nausea, vomiting, and malaise was the dose-limiting toxicity of oral NMF administered on this schedule. Other toxicities included hepatic enzyme elevations, mild myelosuppression, and worsening of preexistent toxic peripheral neuropathies. Of interest, three patients who were asymptomatic prior to treatment, rapidly developed symptoms of increased intracranial pressure after starting NMF; and, computerized tomographic brain scans revealed metastatic tumors with significant peritumoral edema. NMF was well tolerated at 600 mg/m2, however, an abrupt increase in toxicity resulted when the dose was increased to 700 mg/m2. Although NMF peak plasma concentrations (Cmax) and areas under the plasma disappearance curves (AUC) differed between the 600 and 700 mg/m2 dose levels, these differences were not striking, and similar NMF plasma concentrations and exposures were well tolerated during intravenous trials. Based on this study, the recommended phase II dose for oral NMF administered three times weekly for 4 of 6 weeks was 600 mg/m2.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical and pharmacologic reappraisal of dichloromethotrexate.

Dichloromethotrexate (DCMTX) has been the subject of sporadic clinical development for the last 30 years. Although DCMTX was developed in hopes of discovering a more potent antifolate, the potential pharmacologic and toxicologic advantages of the analog have become of greater interest. This phase I and pharmacokinetic trial of DCMTX given on days 1, 8, and 15 every 28 days was undertaken to test these potential advantages. The maximally tolerated dose on this schedule was 980 mg/m2. Hepatic toxicity was dose limiting. Malaise, myelosuppression, and mucositis were also major toxic effects. The recommended dose for subsequent phase II studies of DCMTX administered on this schedule is 785 mg/m2 with a reduction to 625 mg/m2 for patients with a poor performance status or extensive prior therapy. Plasma disappearance curves for most patients were biphasic or triphasic, although several demonstrated more complex kinetic patterns that suggested significant enterohepatic circulation. The magnitude of the area under the plasma disappearance curve was related to the severity of DCMTX-induced hepatotoxicity. The elimination kinetics were linear, with a mean plasma clearance of 294 mL/min (range, 128-715). The pharmacokinetic behavior of DCMTX does not support its use over methotrexate in regional perfusion. DCMTX's primarily nonrenal elimination suggests that it may have an advantage over methotrexate when combined with nephrotoxic drugs such as cisplatin. However, there is little reason to commit major resources to further evaluation of DCMTX unless significant advantages in antineoplastic activity are identified.