蒙药小白蒿的炮制工艺及炮制品的药理研究

目的:优选小白蒿蒙医炮制工艺,并观察其饮片安全有效性。方法:以炮制品绿原酸含量为主要指标并参考槲皮素含量进行正交试验,以考察炒制温度、时间和药材粒度的影响,确定最佳工艺;采用小白鼠急性毒性实验,断尾实验测定出血时间,眼眶静脉丛取血测定凝血时间,断头采全血计数血小板总数,评价安全有效性。结果:本品在270℃温度下翻动炒制20 min效果最佳,经方差分析证明炒制温度、时间和粒度因素对所监测的两种成分的含量均没有显著影响;小白蒿炮制后可缩短小白鼠的出血时间,显著增高血小板计数。结论:小白蒿经过合理的炒制后,可提高其安全性和止血药效,为验证传统蒙药小白蒿用药理论,提供了参考依据。     

Malaria in Mazandaran,Northern Iran: Passive Case Finding During 1997-2012

Background

Malaria is one of the most important parasitic diseases in tropical and temperate regions. The aim of this study was to determine the trend of malaria in Mazandaran Province, northern Iran during 1997-2012.

Methods

This retrospective study was conducted from 1997 to 2012. The population''s study was individuals who registered at health centers of Mazandaran Province. Peripheral blood smear were prepared for each case, stained with Giemsa and examined by light microscope. In addition to demographic data, other parameters including Slide Positive Rate (SPR), Annual Parasite Incidence (API) and Annual Blood Examination Rate (ABER) were analyzed.

Results

In total, 844 cases of malaria were reported. Plasmodium vivax was predominant species with 821 cases (97.4%). The number of malaria cases increased from 1997 to 2005 and then decreased to 3 cases in 2011. Some cities had not reported any cases during last three years. The highest infection rate, 163(20.07%), was seen in 2001-02. The SPR had the highest value (0.54%) in 2004-05. The maximum API and ABER were observed in 2001-02 and 1997-98. 641(75.9%) of cases were imported from hyperendemic areas such as Afghanistan and South-eastern Iran and 94 (11.1%) malaria patients were recorded as introduced cases. The highest infection rate of malaria (21.3%) was seen in Babolsar.

Conclusion

Extensive malaria control should be continued to Mazandaran to become malaria-free region and in prevention of re-introduction stage.     

Some properties of marrow derived adherent cells in tissue culture

It has previously been shown that monolayer cultures derived adherent cells (MDAC), apparently consisting of fibroblasts, macrophages, epithelioid cells, and fat cells, can support long-term stem cell proliferation in vitro. In the present study, the hematopoietic support capability of murine MDAC monolayers was confirmed and the cultured cells further characterized with respect to the following properties: esterase I activity, complement (C3) receptors, IgG (Fc) receptors, colony stimulating activity (csa) production, and collagen synthesis. The cultures were also examined immunohistochemically to localize fibronectin, laminin, and collagen synthesis and to identify the collagen subtypes synthesized. MDAC morphology was as described in previous studies, although fat cells were few in number. It was found that MDAC included some cells with esterase I activity and C3 receptors. Fc receptors were not, however, detected, nor did the cultures produce csa, indicating that mononuclear phagocytes were not present. MDAC synthesized collagen types I and III and also fibronectin. Staining for epithelial basement membrane proteins (collagen types IV and V and laminin) was negative. The results indicate that the vast majority of these cultured MDAC were fibroblasts.     

The kidneys in paroxysmal nocturnal hemoglobinuria

Long-term study of 21 PNH patients revealed an unexpectedly high incidence of functional and anatomic renal abnormalities. Most patients demonstrated varying degrees of hematuria and proteinuria distinct from hemoglobinuria. Evaluation of renal function revealed hyposthenuria, abnormal tubular function, and declining creatinine clearance. Radiologically these patients had enlarged kidneys, cortical infarcts, cortical thinning, and papillary necrosis which were confirmed by autopsy studies. Hypertension developed in eight patients. Urinary tract infection was uncommon. The renal findings bear striking similarity to those of sickle cell anemia. Contrary to the usual opinion, out studies clearly showed evidence of widespread renal pathology in PNH most likely due to repeated microvascular thrombosis similar to the venous thrombosis involving other organs in this disorder.     

Thrombocytopoietic properties of oncostatin M

Oncostatin M (OM) is a 28-kD glycoprotein that exhibits a panoply of biologic effects. Based on histologic observations of increased splenic megakaryocytes in nude mice implanted with an OM-secreting cell line, the thrombocytopoietic properties of OM in mice were investigated in culture and in vivo. Alone, OM did not induce megakaryocytic colony formation, but in combination with murine interleukin-3 (IL-3), OM markedly enhanced colony formation. The effects of OM on colony formation were similar to those of IL-6. OM alone augmented acetylcholinesterase in short-term marrow cultures. In normal mice, the administration of OM augmented platelet counts without increasing other circulating blood cell counts. The increment in counts exceeded that observed with IL-6. The kinetics of the OM response suggested that maximal increases in platelets occurred 3 days after the cessation of OM administration, irrespective of the duration of administration. In irradiated mice, OM administration accelerated platelet recovery and prevented the decrease in red blood cells observed in irradiated control animals. The data show that OM behaves as a megakaryocytic maturation factor in vitro and augments platelet production in vivo. Based on these animal data, OM may have potential clinical utility as a thrombocytopoietic agent.     

Tranexamic acid, an inhibitor of plasminogen activation, reduces urinary collagen cross-link excretion in both experimental and rheumatoid arthritis

The plasminogen activation system is one of the enzyme systems held responsible for bone and cartilage degradation in rheumatoid arthritis (RA). In this study, we evaluated the effect of tranexamic acid (TEA), an inhibitor of plasminogen activation, on urinary collagen cross-link excretion and radiological joint damage in rat adjuvant arthritis (AA) and on urinary collagen cross-link excretion in patients with RA. In the animal study, adjuvant arthritis was induced in male Lewis rats. From day 7 onward, high-dose TEA (500 mg/kg body weight, once daily) or placebo was administered orally. Study groups consisted of TEA-treated normal rats (C + TEA), placebo-treated normal rats (C + plac), AA rats treated with TEA (AA + TEA) or with placebo (AA + plac). To monitor joint destruction, urinary collagen cross-link excretion (pyridinoline, HP; deoxypyridinoline, LP) was measured by high-performance liquid chromatography at days 14 and 21. Radiological evaluation of joints was performed at day 21. In the patient study, TEA was administered to nine patients with RA as adjuvant medication (approximately 20 mg/kg body weight, three times daily) for 12 weeks. Urinary HP and LP excretion levels were measured before and during TEA treatment, and 4 weeks after the cessation of TEA treatment. In AA + TEA rats, a significant reduction of HP and a tendency towards a reduction of LP excretion were found compared with AA + plac rats (P < 0.05), at day 14, whereas the HP/LP ratio did not change. No difference was observed in HP, LP excretion, HP/LP ratio and radiological damage score between the TEA- and placebo-treated AA rats at day 21. In RA patients, a significant reduction of HP and LP excretion was found during the TEA treatment period (P < 0.05). After the cessation of TEA treatment, HP and LP excretion increased towards baseline levels. No effect on disease activity was observed. The plasmin antagonist TEA reduced the excretion of collagen pyridinoline cross-links in both experimental and rheumatoid arthritis. As such, this study not only supports the involvement of the plasminogen activation system in the destructive phase of arthritis, but also suggests a beneficial effect of therapeutic strategies directed against inhibition of matrix proteolysis.      

The management of stage I--II Hodgkin's disease with irradiation alone or combined modality therapy: the Stanford experience

At Stanford University, between 1968 and 1978, 230 patients with pathologic stage I--II Hodgkin's disease were treated on prospective clinical trials with either irradiation alone or irradiation followed by 6 cycles of adjuvant combination chemotherapy. The actuarial survival at 10 yr was 84% for patients in either treatment group. Freedom from relapse at 10 yr was 77% among patients treated with irradiation alone and 84% after treatment with combined modality therapy [p(Gehan) = 0.09]. Freedom from second relapse at 10 yr was 89% and 94%, respectively [p(Gehan) = 0.56]. Several prognostic factors were evaluated in order to identify patients at high risk for relapse or with poor ultimate survival after initial treatment with irradiation alone. Systemic symptoms, histologic subtype, age, and limited extranodal involvement (E-lesions) did not affect the prognosis of patients and failed to identify patients whose survival could be improved by the routine use of combined modality therapy. Patients with large mediastinal masses (mediastinal mass ratio greater than or equal to 1/3) had a significantly poorer freedom from relapse when treated with irradiation alone than when treated initially with combined modality therapy [45% versus 81% at 10 yr, p(Gehan) = 0.03). The 10-yr survival of these patients, however, was not significantly different (84% versus 74%). The implications of these observations on the management of patient with early stage Hodgkin's disease are discussed.     

Development of a marrow transplant regimen for acute leukemia using targeted hematopoietic irradiation delivered by 131I-labeled anti-CD45 antibody, combined with cyclophosphamide and total body irradiation

In an attempt to decrease the relapse rate after bone marrow transplantation (BMT) for advanced acute leukemia, we initiated studies using 131I-labeled anti-CD45 antibody (BC8) to deliver radiation specifically to hematopoietic tissues, followed by a standard transplant preparative regimen. Biodistribution studies were performed in 23 patients using 0.5 mg/kg trace 131I-labeled BC8 antibody. The BC8 antibody was cleared rapidly from plasma with an initial disappearance half-time of 1.5 +/- 0.2 hours, presumably reflecting rapid antigen- specific binding. The mean radiation absorbed doses (cGy/mCi131I administered) were as follows: marrow, 7.1 +/- 0.8; spleen, 10.8 +/- 1.4; liver, 2.7 +/- 0.2; lungs, 2.1 +/- 0.1; kidneys, 0.7 +/- 0.1; and total body, 0.4 +/- 0.03. Patients with acute myelogenous leukemia (AML) in relapse had a higher marrow dose (11.4 cGy/mCi) than those in remission (5.2 cGy/mCi; P = .001) because of higher uptake and longer retention of radionuclide in marrow. Twenty patients were treated with a dose of 131I estimated to deliver 3.5 Gy (level 1) to 7 Gy (level 3) to liver, with marrow doses of 4 to 30 Gy and spleen doses of 7 to 60 Gy, followed by 120 mg/kg cyclophosphamide (CY) and 12 Gy total body irradiation (TBI). Nine of 13 patients with AML or refractory anemia with excess blasts (RAEB) and two of seven with acute lymphocytic leukemia (ALL) are alive disease-free at 8 to 41 months (median, 17 months) after BMT. Toxicity has not been measurably greater than that of CY/TBI alone, and the maximum tolerated dose has not been reached. This study demonstrates that with the use of 131I-BC8 substantially greater doses of radiation can be delivered to hematopoietic tissues as compared with liver, lung, or kidney, which may improve the efficacy of marrow transplantation.