Adsorptive stripping voltammetric determination of cefetamet in human urine

On the basis of previously established mechanism of cefetamet (CEF) reduction, two methods were suggested for CEF determination-differential pulse polarographic and differential pulse adsorptive stripping voltammetric method. Two pH values were chosen, 2.0 and 8.4, where the electrochemical process was defined as one four-electron and two two-electron processes, respectively. The methods were performed in Britton-Robinson (BR) buffer and the corresponding calibration graphs were constructed and statistical parameters were evaluated. Applying the AdSV method at pH 2.0 linearity was achieved from 2 x 10(-8) to 2 x 10(-7) M with limit detection and limit determination of 4 x 10(-9) and 1.4 x 10(-8) M, respectively. At pH 8.4, the linearity was obtained between 6 x 10(-8) and 6 x 10(-7) M, with limit detection and limit determination of 1.5 x 10(-8) and 5 x 10(-8) M, respectively. Since the AdSV method enabled lower concentrations of CEF to be determined, this method was tested for CEF determination in spiked urine samples, and DPP method was used as a comparative one.     

Association of interleukin-10, tumor necrosis factor-α and transforming growth factor-β gene polymorphisms with the outcome of diffuse large B-cell lymphomas

Background

Published data indicate that common genetic variants in immune/inflammatory response genes can affect the outcome of diffuse large B-cell lymphomas (DLBCL). This study investigated the association of interleukin (IL)-10 (?3575, ?1082), tumor necrosis factor (TNF)-α ?308 and transforming growth factor (TGF)-β Leu10Pro gene polymorphisms with clinical characteristics and outcome of DLBCL patients treated with rituximab–CHOP therapy.

Methods

Between January 2004 and December 2007, a total of 84 patients with newly diagnosed DLBCL entered into this study. Genotypes were determined with PCR-based methodology.

Results

Patients presenting with B symptoms had IL-10 ?3575 TA/AA genotypes more frequently than TT genotype [odds ratio (OR) 2.89, 95 % confidence interval (CI) 1.11–7.57; p = 0.03]. Carriers of TGF-β Pro10 allele more frequently had an advanced clinical stage III/IV (OR 4.65, 95 % CI 1.33–16.19; p = 0.016) and intermediate-high/high IPI score (OR 5.37, 95 % CI 1.45–20.0; p = 0.012). In rituximab–CHOP-treated patients (n = 64), the TNF-α ?308 AG/AA carriers had shorter overall (p = 0.048) and event-free survival (p = 0.07) compared to GG carriers. In multivariate analysis of prognostic factors for survival, the TNF-α AG/AA genotypes were significantly associated with inferior survival of lymphoma patients (OR 0.23, 95 % CI 0.07–0.78; p = 0.018).

Conclusion

Our results indicate the association of IL-10 ?3575 and TGF-β Leu10Pro gene variations with clinical characteristics. In patients treated with rituximab–CHOP therapy, the TNF-α ?308 AG/AA genotypes showed a significantly less favorable survival than the GG genotype.     

Translational aspects of cytochrome P450-mediated drug–drug interactions: A case study with clopidogrel

Multimorbidity, polypharmacotherapy and drug interactions are increasingly common in the ageing population. Many drug–drug interactions (DDIs) are caused by perpetrator drugs inhibiting or inducing cytochrome P450 (CYP) enzymes, resulting in alterations of the plasma concentrations of a victim drug. DDIs can have a major negative health impact, and in the past, unrecognized DDIs have resulted in drug withdrawals from the market. Signals to investigate DDIs may emerge from a variety of sources. Nowadays, standard methods are widely available to identify and characterize the mechanisms of CYP-mediated DDIs in vitro. Clinical pharmacokinetic studies, in turn, provide experimental data on pharmacokinetic outcomes of DDIs. Physiologically based pharmacokinetic (PBPK) modelling utilizing both in vitro and in vivo data is a powerful tool to predict different DDI scenarios. Finally, epidemiological studies can provide estimates on the health outcomes of DDIs. Thus, to fully characterize the mechanisms, clinical effects and implications of CYP-mediated DDIs, translational research approaches are required. This minireview provides an overview of translational approaches to study CYP-mediated DDIs, going beyond regulatory DDI guidelines, and an illustrative case study of how the DDI potential of clopidogrel was unveiled by combining these different methods.     

Aging oppositely affects TNF-α and IL-10 production by macrophages from different rat strains

Altered functions of macrophages with aging contribute to impairment of both innate and adaptive immunity in the elderly. The present study aimed to examine strain specificity of age-related changes in the phenotypic and functional characteristics of macrophages from DA and AO rats, which differ in average life span. Resident peritoneal macrophages from young (10–12 weeks old) and aged (98–104 weeks old) rats were tested for: (a) the surface expression of TLR4 and CD14; (b) the basal and LPS-induced production of TNF-α and IL-10; and (c) the basal and LPS-induced activity of iNOS and arginase, by measuring the levels of NO and urea, respectively, in the culture supernatants. Aging elevated TLR4 macrophage surface density in rats of both strains. Conversely, the age-related decrease in the surface density of CD14 co-receptor was detected only on macrophages from aged DA rats. Accordingly, with aging in DA rats, contrary to AO rats, upon LPS-stimulation both TNF-α and IL-10 levels decreased in culture supernatants. However, in rats of both strains TNF-α stimulation index (LPS-induced over basal production) remained stable with aging, but it was significantly greater in AO rats. Furthermore, with aging, IL-10 stimulation index decreased and increased in DA and AO rats, respectively. Age-related shift in urea stimulation index complied with the changes of IL-10 stimulation index during aging. In conclusion, the study suggests that the preserved ability of macrophages from aged AO rats to synthesize not only proinflammatory TNF-α, but also immunoregulatory IL-10 cytokine most likely contributes to their longer average life compared with DA rats.     

Quantitative and qualitative evaluation tool in planning stroke treatment strategies: the “Safe implementation of treatments in stroke Monitoring Study (SITS MOST)” registry

A decade ago, stroke was the first leading cause of morbidity and mortality in Croatia. Nowadays, we record reduction in stroke incidence, as well as stroke consequences—invalidity and mortality. These are due to long-term planned actions in the field of public health as well as actions performed by professional organizations. Today, we can be satisfied with improvement in that field, but there are still things we can improve, at the first place improvement of the emergency medicine network due to Croatian-specific topographical characteristics to reduce onset-to-door time. In this paper, we evaluated results from 11 Croatian hospitals in the period 11/2005–11/2012. To find out about the past and present state in applying thrombolytic therapy in Croatia and to plan further actions in light of new studies and efforts in Europe and in the world, all with the aim of improvement in stroke prevention and acute treatment resulting in reduction of stroke morbidity, mortality and symptomatic intracerebral hemorrhage as well as better functional outcome. Our results have shown that we improved stroke treatment in the last decade, but further actions should be performed to raise public stroke awareness and to improve emergency medicine network as well as in hospital protocols.