Antiproliferative Activity Against MCF‐7 Breast Cancer Cells by Diamino‐Triazaspirodiene Antifolates

Two triazaspirodienes, having similar phenoxy propyloxy side chain, were identified as potent mammalian dihydrofolate reductase inhibitors; one having a 6,5‐spiro bicyclic ring system (IC₅₀ = 2.3 nm ) and the other a 6,6‐spiro bicyclic system (IC₅₀ = 6.9 nm ). They also showed more than 50% antiproliferative activity against the MCF‐7 breast cancer cells at 20 μm . This study demonstrated the potential lead of the diamino‐triazaspirodienes in anticancer chemotherapeutical agents’ discovery.     

A systematic review of resident‐as‐teacher programmes

Context Residents in all disciplines serve as clinical teachers for medical students. Since the 1970s, there has been increasing evidence to demonstrate that residents wish to teach and that they respond positively to formal teacher training. Effective resident‐as‐teacher (RaT) programmes have resulted in improved resident teaching skills. Current evidence, however, is not clear about the specific features of an effective RaT programme. Objectives This study was performed in order to investigate the effectiveness of RaT programmes on resident teaching abilities and to identify the features that ensure success. Methods of assessment used to ascertain the effectiveness of RaT programmes are also explored. Methods The literature search covered the period between 1971 and 2008. Articles focusing on improving resident teaching skills were included. Each study was reviewed by two reviewers and data were collected using a standard abstraction summary sheet. Study outcomes were graded according to a modified Kirkpatrick's model of educational outcomes. Results Twenty‐nine studies met review inclusion criteria. Interventions included workshops, seminars, lectures and teaching retreats. Twenty‐six studies used a pre‐ and post‐intervention outcome comparison method. Subjective outcome measures included resident self‐evaluation of teaching skills or evaluation by medical students, peers and faculty members. Objective outcome measures included written tests, evaluation of teaching performance by independent raters and utilisation of objective structured teaching examinations. One study objectively measured learning outcomes at the level of medical students, utilising the results of an objective structured clinical examination. Overall resident satisfaction with RaT programmes was high. Participants reported positive changes in attitudes towards teaching. Participant knowledge of educational principles improved. Study methodologies allowed for significant risks of bias. Conclusions More rigorous study designs and the use of objective outcome measures are needed to ascertain the true effectiveness of RaT programmes. Future research should focus on determining the impact of RaT programmes on learning achievement at the level of medical students.     

A Contribution for the Definition of Serum Chemistry Values in Captive Adults Antillean Manatees (Trichechus manatus manatus Linnaeus, 1758)

Serum chemistry analyses represents a fundamental tool for the diagnosis and understanding of diseases in marine mammals. Although several studies are being conducted within the field of clinical pathology, haematological and serum chemistry data for Antillean manatees are deficient. The purpose of this study was to determine serum chemistry values for captive Antillean manatees within the CMA/Ibama facility in Brazil. Serum samples were obtained from five captive adult Antillean manatees fed with seagrass and analysed for aspartate aminotransferase, alanine aminotransferase, bilirubin, alkaline phosphatase, urea, creatinine, glucose, triglycerides, cholesterol, total protein, albumin, globulin, phosphate, chloride, calcium and uric acid. Blood chemistry parameters were determined using a semi‐automatic analyzer. Maximum, minimum, mean and standard deviations were calculated for each serum chemistry parameter. Differences on the values of males and females were verified using an unpaired Student's t‐test. All the parameters analysed were similar between sexes, with exception of AP, which was higher in females (191.43 ± 31.86 U/l). Alanine aminotransferase and uric acid values for Trichechus manatus manatus are reported for the first time in this paper. This study is the first to report serum chemistry parameter values for long‐term captive male and female Antillean manatees. Therefore, the lower values of albumin, phosphate, chloride, cholesterol and triglycerides obtained here highlight the importance of clinical pathology during health monitoring of captive marine mammals.     

Serum IgA and IgG functional antibodies and their subclasses to Streptococcus pneumoniae capsular antigen found in two aged‐matched cohorts of children with and without otitis media with effusion

Serum IgA and IgG functional antibodies and their subclasses to Streptococcus pneumoniae capsular antigen found in two aged‐matched cohorts of children with and without otitis media with effusion The relationship between acute otitis media and otitis media with effusion (OME) is uncertain and the aetiology of OME is multifactorial. Otitis media with effusion may be an inflammatory condition; both bacteria and viral infections could play a part in this inflammation. The four bacteria Streptococcus pneumoniae, Haemophilus influenza, Staphylococcus aureus and Branhamella catarrhalis cause 60% of the infections whereas S. pneumoniae accounts for up to 35%. IgA provides the dominant surface response to polysaccharide and lipopolysaccharide antigens, of which IgA₂ is the main subclass. Once the mucosa has been breached, most protection is provided by IgG. IgG₂ acts mainly against bacterial capsular antigens. This study looked at two groups of 50 children with and without OME who were aged between 3 and 10 years. The aims were to determine if, firstly, the levels of the serum immunoglobulins were different in the two groups, secondly whether these children made the appropriate antibody response to the capsular antigen to S. pneumoniae (PCP), and finally if there was a delay in the maturity of the IgA response. The total IgG, IgA and all subclass levels were measured using radial immunodiffusion. Levels of functional IgA and IgG were measured using ELISAs (25 patients in each group). The results were analysed with non‐parametric tests. The immunoglobulin levels were within the normal levels for both groups. There were very good correlations between the IgG total anti‐PCP and the IgG₂ anti‐PCP (R > 0.9, p = 0.001). There was a good correlation between the levels of both IgG total and IgG₂ anti‐PCP against IgA total anti‐PCP in both groups (R > 0.85, p > 0.01). This confirms a normal antibody response between both groups of patients. The ages of the controls and patients (50 samples) were correlated with increasing titres of circulating functional antibodies (P = 0.001). This is highly suggestive of a normal age‐related response. In conclusion, the findings were contradictory to our original hypothesis that there is a subtle difference in surface protection between children with and without OME. We believe that a previous history of recurrent acute otitis media is unrelated to the development of OME after 3 years of age.     

Chromogranin A: friend or foe of the failing myocardium?

Chronic heart failure is defined as the inability of the heartto meet the circulatory demands of the organism. While cardiacinjury, e.g. of ischaemic, toxic, metabolic, or genetic cause,is the initial abnormality, secondary changes occur over thecourse of the disease affecting most organ systems. This leadsto a variety of pathologic changes including endothelial, pulmonary,hepatic, renal, endocrine and skeletal muscle abnormalities,and the state of multi-organ impairment in chronic heart failureis now considered the syndrome of chronic heart failure.¹ A neuroendocrine activation has been described early in