Pluronic P-85 (poly(55)(oxypropylene)dipoly(s)(oxyethylene)) was used to form daunorubicin containing micelles. This new carrier was tested in vitro on sensitive and resistant ovarian cancer cell lines. Drug incorporation was measured by cytofluorometry and the cytotoxicity was measured by the tetrazolium formazan XTT assay. ID50 of 0.16 and 25 mu g/ml were obtained for conjugated and free daunorubicin respectively. The results obtained suggest that this approach may be used in combination with a chemotherapeutic agent to overcome multidrug resistance. 相似文献
Some patients with an 18p- syndrome show dystonia, and a focal dystonia gene has been mapped to chromosome 18p. The authors evaluated the extent of the deletion in three patients with an 18p- syndrome and dystonia using 14 DNA markers on 18p. A common deleted area, covering the DYT7 locus, places the putative dystonia gene between the telomere of 18p and D18S1104 (49.6 cM). Dystonia in these patients may be caused by haploinsufficiency of the DYT7 gene, a new dystonia gene on 18p, or may result from developmental brain anomalies. 相似文献
Rationale: The forced swimming test (FST) is a behavioral test in rodents that predicts the clinical efficacy of many types of antidepressant
treatments. Recently, a behavior sampling technique was developed that scores individual response categories, including swimming,
climbing and immobility. Although all antidepressant drugs reduce immobility in the FST, at least two distinct active behavioral
patterns are produced by pharmacologically selective antidepressant drugs. Serotonin-selective reuptake inhibitors increase
swimming behavior, while drugs acting primarily to increase extracellular levels of norepinephrine or dopamine increase climbing
behavior. Distinct patterns of active behaviors in the FST may be mediated by distinct neurotransmitters, but this has not
been shown directly. Objectives: The present study examined the role of serotonin in mediating active behaviors in the forced swimming test after treatment
with two antidepressant drugs, the selective serotonin reuptake inhibitor, fluoxetine and the selective norepinephrine reuptake
inhibitor, desipramine. Methods: Endogenous serotonin was depleted by administering para-cholorophenylalanine (PCPA, 150 mg/kg, IP.) to rats 72 h and 48 h
prior to the swim test. Fluoxetine (10 mg/kg, SC) or desipramine (10 mg/kg, SC) was given three times over a 24-h period prior
to the FST. Behavioral responses, including immobility, swimming and climbing, were counted during the 5-min test. Results: Pretreatment with PCPA blocked fluoxetine-induced reduction in immobility and increase in swimming behavior during the FST.
In contrast, PCPA pretreatment did not interfere with the ability of desipramine to reduce immobility and increase climbing
behavior. Conclusions: Depletion of serotonin prevented the behavioral effects of the selective serotonin reuptake inhibitor fluoxetine in the rat
FST. Furthermore, depletion of serotonin had no impact on the behavioral effects induced by the selective norepinephrine reuptake
inhibitor, desipramine. The effects of antidepressant drugs on FST-induced immobility may be exerted by distinguishable contributions
from different neurotransmitter systems.
Received: 4 February 1999 / Final version: 2 June 1999 相似文献
The use of theophylline for the treatment of asthma for 45 of the past 50 years has been for its ability to dilate bronchi. The problem has been that at the most effective bronchodilating dose, toxicity was too close for comfort. In the past 5 years, there has been resurgence in theophylline use at lower doses because of some well-documented anti-inflammatory and steroid sparing effects. 相似文献
Objectives. Mexican Americans (MAs), compared to white non‐Hispanics (WNHs), have higher rates of biliary disease, noninsulin dependent diabetes, and endstage renal disease but lower rates of lung cancer, hip fractures, and mortality from coronary heart disease. Relatively little research has been done to identify other ethnic differences in disease incidence. We used surgical procedure rates to confirm known ethnic differences and to explore our clinical suspicion that MAs have higher rates of appendectomy than WNHs.
Methods. We used a registry of surgical procedures at two teaching hospitals in South Texas to calculate proportional operation ratios (PORs) for MAs versus WNHs. These two hospitals are the primary source of acute hospital care for the indigent in the area. The POR is arithmetically identical to proportional incidence and mortality ratios.
Results. MAs underwent appendectomy proportionally more often than WNHs at both hospitals (POR = 1.41 and 1.75, p < 0.0001). Other significant PORs were consistent with known ethnic disease differences in biliary tract operations, vascular access for chronic hemodialysis, lung cancer, and coronary artery bypass.
Conclusions. These findings support the hypothesis that MAs may undergo appendectomy more often than WNHs and so may be at higher risk of appendicitis. 相似文献
A group B streptococcus (GBS) isolated from human neonates diagnosed with sepsis and respiratory distress (early-onset disease) produces a polysaccharide exotoxin (GBS toxin) that, when infused in sheep, causes lung pathophysiology similar to that seen in humans. Histological studies have demonstrated that GBS toxin induces a strong inflammatory response in the lung, with pulmonary sequestration of granulocytes and extensive capillary endothelial damage. The susceptibility of humans to GBS toxin is age-dependent and limited to about 4 days after birth. It is rarely evident thereafter. This suggests that the binding of GBS toxin to the target endothelium occurs via specific components in the developing lung endothelial cells of the newborn that are later lost. We report here that GBS toxin can also bind to developing endothelium associated with neoplasia and induce an inflammatory response. GBS toxin was shown by immunohistochemistry to bind to capillary endothelium of human large-cell carcinomas. In nude mice bearing human tumor xenografts, intravenously administered GBS toxin caused tumor necrosis and hemorrhagic lesions, and substantially inhibited the rate of growth of the tumors. In BALB/c mice bearing Madison lung tumors, GBS toxin induced an inflammatory response resulting in marked changes in tumor morphology, including vasodilation, endothelial and tumor cell necrosis, invasion of lymphocytes and macrophages, and capillary thrombosis. In these tumor models, no evidence of toxicity to the vasculature of other tissues was observed. The reported pathophysiology of GBS in human neonates, the lack of disease in non-neonates colonized with GBS, and these results suggest that GBS toxin may have potential as a well tolerated agent in cancer therapy of some human tumors.Abbreviations GBS
group BStreptococcus
- PBS
phosphate-buffered saline
This work was supported in part by a grant from the March of Dimes Foundation 相似文献