Acute and Subacute Toxicity of Aspilia Africana Leaves

This study was designed to evaluate the toxicity of the aqueous extract of Aspilia africana leaves. Oral doses of 500 mg/kg and 1000 mg/kg were administered for 28 days to rats after every 2 days for sub-acute toxicity. For acute toxicity, 5 doses of 2, 4, 8, 12 and 16g/Kg body weight were investigated in mice. The control groups consisted of mice or rats administered with distilled water. The signs of toxicity fluctuated lightly from one mammal to another throughout the experiment. The liver, kidneys and heart weight of rats revealed no significant differences between the test groups and the control. The results indicated that the medium lethal dose (LD₅₀) was found to be greater in females than males with an average of 6.6g/Kg body weight for both sexes. Regardless of the significant differences observed at certain points in some biochemical parameters (ALT, AST, ALP, Creatinine and Glutathione); none showed any linear dose responsiveness. On the other hand, most of the parameters investigated were found to be gender dependent. These results suggested that A Africana can be classified among substances with low toxicity.     

X(γ)刀输出吸收剂量的测量与验证

目的：目前，国内X（γ）刀的国家检定规程正在起草之中，本文的目的是为X（γ）刀剂量测量提供合理的设备与吸收剂量计算方法。材料与方法：利用德国PTW-UNIDOS剂量仅与有效体积为0．015cc的针尖电离室及自制的小体积半导体探测器相匹配，在160mm直径的有机玻璃球形模体内测量X（γ）刀的输出吸收剂量，并验证其治疗计划的实际输出剂量，得到较满意的结果。结论：为了保证剂量的准确度，X（γ）刀治疗计划系统的实际输出剂量应定期在现场测量与验证，所用探测器的直径应小于射野直径的1／2，小灵敏体积的半导体探测器适宜X（γ）刀小野(如：Ф4mm)的测量。     

Role of ventricular assist devices in the German heart allocation system

The Eurotransplant (ET) allocation algorithm, newly implemented in 2000, gives priority for heart transplantation (HTx) to patients with high urgency (HU) status, but now this status is rescinded upon ventricular assist device (VAD) implantation and only regained if severe complications occur during mechanical circulatory support (MCS). We studied the effects of this change on the patients in our institute who were waiting for HTx with MCS. The median duration of MCS until HTx in adult patients gradually increased from 3.1 months in 1994, reaching a peak of 16.7 months in 2000, and then gradually decreased to 6.0 months in 2003. Among the patients with VAD implantation as a bridge to HTx, two patients were on MCS for more than 1 year (the longest duration of MCS being 1.6 years) at the end of 1999, and this figure increased to nine patients and a maximum MCS duration of 3.7 years at the end of 2003. These data imply that the patients in whom a complication occurred in the early phase of MCS and who had overcome this complication underwent HTx early with HU status, and those who were stable during MCS waited a long time for HTx. Furthermore, the number of patients in the latter group is increasing. The new allocation algorithm imposes on patients with MCS waiting for HTx who are relatively young and free from complications and serious coexisting disease, very long-term MCS without an end to VAD bridging, which is almost equivalent to destination therapy. Part of this paper was presented at the 42nd JSAO Conference (Tokyo, October 5–7, 2004)     

脑康复冲剂对大鼠软脑膜微循环作用的实验研究

目的：脑康复冲剂临床用于治疗脑血栓血瘀证患者，本实验观察其对在大鼠实验性软脑膜微循环障碍的影响。方法：大鼠预防性给药，用高分子右旋糖酐水溶液静脉注射形成大鼠软脑膜的微循环障碍，观察脑康复冲剂对大鼠微循环的影响。结果：用高分子右旋糖酐造模后，大鼠软脑膜的微循环发生障碍，表现为血液流速减慢、血细胞聚集等，脑康复冲剂组血流速度开始减慢的时间明显比生理盐水对照组延长，且分级数也明显优于生理盐水组，对高分子右旋糖酐造成的血液流态障碍，脑康复组明显好于生理盐水组（P＜0．05），毛细血管网交叉点数开始减少的时间也比生理盐水对照组延长，差异显著（P＜0．01）。结论：脑康复冲剂使大鼠血流速度和血液流态得到改善，具有预防和改善动物脑微循环障碍的作用。     

Pharmacokinetic studies of high-dose metoclopramide with and without forced diuresis

Summary The pharmacokinetics of high-dose metoclopramide (10 mg/kg body wt. in five infusions of 2 mg/kg body wt. each) was studied in 11 patients (5 females, 6 males) in two groups: group A with and group B (consisting of five patients) without forced diuresis. When the drug was infused, forced diuresis had no influence on the pharmacokinetics of metoclopramide (serum level after the 1st infusion was 851±361 ng/ml in group A versus 840±348 ng/ml in group B; after the 5th infusion it was 2,005±588 ng/ml in group A versus 2,463±1,350 ng/ml in group B). There were significant differences in the 24-h serum levels (582±308 ng/ml in group A versus 379±170 ng/ml in group B;P<0.05) and in the elimination half life (8.5±2.6 h in group A versus 6.1±1.1 h in group B;P<0.05). The results demonstrate that the dosage regimen originally suggested by Gralla for cytostatic drugs, with forced diuresis for high-dose metoclopramide therapy, may also be applied, with no dosage reduction, with to other cytostatic drugs which do not require forced diuresis.     

急进高原人群脑血流量测定对急性高原病易感人群预测的临床与实验观察

本文对三级急进高原人群资料回顾分析了急进高海拔区（＞4500M）人群脑皿流量测定的临床意义。结果表明急进高原人群脑血流量较在低海拔区明显增高，有显著性差异；而急进高原人群中的急性高原反应和急性高原病患者脑血流量又显著高于高原适应人群。采用药物和吸氧治疗急进高原人群中急性高原反应人群，脑血流量明显降低，急进高原人群的高原反应程度和急性高原病的发病率亦相应降低。因此监测急进高原人群的脑血流量，不仅可以早期发现急性高原反应及急性高原病患者，更可以预测急性高原易感者，可为急性高原病的早期治疗和预防，扩大高原适应人群提供重要的理论依据。     

Role of O2-sensitive K and Ca channels in the regulation of the pulmonary circulation: Potential role of caveolae and implications for high altitude pulmonary edema

High altitude pulmonary edema (HAPE) is a potentially fatal complication in response to exposure to low O₂ at high altitudes. Hypoxia, by causing pulmonary vasoconstriction, increases pulmonary vascular resistance and pulmonary arterial pressure, both of which are features in the pathogenesis of HAPE. Uneven hypoxic pulmonary vasoconstriction is thought to be responsible for increased capillary pressure and leakage, resulting in edema. O₂-sensitive ion channels are known to play pivotal roles in determining vascular tone in response to hypoxia. K⁺, Ca²⁺ and Na⁺ channels are ubiquitously expressed in both endothelial and smooth muscle cells of the pulmonary microvasculature, subfamilies of which are regulated by local changes in P_O2. Hypoxia reduces activity of voltage-gated K⁺ channels and down-regulates their expression leading to membrane depolarization, Ca²⁺ influx in pulmonary artery smooth muscle cells (by activating voltage-dependent Ca²⁺ channels) and vasoconstriction. Hypoxia up-regulates transient receptor potential channels (TRPC) leading to enhanced Ca²⁺ entry through receptor- and store-operated Ca²⁺ channels. Altered enrichment of ion channels in membrane microdomains, in particular in caveolae, may play a role in excitation–contraction coupling and perhaps in O₂-sensing in the pulmonary circulation and thereby may contribute to the development of HAPE. We review the role of ion channels, in particular those outlined above, in response to low O₂ on vascular tone and pulmonary edema. Advances in the understanding of ion channels involved in the physiological response to hypoxia should lead to a greater understanding of the pathogenesis of HAPE and perhaps in the identification of new therapies.     

Unusual reactions following insect stings. Clinical features and immunologic analysis.

Fifteen patients were studied who had unusual reactions following insect stings. These included serum sickness, neurologic disease, renal disease, and delayed hypersensitivity-type reactions. The clinical features are briefly outlined. Measurements were made of serum venom-specific IgE and IgG antibodies. These antibodies were present in some patients and in these instances suggested an immunologic pathogenesis for the reactions. Alternative etiologies for the unusual reactions are also discussed.     

High endothelial-like venules in chronically inflamed periodontal tissues exchange polymorphs

A survey of 58 gingival biopsies revealed the presence of periodontal high endothelial-like venules (PHELVs) in chronically inflamed gingival tissues. PHELVs were found to exchange polymorphonuclear cells (PMNs) almost exclusively in advanced periodontitis, with PMNs greatly exceeding the number of mononuclear cells found in PHELVs (P less than 0.001). Electron microscopy confirmed the emigration of PMNs from these vessels. The enzyme histochemical and ultrastructural features as well as the 35SO4 uptake properties of PHELVs were similar to those of the well-characterized high endothelial venules (HEVs) of rat lymph nodes. It is generally accepted that HEVs in lymphoid tissues and inflammatory sites are specially adapted to assist in the emigration of lymphocytes. However, the observation of preferential PMN emigration in the apparent absence of lymphocyte exchange from PHELVs compels further investigation of other possible functions for HEVs. In relation to this, endothelial cells are capable of producing potent cytokines and inflammatory mediators which may contribute to the development of lesions, and the possibility is discussed that high endothelial cells are functionally adapted to enhance the production of such factors.     

Characteristics of histopathological and ultrastructural features of placental villi in pregnant Nepalese women

The placenta is an important functional unit for gas transfer between mother and fetus. The placental membrane, consisting of trophoblast layer interposed between maternal and fetal blood, plays an active role for intensity of respiration, but no morphological evidence has been documented. Until now, it has been reported that fetal growth retardation and increased fetal mortality rate usually could be seen at high altitude. In an attempt to find the cause of high perinatal mortality rate in Nepal, this study was undertaken to examine pathologically about 1000 Himalayan placentas obtained in Nepal and Tibet since 1977, and the results were compared with those of 5500 Japanese placentas at Saitama Medical School since 1990. In this study, characteristics of ultrastructural features of the Nepalese placental villi investigated in recent years are reported. (1) The gross characteristics of placental pathology in the Himalayan group were represented by marked subchorionic fibrin deposits and increased chorionic cysts in contrast to low incidence of intervillous thrombosis compared with those of the Japanese group. (2) As characteristics of histological findings of the placental villi between Himalayan and Japanese groups, the incidence of chorangiosis and chorangioma in the Himalayan group was significantly higher than that in the Japanese group. (3) Accompanying an increase of vasculosyncytial membrane (VSM) in the villi, thickness and separation of basement membrane of the syncytium in addition to increased apoptosis of syncytial cell nuclei were recognized. (4) As characteristic ultrastructural features of chorionic villi of Nepalese placentas, an increase of mitochondria and cystic formation of rough endoplasmic reticulum (rER), in addition to appearance of lamellar bodies similar to alveolar epithelial type II cell in organellae of the syncytium, were observed. These ultrastructural changes of the placental villous capillaries may be ascribed to hypevascularization caused by the chronic hypoxic state. It is, therefore, presumed that trophoblast cells may play an important role for gas transfer mecha-nism under such a hypoxic state at high altitude.