In vitro cytotoxic dose-relation of cisplatin and sodium thiosulphate in human tongue and oesophageal squamous carcinoma cell lines.

BACKGROUND: Intraarterial chemotherapy of oral and oropharyngeal cancer with cisplatin (cis-diamminedichloroplatinum [II]) has experienced a revival in the last decade. Side-effects of the therapy were very low with concomitant systemic infusion of the neutralizing agent sodium thiosulphate. The requisite dose of the chemotherapeutic agent which safely leads to apoptosis of oral cancer cells has not yet been assessed in vitro, nor has the combination of cisplatin and sodium thiosulphate been examined for the potential reduction of cytotoxicity in oral cancer cells. STUDY DESIGN: In a panel of two tongue squamous cancer cell lines and an oesophageal cancer cell line as control and comparison, cisplatin (0.2-10 microgram/ml) was combined with sodium thiosulphate (0-0.5 mg/ml). RESULTS: 10 microgram/ml of cisplatin proved to be 100% antiproliferative, while any additional concentration of sodium thiosulphate decreased this effect. At the maximum dose of cisplatin, a sodium thiosulphate/cisplatin concentration relation of less than 6:1 still effected cytotoxic activity of >80%. An increase of cisplatin concentration led to higher cytotoxicity irrespective of sodium thiosulphate concentration. The oesophageal cell line was more sensitive to cisplatin and to sodium thiosulphate than the tongue cell lines. CONCLUSIONS: In this study, it was found that high concentrations of cisplatin are necessary in oral cancer to reach cytotoxic levels which support high-dose intraarterial chemotherapy by which these levels might be reached. A sodium thiosulphate/cisplatin concentration ratio within the tumour of less than 6:1 may be allowed without compromising the cytotoxic activity of cisplatin.     

Implantable left ventricular assist systems (LVAS): recent results. A report from a series of meetings sponsored by the Study Group on Advanced Heart Failure of the Working Group on Heart Failure

Implantable left ventricular assist systems (LVAS) consist of implantable pumps with small control consoles and power sources that can be worn externally. These systems provide far greater patient mobility and independence than external pumps with bulky control consoles. Patients with implantable LVAS can be discharged from hospital and are able to return to work and resume active sports. Most patients have received these systems as a bridge to heart transplantation. Clinical status and quality of life improve dramatically after device implantation and survival on support (60-70% after approx. 100 days of support) is acceptable compared with transplant candidates on medical therapy. Patient selection and adverse events, primarily bleeding, thromboembolism and infection, are important issues with LVAS. In the future, long-term support and bridging to myocardial recovery may become important indications for LVAS.     

Differential effects of intravenous anesthetics on hepatosplanchnic microcirculation in rats: sidestream dark-field imaging study

This study aimed to investigate the effects of intravenous anesthetics on hepatosplanchnic microcirculation in laparotomized mechanically ventilated rats using Sidestream Dark-field (SDF) imaging. Thirty male Wistar rats were divided into 5 groups (n = 6 each). All rats were initially anesthetized with 60 mg/kg pentobarbital (i.p.) for instrumentation. This was followed by either ketamine, propofol, thiopental, midazolam or saline+fentanyl (iv bolus over 5 min and then maintenance over 90 min). SDF imaging of the liver and distal ileum microcirculation was performed at the baseline and at t = 5, 35, 65 and 95 min. In propofol group there was increase of functional sinusoidal density (FSD) following induction (+25%, P < 0.05) and maintenance at t = 95 min (+10.3%, P < 0.05), in ketamine and midazolam group decrease of FSD was observed after induction (-20.4%, P < 0.05; -10.1%, P < 0.05) and during maintenance at t = 65 min (-11.6%, P < 0.05; -11.4%, P < 0.05) when compared to baseline. Following induction with propofol functional capillary density (FCD) of ileal longitudinal muscle layer increased (+10.6%, P < 0.05) and returned to baseline values during maintenance. Ketamine and midazolam decreased FCD of longitudinal layer after induction (-24.6%, P < 0.05; -21.1%, P < 0.05) and remained decreased during maintenance at t = 95 min (-10.8%, P < 0.05; -15.5%, P < 0.05). In thiopental and control group, changes in microcirculatory parameters were not significant throughout the study. In conclusion, intravenous anesthetics affect the hepatosplanchnic microcirculation differentially, propofol has shown protective effect on the liver and intestinal microcirculation.     

Exosomal vaccines containing the S protein of the SARS coronavirus induce high levels of neutralizing antibodies

Infection with the SARS-associated coronavirus (SARS-CoV) induces an atypical pulmonary disease with a high lethality rate. Although the initial SARS epidemic was contained, sporadic outbreaks of the disease still occur, suggesting a continuous need for a vaccine against this virus. We therefore explored exosome-based vaccines containing the spike S proteins of SARS-CoV. S-containing exosomes were obtained by replacing the transmembrane and cytoplasmic domains of the S protein by those of VSV-G. The immunogenicity and efficacy of the S-containing exosomes were tested in mice and compared to an adenoviral vector vaccine expressing the S protein. Both, S-containing exosomes and the adenoviral vector vaccine induced neutralizing antibody titers. After priming with the SARS-S exosomal vaccine and boosting with the adenoviral vector the neutralizing antibody titers exceeded those observed in the convalescent serum of a SARS patient. Both approaches were effective in a SARS-S-expressing tumor challenge model and thus warrant further investigation.     

The leukocyte integrin antagonist Del-1 inhibits IL-17-mediated inflammatory bone loss

Aging is linked to greater susceptibility to chronic inflammatory diseases, several of which, including periodontitis, involve neutrophil-mediated tissue injury. Here we found that aging-associated periodontitis was accompanied by lower expression of Del-1, an endogenous inhibitor of neutrophil adhesion dependent on the integrin LFA-1, and by reciprocal higher expression of interleukin 17 (IL-17). Consistent with that, IL-17 inhibited gingival endothelial cell expression of Del-1, thereby promoting LFA-1-dependent recruitment of neutrophils. Young Del-1-deficient mice developed spontaneous periodontitis that featured excessive neutrophil infiltration and IL-17 expression; disease was prevented in mice doubly deficient in Del-1 and LFA-1 or in Del-1 and the IL-17 receptor. Locally administered Del-1 inhibited IL-17 production, neutrophil accumulation and bone loss. Therefore, Del-1 suppressed LFA-1-dependent recruitment of neutrophils and IL-17-triggered inflammatory pathology and may thus be a promising therapeutic agent for inflammatory diseases.