蝙蝠葛中的新生物碱——蝙蝠葛新林碱

防已科植物蝙蝠葛(Menispermum daurioum DC.)的根茎,即北豆根,是一种重要的中药,具有清热解毒、消肿止痛等功效。已知含有近二十种生物碱,其中五种属双苄基四氢异喹啉类,即蝙蝠葛碱(dauricine,Ⅰ)、蝙蝠葛诺林碱(daurinoline,Ⅱ)、蝙蝠葛新诺林碱     

Adjuvant systemic therapy in "early" breast cancer.

"Early" breast cancer is a systemic disease in the majority of cases. Progress has been and is being made toward the determination of those women at risk of recurrence. Attractive as it seems, the value of systemic adjuvant therapy, given at the time of minimal tumour load i.e., after mastectomy, is not proven. Therefore, for the average case it is better to treat the cancer locally and to observe and leave further evaluation of systemic therapy to those centres which are able to conduct controlled, randomized trails.     

Identification of differentially expressed genes in aflatoxin B1- treated cultured primary rat hepatocytes and Fischer 344 rats

Aflatoxin B1 (AFB1), a mutagen and hepatocarcinogen in rats and humans, is a contaminant of the human food supply, particularly in parts of Africa and Asia. AFB1-induced changes in gene expression may play a part in the development of the toxic, immunosuppressive and carcinogenic properties of this fungal metabolite. An understanding of the-role of AFB1 in modulating gene regulation should provide insight regarding mechanisms of AFB1-induced carcinogenesis. We used three PCR- based subtractive techniques to identify AFB1-responsive genes in cultured primary rat hepatocyte RNA: differential display PCR (DD-PCR), representational difference analysis (RDA) and suppression subtractive hybridization (SSH). Each of the three techniques identified AFB1- responsive genes, although no individual cDNA was isolated by more than one technique. Nine cDNAs isolated using DD-PCR, RDA or SSH were found to represent eight genes that are differentially expressed as a result of AFB1 exposure. Genes whose mRNA levels were increased in cultured primary rat hepatocytes after AFB1 treatment were corticosteroid binding globulin (CBG), cytochrome P450 4F1 (CYP4F1), alpha-2 microglobulin, C4b-binding protein (C4BP), serum amyloid A-2 and glutathione S-transferase Yb2 (GST). Transferrin and a small CYP3A-like cDNA had reduced mRNA levels after AFB1 exposure. Full-length CYP3A mRNA levels were increased. When liver RNA from AFB1-treated male F344 rats was evaluated for transferrin, CBG, GST, CYP3A and CYP4F1 expression, a decrease in transferrin mRNA and an increase in CBG, GST, CYP3A and CYP4F1 mRNA levels was also seen. Analysis of the potential function of these genes in maintaining cellular homeostasis suggests that their differential expression could contribute to the toxicity associated with AFB1 exposure.      

Immune responses against SARS-coronavirus nucleocapsid protein induced by DNA vaccine

The nucleocapsid （N） protein of SARS-coronavirus （SARS-CoV） is the key protein for the formation of the helical nucleocapsid during virion assembly. This protein is believed to be more conserved than other proteins of the virus, such as spike and membrane glycoprotein. In this study, the N protein of SARS-CoV was expressed in Escherichia coli DHSalpha and identified with pooled sera from patients in the convalescence phase of SARS. A plasmid pCI-N, encoding the full-length N gene of SARS-CoV, was constructed. Expression of the N protein was observed in COS1 cells following transfection with pCI-N. The immune responses induced by intramuscular immunization with pCI-N were evaluated in a murine model. Serum anti-N immunoglobutins and splenocytes proliferative responses against N protein were observed in immunized BALB/c mice. The major immunoglobulin G subclass recognizing N protein was immunoglobulin G2a, and stimulated splenocytes secreted high levels of gamma interferon and IL-2 in response to N protein. More importantly, the immunized mice produced strong delayed-type hypersensitivity （DTH） and CD^8＋ CTL responses to N protein.     

Impact of the '2 week wait' directive for suspected cancer on service provision in a symptomatic breast clinic

BACKGROUND: The '2 week wait' directive (Health Service Circular (HSC) 1998/242) guaranteeing that 'everyone with suspected breast cancer will be able to see a specialist within two weeks of their general practitioner (GP) deciding they need to be seen urgently' is a unique audited approach to access for the British National Health Service, the effects of which have been assessed in a non-academic symptomatic breast clinic. METHODS: New GP referrals (n = 607) were reviewed prospectively in two comparable 3-month intervals, beginning 1 April 1998 and 1 April 1999, to determine the probability of a breast cancer diagnosis from the referral letter and the effects of the directive on waiting times for appointments and utilization of clinics. RESULTS: The urgency of referral was not specified in 53 per cent of GP referrals. For the 'urgent' cases (25 per cent of all new referrals) the probability of a final diagnosis of breast cancer was 0.19. The breast specialists prospectively achieved a rate of 0.26 from 99 per cent of the same referral letters. 'Urgent' referrals did not wait significantly longer in 1999 (median 9 versus 10 days) but waiting times for new appointments overall increased (13 versus 16 days; P < 0.01), and this was greatest for 'routine' [14] versus 21 days; P < 0.001). These changes were caused by an increase in the number of clinic appointments, due to significant increases in median number of visits to diagnosis or discharge and clinic non-attendance in 1999, resulting in overbooking. Telephonic communications were associated with faster median access times (fax 8 days; telephone 2 days), relative to mailed [19] days) (P < 0.01). CONCLUSION: Breast specialists were better overall at assessing the probability of a breast cancer diagnosis. The waiting time for 'urgent' appointments was unchanged following HSC 1998/242, but there was an increased wait for other patients, especially those assessed as having a lower probability of cancer.     

In vivo biocompatibility of the PLGA microparticles in parotid gland

Poly(lactic-co-glycolic acid) (PLGA) microparticles are used in various disorders for the controlled or sustained release of drugs, with the management of salivary gland pathologies possible using this technology. There is no record of the response to such microparticles in the glandular parenchyma. The purpose of this study was to assess the morphological changes in the parotid gland when injected with a single dose of PLGA microparticles. We used 12 adult female Sprague Dawley rats (Rattus norvegicus) that were injected into their right parotid gland with sterile vehicle solution (G1, n=4), 0.5 mg PLGA microparticles (G2, n=4), and 0.75 mg PLGA microparticles (G3, n=4); the microparticles were dissolved in a sterile vehicle solution. The intercalar and striated ducts lumen, the thickness of the acini and the histology aspect in terms of the parenchyma organization, cell morphology of acini and duct system, the presence of polymeric residues, and inflammatory response were determined at 14 days post-injection. The administration of the compound in a single dose modified some of the morphometric parameters of parenchyma (intercalar duct lumen and thickness of the glandular acini) but did not induce tissue inflammatory response, despite the visible presence of polymer waste. This suggests that PLGA microparticles are biocompatible with the parotid tissue, making it possible to use intraglandular controlled drug administration.     

Traditional vs wireless intragastric pH monitoring: are the two techniques comparable?

Background Few data are available comparing intragastric pH measured with the traditional catheter‐based and the more recent wireless system (Bravo), and also comparing intraesophageal and intragastric pH during reflux events. Aims of our study were to elucidate these points. Methods Eleven subjects with functional dyspepsia underwent placement of a Bravo capsule 9 cm below the squamo‐columnar junction (SCJ) and of a dual‐electrode catheter, so that the distal electrode was located 9 cm below and the proximal one 6 cm above the SCJ. Key Results The wireless system showed lower intragastric pH than the traditional catheter in the postprandial period (median 2.2 wireless vs 2.7 catheter, P < 0.05) but not in the whole 24 h. Moreover, during the 24 h, minimum intraesophageal pH during reflux events was lower than the simultaneous pH in the gastric body recorded using the catheter (2.2 vs 2.4, P < 0.01) and in the postprandial period lower than the one recorded using both techniques (2.3 vs 2.8 wireless and 3.2 catheter, P < 0.001). Conclusions & Inferences (i) after meals, in the 1st 2 h postprandial pH in the gastric body is significantly lower when measured with the wireless capsule than with the traditional catheter, presumably because of less buffering by food in proximity of the mucosa, (ii) during reflux events intraesophageal pH is lower than pH in the gastric body, in accordance with the notion of greater intragastric acidity in the subcardial region.