Influence of metronidazole, chloramphenicol, clindamycin and penicillin G on growth and neuraminidase activity of Bacteroides fragilis

The effects of subinhibitory concentrations of metronidazole, chloramphenicol, clindamycin and penicillin G on cell growth and neuraminidase activity of Bacteroides fragilis were tested in six strains from clinical specimens and two type collection strains. All showed significant inhibition of cell growth at one half the MIC after 24 h incubation. Metronidazole at one quarter the MIC was significantly inhibitory after 24 and 48 h incubation. The neuraminidase activity remained unaltered, in comparison with controls, when metronidazole and clindamycin were tested. Chloramphenicol reduced the enzyme activity at both one half and one quarter the MIC. On the other hand, penicillin G enhanced the neuraminidase activity, although the difference was not statistically significant. These in-vitro effects may simulate the behaviour of the bacteria in abscesses in vivo.     

Effects of vaporized perfluorohexane and partial liquid ventilation on regional distribution of alveolar damage in experimental lung injury

Objective To determine whether the patterns of distribution of histological effects of vaporized perfluorohexane (PFH) and partial liquid ventilation (PLV) differ significantly in acute lung injury. Design and setting Experimental study in an animal research laboratory. Subjects Eighteen pigs. Interventions After induction of acute lung injury by means of infusion of oleic acid animals were randomly assigned to PFH, PLV, or gas ventilation (GV) groups. Six hours thereafter animals were killed, and lung tissue samples were taken for analysis. Measurements and results Histopathological analysis revealed less damage with PFH than with GV or PLV in the nondependent and central regions. PFH and PLV showed less injury in the dependent regions than GV. GV and PFH were associated with less histological damage in the nondependent than the dependent regions, whereas PLV presented the opposite pattern. Morphometric analysis showed increased aeration in nondependent than dependent regions with PFH and GV. PLV led to more aeration in the periphery than in central areas. Conclusions PFH was associated with a more homogeneous attenuation of alveolar damage across the lungs, although this therapy had more pronounced effects in nondependent zones. PLV showed the opposite pattern, with more important reduction in alveolar damage in dependent lung regions. Interestingly, reduction in alveolar damage with PFH was as effective as with PLV in dependent zones. Our findings suggest that vaporized perfluorocarbon could be advantageous as adjunctive therapy in the treatment of acute lung injury. Electronic supplementary material Supplementary material is available in the online version of this article at and is accessible for authorized users. This work was supported by grant nos. AB 135/1-1 and HU 818/3-1 from the Deutsche Forschungsgemeinschaft (DFG), Bonn, Germany An erratum to this article can be found at     

The Relationship Between Different Bench Test Methodologies and Accuracy of Insulin Infusion Pumps: A Systematic Literature Review

Diabetes technology has rapidly evolved, and insulin infusion pumps (IIPs) have gained worldwide acceptance in diabetes care. The safety of medical equipment is highly discussed, imposing complex challenges in its use. The accuracy of IIPs can be determined through laboratory tests, generally following the IEC 60601-2-24 protocol. Studies have evaluated the accuracy and precision of IIPs, and there are discrepant results. So, we conducted a Systematic Literature Review to assess the methodologies used to evaluate the accuracy of IIPs, organizing the findings in a compiled perspective. The methodology was based on Kitchenham and Biolchini guidelines, and when possible it was carried out the Bayesian meta-analyses to compare the accuracy of IIPs. Most studies used the microgravimetric technique to evaluate the device accuracy, and some proposed adaptations for the standard protocol. The variation of results was recurrent, and the establishment of a protocol, especially to evaluate patch pumps, is necessary. The present study gives enough data to understand the scenario of the IIPs evaluation, as well as the different protocols that can be explored for its evaluation. This highlights the need for a reliable, practical, and low-cost methodology to assist the evaluation of IIPs.

     

Donor levels of serum alanine aminotransferase activity and antibody to hepatitis B core antigen associated with recipient hepatitis C and non- B, non-C outcomes

BACKGROUND: Hepatitis virus(es) that are neither hepatitis B (HBV) nor hepatitis C (HCV) (non-B, non-C [NBNC]) may be transmitted by transfusion. The present study assessed donor values for alanine aminotransferase (ALT) and antibody to hepatitis B core antigen (anti- HBc) for their association with HCV and NBNC hepatitis outcomes among allogeneic blood recipients. STUDY DESIGN AND METHODS: Data on blood donors and recipients enrolled in the Transfusion- Transmitted Viruses Study in four United States cities from 1974 through 1980 were supplemented by anti-HBc testing of donors and anti-HCV evaluation of recipients. Two statistical approaches estimated the value of these indirect tests in detecting donors associated with HCV seroconversion and NBNC hepatitis in recipients. RESULTS: For HCV cases, donor ALT alone (at > or = 60 IU/L) had a sensitivity and a specificity of 30 and 96 percent, respectively, and anti-HBc alone (at > or = 60% inhibition) had a sensitivity and specificity of 53 and 86 percent, respectively. The two markers combined had a sensitivity and a specificity of 69 and 83 percent. For NBNC hepatitis cases, each measure had low sensitivity (20%) that was not improved by using both (28%) [corrected]. CONCLUSION: The indirect tests proved to be equal in sensitivity to the first-generation anti-HCV tests. The positive predictive power of these indirect tests in the 1980s was sufficient to affect HCV incidence in studies during that period. Improved anti-HCV assays, however, replaced the need for indirect tests. The sensitivity of indirect tests for NBNC hepatitis contributed little.     

Treatment gaps in the management of cardiovascular risk factors in patients with type 2 diabetes in Canada

OBJECTIVES:

To evaluate vascular protection treatment patterns and attainment of the 2003 Canadian Diabetes Association’s recommended targets in ambulatory patients with type 2 diabetes.

METHODS:

Between 2005 and 2006, 3002 outpatients with type 2 diabetes were enrolled by 229 primary health care settings across Canada. Baseline characteristics, therapeutic regimens and treatment success – defined as the achievement of a blood pressure (BP) of 130/80 mmHg or lower, glycosylated hemoglobin (A1C) of 7% or lower, low-density lipoprotein cholesterol (LDL-C) lower than 2.5 mmol/L and total cholesterol/high-density lipoprotein cholesterol ratio lower than 4.0 – are reported.

RESULTS:

Overall, 46% of individuals had a BP that was above the Canadian Diabetes Association’s recommended target. Of these, 11% were untreated, 28% were receiving monotherapy, 38% were not receiving an angiotensin-converting enzyme inhibitor and 16% were not receiving either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Optimal A1C levels were achieved in 53% of patients. Of those who did not attain A1C targets, 3% were not on glucose-lowering pharmacotherapy and 27% were receiving monotherapy. A total of 74% of patients were treated with statins. Overall, 64% and 62%, respectively, met the target LDL-C and the target total cholesterol/high-density lipoprotein cholesterol ratio. Statins were not prescribed to 43% of patients with LDL-C above target. Antiplatelet therapy was implemented in 81% of patients. In total, 21% achieved the combined targets for BP, A1C and LDL-C.

INTERPRETATION:

A substantial proportion of patients did not achieve guideline-recommended targets and were not receiving evidence-based therapy for vascular protection two years after publication of the Canadian guidelines. More research is warranted, and novel and effective strategies must be tested and implemented to correct this ongoing treatment gap.     

Predicting interactions between T cell receptors and MHC-peptide complexes

Conserved interactions between T cell receptors (TCRs) and major histocompatibility complex (MHC) proteins with bound peptide antigens are not well understood. In order to gain a better understanding of the interaction modes of human TCR variable (V) regions, we have performed a structural analysis of the TCRs bound to their MHC-peptide ligands in human, using the available structural models determined by X-ray crystallography. We identified important differences to previous studies in which such interactions were evaluated. Based on the interactions found in the actual experimental structures we developed the first rule-based approach for predicting the ability of TCR residues in the complementarity-determining region (CDR) 1, CDR2, and CDR3 loops to interact with the MHC-peptide antigen complex. Two relatively simple algorithms show good performance under cross validation.     

Uncaria tomentosa aqueous-ethanol extract triggers an immunomodulation toward a Th2 cytokine profile

Uncaria tomentosa (Willd.) DC (Rubiaceae) is a large woody vine that is native to the Amazon and Central American rainforests and is used widely in traditional medicine for its immunomodulatory and antiinflammatory activities. The present work used in vivo immunotoxic and in vitro immunomodulatory experiments to investigate the effects of a pentacyclic oxindole alkaloid extract from U. tomentosa bark on lymphocyte phenotype, Th1/Th2 cytokine production, cellular proliferation and cytotoxicity. For the in vivo immunotoxicity testing, BALB/c male mice were treated once a day with 125, 500 or 1250 mg/kg of U. tomentosa extract for 28 days. For the in vitro protocol, lymphocytes were cultured with 10–500 μg/mg of the extract for 48 h. The extract increased the cellularity of splenic white pulp and the thymic medulla and increased the number of T helper lymphocytes and B lymphocytes. Also, a large stimulatory effect on lymphocyte viability was observed. However, mitogen‐induced T lymphocyte proliferation was significantly inhibited at higher concentrations of U. tomentosa extract. Furthermore, an immunological polarization toward a Th2 cytokine profile was observed. These results suggest that the U. tomentosa aqueous‐ethanol extract was not immunotoxic to mice and was able to modulate distinct patterns of the immune system in a dose‐dependent manner. Copyright © 2011 John Wiley & Sons, Ltd.