Transforming growth factor-beta1 and IL-13 response to allergen predict steroid needs in asthmatic children

BackgroundThe remission of asthma, which is induced during specific immunotherapy (SIT) or appears spontaneously in children is not completely understood and predictors of this phenomenon are still undefined.ObjectiveTo assess CD4⁺CD25⁺Foxp3⁺ Treg cells and cytokine/proliferation response to allergen-specific stimulation of PBMC as predictors of steroid sparing effect of SIT and steroid dosage needs without SIT during 5 years of follow-up in asthmatic children.MethodsThis is a 5-year long study of 32 asthmatic children, sensitive only to house dust mite (HDM). Eighteen children who had completed 5 years of HDM SIT – SIT group, and 14 children without SIT as a control group were studied. All patients had baseline clinical/immunological assessment; before and after observation the minimum effective ICS dose was defined and lung function was measured.ResultsIn children from SIT group minimum effective ICS dose was reduced more than in children from control group (median reduction 65% vs. 0%; p < 0.001). Among patients in control group asthma severity was reduced after 5 years of observation in those who had at baseline higher TGF-beta1 and lower IL-13 answer to allergen stimulation of PBMC. Better response to 5 years immunotherapy was observed in those who had at baseline higher TGF-beta1 and lower proliferation answer to allergen stimulation of PBMC.ConclusionSimilar processes may decide on both, SIT-induced and spontaneously appearing, reduction in asthma severity. Immunotherapy was much more effective than pharmacotherapy in our study. IL-13 overproduction may impede reduction of disease severity in asthmatic children independently from TGF-beta pathway.     

Seemingly healthy skin in atopic dermatitis: observations with the use of high‐frequency ultrasonography,preliminary study

Background: Atopic dermatitis (AD) is a chronic, relapsing skin disorder which is strictly determined by the epidermal barrier function. In previous studies, there is conclusive evidence that normal‐looking, nonlesional skin presents meaningful barrier function defect and a sub‐clinical eczematous skin reaction. Aim: The authors intended to visualize nonlesional AD skin with the use of high frequency ultrasonography to show that the normal‐looking, nonlesional skin may present significant abnormalities in USG examination. Methods: We have performed analysis with the use of high‐frequency 20 MHz skin sonography in the cases of 15 AD patients of the Department of Dermatology, Medical University, Poznań, Poland. The clinical score has been evaluated on the basis of W‐AZS index and EASI. The results were presented in the form of ultrasonographic images. Results: High frequency ultrasonography revealed an echopoor band within nonlesional skin of six (40%) examined AD patients and in all cases within skin lesions. Conclusion: Our results indicate the significant role of skin ultrasonography in the complete clinical evaluation of patients with AD, which may serve as an element in selection of the most appropriate topical treatment. An echopoor band beneath the echo entry within nonlesional skin of some AD patients may reflect subclinical eczematous reaction and the readiness for the development of typical skin lesions. For this purpose, we suggest to name an intact skin in AD as seemingly healthy skin.     

Negative D-dimers and exclusion of venous thromboembolism--own experience

The assessment of D-dimer concentration has become essential step during diagnostic algorithm of venous thromboembolism (VTE). This test characterizes high sensitivity but limited specificity. Negative D-dimer with high probability excludes VTE. The aim of this study was to assess the percentage of patients treated in Department of Internal Medicine, Endocrinology and Haemostatic Disorders, Medical University of Gdańisk, who in spite of clinical signs of VTE showed normal D-dimer level. Between 2000 and 2004 in our department 57 cases with recent deep vein thrombosis (DVT) were diagnosed, in 2 cases with co-existence of pulmonary embolism (PE). The D-dimer concentration was assessed in patients' plasma with the use of immunoturbidometry. Between 57 cases with VTE, 7 patients (12%) showed normal D-dimer level (<500 microg/ml). This group consisted of 4 men and 3 women, aged from 40 to 82 years (the mean age of 58 years). In all 7 cases DVT was diagnosed, in 2 patients with concomitent PE. The final diagnosis was confirmed by compression ultrasonography and pulmonary scintigraphy. Our analysis underlines the observation that occurrence of VTE and negative d-dimer concentration is possible and may probably be related to methodological limitations. However, the lack of increase of D-dimer could also be caused by fibrinolysis alteration.     

Gentamicin affects melanogenesis in normal human melanocytes

Background: Aminoglycoside antibiotics, including gentamicin, despite their ability to induce adverse effects on pigmented tissues, remain valuable and sometimes indispensable for the treatment of various infections. It is known that gentamicin binds to melanin biopolymers, but the relation between this drug affinity to melanin and its toxicity is not well documented. The aim of this work was to examine the impact of gentamicin on viability and melanogenesis in HEMa-LP (light pigmented) and HEMn-DP (dark pigmented) normal human melanocytes.

Methodology/principal findings: The effect of gentamicin on cell viability was determined by 4-[3-(4-iodophenyl)-2-(4-nitrophenyl)-2H-5-tetrazolio]-1,3-benzene disulfonate (WST-1) assay; melanin content and tyrosinase activity were measured spectrophotometrically. It has been demonstrated that gentamicin induces concentration-dependent loss in melanocytes viability. The application of antibiotic in concentration of 10?mM causes higher reduction in viability of the light pigmented melanocytes (by about 74%) when compared with the dark pigmented ones (by about 62%). The value of the concentration of a drug that produces loss in cell viability by 50% (EC₅₀) for both cell lines was found to be ～7.5?mM. It has been shown that gentamicin causes inhibition of tyrosinase activity and reduces melanin content in light pigmented melanocytes significantly more than in the dark pigmented cells.

Conclusion/significance: We have found that gentamicin modulates melanization process in melanocytes in vitro, what may explain the potential role of melanin biopolymer in the mechanisms of undesirable toxic effects of this drug in vivo, as a result of its accumulation in pigmented tissues. We have also stated that the melanogenesis process in light pigmented melanocytes is more sensitive to the inhibitory effect of gentamicin than in the dark pigmented cells.     

“Cerebral small vessel disease and other influential factors of cognitive impairment in the middle-aged: a long-term observational cohort PURE-MIND study in Poland”

GeroScience - A complex picture of factors influencing cognition is necessary to be drawn for a better understanding of the role of potentially modifiable factors in dementia. The aim was to assess...     

Renal impairment in patients with chronic hepatitis C treated with first generation protease inhibitors

Background: The incidence, course and risk factors associated with renal impairment (RI) in patients treated with triple therapy (TT) with pegylated interferon, ribavirin and telaprevir/boceprevir (PR/TVR/BOC) vs. dual therapy (DT) with PR were analyzed in this study. The association between RI and the decline of hemoglobin (Hb) was also examined.

Methods: Retrospective analysis included 110 patients with genotype 1b chronic HCV infection, aged 18 – 80 years, who underwent TT (48TVR/14BOC) or DT (48 patients). The estimated glomerular filtration rate (eGFR), serum creatinine concentration (SCr) and Hb were measured at baseline, at weeks 4, 12, 24, 48 of treatment, and post-treatment week 24.

Results: RI occurred in 9/62 (14.5%) patients who underwent TT, eight of whom were treated with TVR, one with BOC, and none treated with DT. The risk factors associated with RI were the following: TT (p = 0.0078), usage of nephrotoxic drugs (p = 0.0288), and older age (p < 0.0001). RI was reversible. A drop of Hb was associated with RI, older age and TT.

Conclusions: RI is not a rare but a reversible complication of TT. It is necessary to monitor SCr and eGFR, especially in patients with a potential risk factor of RI occurrence. The Hb drop is more severe in patients with RI than in those without it.     

11p15 duplication and 13q34 deletion with Beckwith–Wiedemann syndrome and factor VII deficiency

Here we report a patient with 11p15.4p15.5 duplication and 13q34 deletion presenting with Beckwith–Wiedemann syndrome (BWS) and moderate deficiency of factor VII (FVII). The duplication was initially diagnosed on methylation‐sensitive multiplex ligation‐dependent probe amplification. Array comparative genome hybridization confirmed its presence and indicated a 13q34 distal deletion. The patient's clinical symptoms, including developmental delay and facial dysmorphism, were typical of BWS with paternal 11p15 trisomy. Partial 13q monosomy in this patient is associated with moderate deficiency of FVII and may also overlap with a few symptoms of paternal 11p15 trisomy such as developmental delay and some facial features. To our knowledge this is the first report of 11p15.4p15.5 duplication associated with deletion of 13q34 and FVII deficiency. Moreover, this report emphasizes the importance of detailed clinical as well as molecular examinations in patients with BWS features and developmental delay.     

Favorable four‐yr outcome after renal transplantation in a patient with complement factor H antibody and CFHR1/CFHR3 gene mutation‐associated HUS

aHUS is a clinical challenge for successful renal transplantation. Case report: A 14‐yr‐old girl lost her kidneys at the age of 7, due to CFH antibodies and CFH‐related protein (CFHR1/CFHR3) homozygous deletion‐associated aHUS. CFH, CFI, and MCP gene mutations were excluded. The patient was a candidate for renal transplantation despite persistent presence of CFH antibodies (up to 539 AU/mL). Treatment with MMF, IVIG, and repeated PF (n = 8) was introduced while being placed on urgent waiting list. Three years after aHUS onset, the patient underwent the deceased donor renal transplantation “under cover” of PF, as PF was performed directly prior to surgery and, then, PFs were repeated up to overall 14 sessions. Quadruple immunosuppression (basiliximab + tacrolimus + MMF + prednisolone) was used. Moderate symptoms of aHUS (hemolysis, low platelets, and low C3) were present within first seven days post‐transplant and then normalized with PF therapy. The patient remained stable during four yr of further follow‐up after transplantation. Conclusion: Specific pre‐ and post‐transplant management allowed successful renal transplantation in a CFH antibody‐positive patient.     

Association Between Self-reported Physical Activity and Skin Autofluorescence,a Marker of Tissue Accumulation of Advanced Glycation End Products in Adults With Type 1 Diabetes: A Cross-sectional Study

Purpose

The accumulation of advanced glycation end products (AGEs) in local tissue is an important cause of low-grade inflammation and oxidative stress and is linked to late diabetic complications. Physical activity has various beneficial cardiometabolic effects in type 1 diabetes (T1D) and is associated with lower frequency of chronic complications of diabetes, although the specific mechanisms still remain unclear. The present study determines the association between self-reported physical activity and skin autofluorescence (AF), a marker of tissue accumulation of AGEs in adults with T1D.