Anguidine potentiates cis-platinum in human brain tumor cells

Summary Anguidine pretreatment was previously shown to potentiate cis-platinum in Chinese hamster ovary cells by 100-fold, probably by enhancing cellular cis-platinum. uptake. Since both cis-platinum and anguidine have been reported to have clinical efficacy in human brain tumors, the present study was initiated to investigate whether anguidine's potentiation of cis-platinum was applicable to human brain tumor cells in culture. Using the colony formation assay, it was found that anguidine enhanced cis-platinum's cytotoxicity by ten-fold, producing a dose modification factor of 1.74. Alkaline elution analysis of cis-platinum-induced DNA crosslinks found that anguidine enhanced cross-linking by a factor of 1.55, 1.76, 1.63, and 1.48 at 0, 6, 24, and 48 hr, respectively, after cis-platinum treatment. This enhancement of cross-linking is evidence for anguidine increasing cis-platinum uptake. Thus, anguidine enhances cis-platinum-induced DNA cross-linking and subsequent cytotoxicity in human brain tumor cells, and may be clinically useful in combination with cis-platinum in those tumors.     

Exploring the oral bacterial flora: current status and future directions

Oral Diseases (2010) 16 , 136–145 Objective: The oral cavity forms an indispensable part of the human microbiome, for its unique and diverse microflora distributed within various niches. While majority of these organisms exhibit commensalism, shifts in bacterial community dynamics cause pathological changes within oral cavity and distant sites. The aim of this review was to appraise the current and emerging methods of detecting bacteria of the oral cavity paying particular attention to the cultivation independent methods. Design: Literature pertaining to cultivation based and cultivation independent methods of oral bacterial identification was reviewed. Methods: The specific advantages and disadvantages of cultivation based, microscopic, immunological and metagenomic identification methods were appraised. Results: Because of their fastidious and exacting growth requirements, cultivation based studies grossly underestimate the extent of bacterial diversity in these polymicrobial infections. Culture independent methods deemed more sensitive in identifying difficult to culture and novel bacterial species. Conclusion: Apart from characterizing potentially novel bacterial species, the nucleic acid sequence data analyzed using various bioinformatics protocols have revealed that there are in excess of 700 bacterial species inhabiting the mouth. Moreover, the latest pyrosequencing based methods have further broadened the extent of bacterial diversity in oral niches.     

Developmental enamel defects in the primary dentition: aetiology and clinical management

Developmental enamel defects, presenting as enamel hypoplasia or opacities are caused by damage or disruption to the developing enamel organ as a result of inherited and acquired systemic conditions. The high prevalence of these defects in the primary dentition demonstrates the vulnerability of the teeth to changes in the pre‐ and postnatal environment. The presence of enamel hypoplasia increases the risk of primary teeth to early childhood caries and tooth wear as the defective enamel is thinner, more plaque retentive and less resistant to dissolution in acid compared to normal enamel. The purpose of this paper was to critically review the aetiology and clinical complications of developmental enamel defects in the primary dentition and propose recommendations for the clinical management of affected teeth.     

Diabetic retinal photographic screening: a model for introducing audit and improving general practitioner care of diabetic patients in a rural setting

ABSTRACT: This paper describes the addition of diabetic retinal screening using retinal photography to an existing immunisation audit by a General Practitioner (GP) Network in a semi-rural area 60-min drive from central Wellington, New Zealand. The employment of a nurse-facilitator who visited practices to assist the setting up of diabetic registers and the subsequent auditing of patterns of referral for retinal photography was seen as a first step in a process that would lead to audit of the care of diabetic patients by GPs in the Network. This should lead to a measurable improvement in health-care delivery to diabetic patients in this area and is a model that could be adapted by any group of rural or semirural GPs within a defined geographical area.     

朝藿素D的分离和结构

从朝鲜淫羊藿(Epimedium koreanum)地上部分分离得到一新黄酮成分(I)和一已知化合物(II)。经光谱解析,证明I的结构为5,7,3',4'-tetrahydroxy-5'-prenylflavone,命名为朝藿素D(epimedokoreanin D);II为2-hydroxy-3,4,6,7-tetramethoxy-9,10-dihydrophenanthren。     

Patterns of regional lymph node metastasis of nasopharyngeal carcinoma: A meta-analysis of clinical evidence

Background

Abnormal NF-??B2 activation has been implicated in the pathogenesis of multiple myeloma, a cancer of plasma cells. However, a causal role for aberrant NF-??B2 signaling in the development of plasma cell tumors has not been established. Also unclear is the molecular mechanism that drives the tumorigenic process. We investigated these questions by using a transgenic mouse model with lymphocyte-targeted expression of p80HT, a lymphoma-associated NF-??B2 mutant, and human multiple myeloma cell lines.

Methods

We conducted a detailed histopathological characterization of lymphomas developed in p80HT transgenic mice and microarray gene expression profiling of p80HT B cells with the goal of identifying genes that drive plasma cell tumor development. We further verified the significance of our findings in human multiple myeloma cell lines.

Results

Approximately 40% of p80HT mice showed elevated levels of monoclonal immunoglobulin (M-protein) in the serum and developed plasma cell tumors. Some of these mice displayed key features of human multiple myeloma with accumulation of plasma cells in the bone marrow, osteolytic bone lesions and/or diffuse osteoporosis. Gene expression profiling of B cells from M-protein-positive p80HT mice revealed aberrant expression of genes known to be important in the pathogenesis of multiple myeloma, including cyclin D1, cyclin D2, Blimp1, survivin, IL-10 and IL-15. In vitro assays demonstrated a critical role of Stat3, a key downstream component of IL-10 signaling, in the survival of human multiple myeloma cells.

Conclusions

These findings provide a mouse model for human multiple myeloma with aberrant NF-??B2 activation and suggest a molecular mechanism for NF-??B2 signaling in the pathogenesis of plasma cell tumors by coordinated regulation of plasma cell generation, proliferation and survival.     

A randomized prospective comparison of oral versus intraperitoneal ofloxacin as the primary treatment of CAPD peritonitis

Summary: Oral ofloxacin has been successfully used in our centres for the primary treatment of peritonitis complicating continous ambulatory peritoneal dialysis (CAPD). In view of the progressive rise in the resistance rate to ofloxacin among peritoneal bacterial isolates, a study was conducted to determine if oral ofloxacin remains a viable first line treatment for CAPD peritonitis in our centres and if the result can be improved by changing from an oral to an intraperitoneal (i.p.) route. In patients on three 2 L daily CAPD exchanges, ofloxacin given at the i.p. dosage of 200 mg loading followed by 25 mg/L of peritoneal dialysate achieved overnight trough peritoneal levels which are at least four times the minimal 90% inhibitory concentration (MIC90) of most bacterial pathogens without significant accumulation in the systemic circulation. This i.p. dosage was therefore chosen for the clinical study and the result was compared to that using ofloxacin given in the oral dosage of 400 mg loading followed by 300 mg once daily as maintenance. of all the recruited episodes, 35 were eligible for analysis. the overall primary cure rate including primary failures and relapses was 55.6% (10/18) in the oral treatment group and 70.6% (12/17) in the i.p. treatment group. the corresponding figures for gram positive bacterial (g +) infections were 36.4% and 50%, for gram negative bacterial (g -) infections were 66.7 and 80% and for culture negative infections were 75 and 80%. In culture positive cases, all treatment failures were due to resistant infections which were observed in 42.3% of all bacterial isolates, 47.1% of g + isolates and 33.3% of g - isolates. Due to the high background level of bacterial resistance among our CAPD population, ofloxacin monotherapy given either by the oral or the i.p. route can no longer be recommended for the primary treatment of CAPD peritonitis.     

The Personality of Young Smokers

In a sample of 808 middle-class children more than half of the boys and girls had tried smoking cigarettes by the age of 15 years. These children were found to be particularly extreme on the psychoticism (+), neuroticism (+) and lie scale (-) dimensions of personality, and also somewhat high on the extroversion dimension. This pattern is identical to that of children who misbehave and do not conform in a general sense. The implications for an anti-smoking campaign were briefly discussed.