Inflamed fibronectin: an altered fibronectin enhances neutrophil adhesion

Recent investigations have emphasized the role of activated granulocytes in mediating vascular endothelial injury in the pathogenesis of shock lung. In vitro studies have indicated that tight adherence of the neutrophil to the endothelium is crucial for the development of cellular injury. Fibronectin is critical to cell-to- substratum and cell-to-cell interactions. Since fibronectin resides in plasma, on endothelial cell surfaces and is secreted into cell matrices, the adhesive properties of fibronectin must be modulated, lest universal cell agglomeration occur, yet be enhanced when cell attachment is appropriate. In these studies, treatment of fibronectin- coated surfaces with neutrophil release products increased the adhesion of activated neutrophils. Similarly, endothelial cells treated with neutrophil release products become a more adherent substrate for neutrophils. This enhanced adherence generated by treatment of fibronectin with neutrophil supernatants is inhibitable by heat and the lysosomal proteinase inhibitor, pepstatin-A. Neutrophil release products cause proteolytic fragmentation of fibronectin and enhanced fibronectin immunofluorescence on endothelial cells. In addition, neutrophils are more injurious to endothelial cells that have been pretreated with neutrophil release products. Neutrophils may enhance their own adherence to endothelial cells by altering fibronectin, and this altered, or "inflamed," fibronectin may serve as an amplifier of inflammation.     

Tussive effect of a fentanyl bolus

The aim of this study was to investigate the incidence of pre-induction coughing, after an iv bolus of fentanyl. The study sample was 250 ASA physical status I-II patients, scheduled for various elective surgical procedures. The first 100 were randomly allocated to receive 1.5 micrograms.kg-1 fentanyl via a peripheral venous cannula (Group 1), or an equivalent volume of saline (Group 2). Twenty-eight per cent of patients who received fentanyl, but none given saline, coughed within one minute (P less than 0.0001). The second 150 patients were then randomly assigned to three equal pretreatment groups. Group 3 received 0.01 mg.kg-1 atropine iv one minute before fentanyl. Groups 4 and 5 received 0.2 mg.kg-1 morphine im, and 7.5 mg midazolam po, respectively, one hour before fentanyl. Thirty per cent of patients in Group 3, 6% in Group 4, and 40% in Group 5, had a cough response to fentanyl. Fentanyl, when given through a peripheral cannula, provoked cough in a considerable proportion of patients. This was not altered by premedication with atropine or midazolam, but was reduced after morphine (P less than 0.01). Coughing upon induction of anaesthesia is undesirable in some patients, and stimulation of cough by fentanyl in unpremedicated patients may be of clinical importance.     

Paraneoplastic optic neuropathy in nasopharyngeal carcinoma--report of a case

A 31-year-old Chinese man developed left optic neuritis with left sectorial field loss as a remote effect of nasopharyngeal carcinoma. The field defect showed interesting fluctuations in response to the dosage of systemic steroid therapy. Neuropathologic findings from an exploratory craniotomy did not show any gross tumour mass around the left optic nerve nor any histological evidence of tumour infiltration. This case illustrates that "optic neuritis" could be a paraneoplastic effect of nasopharyngeal carcinoma.     

In vitro and in vivo antifungal activities of the eight steroid saponins from Tribulus terrestris L. with potent activity against fluconazole-resistant fungal pathogens

Antifungal activity of natural products is being studied widely. Saponins are known to be antifungal and antibacterial. We have isolated eight steroid saponins from Tribulus terrestris L. , namely TTS-8, TTS-9, TTS-10, TTS-11, TTS-12, TTS-13, TTS-14 and TTS-15. TTS-12 and TTS-15 were identified as tigogenin-3-O-β-D-xylopyranosyl（1→ 2）-[-β-D-xylopyranosyl（ 1 → 3 ） 3-β- D-glucopyranosyl （ 1 → 4 ）- 1- α-L-rhamnopyranosyl （ 1 → 2 ） 3-β-D-galactopyranoside and tigogenin-3-O-β-D-glucopyranpyranosyl（1→2）-[-β-D-xylopyranosyl（1→ 3）3-β-D-glucopyranosyl（1→4）-β-D-galactopyranoside, respectively. The in vitro antifungal activities of the eight saponins against six fluconazole-resistant yeasts, Candida albicans, Candida glabrata, Candida para psilosis , Candida tropicalis , Candida krusei , and Cryptococcus neo f ormans were studied using microbroth dilution assay. The results showed that TTS-12 and TTS-15 were very effective against several pathogenic candidal species and C. neoformans in vitro. It is noteworthy that TTS-12 and TTS-15 were very active against fluconazole-resistant C. albicans （MIC80 = 4.4, 9.4 mg/ml）, C. neoformans （MIC80 =10.7, 18.7 mg/ml） and inherently resistant C. krusei （MIC80 =8.8, 18.4 mg/ml）. So in vivo activity of TTS-12 in a vaginal infection model with fluconazole-resistant C. albicans was studied in particular. Our studies revealed TTS-12 also showed in vivo activities against fluconazole-resistant yeasts. In conclusion, steroid saponins TTS-12 and TTS-15 from Tribulus terrestris L. have significant in vitro antifungal activity against fluconazole-resistant fungi, especially TTS-12 also showed in vivo activity against fluconazole-resistant C. albicans.     

二乙酰基莲心碱对猪冠状动脉条的影响

目的:观察二乙酰基莲心碱拮抗氯化钾、乙酰胆碱(Ach)和组胺(His)所致猪冠状动脉条收缩的作用.方法:离体平滑肌实验方法,观察二乙酰基莲心碱对氯化钾,Ach,His所致猪冠状动脉条收缩曲线的影响以及在无钙克氏液中,对His引起猪冠状动脉条第一相收缩和钙引起第二相收缩的影响.结果:不同剂量二乙酰基莲心碱可使氯化钾,Ach,His所致冠脉条收缩量效曲线呈非竞争性拮抗作用,对冠脉条第一相和第二相收缩都有明显的抑制作用结论:二乙酰基莲心碱具有扩张冠脉的作用,此作用与拮抗细胞内钙的释放和抑制外钙内流有关.     

Infections in patients with chronic lymphocytic leukaemia: Mitigating risk in the era of targeted therapies

Chronic lymphocytic leukaemia (CLL) is the most common leukaemia with infections a leading cause of morbidity and mortality. Recently there has been a paradigm shift from the use of chemo-immunotherapies to agents targeting specific B-lymphocyte pathways. These agents include ibrutinib, idelalisib and venetoclax. In this review, the risks and timing of infections associated with these agents are described, taking into account disease and treatment status. Treatment with ibrutinib as monotherapy or in combination with chemo-immunotherapies is not associated with additional risk for infection. In contrast, the use of idelalisib is associated with a 2-fold risk for severe infection and opportunistic infections. Venetoclax does not appear to be associated with additional infection risk. The evolving spectrum of pathogens responsible infections in CLL patients, especially those with relapsed and refractory disease are described, and prevention strategies (prophylaxis, monitoring and vaccination) are proposed.