天绿香体外安全性毒理学评价研究

目的:对野生蔬菜天绿香匀浆液的细胞毒性和遗传毒性进行评价.方法:天绿香匀浆液分别以1 450、725、363、181、90.6、45.3、22.6、11.3 mg/ml浓度对人胚肺细胞MRC-5及人肝肿瘤细胞Hep G2染毒,24h后以中性红摄入法对天绿香匀浆液的细胞毒性进行测定,计算IC50;根据细胞毒性结果,以72.5、36.3、18.1 mg/ml天绿香匀浆液处理Hep G2细胞,并同时设阴性对照组(仅加DMEM培养液)和阳性对照组[B(a)P],进行体外微核分析,记录微核细胞数,计算微核率.结果:染毒24 h后观察到天绿香匀浆液对MRC-5细胞的IC50为133.1 mg/ml,而对Hep G2细胞的IC50为185.1 mg/ml,天绿香匀浆液对肺来源细胞的毒性明显大于肝来源的细胞.不同浓度天绿香匀浆液染毒的Hep G2细胞微核率与阴性对照组比较,差异均无统计学意义(P>0.05).结论:天绿香匀浆液对细胞的损伤作用具有一定的组织选择性,对人肺组织来源的细胞损伤作用大于肝组织来源的细胞.未发现到天绿香对Hep G2细胞遗传物质具有损伤作用.     

Contractile responses and structure of small bronchi isolated from rats after 20 months' exposure to ozone

Short-term exposure to high concentrations of ozone has been shown to increase airway responsiveness in normal humans and in all laboratory animal species studied to date. While our knowledge concerning the pulmonary effects of single exposures to ozone has increased rapidly over recent years, the effects of repeated exposures are less understood. The goal of the present study was to determine whether airway responsiveness is increased after near-lifetime exposure to ozone. Airway segments representing approximately eighth generation airways were isolated from Fischer 344 rats of both genders that had been exposed for 6 hr per day, 5 days per week for 20 months to 0, 0.12, 0.5, or 1.0 parts per million (ppm) ozone. Circumferential tension development was measured in isolated airways in response to bethanechol, acetylcholine, and electrical field stimulation. Responsiveness of the airways to the contractile stimuli was described by the effective dose or frequency that elicited half-maximum contraction (ED50) and the maximum response. Since ozone exposure is associated with remodeling of peripheral airways, smooth muscle area was determined and tension responses were normalized to the area measurements. Before normalization of tension data to smooth muscle area, neither the ED50 nor maximum response of small bronchi to the contractile stimuli was altered after chronic ozone exposure. Smooth muscle area was greater in airways isolated from animals that had been exposed to 0.5 ppm ozone. After accounting for smooth muscle area, maximum responses of the small bronchi isolated from male rats were significantly reduced after 0.12 and 0.5 ppm ozone. Although not significant statistically, a similar trend was observed in airways isolated from female rats. These results suggest that the increase in airway responsiveness associated with acute ozone exposure does not persist during near-lifetime exposure. Although the mechanism responsible for the adaptation to the effects of O3 on airway responsiveness is unknown, the results indicate that smooth muscle cell function was compromised by the chronic exposure. The mechanism(s) responsible for mediating this effect and the relevance of these results to humans remains to be determined.     

Relevance of tumor necrosis factor to graft-versus-host disease after small bowel transplantation

The small bowel (SB), an organ replete with lymphocytes, may provoke graft-versus-host disease (GVHD) after transplantation (Tx). Since tumor necrosis factor (TNF) has been suspected of mediating the tissue lesions of GVHD, we sought to determine whether TNF could be detected in the serum of rats undergoing GVHD after SBTx or lymphocyte transfer. For this purpose, postoperative serum TNF activity was determined in Lewis x Brown Norway (LBNF1) hybrid rats suffering from GVHD after undergoing transplantation of an entire (group 1; n = 8) or a segmental (group 2; n = 4) Lew SB, or after i.p. injection with lethal doses (500 x 10(6)) of Lew lymphocytes (group 3; n = 3). Control LBNF1 received i.p. small doses (50 x 10(6)) of Lew lymphocytes (group 4; n = 4). Serum TNF activity was assessed using the WEHI bioassay. In rats with acute and lethal GVHD after entire SBTx (group 1) or injection with large doses of lymphocytes (group 3), TNF activity gradually increased and reached high levels by the time the rats were agonal. In segmental SBTx rats (group 2), GVHD was less severe than in entire SBTx rats. Similarly, the increase in TNF activity was less intense and only transient since it had returned to control levels by the time the rats had completely recovered from GVHD. In control rats primed with small doses of lymphocytes (group 4), GVHD did not occur and no increase in TNF activity was detected.(ABSTRACT TRUNCATED AT 250 WORDS)     

Intestinal adaptation after extensive resection of the small intestine and prolonged administration of parenteral nutrition

After a superior mesenteric thrombosis in a 77 year old man, all but 24 centimeters of the jejunum were resected and anastomosed to the remaining left colon. After being maintained on parenteral nutrition on a 24 hour basis for six weeks, the patient was placed on overnight parenteral nutrition in which he received 2 liters of parenteral nutrition solution containing about 2,200 calories. Over a period of nine months, hypertrophy, lengthening and dilatation took place so that the patient was almost able to support himself by mouth. We believe that this is the first patient in whom documented lengthening of the small intestine has been reported. The factors entering into the hypertrophy and dilatation are discussed. Many patients in this age group are denied therapy because of the consequences of massive enterectomy. With adaptation using prolonged parenteral nutrition, it should be possible for most patients to sustain themselves completely by mouth. Patients with massive necrosis of the small intestine should not be denied therapy even if only 1 foot of small intestine remains. This is likely to hypertrophy in length until parenteral nutrition is no longer necessary.     

Testicular secretions of androgens after prolonged physical effort in man

Variations in plasma testosterone, dihydrotestosterone. delta 4 androstenedione, LH, FSH and cortisol were measured before and after 6 succesive effort tests in 11 male subjects. Testicular secretion and the extra-hepatic consumption of androgens are increased by the haemodynamic conditions of effort but plasma levels of testosterone and dihydrotestosterone fall with repeated effort, indicating a progressive imbalance between production and consumption. These variations suggest that the testis, rather than glucocorticoid function of the adrenal, might play a major limiting role, psychological and metabolic, in tolerance of prolonged effort.     

Neonatal sepsis after prolonged premature rupture of membranes

The objective of this study was to prospectively evaluate the incidence of neonatal sepsis after prolonged premature rupture of membranes (PROM), to correlate sepsis with gestational age and with the duration of PROM, and to evaluate the necessity for prophylactic antibiotic therapy in neonates born after PROM. Of 12,182 infants, 135 (1.1%) were delivered after PROM with a latency period of > 24 hours. Neonatal sepsis occurred in 11 infants (8.1%), 10 of whom were premature. The only term, septic newborn was a small-for-gestational-age infant. A latency period > 72 hours was not associated with an increased incidence of sepsis. Maternal fever, neonatal signs of infection including leukopenia, leukocytosis, thrombocytopenia, and positive gastric aspirate cultures, were not good predictors of sepsis. Of premature infants with PROM, 15% had sepsis, and thus the administration of prophylactic antibiotic therapy in these cases may be warranted. However, it may be unnecessary to administer prophylactic antibiotics to term, appropriate-for-gestational-age infants born after PROM.     

Acid phosphatases in the human testis after prolonged estrogen treatment

The testes of 2 autopsied adult men and 6 subjects, suffering from prostatic carcinoma, were analysed for acid phosphatase activities, Two of the prostatic patients had been receiving estrogen treatment at least for a year and had completely regressed testes. Testes of other subjects contained well-defined tubules with different spermatogenic cells in abundance. The total acid phosphatase activity, assayed in the homogenate, showed a marked reduction in the testes of estrogen-treated subjects. Enzymes were separated by cellulose chromatography or by gel filtration combined with cellulose chromatography. Three activity peaks were resolved by the former and four by the latter technique, when homogenates of the control testes were used. In contrast, two to three strongly reduced activities could be discerned from the testes of estrogen-treated subjects. The specific activity of each enzyme after fractionation was compared between control and regressed testes. No difference was observed in the activities of enzyme I. Enzyme II was markedly reduced in the regressed testes, but was clearly present. Enzymes III and IV were either totally absent or showed a marked reduction in the regressed testes. It is suggested that a correlation exists between the destruction of germ cells, as a consequence of estrogen treatment, and the marked reduction in the activity of enzymes III and IV.     

Awakening of intensive care patients after prolonged continuous sedation

OBJECTIVE: To investigate the relevance of the Symptom Checklist 90-R Obsessive-Compulsive subscale to cognition in individuals with brain tumor. DESIGN: A prospective study of patients assessed with a neuropsychological test battery. SETTING: A university medical center. PATIENTS: Nineteen adults with biopsy-confirmed diagnoses of malignant brain tumors were assessed prior to aggressive chemotherapy. MAIN OUTCOME MEASURES: Included in the assessment were the Mattis Dementia Rating Scale, California Verbal Learning Test, Trail Making Test B, Symptom Checklist 90-R, Mood Assessment Scale, Beck Anxiety Inventory, and Chronic Illness Problem Inventory. RESULTS: The SCL 90-R Obsessive-Compulsive subscale was not related to objective measures of attention, verbal memory, or age. It was related significantly to symptoms of depression (r = .81, P < .005), anxiety (r = .66, P < .005), and subjective complaints of memory problems (r = .75, P < .005). Multivariate analyses indicated that reported symptoms of depression contributed 66% of the variance in predicting SCL 90-R Obsessive-Compulsive Scores, whereas symptoms of anxiety contributed an additional 6% (P < .0001). CONCLUSIONS: Our data suggest that the SCL 90-R is best viewed as an indicator of unidimensional emotional distress and somatic effects of structural brain injury.     

Resuscitating effect of melanocortin peptides after prolonged respiratory arrest

1. The resuscitating activity of melanocortin peptides (MSH-ACTH peptides) was tested in an experimental model of prolonged respiratory arrest. 2. Anaesthetized, endotracheally intubated rats subjected to a 5 min period of ventilation interruption, invariably died from cardiac arrest within 6-9 min of resumption of ventilation. 3. When resumption of ventilation was associated with the simultaneous intravenous (i.v.) injection of a melanocortin peptide (alpha-MSH or ACTH-(1-24)) (160 microg kg(-1) there was an almost immediate (within 1 min), impressive increase in cardiac output, heart rate, mean arterial pressure (+ 560% of the before-treatment value) and pulse pressure (+356% of the before-treatment value), with full recovery of electroencephalogram after 30-45 min. Blood gases and pH were normalized within 15-60 min after treatment, and all treated animals eventually recovered completely and survived indefinitely (= more than 15 days). 4. The same response was observed in adrenalectomized animals, as well as in animals pretreated with a beta1-adrenoceptor blocking agent (atenolol, 3 mg kg(-1), i.v.), or with an alpha1-adrenoceptor blocking agent (prazosin, 0.1 mg kg(-1), i.v.), or with an adrenergic neurone blocking agent (guanethidine, 10 mg kg(-1), intraperitoneally). 5. An effect quite similar to that produced by melanocortins was obtained with ouabain (0.1 mg kg(-1), i.v.); the antioxidant drug, glutathione (75 mg kg(-1), i.v.) also produced 100% resuscitation, but the effect was slower in onset. On the other hand, adrenaline (0.005 mg kg(-1), i.v.) was able to resuscitate only 1 out of 8 rats and dobutamine (0.02 mg kg(-1), i.v.) resuscitated 4 out of 8 rats; moreover, the effect of both catecholamines was much slower in onset than that of melanocortins and the initial, impressive stimulation of cardiovascular function was absent. 6. These results show that melanocortin peptides have a resuscitating effect in a pre-terminal condition produced in rats by prolonged asphyxia. This effect seems primarily due to the restoration of cardiac function, not mediated by catecholamines. These data also suggest that these peptides may have potential therapeutic value in conditions of transient cardiac hypoxia and re-oxygenation such as occur in coronary artery disease.     

Outcome of Graves' disease after antithyroid drug treatment in Taiwan

The outcome of Graves' disease after treatment with antithyroid drugs (ATDs) varies widely among countries, and large-scale studies in Asia are rare. We investigated the associations of various clinical and laboratory features with the outcome of ATD therapy for Graves' disease in Taiwan. A total of 210 patients (177 women, 33 men; mean +/- SD age, 41.7 +/- 15.1 yr) treated with ATD in Taiwan were included. ATD therapy started with methimazole 30 mg daily or propylthiouracil 300 mg daily and was continued until a euthyroid state was achieved. Afterwards, 154 patients received a maintenance dose of ATD alone, while 56 patients received a combination of an ATD and thyroxine (L-T4). Patients were considered to be in remission if they remained in a euthyroid state for more than 2 years after drug withdrawal. The mean follow-up periods were 45.0 +/- 20.9 months for patients with remission and 30.4 +/- 19.8 months for those with relapse. Relapse occurred in 126 (60%) patients during the follow-up period, within 3 months after drug withdrawal in 47 (37%), and within 6 months in 60 (46%). The relapse rate was 100% among patients with two or more previous relapses. Patients with a second occurrence had a higher relapse rate than those with a first occurrence (84% vs 43%). Past history of recurrence, goiter size, thyroid-stimulating hormone level and thyrotropin-binding inhibition immunoglobulin activity at the end of ATD treatment were independently associated with relapse. Prolonged duration of treatment did not yield better results in patients with larger goiters or a history of recurrence, or both. Combination therapy with L-T4 yielded similar results to those achieved with ATD treatment alone. In conclusion, the relapse rate of Graves' disease after ATD treatment in Taiwanese patients was high, especially in those with a history of recurrence. The treatment duration and drug regimen did not affect the outcome.     

Ultrastructural changes in the rat neurohypophysis after a prolonged protein-free diet

The effects on gallbladder contraction of three structurally related peptides, secretin, glucagon and the vasoactive intestinal peptide (VIP) have been compared in urethane-anesthetized guinea pigs. Secretin and glucagon had no effect alone but augmented cholecystokinin (CCK)-induced contractions. VIP decreased CCK-induced contractions.     

Reversible signal abnormalities in the hippocampus and neocortex after prolonged seizures

PURPOSE: To investigate the phenomenon of reversible increased signal intensity of medial temporal lobe structures and cerebral neocortex seen on MR images of six patients with recent prolonged seizure activity. METHODS: After excluding patients with known causes of reversible signal abnormalities (such as hypertensive encephalopathy), we retrospectively reviewed the clinical findings and MR studies of six patients whose MR studies showed reversible signal abnormalities. MR pulse sequences included T2-weighted spin-echo coronal views or conventional short-tau inversion-recovery coronal images of the temporal lobes. RESULTS: All six MR studies showed increased signal intensity within the medial temporal lobe, including the hippocampus in five studies. All follow-up MR examinations showed partial or complete resolution of the hyperintensity within the medial temporal lobe and the neocortex. In one patient, results of a brain biopsy revealed severe cerebral cortical gliosis. Temporal lobectomy performed 4 years later showed moderate cortical gliosis and nonspecific hippocampal cell loss and gliosis. CONCLUSION: Significant hyperintensity within the temporal lobe is demonstrable on MR images after prolonged seizure activity, suggestive of seizure-induced edema or gliosis. Damage to medial temporal lobe structures by prolonged seizure activity indicates a possible mechanism of epileptogenic disorders.     

Marked increase in plasma high-density-lipoprotein cholesterol after prolonged fasting during Ramadan

We evaluated the effect of the Ramadan fasting on plasma lipids and lipoproteins in normal individuals. Twenty-four healthy subjects were studied before the end of the Ramadan month (Ram) and for 1 mo thereafter. Plasma total cholesterol (TC), triglycerides, low-density-lipoprotein cholesterol (LDL-C), and very-low-density-lipoprotein cholesterol (VLDL-C) did not change. High-density-lipoprotein cholesterol (HDL-C) was 30% higher (P < 0.005) at the end of Ram; apolipoprotein A-I also increased (P < 0.0001). Both the ratios of TC to HDL-C and LDL-C to HDL-C (P < 0.001) decreased at Ram. There was a striking nonpharmacologic improvement in plasma HDL-C and ratios of TC to HDL-C and LDL-C to HDL-C, which were most probably induced by eating one large evening meal a day. Further studies to determine the mechanism of this observation are underway.     

Determinants of prolonged mechanical ventilation after coronary artery bypass grafting

BACKGROUND: Early extubation of cardiac surgical patients enhances ambulation, improves cardiopulmonary function, and can lead to savings in health care costs. METHODS: We retrospectively examined the role of 48 variables in determining the period of ventilatory support in 507 patients having coronary artery bypass grafting. RESULTS: Fifteen (< 3%) of 507 patients required ventilatory support in excess of 24 hours. Among the remaining patients, extubation was achieved early (< or = 8 hours) (mean time, 5.65 +/- 1.31 hours) in 53% and late (> 8 hours) (mean time, 13.7 +/- 3.4 hours) in 47%. Logistic and linear multivariate regression analyses implicated increased age, New York Heart Association functional class IV, intraoperative fluid retention, postoperative intraaortic balloon pump requirement, and bank blood transfusions as predictors of late extubation. Also, the linear regression linked lower body weight and number of anastomoses (or grafts) to increased mechanical ventilatory support. CONCLUSIONS: Analysis of the fluid balance and cardiopulmonary bypass data suggests that earlier extubation may be achieved by actively reducing fluid retention (eg, by hemoconcentration) and time on bypass (eg, normothermia). Finally, intensive care unit stay and postoperative length of stay were significantly lower in the early versus late extubation groups without an increase in pulmonary complications.     

Pharmacodynamic profile of prolonged etoposide administration in patients with small cell lung cancer and non-Hodgkin''s lymphoma

The thyrotropin (TSH) receptor belongs to a subfamily of G protein-coupled receptors, which also includes luteinizing hormone and follicle-stimulating hormone receptors. The TSH receptor (TSHR) differs from the latter by the presence of an additional specific segment in the C-terminal part of its ectodomain. We show here that this insertion is excised in the majority of receptor molecules. Preparation of specific monoclonal antibodies to this region, microsequencing, enzyme-linked immunosorbent assay, and immunoblot studies have provided insight into the mechanisms of this excision. In the human thyroid gland, N termini of the transmembrane receptor beta subunit were found to be phenylalanine 366 and leucines 370 and 378. In transfected L cells a variety of other more proximal N termini were found, probably corresponding to incomplete excisions. The most extreme N terminus was observed to lie at Ser-314. These observations suggest that after initial cleavage at Ser-314 the inserted fragment of TSHR is progressively clipped out by a series of cleavage reactions progressing up to amino acids 366-378. The impossibility of recovering the excised fragment from purified receptor, cell membranes, or culture medium supports this interpretation. The cleavage enzyme has previously been shown to be inhibited by BB-2116, an inhibitor of matrix metalloproteases. However, we show here that it is unaffected by tissue inhibitors of metalloproteases. The cleavage enzyme is very similar to TACE (tumor necrosis factor alpha-converting enzyme) in both these characteristics. However, incubation of the TSH receptor with the purified recombinant catalytic domain of TACE, co-transfection of cells with TACE and TSHR expression vectors, and the use of mutated Chinese hamster ovary cells in which TACE is inactive suggested that the TSHR cleavage enzyme is different from TACE. TACE and TSHR cleavage enzyme may thus possibly be related but different members of the adamalysin family of metzincin metalloproteases.     

Segmental right ventricular function after acute myocardial infarction: two-dimensional echocardiographic study in 63 patients

Right ventricular (RV) segmental contraction was studied in 63 patients with acute myocardial infarction (MI), using 2-dimensional (2-D) echocardiography. Group A included 32 patients with ischemic RV dysfunction: 19 had a disproportionate increase in right atrial pressure at the time of the examination (Group AI) and in 13 patients, right atrial pressure was normal when the echocardiogram was obtained (Group AII). Group B included 31 patients without ischemic RV dysfunction. Alkinesia or dyskinesia of the RV wall was found in 30 patients: 19 from Group AI, 8 from Group AII, and 3 from Group B. Asynergy could be identified in all segments of the RV wall including the outflow tract, RV apex, and anterior wall, but was more frequently found in the posterior wall (29 patients), best seen in the transversal subcostal short-axis view. A significant difference was found either in the frequency of wall motion abnormalities or in the number of segments with asynergy among the 3 groups (p less than 0.001). However, asynergy of the RV wall may be present in some patients with normal right heart hemodynamic function, suggesting that asynergy may be more sensitive than hemodynamic function in the diagnosis of acute RV infarction. Paradoxical septal motion was found in 8 patients, all in Group AI, and all had a right atrial pressure equal to or greater than pulmonary capillary pressure.     

Rapid and prolonged impairment of gut barrier function after thermal injury in mice

OBJECTIVE: To determine the diagnostic yield of the nerve-muscle-skin (NMS) biopsy in paediatric neurology practice. STUDY DESIGN: A consecutive series of 98 paediatric NMS biopsies done 1989-1994 retrospectively reviewed in the context of pre-biopsy clinical and laboratory parameters. Bivariate associations based on chi-square test. Unconfounded associations between pre-biopsy variables and positive diagnostic yield (PDY) assessed by multiple logistic regression. RESULTS: Fifty seven out of 98 patients central (global delay, seizures, abnormal CNS imaging) process; 41/98 patients peripheral (motor delay, weakness) process, electromyography-nerve conduction studies (EMG-NCS) 87/98 cases; abnormal 43/87. Positive diagnostic yield (PDY) in 42/98 (43%) biopsies. Statistically significant bivariate associations between PDY and pre-biopsy; age, presenting symptom, developmental delay, weakness, reflexes, CPK, lactate, EMG-NCS and process. Unconfounded associations demonstrated with PDY and age, reflexes and process. The presence of a peripheral process or an abnormal EMG-NCS strongly predictive of PDY: 34/41 (83%) peripheral process cases had PDY, 32/40 (80%) abnormal EMG-NCS cases had PDY, and 29/31 (93.5%) peripheral process and abnormal EMG-NCS cases had PDY. Abnormal EMG-NCS with central process improved PDY to 3/9 (33%) from 4/37 (11%) for normal EMG-NCS. CONCLUSION: NMS biopsy is a valuable diagnostic tool, particularly in the context of a suspected peripheral process or a central processes with an abnormal EMG-NCS.     

Renewal of drug seeking by contextual cues after prolonged extinction in rats.

Contextual stimuli associated with drug exposure can modulate various effects of drugs, but little is known about their role in relapse to drug seeking. Using a renewal procedure, the authors report that drug-associated contextual stimuli play a critical role in relapse to drug-seeking previously maintained by a heroin-cocaine mixture (speedball). Rats were trained to self-administer speedball, after which drug-reinforced behavior was extinguished over 20 days in the self-administration context or in a different context. On the test day, rats exposed to the drug-associated context, after extinction in a different context, reliably renewed drug seeking. The authors suggest that the renewal procedure can be used to study mechanisms underlying relapse to drug seeking elicited by drug-associated contextual stimuli. (PsycINFO Database Record (c) 2010 APA, all rights reserved)