青蒿琥酯皮肤擦剂在小鼠和兔体内的药代动力学研究

将青蒿琥酯溶于苯二甲酸二甲酯,加适量氨酮制成皮肤擦剂。给兔脱毛后,皮肤涂抹此擦剂25mg/kg后,血药浓度达峰时间平均为2 h,峰浓度平均为1.80μg/ml。药物在兔体内平均驻留时间为3.54 h,清除半衰期约为2.46 h。给小鼠脱毛皮肤涂抹擦剂6.7,31.3和71.4 mg/kg,血药浓度在给药后0.5～4 h达高峰,峰浓度分别为0.82,2.05和7.11μg/ml,体内药物平均驻留时间为3.39,2.79及3.54 h,清除半衰期为2.35,1.93及2.45 h。可见,给兔及小鼠皮肤擦剂后,青蒿琥酯吸收良好,血药浓度维持时间较长。     

Disturbance of systemic antioxidant profile in nonsmall cell lung carcinoma.

The present study aimed to determine the alterations of antioxidant activities in erythrocytes from patients with nonsmall cell lung carcinoma (NSCLC). A comparative study of the systemic antioxidant activities in red blood cell lysate from subjects with NSCLC and healthy control subjects was conducted. The antioxidants catalase, superoxide dismutase (SOD) and glutathione peroxidase (GPx) were measured using chemical kinetic reactions under spectrophotometry. In total, 189 cases of mostly advanced-stage IIIB or stage IV NSCLC and 202 healthy controls were studied. In subjects with lung cancer, there was similar catalase activity, lower SOD activity (median (interquartile range) 13.4 (9.0-27.2) versus 48.7 (27.0-64.3) U x (ghaemoglobulin(Hb)(-1)), and higher GPx activity (175.2 (126.6-288.3) versus 49.2 (39.5-59.2) mU x (gHb)(-1)) compared with controls. The antioxidant activities in lung cancer subjects were not associated with age, sex, smoking status, or tumour cell types. However, more advanced disease (stage IV compared with stage IIIB) was associated with lower SOD activity. Using multivariable analysis, the presence of lung cancer independently predicted SOD and GPx activities. In conclusion, nonsmall cell lung carcinoma in Chinese subjects is associated with alterations in systemic antioxidant activities, which may play an important role in carcinogenesis.     

Role of prolactin in modulating the effects of tamoxifen on growth of the Dunning R3327 rat prostate adenocarcinoma

Tamoxifen (TAM) has previously been shown to inhibit growth of the Dunning R3327 rat prostate adenocarcinoma and to elevate serum prolactin levels. The purpose of this study was to determine the role of prolactin in modulating the effects of tamoxifen on growth of the R3327 prostatic adenocarcinoma. Intact and castrated Copenhagen-Fischer male rats bearing the Dunning R3327 rat prostatic tumor were divided into groups and injected sc five times per week for 16 weeks as follows: vehicle; TAM (0.5 mg/kg); haloperidol (HALO; 0.5 mg/kg); bromocriptine (CB-154; 5 mg/kg); TAM plus HALO; or TAM plus CB-154. In both intact and castrated rats, agents that either raised (HALO) or lowered (CB-154) serum prolactin had little effect on prostatic tumor growth when administered singly. In intact rats, average tumor diameter in vehicle-treated controls increased 421% 16 weeks after the start of the experiment, and treatment with TAM or TAM plus HALO reduced this tumor growth by approximately one-half. Interestingly, CB-154 administered in combination with TAM completely blocked TAM inhibition of tumor growth in intact rats. In contrast to these results in intact rats, average tumor diameter increased 129% in TAM- and 118% in TAM plus HALO-treated castrated rats and was significantly greater than the characteristic retardation of tumor growth (49% increase) that occurred in the vehicle-treated castrate controls. In addition, combined treatment of TAM plus CB-154 in castrate rats resulted in an even greater increase (188%) in average tumor diameter. The inhibitory effect of TAM on R3327 prostatic tumor growth in intact rats appears to be an indirect effect resulting from its ability to reduce serum testosterone levels. In contrast, the stimulatory effect of TAM in castrate rats appears to result directly from an estrogen-like action, which can directly enhance prostatic tumor growth in the presence of low levels of circulating androgens; this stimulatory effect of TAM is more pronounced when prolactin levels are suppressed by CB-154. Clearly, castration alone is more effective than TAM therapy alone or in combination with castration in the retardation of the growth of the androgen-dependent R3327 prostatic tumor in rats.     

Mycobacterium marinum infection of the hand and wrist. Results of conservative treatment in twenty-four cases

Inadequate débridement, extensive scarring, and breakdown of the wound have been commonly encountered after surgical débridement has been employed as the initial treatment of infection with Mycobacterium marinum involving the deep structures of the hand. Because of our disappointment with the results of this form of treatment, from 1982 to 1986 we treated twenty-four patients who had such an infection with rifampicin and ethambutol after a diagnostic biopsy was done. Surgical treatment was deferred until it was determined that the infection had not been controlled by the chemotherapy. The clinical outcome for these patients could be divided into three patterns: eleven patients (Group I) had a good result with no complications, three patients (Group II) had delayed healing of the wound, and ten patients (Group III) did not have a good response to conservative treatment and required one or more surgical débridements. Complications were sometimes associated with use of the drugs, and loss of visual acuity was a concern in three patients. In twenty-one (87 per cent) of the patients, at follow-up the function of the treated hand was equal to that of the other hand. Persistent pain, a discharging sinus, and previous local injection of steroids were unfavorable prognostic factors. If these factors are present, surgical débridement is advised.     

Systemic effects of inflammation in bronchiectasis

A group of bronchiectatic subjects in the clinically stable state were studied for systemic evidence of inflammation. The following parameters were evaluated: body weight, serum albumin, serum globulin, serum alpha 1-antitrypsin (alpha 1 AT) and peripheral white cell count. For serum albumin and globulin, comparison was made between subjects with bronchiectasis and control subjects with no known pulmonary disease matched for sex and age, and for serum alpha 1 AT and peripheral white cell count, matched for smoking habit as well. The bronchiectatic subjects showed systemic effects of inflammation as indicated by lower body weight and serum albumin (P less than 0.01), higher serum globulin (P less than 0.001), serum alpha 1 AT (P less than 0.05) and total leucocyte count (P less than 0.05). Differential white cell count showed that the elevation was distributed in most cell types. Correlation matrix was done for the above systemic parameters and indices of airway inflammation including sputum volume, purulence, and polymorph count and FEV1. There was an inverse correlation between total peripheral WBC count and FEV1 in percentage of predicted (P less than 0.01), and a positive correlation between sputum purulence and sputum polymorph score (P less than 0.05). This suggests that host peripheral leucocyte response may be a factor in the determination of lung function.     

Polymorphisms in manganese superoxide dismutase and catalase genes: functional study in Hong Kong Chinese asthma patients

BACKGROUND: Reactive oxygen species may contribute to the pathogenesis of asthma. Functional genetic polymorphisms of antioxidant enzymes, superoxide dismutase (SOD) and catalase are good candidates for asthma susceptibility. OBJECTIVE: To investigate the association of the manganese-containing form of SOD (MnSOD) gene at amino acid position 16 (Val16Ala) and catalase gene in the promoter at A-21T and C-262T polymorphisms and asthma in a Hong Kong Chinese population. METHODS: The association study was conducted in a case-control design in asthma patients (n=251) and healthy controls (n=316) by genotyping. The functional significance was assessed by determining erythrocyte SOD and catalase activity. RESULTS: The Val allele of MnSOD at Val16Ala and the A allele of catalase gene at A-21T were not different between patients and controls, while the C allele of catalase gene at C-262T was found to be significantly different between patients and controls (P=0.033). The less frequent variant of catalase gene (-262T) was found to be protective from the development of asthma in a Hong Kong Chinese non-smoking population (adjusted odds ratio=0.35, 0.15-0.85; P=0.017). Asthma patients had elevated erythrocyte SOD and catalase activities in comparison with healthy controls (P<0.01). However, their activities were not associated with different genotypes within healthy controls or asthma patients. CONCLUSION: This is the first report showing that SOD and catalase functional activities are not associated with their respective genetic polymorphisms but related to the presence of asthma in a Hong Kong Chinese population.     

Maintenance of body temperature in elderly patients who have joint replacement surgery A comparison between the heat and moisture exchanger and heated humidifier

The effect of a heat and moisture exchanger on intra-operative aural canal (core) and mean skin temperatures was investigated in elderly patients who had elective total hip arthroplasty under general anaesthesia with artificial ventilation of the lungs. Group 1 (n = 20) did not receive any form of artificial humidification while in group 2 (n = 20) a heat and moisture exchanger was inserted in the breathing system and in group 3 (n = 20) the inspired gases were humidified and warmed at 40 degrees C by means of a heated humidifier. Time of surgery, intravenous fluid administration and operating theatre temperature were standardised. Mean (SD) aural canal (core) temperature decreased significantly in groups 1 and 2 (p less than 0.001), while there was a fall of 0.3 degrees C (0.6) in group 3, which was not significant. Mean skin temperature decreased during anaesthesia and surgery in both groups 1 and 2 (p less than 0.05), while it increased in group 3. There was a significantly greater loss of body heat in groups 1 and 2 compared with group 3 intra-operatively (p less than 0.001). We conclude tha a heat and moisture exchanger did not prevent the decrease in intra-operative body temperature in elderly patients.