Inhibition of cigarette smoke-related lipophilic DNA adducts in rat tissues by dietary oltipraz

The present study investigated the effects of dietary oltipraz on cigarette smoke-related lipophilic DNA adduct formation. Female Sprague- Dawley rats were exposed daily to sidestream cigarette smoke in a whole- body exposure chamber 6 h/day for 4 consecutive weeks. One group of rats was maintained on control diet while another group received the same diet supplemented with either a low (167 p.p.m.) or high (500 p.p.m.) dose of oltipraz, starting 1 week prior to initiation of smoke exposure until the end of the experiment. Analysis of lipophilic DNA adducts by the nuclease P1-mediated 32P-post-labeling showed up to five smoke-related adducts. Adduct no. 5 predominated in both the lung and the heart while adduct nos 3 and 2 predominated in the trachea and bladder, respectively. Quantitative analysis revealed that the total adduct level was the highest in lungs (270+/-68 adducts/10(10) nucleotides), followed by trachea (196+/-48 adducts/10(10) nucleotides), heart (141+/-22 adducts/10(10) nucleotides) and bladder (85+/-16 adducts/10(10) nucleotides). High dose oltipraz treatment reduced the adduct levels in lungs and bladder by >60%, while the reduction in lungs in the low-dose group was approximately 35%. In trachea, the effect of low and high dietary oltipraz on smoke DNA adduction was equivocal, while smoke-related DNA adducts in the heart were minimally inhibited by high-dose oltipraz. In a repeat experiment that employed a 3-fold lower dose of cigarette smoke, oltipraz (500 p.p.m.) was found to inhibit the formation of DNA adducts in rat lungs and trachea by 80 and 65%, respectively. These data clearly demonstrate a high efficacy of oltipraz in inhibiting the formation of cigarette smoke-induced DNA adducts in the target tissues.      

马蓝的化学成分研究

Seven compounds have been isolated from the whole plant of Strobilanthes cusia (Nees) O. Ktze. Three of them are triterpenes (Ⅰ～Ⅲ), two are indole alkaloids (Ⅳ, Ⅴ), two are quinazolinone alkaloids (Ⅵ, Ⅶ). On the basis of spectral analysis and physicochemical properties, their structures were established as lupeol (Ⅰ), betulin (Ⅱ), lupenone (Ⅲ), indigo (Ⅳ), indirubin (Ⅴ), 4 (3H)-quinazolinone (Ⅵ), 2, 4 (1H, 3H)-quinazolinedione (Ⅶ). Ⅵ and Ⅶ were found from natural plant for the first time.The results of the pharmacological tests demonstrate that compound Ⅴ has anticancer activity and compound Ⅵ has hypotensive action. Compound Ⅶ can be quantitatively determined by HPLC, which may serve as a quality control standard for materia medica and its preparations. Compounds Ⅵ and Ⅶ have been confirmed by means of synthesis.     

差示分光光度法测定制剂中硝苯啶的含量

利用硝苯啶溶液对光不稳定的性质,在波长350nm处测其光照前后的吸收度差值(△A),△A与硝苯啶乙醇溶液浓度在10～60μg/ml范围内呈线性关系。使用本法对硝苯啶片进行了含量测定,并对其类似物进行了干扰试验,排除了组分的干扰。该法的精密度日内为1.3%,日间为1.9%,平均回收率为99.96%。方法简便、快速,不需色谱等分离手段即可达到分析目的,专一性、重复性均较好,是分析硝苯啶制剂的一种新途径。     

B19 parvovirus replicates in circulating cells of acutely infected patients

B19 parvovirus is the etiologic agent of fifth disease and transient aplastic crisis. In natural infections, B19 antigen and DNA have been detected in sera early in the course of aplastic crisis and only rarely in fifth disease. We have found B19 DNA in circulating cells of infected patients by DNA dot blot with a virus-specific probe: in four of four sickle cell patients with aplastic crisis, in one asymptomatic sibling, and in one normal adult with fifth disease. Only two of the sera showed B19 DNA. High-molecular weight intermediate forms were detected by Southern analysis of DNA extracted from cells, thus indicating active replication of virus in cells rather than passive adsorption to their surface membranes. Separation of cells into high- and low-density fractions resulted in a concentration of the virus DNA in the granulocytic fraction.     

In Vitro free radical production in rat esophageal mucosa induced by nicotine

Oxidative stress induced by nicotine was investigated in the esophageal mucosa of rats. The homogenized mucosa was incubated for 30 min with 50, 100, 200, 400, and 800 ng/mg protein/ml nicotine or with 200 ng/mg protein/ml nicotine for 15, 30, 45, and 60 min. Esophageal mucosa was also incubated for 30 min with 200 ng/mg protein/ml nicotine with or without the scavengers superoxide dismutase (SOD), catalase, SOD + catalase, inactivated SOD, inactivated catalase, or albumin. Incubation with 0.9% NaCl served as control. There was a strong correlation between chemiluminescence and the nicotine dose (r=0.75) or the nicotine incubation time (r=0.77). Thirty-minute incubation of the esophageal mucosa with 200 ng/mg protein/ml nicotine increased chemiluminescence 5.5-fold and lipid peroxidation 3.3-fold. This response was dampened by SOD or catalase and abolished by SOD + catalase. Inactivated enzymes or albumin had no scavenging effect. These results demonstrate that nicotine causes oxidative stress to the esophageal mucosa.     

Eosinophil autofluorescence and its use in isolation and analysis of human eosinophils using flow microfluorometry

Unstained human eosinophils exhibit unusually bright autofluorescence, which allows them to be distinguished from other leukocytes using fluorescence microscopy. Eosinophil fluorescence is associated with the cytoplasmic granules of the cells. Eosinophil granule extracts, containing an as-yet-undefined eosinophil fluorescence factor, exhibited excitation maxima at 370 nm and 450 nm, with maximum emission at 520 nm. Eosinophils adhering to opsonized parasites in vitro deposit fluorescent material onto the parasite surface. Eosinophil fluorescence was of sufficient intensity to allow the preparation of viable, highly enriched (greater than or equal to 98%), eosinophil suspensions from peripheral blood of normal and eosinophilic donors using a fluorescence- activated cell sorter. Quantitative studies of eosinophil autofluorescence were performed using flow microfluorometry. Fluorescence intensity of blood eosinophils from normal volunteers and eosinophilic patients varied inversely with the log of the donor's absolute eosinophil count regardless of clinical diagnosis.     

Renal cell carcinoma metastases to gallbladder

A 74-year old man underwent a radical cholecystectomy for presumed gallbladder cancer. The histology of the resected specimen in fact revealed the lesion to be metastatic renal cell carcinoma from his resected right nephrectomy performed 14 years previously.     

Hydroxyurea-induced augmentation of fetal hemoglobin production in patients with sickle cell anemia

Five patients with sickle cell anemia were treated with hydroxyurea (HU), in hopes of augmenting their production of fetal hemoglobin. Laboratory responses in two patients treated for more than 2 years were encouraging and there were suggestions of clinical improvement. Long- term HU therapy should be considered for severely affected adults with sickle cell anemia who are willing to accept what is probably a small risk of carcinogenesis. Preliminary chromosomal analysis and knowledge of the clastogenic properties of HU suggest that conception and pregnancy should be avoided. Pharmacokinetic studies will probably be necessary to adjust individual dosage schedules so that cytotoxicity is avoided. F cell responses can be seen in 2 to 3 weeks if the HU dose is optimal, but establishment of a large number of F cells in the circulation may take a month or longer.     

Pre-B acute lymphoblastic leukemia cells may induce T-cell anergy to alloantigen

Even if neoplastic cells express tumor associated antigens they still may fail to function as antigen presenting cells (APC) if they lack expression of one or more molecules critical for the induction of productive immunity. These cellular defects can be repaired by physiologic activation, transfection, or fusion of tumor cells with professional APC. Although such defects can be repaired, antitumor specific T cells may still fail to respond in vivo if they may have been tolerized. Here, human pre-B cell acute lymphoblastic leukemia (pre-B ALL) was used as a model to determine if primary human tumor cells can function as alloantigen presenting cells (alloAPC) or alternatively whether they induce anergy. In the present report, we show that pre-B cell ALL express alloantigen and adhesion molecules but uniformly lack B7-1 (CD80) and only a subset express B7-2 (CD86). Pre-B ALL cells are inefficient or ineffective alloAPC and those cases that lack expression of B7-1 and B7-2 also induce alloantigen specific T- cell unresponsiveness. Under these circumstances, T-cell unresponsiveness could be prevented by physiologic activation of tumor cells via CD40, cross-linking CD28, or signaling through the common gamma chain of the interleukin-2 receptor on T cells. Taken together, these results suggest that pre-B ALL may be incapable of inducing clinically significant T-cell-mediated antileukemia responses. This defect may be not only due to their inability to function as APC, but also due to their potential to induce tolerance. Attempts to induce clinically significant antitumor immune responses may then require not only mechanisms to repair the antigen presenting capacity of the tumor cells, but also reversal of tolerance.