Publications

5 % vanillin acetum and perchloric acid as color developer, the content of ursolic acid of kud- ingcha growed in Hainan province was determined at 548 nm. The linear regression equation is Y=0. 04473X+0. 08073, r=0.9983. The average recovery was 101.2 %, and RSD=2.01%(n=5). The method is simple, repro- ducible and practicable for the determination of ursolic acid.

Tumor samples most often comprise a mixture of different cell lineages. Multiregional trees built from bulk mutational profiles do not consider this heterogeneity and can potentially lead to erroneous evolutionary inferences, including biased timing of somatic mutations, spurious parallel mutation events, and/or incorrect chronological ordering of metastatic events.

Administration of valsartan at bedtime as opposed to upon wakening improves the sleep-time relative blood pressure (BP) decline towards a more normal dipper pattern without loss of 24-h efficacy. Amlodipine, however, has been shown to be effective in reducing BP throughout the day and night, independent of dosing time. A large proportion of hypertensive subjects cannot be properly controlled with a single medication. However, no study has yet investigated the potential differing effects of combination therapy depending of the time-of-day of administration. Accordingly, the authors investigated the administration-time-dependent BP-lowering efficacy of valsartan/amlodipine combination. The authors studied 203 hypertensive subjects (92 men/111 women), 56.7 +/- 12.5 yrs of age, randomized to receive valsartan (160 mg/day) and amlodipine (5 mg/day) in one of the following four therapeutic schemes: both medications on awakening, both at bedtime, either one administered on awakening and the other at bedtime. BP was measured by ambulatory monitoring for 48 consecutive hours before and after 12 wks of treatment. Physical activity was simultaneously monitored every min by wrist actigraphy to accurately determine the beginning and end of daytime activity and nocturnal sleep. BP-lowering efficacy (quantified in terms of reduction of the 48-h mean of systolic/diastolic BP) was highest when both hypertension medications were ingested at bedtime, as compared to any one of the three other tested therapeutic schemes (17.4/13.4 mm Hg reduction with both medications on awakening; 15.1/9.6 mm Hg with valsartan on awakening and amlodipine at bedtime; 18.2/12.3 mm Hg with valsartan at bedtime and amlodipine on awakening; 24.7/13.5 mm Hg with both medications at bedtime; p < .018 between groups). The sleep-time relative BP decline was significantly increased towards a more normal dipper pattern only when both medications were jointly ingested at bedtime (p < .001). Bedtime dosing of the combination of the two medications also resulted in the largest percentage of controlled subjects among all the assessed therapeutic schemes (p = .003 between groups). In subjects requiring combination therapy to achieve proper BP control, the association of amlodipine and valsartan efficiently reduces BP for the entire 24 h independent of dosing time. However, the greater proportion of controlled patients, improved efficacy on lowering asleep BP mean, and increased sleep-time relative BP decline suggest valsartan/amlodipine combination therapy should be preferably administered at bedtime.

Resumen La gestion genetica de poblaciones pequenas, cualquiera que sea el objetivo perseguido, viene condicionada precisamente por su tamano. Hoy en dia, la distincion entre programas de conservacion y programas de seleccion tiende a difuminarse ya que en ambos tipos de programas hay que prestar atencion tanto al aumento de la consanguinidad como a la mejora o mantenimiento de algunos caracteres de interes. Para el mantenimiento de la diversidad el criterio que debe seguirse es el de maximizar el censo efectivo. Para ello durante las ultimas decadas se han desarrollado unas reglas sencillas aunque tambien existe una solucion sofisticada y al parecer optima. En programas de seleccion existen tambien reglas sencillas y una solucion optima aunque en este caso la solucion implica tambien la consideracion del progreso genetico deseado. El diseno de apareamientos optimos, aunque es mas complejo desde el punto de vista teorico, tiene tambien una respuesta practica satisfactoria. Palabras clave: Mejora genetica, Conservacion, Consanguinidad, Diversidad genetica, Poblaciones pequenas, Censo efectivo Summary Genetic improvement and management of small populations The genetic management of small populations, irrespective of the objective pursued, it is conditioned by their census. Actually the distinction between conservation and selection programmes tends to vanish because in both types of programmes attention should be paid to the increase of inbreeding and to the maintenance or improvement of some traits of interest. To maintain genetic diversity the criterion to follow is to maximize the effective population size. For this purpose several simple rules have been developed during the last decades although there exist also a sophisticated solution, probably optimal. For selection programmes there are also simple rules and an optimal solution although now the desired genetic progress should be included. The design of optimal mating systems, although it presents more problems from a theoretical point of view, it has also a reasonable practical solution.

Independent prospective studies have found that ambulatory blood pressure (BP) monitoring (ABPM) is more closely correlated with target organ damage and cardiovascular disease (CVD) risk than clinic BP measurement. This is based on studies in which BP was sampled every 15-30 min for ≤24 h, without taking into account that reproducibility of any estimated parameter from a time series to be potentially used for CVD risk assessment might depend more on monitoring duration than on sampling rate. Herein, we evaluated the influence of duration (48 vs. 24 h) and sampling rate of BP measurements (form every 20-30 min up to every 2 h) on the prognostic value of ABPM-derived parameters. We prospectively studied 3344 subjects (1718 men/1626 women), 52.6 ± 14.5 yrs of age, during a median follow-up of 5.6 yrs. Those with hypertension at baseline were randomized to ingest all their prescribed hypertension medications upon awakening or ≥1 of them at bedtime. At baseline, BP was measured at 20-min intervals from 07:00 to 23:00 h and at 30-min intervals at night for 48 h, and physical activity was simultaneously monitored every min by wrist actigraphy to accurately derive the awake and asleep BP means. Identical assessment was scheduled annually and more frequently (quarterly) if treatment adjustment was required. ABPM profiles were modified to generate time series of identical 48-h duration but with data sampled at 1- or 2-h intervals, or shorter, i.e., first 24 h, time series with data sampled at the original rate (daytime 20-min intervals/nighttime 30-min intervals). Bland-Altman plots indicated that the range of individual differences in the estimated awake and asleep systolic (SBP) and diastolic BP (DBP) means between the original and modified ABPM profiles was up to 3-fold smaller for data sampled every 1 h for 48 h than for data sampled every 20-30 min for the first 24 h. Reduction of ABPM duration to just 24 h resulted in error of the estimated asleep SBP mean, the most significant prognostic marker of CVD events, in the range of -21.4 to +23.9 mm Hg. Cox proportional-hazard analyses adjusted for sex, age, diabetes, anemia, and chronic kidney disease revealed comparable hazard ratios (HRs) for mean BP values and sleep-time relative BP decline derived from the original complete 48-h ABPM profiles and those modified to simulate a sampling rate of one BP measurement every 1 or 2 h. The HRs, however, were markedly overestimated for SBP and underestimated for DBP when the duration of ABPM was reduced from 48 to only 24 h. This study on subjects evaluated prospectively by 48-h ABPM documents that reproducibility in the estimates of prognostic ABPM-derived parameters depends markedly on duration of monitoring, and only to a lesser extent on sampling rate. The HR of CVD events associated with increased ambulatory BP is poorly estimated by relying on 24-h ABPM, indicating ABPM for only 24 h may be insufficient for proper diagnosis of hypertension, identification of dipping status, evaluation of treatment efficacy, and, most important, CVD risk stratification.

Hermida, R. C.1; Vesely, D. L.2; Kanabrocki, E. L.3; Bremner, F. W.4; Third, J. L.H.C.3; Ryan, M.3; Shirazi, P.3; Nemchausky, B. A.3; Scheving, L. E.5 Author Information

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Several studies have indicated that the use of the 24 h mean blood pressure, mainly using reference thresholds derived from general nonpregnancy practice, does not provide an effective test for an individualized early diagnosis of hypertension in pregnancy, thus concluding that ambulatory blood pressure monitoring is not a valid approach in pregnancy. With the use of ambulatory blood pressure monitoring, epidemiologic studies have reported gender differences in the circadian variability of blood pressure and heart rate. Typically, men exhibit a lower heart rate and higher blood pressure than women, the differences being larger for systolic than for diastolic blood pressure. Moreover, normotensive and hypertensive pregnant women are characterized by differing but predictable patterns of blood pressure variability throughout gestation. However, the diminished blood pressure in nongravid women as compared with men, the added decrease in blood pressure during the second trimester of gestation in normotensive but not in hypertensive pregnant women and the large amplitude of the circadian pattern that characterizes the blood pressure of healthy pregnant women at all gestational ages, have not been taken into account when establishing reference thresholds for the diagnosis of hypertension in pregnancy. This review will describe these issues, summarize previous results from independent groups on the prognostic value of ambulatory blood pressure monitoring in pregnancy, propose answers as to an accurate reference threshold for blood pressure at different stages of gestation and suggest how this information should be used in order to identify those women at a higher risk of hypertension, who will also be more suitable for prophylactic and/or therapeutic intervention in the early stages of pregnancy.