RESUMEN
Dipcadi (Scilloideae: Asparagaceae) is a genus of bulbous monocots with approximately 40 species, of which 13 occur in India. Species delimitation within the genus has been troublesome hindering a comprehensive phylogenetic analysis. The most recent phylogeny of the subfamily Ornithogaloideae included six species of Dipcadi only from Africa. Here, we reconstructed the phylogeny of Ornithogaloideae including 23 accessions comprising 13 recognized taxa (11 species and two varieties) of Indian Dipcadi. The phylogenetic analyses were based on nucleotide sequences of three plastid regions (rbcL, matK and trnL-F spacer) and one nuclear region (ITS). Pseudogaltonia clavata exhibited sister relationship to Dipcadi. Our combined nuclear + plastid dataset analyses revealed a monophyletic Dipcadi with five clades, Clade I-V. Clade I, II and III included mainly Indian species whereas Clade V included mostly African species. Clade IV comprised D. serotinum. Clade I included nine taxa including our newly described species, D. mukaianum. The new species was phylogenetically placed with D. erythraeum, D. saxorum and D. ursulae. Morphologically, the species resembled D. montanum and D. ursulae but differed in characters such as tepal cohesion, number of ovules per locule and foul-smelling flowers. Clade II and III included 11 and six taxa, respectively. D. erythraeum which has a native range from Egypt to western India was found in Clades I and V. The widespread Dipcadi species, viz. D. erythraeum and D. serotinum showed polyphyly however, the monophyly of Dipcadi is established. Our studies suggest that additional molecular markers (plastid as well as nuclear) should be tested for their taxonomy utility. Further work on the historical biogeography of Dipcadi on the subfamily Ornithogaloideae with more genetic data will yield insights how aridification of the landscape would have shaped the evolution of the geographical clades.
RESUMEN
Vast size hydrate formation reactors with fast conversion rate are required for the economic implementation of seawater desalination utilizing gas hydrate technology. The commercial target production rate is order of thousand tons of potable water per day per train. Various heat and mass transfer enhancement schemes including agitation, spraying, and bubbling have been examined to maximize the production capacities in scaled up design of hydrate formation reactors. The present experimental study focused on acquiring basic knowledge needed to design variable volume reactors to produce tetrafluoroethane hydrate slurry. Test vessel was composed of main cavity with fixed volume of 140 ml and auxiliary cavity with variable volume of 0 â¼ 64 ml. Temperatures at multiple locations within vessel and pressure were monitored while visual access was made through front window. Alternating evaporation and condensation induced by cyclic volume change provided agitation due to density differences among water and vapor, liquid and hydrate R134a as well as extended interface area, which improved hydrate formation kinetics coupled with latent heat release and absorption. Influences of coolant temperature, piston stroke/speed, and volume change period on hydrate formation kinetics were investigated. Suggestions of reactor design improvement for future experimental study are also made.
Asunto(s)
Sangre Fetal/citología , Embarazo/sangre , Diagnóstico Prenatal/métodos , Sondas de ADN , Femenino , Citometría de Flujo/métodos , Antígenos HLA/análisis , Humanos , Intercambio Materno-Fetal , Paridad , Reacción en Cadena de la Polimerasa , Análisis para Determinación del Sexo , Cromosoma YRESUMEN
In this first part of a two-part investigation, the intravenous dose proportionality of dolasetron mesylate, a 5-HT3 receptor antagonist, and the absolute bioavailability of oral dolasetron mesylate were investigated. In an open-label, randomized, four-way crossover design, 24 healthy men between the ages of 19 and 45 years received the following doses: 50, 100, or 200 mg dolasetron mesylate administered by 10-min intravenous infusion or 200 mg dolasetron mesylate solution administered orally. Serial blood and urine samples were collected for 48 h after dosing. Following intravenous administration, dolasetron was rapidly eliminated from plasma, with a mean elimination half-life (t1/2) of less than 10 min. Dolasetron was rarely detected in plasma after oral administration of the 200 mg dose. Hydrodolasetron, the active primary metabolite of dolasetron, appeared rapidly in plasma following both oral and intravenous administration of dolasetron mesylate, with a mean time to maximum concentration (t(max)) of less than 1 h. The mean t1/2 of hydrodolasetron ranged from 6.6-8.8 h. The plasma area under the concentration-time curve (AUC0-infinity)) for both dolasetron and hydrodolasetron increased proportionally with dose over the intravenous dose range of 50-200 mg dolasetron mesylate. Approximately 29-33%) and 22% of the dose was excreted in urine as hydrodolasetron following intravenous and oral administration of dolasetron, respectively. For dolasetron as well as hydrodolasetron, mean systemic clearance (C1), volume of distribution (Vd), and t1/2 were similar at each dolasetron dose. The mean 'apparent' bioavailability of dolasetron calculated using plasma concentrations of hydrodolasetron was 76%. The R(+) enantiomer of hydrodolasetron represented the majority of drug in plasma (> 75%) and urine (> 86%). Dolasetron was well tolerated following both oral and intravenous administration.
Asunto(s)
Indoles/farmacocinética , Quinolizinas/farmacocinética , Antagonistas de la Serotonina/farmacocinética , Administración Oral , Adulto , Análisis de Varianza , Área Bajo la Curva , Disponibilidad Biológica , Estudios Cruzados , Semivida , Humanos , Indoles/administración & dosificación , Indoles/sangre , Indoles/orina , Infusiones Intravenosas , Masculino , Persona de Mediana Edad , Quinolizinas/administración & dosificación , Quinolizinas/sangre , Quinolizinas/orina , Antagonistas de la Serotonina/administración & dosificación , Antagonistas de la Serotonina/sangre , Antagonistas de la Serotonina/orina , EstereoisomerismoRESUMEN
The single- and multiple-dose pharmacokinetics and dose-proportionality of oral dolasetron and its active metabolites over the therapeutic dose range was investigated in 18 healthy men. In an open-label, randomized, complete three-way crossover design, each subject received three separate doses: 50, 100, and 200 mg doses of dolasetron mesylate solution given orally. Each dose was administered on the morning of Days 1 and 3-7 during each of the three treatment periods. Serial blood and urine samples were collected for 48 h after the first and last doses. Blood was analysed for dolasetron and hydrodolasetron concentrations; urine was analysed for dolasetron, the R(+) and S(-)-enantiomers of hydrodolasetron, and the 5'-hydroxy and 6'-hydroxy metabolites of hydrodolasetron. Dolasetron was rarely detected in plasma. Hydrodolasetron was formed rapidly, with a time to maximum concentration (t(max)) of less than 1 h. Steady-state conditions for hydrodolasetron were reached 2-3 days after starting once-daily dosing. Although statistical significance was found for hydrodolasetron AUC(0->infinity) and C(max) between dose groups after both single and multiple doses of dolasetron, the differences were small and unlikely to be of clinical significance. About 17-22% of the dose was excreted in urine as hydrodolasetron, with the majority (> 83%) as the R(+) enantiomer.
Asunto(s)
Indoles/sangre , Indoles/metabolismo , Indoles/farmacocinética , Quinolizinas/sangre , Quinolizinas/metabolismo , Quinolizinas/farmacocinética , Antagonistas de la Serotonina/metabolismo , Antagonistas de la Serotonina/farmacocinética , Administración Oral , Adulto , Análisis de Varianza , Área Bajo la Curva , Presión Sanguínea/efectos de los fármacos , Estudios Cruzados , Relación Dosis-Respuesta a Droga , Electrocardiografía , Semivida , Humanos , Indoles/administración & dosificación , Masculino , Tasa de Depuración Metabólica , Persona de Mediana Edad , Quinolizinas/administración & dosificación , Antagonistas de la Serotonina/administración & dosificación , EstereoisomerismoRESUMEN
Gemifloxacin mesylate (SB-265805-S, LB-20304a) is a potent, novel fluoroquinolone agent with a broad spectrum of antibacterial activity. The pharmacokinetics and tolerability of oral gemifloxacin were characterized in two parallel group studies in healthy male volunteers after doses of 160, 320, 480, and 640 mg once daily for 7 days. Multiple serum or plasma and urine samples were collected on days 1 and 7 and were analyzed for gemifloxacin by high-performance liquid chromatography (HPLC)-fluorescence (study 1) or HPLC-mass spectrometry (study 2). Safety assessments included vital signs, 12-lead electrocardiogram (ECG) readings, hematology, clinical chemistry, urinalysis, and adverse experience monitoring. Gemifloxacin was rapidly absorbed, with a time to maximum concentration of approximately 1 h after dosing followed by a biexponential decline in concentration. Generally, maximum concentration and area under the concentration-time curve (AUC) increased linearly with dose after either single or repeat doses. Mean +/- standard deviation values of AUC(0-tau) on day 7 were 4.92 +/- 1.08, 9.06 +/- 2.20, 12.2 +/- 3.69, and 20.1 +/- 3.67 microg x h/ml following 160-, 320-, 480-, and 640-mg doses, respectively. The terminal-phase half-life was approximately 7 to 8 h, independent of dose, and was similar following single and repeated administrations. There was minimal accumulation of gemifloxacin after multiple dosing. Approximately 20 to 30% of the administered dose was excreted unchanged in the urine. The renal clearance was 160 ml/min on average after single and multiple doses, which was slightly greater than the accepted glomerular filtration rate (approximately 120 ml/min). These data show that the pharmacokinetics of gemifloxacin are linear and independent of dose. Gemifloxacin was generally well tolerated, although one subject was withdrawn from the study after 6 days at 640 mg for mild, transient elevations of alanine aminotransferase and aspartate aminotransferase not associated with any clinical signs or symptoms. There were no other significant changes in clinical chemistry, hematology or urinalysis parameters, vital signs, or ECG readings. In conclusion, the results of these studies, combined with the antibacterial spectrum and potency, support the further investigation of once-daily administration of gemifloxacin for indications such as respiratory tract and urinary tract infections.
Asunto(s)
Antiinfecciosos/efectos adversos , Antiinfecciosos/farmacocinética , Fluoroquinolonas , Naftiridinas/efectos adversos , Naftiridinas/farmacocinética , Adulto , Área Bajo la Curva , Cromatografía Líquida de Alta Presión , Método Doble Ciego , Gemifloxacina , Semivida , Humanos , Masculino , Espectrometría de MasasRESUMEN
Gemifloxacin (known as SB-265805 or LB-20304) is a potent, novel fluoroquinolone compound with a broad spectrum of antibacterial activity. The pharmacokinetics and tolerability of oral gemifloxacin were characterized in healthy male volunteers after a single dose of 20, 40, 80, 160, 320, 600, or 800 mg. Multiple serum and urine samples were collected and analyzed for gemifloxacin using high-performance liquid chromatography with fluorescence detection. Safety assessments included vital signs, 12-lead electrocardiogram readings, hematology, clinical chemistry, urinalysis, and adverse-experience monitoring. Gemifloxacin was rapidly absorbed after all doses. Maximum concentrations of gemifloxacin in serum (C(max)) were achieved approximately 1 h after dosing, after which concentrations in serum declined in a biexponential manner. Values of C(max) and the area under the concentration-time curve in serum from 0 h to infinity (serum AUC(0-infinity)) increased linearly with dose. Serum AUC(0-infinity) values (mean +/- standard deviation) were 0.65+/-0.01, 1.28+/-0.22, 2.54+/-0.31, 5.48+/-1.24, 9.82+/-2.70, 24.4+/-7.1, and 31.4+/-7.6 microg. h/ml following 20-, 40-, 80-, 160-, 320-, 600-, and 800-mg doses, respectively. The terminal phase elimination half-life was independent of dose, with an overall mean of 7.4+/-2.0 h. The profiles indicated that the pharmacokinetic profile is suitable for a once-daily dosing regimen. Approximately 25 to 40% of the administered dose was excreted unchanged in the urine, and renal clearance (ca. 150 ml/min) was independent of dose. There were no significant changes in clinical chemistry, hematology, or urinalysis parameters, vital signs, or 12-lead electrocardiogram readings in subjects, irrespective of dose. The results of these studies support the further investigation of once-daily administration of gemifloxacin.