大丁草中抗菌活性成分的研究Ⅳ

从秋季采收的菊科植物大丁草Gerbera anandria(L.)Sch Bip.全草中共分出十三种成分。本文报道其中三个新化合物的结构鉴定.它们分别是3,8-dihydroxy-4-methoxy-coumarin(ⅪⅩ),3,8-dihydroxy-4-methoxy-2-oxo-2 H-1-benzopyran-5-carboxylic acid(ⅩⅦ),和5,8-dihydroxy-7-(4-hydroxy-5-methyl-coumarin-3-)-coumarin(ⅩⅪ)。     

Total radical trapping antioxidant potential (TRAP) and exercise

The relationship between physical activity, physical fitness and total radical trapping antioxidant potential (TRAP) was examined in the Northern Ireland Health and Activity Survey. This was a cross-sectional population study (n = 1600) using a two-stage probability sample of the population. TRAP was calculated using the sum of the individual serum antioxidant concentrations (urate, protein thiols, ascorbate, alpha tocopherol and bilirubin) multiplied by their respective stoichiometric values. Physical fitness was determined by estimation of VO2max by extrapolation from submaximal oxygen uptake, and physical activity was recorded by computer-assisted interview. Mean serum TRAP concentrations were significantly higher in males (653 +/- 8.2 mumol/l, mean +/- SEM) compared to females (564 +/- 8.0 mumol/l) (p < 0.0001). Both male and female smokers had significantly lower TRAP values than non-smokers (males p < 0.0001, females p = 0.02). In females, there was a positive relationship of TRAP with age (p < 0.001) and body mass index (p < 0.001) but a negative relationship with physical fitness (p < 0.05). The known beneficial effects of exercise and activity do not appear to be directly mediated through increased antioxidant status.      

Paliperidone extended-release tablets for the acute and maintenance treatment of schizophrenia

Background: Paliperidone, which is available in extended-release (ER) tablets, was approved by the US Food and Drug Administration in 2007 for the acute and maintenance treatment of schizophrenia. It is the seventh second-generation antipsychotic (SGA) to be introduced to the US market. Paliperidone is the major active metabolite of risperidone, an established anti-psychotic agent. Objective: This article reviews the available literature on the pharmacodynamics, pharmacokinetics, clinical efficacy, and tolerability of paliperidone. Methods: A comprehensive search of MEDLINE using the terms paliperidone, 9-hydroxy-risperidone, and Invega was performed for the years 1950 through December 2007. Articles that discussed the efficacy and tolerability of 9-hydroxy-risperidone formed as a metabolite of risperidone were excluded; all others were included. Abstracts and posters presented at recent national and international scientific meetings were also included in the review. Results: At therapeutic doses (3-12 mg), paliperidone ER follows linear pharmacokinetics. Like that of its parent drug, paliperidone's mechanism of action is thought to be through antagonistic actions at dopamine D(2) and serotonin-2A receptors. In vivo studies suggest that the cytochrome P450 enzyme system plays a minimal role in paliperidone metabolism, with none of the metabolites accounting for >10% of a dose. The majority (59%) of paliperidone is eliminated through the kidneys as unchanged drug. The results of three 6-week, randomized, double-blind, parallel-group trials indicated the efficacy of paliperidone ER compared with placebo in the treatment of acute exacerbations of schizophrenia, with response rates ranging from 39.8% to 61.0% for paliperidone ER, compared with 18.3% to 34.0% for placebo. During a 52-week, double-blind, relapse-prevention trial, the time to 25% of patients experiencing a recurrence was 83 days for paliperidone ER, compared with 23 days for placebo. The proportions of patients in the 6-week trials who reported at least 1 extrapyramidal symptom-related adverse event were 13%, 10%, 25%, 26%, and 24% for paliperidone ER 3, 6, 9, 12, and 15 mg/d, respectively; the pooled incidence rate was not statistically different from that with placebo (11%). Headache and insomnia were the most common adverse events in patients treated with paliperidone ER in the 6-week trials (pooled data: 11%-18% and 4%-14%, respectively). In the relapse-prevention trial, the incidence of prolactin-related adverse events was 4% for paliperidone ER and 0% for placebo. Conclusions: Current evidence supports the efficacy and tolerability of paliperidone ER in the acute and long-term treatment of schizophrenia. Randomized, head-to-head comparisons with other SGAs, particularly risperidone, are needed to define the role of paliperidone ER in the treatment of schizophrenia.     

Granulocyte colony-stimulating factor crosses the placenta and stimulates fetal rat granulopoiesis

We studied the effect of recombinant human granulocyte colony- stimulating factor (rhG-CSF) administration to pregnant rats upon fetal and neonatal myelopoiesis. Pregnant rats were treated with rhG-CSF twice daily for 2, 4, and 6 days before parturition. rhG-CSF crossed the placenta and reached peak fetal serum concentrations 4 hours after administration. Peak fetal serum levels were 1,000-fold lower than levels detected in the dam. Hematopoietic effects of rhG-CSF were assessed by cytologic analysis of the newborn blood, spleen, bone marrow, thymus, and liver. White blood cell counts were increased twofold to fourfold in newborns. This increase was due to circulating numbers of polymorphonuclear cells (PMN). rhG-CSF induced a myeloid hyperplasia in the newborn marrow consisting of immature and mature myeloid cells in the day-2 and day-4 treated pups. Bone marrow of pups treated for 6 days contained mostly hyper-segmented PMN with little or no increase in myeloid precursors. An increase in the number of postmitotic (PMN, bands, and metamyelocytes) and mitotic (promyeloblasts, myeloblasts, and metamyeloblasts) myeloid cells in the spleen of neonates was observed. No change was detected in splenic lymphocytes or monocytes. No effect of rhG-CSF was noted in the newborn liver or thymus. These results demonstrate that maternally administered rhG-CSF crosses the placenta and specifically induces bone marrow and spleen myelopoiesis in the fetus and neonate. The significant myelopoietic effects of rhG-CSF at low concentrations in the fetus suggest an exquisite degree of developmental sensitivity to this cytokine and may provide enhanced defense mechanisms to the neonate.     

Global cost of correcting vision impairment from uncorrected refractive error

Objective

To estimate the global cost of establishing and operating the educational and refractive care facilities required to provide care to all individuals who currently have vision impairment resulting from uncorrected refractive error (URE).

Methods

The global cost of correcting URE was estimated using data on the population, the prevalence of URE and the number of existing refractive care practitioners in individual countries, the cost of establishing and operating educational programmes for practitioners and the cost of establishing and operating refractive care facilities. The assumptions made ensured that costs were not underestimated and an upper limit to the costs was derived using the most expensive extreme for each assumption.

Findings

There were an estimated 158 million cases of distance vision impairment and 544 million cases of near vision impairment caused by URE worldwide in 2007. Approximately 47 000 additional full-time functional clinical refractionists and 18 000 ophthalmic dispensers would be required to provide refractive care services for these individuals. The global cost of educating the additional personnel and of establishing, maintaining and operating the refractive care facilities needed was estimated to be around 20 000 million United States dollars (US$) and the upper-limit cost was US$ 28 000 million. The estimated loss in global gross domestic product due to distance vision impairment caused by URE was US$ 202 000 million annually.

Conclusion

The cost of establishing and operating the educational and refractive care facilities required to deal with vision impairment resulting from URE was a small proportion of the global loss in productivity associated with that vision impairment.     

High-dose cytosine arabinoside and daunorubicin as consolidation therapy for acute nonlymphocytic leukemia in first remission: a pilot study

High-dose (HD) cytosine arabinoside (ARA-C) is more effective treatment than conventional-dose ARA-C regimens for patients with relapsed acute nonlymphocytic leukemia (ANLL). We report here that HD ARA-C given during the first remission of ANLL has resulted in long remission durations and a high proportion of patients who survive more than three years free of disease. From August 1979 to September 1983, 36 adult patients with ANLL in first remission received one to three courses of HD ARA-C (3 g/m2 by one-hour infusion every 12 hours for 12 doses on days 1 through 6) alone or with daunorubicin (30 mg/m2 for two or three doses on days 7 through 9). Three patients died of sepsis or hemorrhage during consolidation, and 14 patients have relapsed from five to 48 months after diagnosis. The remaining 19 patients are in continued complete remission (CCR) from 11 to 62 months. Denoting all deaths in remission as relapse, the actuarial probability of CCR is 42% at 62 months, with an apparent plateau in the survival curve. Of the first 22 patients treated, ten remain in CCR from 37 to 62 months with no therapy for at least three years. Due to its heightened anti-leukemic activity, HD ARA-C allows brief but effective consolidation of ANLL in first remission, with long-term disease-free survival comparable to other approaches.     

Allogeneic marrow transplantation for refractory anemia: a comparison of two preparative regimens and analysis of prognostic factors

From 1990 to 1993 we performed a prospective study of busulfan (16 mg/kg) and cyclophosphamide (120 mg/kg) in 30 patients with refractory anemia (RA) undergoing related (n = 17) or unrelated (n = 13) donor marrow transplantation. Nineteen patients survive disease free (63% 3- year actuarial disease-free survival [DFS]) and no patient relapsed. These results were compared to those of 38 historical controls with RA treated with cyclophosphamide and total body irradiation, of whom 22 are disease-free survivors and 1 relapsed. After correcting for significant variables between the two treatment groups, we found no statistically significant difference in outcome based on preparative regimen. Combining data from these 68 patients plus 2 additional patients with RA treated before 1993 with busulfan and cyclophosphamide, we identified four variables independently associated with improved survival: younger age, shorter disease duration, lower neutrophil count pretransplant, and lower hematocrit pretransplant. We also found that 15 patients 40 to 55 years of age had a 46% 3-year actuarial DFS and 26 patients receiving unrelated or mismatched related donor marrow had a 50% 3-year actuarial DFS. We conclude that there does not appear to be any significant difference in outcome based on preparative regimen in this patient population. In addition, allogeneic bone marrow transplantation may be a reasonable approach to therapy of RA early after diagnosis. However, whether early intervention with transplantation prolongs survival over that expected without transplantation cannot be ascertained with certainty from available data.