Intratracheal instillation of zinc-cadmium sulfide (ZnCdS) in Fischer 344 rats

The purpose of this study was to assess the bioavailability and pulmonary toxicity of ZnCdS in rats. Groups of 30 male Fischer 344 rats each were anesthetized and dosed via intratracheal instillation with 5 mg of either ZnCdS, quartz (positive control), or titanium dioxide (TiO(2), negative control) suspended in 0.5 ml saline. A vehicle control group received 0.5 ml saline. Ten animals from each test group were sacrificed at 1 day, 1 wk, and 14 wk after dosing for bronchoalveolar lavage fluid (BALF) analysis and histopathology. The BALF was analyzed for alkaline phosphatase, acid phosphatase, lactate dehydrogenase (LDH), beta-glucuronidase (beta-glu), total protein, and cell counts. Two separate groups of 24 rats each were dosed as already described with either ZnCdS or saline. Eight rats from each group were sacrificed at 1 day, 1 wk, and 14 wk after dosing for determination of cadmium (Cd) and zinc (Zn) concentrations in the lung, liver, kidney, and blood. Results indicate that at 1 day after dosing, all enzyme activities (except acid phosphatase) and cell counts in BALF from the quartz and ZnCdS groups were significantly higher than in the TiO(2) and saline groups. At 7 days after dosing, high enzyme activity persisted in the quartz group, while the ZnCdS group showed only LDH and total protein levels significantly higher than the saline group. At 14 wk after dosing, LDH, total protein, beta-glu, and cell counts in the quartz group were significantly higher than all other groups. Histologic examination revealed interstitial inflammation and accumulation of foreign material in the lungs and mediastinal lymph nodes of quartz-, TiO(2)-, and ZnCdS-treated rats. Metal analyses in tissues showed profuse Cd and Zn concentrations in the lung 1 day after dosing, followed by a successive decline at 7 days and 14 wk after dosing. A very small, but statistically significant, amount of Cd and Zn was found in the kidneys at 14 wk after dosing. In conclusion, ZnCdS appears to cause temporary lung inflammation, is cleared slowly, and is poorly bioavailable.     

Kinin metabolism in the perfused ventilated rat lung. II: Influence of ventilation, perfusion, and perfusate composition variation on bradykinin metabolism in uninjured lung.

Bradykinin metabolism by peptidases of the pulmonary endothelium has been investigated in the previously uninjured, ventilated, and asanguinously perfused rat lung. The influence of short-duration (up to 20 min) abnormal ventilation and perfusion conditions on bradykinin metabolism was assessed. Neither variation of the oxygen concentration (0 to 45%) nor omission of carbon dioxide in the ventilatory gas altered bradykinin metabolism significantly. Tidal volume variation did not alter bradykinin metabolism, and exclusion of one lung from the perfusion circuit reduced the capacity to degrade bradykinin proportionately. Acidification of the perfusion medium to pH 5 did not alter bradykinin metabolism. Acetylsalicylic acid in the perfusate protected the lung from an otherwise irreversible pressure increase associated with high-dose bradykinin perfusion. Endotoxin and hydrogen peroxide in the perfusate did not alter bradykinin metabolism. However, ammonia in the ventilatory gas caused immediate pulmonary edema, diminished lung capacity to metabolize bradykinin and altered the pattern of bradykinin metabolic products. The pulmonary endothelium itself, in the absence of blood, maintains its capacity to metabolize bradykinin under an extraordinary range of conditions.     

计算机程序化的初均速法测定双黄连注射液的稳定性

用计算机程序化的初均速法,测定了双黄连溶液中3种主要成分——绿原酸、黄苓甙、连翘甙的活化能及室温贮存期。该方法简便、快速、结果准确。对临床应用有一定价值。     

Dose-dense vinorelbine and docetaxel with Filgrastim support in patients with advanced nonsmall cell lung carcinoma

BACKGROUND: Vinorelbine and docetaxel are active single agents in the treatment of nonsmall cell lung carcinoma (NSCLC) and may provide enhanced activity when combined in a dose-dense fashion. The efficacy and safety of this combination was assessed when it was administered every 14 days with Filgrastim support in a community practice setting. METHODS: This open-label study was conducted at 12 community oncology practices in the United States. Sixty-one chemotherapy-naive patients with Stage IIIB/IV NSCLC received vinorelbine 45 mg/m2 followed by docetaxel 60 mg/m2 on Day 1 and Filgrastim 5 mcg/kg beginning on Day 2, with cycles repeated every 14 days. RESULTS: Among 61 enrolled patients, 44% of patients had either a complete or partial response as their best response, and 27% of patients had confirmed complete or partial responses. The median time to confirmed response was 1.9 months (95% confidence interval [95% CI], 0.9-2.3 mos), and the median duration of confirmed response was 6.0 months (95% CI, 3.1-14.4 mos). The median time to disease progression was 4.9 months (95% CI, 3.8-5.8 mos). With a median follow-up of 14.3 months, the median survival was 12.9 months (95% CI, 8.1-14.3 mos), and the 1-year survival rate was 56% (95% CI, 43-69%). The relative dose intensity was 94% for vinorelbine and 93% for docetaxel. Febrile neutropenia occurred in 9 patients (15%) and during 9 of 351 cycles (3%). CONCLUSIONS: It was possible to administer dose-dense vinorelbine and docetaxel chemotherapy with Filgrastim support, beginning in the first cycle, to patients with NSCLC who were treated in a community practice setting.