Idiopathic hyperzincemia with associated copper deficiency anemia: a diagnostic dilemma

Prompt serum copper and zinc in addition to vitamin B12 levels should be measured in patients suffering from refractory anemia with neurological symptoms. A timely copper supplementation can help revert the hematological and possibly the neurological manifestations.     

Emergence of <Emphasis Type="Italic">Moraxella bovoculi</Emphasis> Associated with Keratoconjunctivitis in an Organized Dairy Farm of India

An investigation was carried out in an organized dairy farm of Tamil Nadu State, India where cattle were reported to have eye infection. Preliminary clinical intervention revealed that the animals had infectious bovine keratoconjunctivitis (IBK). Isolation and identification of pathogen from eye swab revealed the presence of Moraxella spp. On further molecular characterization by Polymerase chain reaction (PCR) suggested that the isolate as Moraxella bovoculi. PCR followed by sequencing was carried and the results showed that the isolate was M. bovoculi and the sequence was submitted in the GenBank with the sequence id. KX121047. Animals were treated with antibiotics as per the results from antibiotic sensitivity test and treatment yielded good results as the animals responded to treatment. This report is the first of its kind from India as there was no previous report regarding M. bovoculi from the country. Further insights into the bacterial genome can aid in identification of the genes or regions involved in pathogenesis of IBK and also to carve out the prevention and control strategies of IBK.     

3T multiparametric MR imaging,PIRADSv2-based detection of index prostate cancer lesions in the transition zone and the peripheral zone using whole mount histopathology as reference standard

Abdominal Radiology - To evaluate 3T mpMRI characteristics of transition zone and peripheral zone index prostate cancer lesions stratified by Gleason Score and PI-RADSv2 with whole mount...     

Macular thickness measurements using Copernicus Spectral Domain Optical Coherence Tomography

Purpose

To provide normal macular thickness measurements using Spectral Domain Optical Coherence Tomography (SDOCT, Copernicus, Optopol Technologies, Zawierci, Poland).

Methods

Fifty-eight eyes of 58 healthy subjects were included in this prospective study. All subjects had comprehensive ophthalmic examination including best-corrected visual acuity (BCVA). All the subjects underwent Copernicus SDOCT. Central foveal thickness (CFT) and photoreceptor layer (PRL) thickness were measured and expressed as mean and standard deviation. Mean retinal thickness for each of the 9 regions defined in the Early Treatment Diabetic Retinopathy Study was reported. The data were compared with published literature in Indians using Stratus and Spectralis OCTs to assess variation in instrument measurements.

Results

The mean CFT in the study sample was 173.8 ± 18.16 microns (131–215 microns) and the mean PRL thickness was 65.48 ± 4.23 microns (56–74 microns). No significant difference (p = 0.148) was found between CFT measured automated (179.28 ± 22 microns) and manually (173.83 ± 18.1 microns). CFT was significantly lower in women (167.62 ± 16.36 microns) compared to men (180.03 ± 18 microns) (p = 0.008). Mean retinal thickness reported in this study was significantly different from published literature using Stratus OCT and Spectralis OCT.

Conclusion

We report the normal mean retinal thickness in central 1 mm area to be between 138 and 242 microns in Indian population using Copernicus SDOCT. We suggest that different OCT instruments cannot be used interchangeably for the measurement of macular thickness as they vary in segmentation algorithms.     

Human hepatocyte assessment of imatinib drug–drug interactions – complexities in clinical translation

Aim

Inducers and inhibitors of CYP3A, such as ritonavir and efavirenz, may be used as part of the highly active antiretroviral therapy (HAART) to treat HIV patients. HIV patients with chronic myeloid leukemia or gastrointestinal stromal tumour may need imatinib, a CYP3A4 substrate with known exposure response–relationships. Administration of imatinib to patients on ritonavir or efavirenz may result in altered imatinib exposure leading to increased toxicity or failure of therapy, respectively. We used primary human hepatocyte cultures to evaluate the magnitude of interaction between imatinib and ritonavir/efavirenz.

Methods

Hepatocytes were pre-treated with vehicle, ritonavir, ketoconazole, efavirenz or rifampicin, and the metabolism of imatinib was characterized over time. Concentrations of imatinib and metabolite were quantitated in combined lysate and medium, using LC-MS.

Results

The predicted changes in imatinib CL_oral (95% CI) with ketoconazole, ritonavir, rifampicin and efavirenz were 4.0-fold (0, 9.2) lower, 2.8-fold (0.04, 5.5) lower, 2.9-fold (2.2, 3.5) higher and 2.0-fold (0.42, 3.5) higher, respectively. These predictions were in good agreement with clinical single dose drug–drug interaction studies, but not with reports of imatinib interactions at steady-state. Alterations in metabolism were similar after acute or chronic imatinib exposure.

Conclusions

In vitro human hepatocytes predicted increased clearance of imatinib with inducers and decreased clearance with inhibitors of CYP enzymes. The impact of HAART on imatinib may depend on whether it is being initiated or has already been dosed chronically in patients. Therapeutic drug monitoring may have a role in optimizing imatinib therapy in this patient population.     

Sequencing of 3-O sulfate containing heparin decasaccharides with a partial antithrombin III binding site

Heparin- and heparan sulfate-like glycosaminoglycans (HLGAGs) represent an important class of molecules that interact with and modulate the activity of growth factors, enzymes, and morphogens. Of the many biological functions for this class of molecules, one of its most important functions is its interaction with antithrombin III (AT-III). AT-III binding to a specific heparin pentasaccharide sequence, containing an unusual 3-O sulfate on a N-sulfated, 6-O sulfated glucosamine, increases 1,000-fold AT-III's ability to inhibit specific proteases in the coagulation cascade. In this manner, HLGAGs play an important biological and pharmacological role in the modulation of blood clotting. Recently, a sequencing methodology was developed to further structure-function relationships of this important class of molecules. This methodology combines a property-encoded nomenclature scheme to handle the large information content (properties) of HLGAGs, with matrix-assisted laser desorption ionization MS and enzymatic and chemical degradation as experimental constraints to rapidly sequence picomole quantities of HLGAG oligosaccharides. Using the above property-encoded nomenclature-matrix-assisted laser desorption ionization approach, we found that the sequence of the decasaccharide used in this study is DeltaU(2S)H(NS,6S)I(2S)H(NS, 6S)I(2S)H(NS,6S)IH(NAc,6S)GH(NS,3S,6S) (+/-DDD4-7). We confirmed our results by using integral glycan sequencing and one-dimensional proton NMR. Furthermore, we show that this approach is flexible and is able to derive sequence information on an oligosaccharide mixture. Thus, this methodology will make possible both the analysis of other unusual sequences in HLGAGs with important biological activity as well as provide the basis for the structural analysis of these pharamacologically important group of heparin/heparan sulfates.     

Usefulness of multidetector CT imaging to assess vascular stents in children with congenital heart disease: An in vivo and in vitro study

Objective : To evaluate varying CT settings to visualize pediatric vascular stents in comparison to digital angiography (DA). Background : There is a great clinical interest in substituting noninvasive methods to follow up children with congenital heart disease after interventional treatment. Materials and Methods : CT studies in small children with transcatheter placed stents were reviewed, retrospectively. Furthermore, eight stents were implanted in tubes and partially obstructed. CT exams were performed on varying scanners (4 up to 64 slices) with corresponding tube settings. The effects of dose on image quality were evaluated regarding stent size, strut thickness, and in‐stent stenoses in comparison to DA. Results : Fourteen children with 28 implanted stents were identified. Significant differences between higher and lower radiation settings were not found, corresponding with the phantom, where moderate tube setting showed the best results. In vitro, there was an improvement with increasing number of detector rows, which resulted in a decrease of stent strut overestimation (295% down to 201%; P < 0.0001) and a better agreement with DA measurements for mild (78% up to 91%; P = 0.003) and moderate in‐stent stenoses (80% up to 99%; P = 0.0001). Conclusion : Higher radiation exposure settings did not improve image quality, suggesting that the exams could be performed at a lower radiation dose. © 2008 Wiley‐Liss, Inc.     

Bilingual deep dysphasia

We report B.R.B., a bilingual Turkish–English speaker with deep dysphasia. B.R.B. shows the typical pattern of semantic errors in repetition with effects of lexicality and imageability on performance in both languages. The question we asked is whether language type (Turkish or English) or language status—that is, first acquired (L1) or second acquired (L2)—has a greater impact on performance. Results showed that repetition in L1 (Turkish) was better than that in L2 (English). We also observed effects of language status on oral reading, writing to dictation, and naming (spoken and written) with greater impairment to repetition than other tasks in both languages. An additional finding was that spoken-word translation in both directions was worse than written-word translation, and word class had an effect on translation from L1 to L2. We argue that interactive activation models of deep dysphasia could explain deep dysphasia in bilingual speakers and interactions between task and language, if the weighted connections that support language processing in L2 are assumed to be weaker, thus causing rapid phonological decay to have more impact on task performance in L2. Implications of the results for models of bilingual language processing are also considered.     

Regulatory Actions of Toll-Like Receptor 2 (TLR2) and TLR4 in Leishmania donovani Infection in the Liver

In livers of susceptible but self-curing C57BL/6 mice, intracellular Leishmania donovani infection enhanced Toll-like receptor 4 (TLR4) and TLR2 gene expression. In the liver, infected TLR4^−/− mice showed reduced gamma interferon (IFN-γ), tumor necrosis factor (TNF), and inducible nitric oxide synthase (iNOS) mRNA expression, higher-level and slowly resolving infection, delayed granuloma formation, and little response to low-dose chemotherapy; in serum, the ratio of IFN-γ to interleukin 10 (IL-10) activity was decreased by 50%. In contrast, in TLR2^−/− mice, control of liver infection, parasite killing, and granuloma assembly were accelerated and chemotherapy''s efficacy enhanced. In livers of infected TLR2^−/− mice, mRNA expression was not increased for inflammatory cytokines or iNOS or decreased for IL-10; however, the serum IFN-γ/IL-10 ratio was increased 6.5-fold and minimal responses to IL-10 receptor blockade suggested downregulated IL-10. In established infection in wild-type mice, blockading TLR2 induced parasite killing and triggering TLR4 strengthened resistance and promoted chemotherapy''s effect. Thus, in experimental L. donovani infection in the liver, TLR4 signaling upregulates and TLR2 signaling downregulates macrophage antileishmanial activity, making both receptors potential therapeutic targets in visceral leishmaniasis for engagement (TLR4) or blockade (TLR2).