Lower expression of mRNA for interferon-gamma in T helper cells of children with newly diagnosed lymphomas

The complex interactions between cancer and host cells are far from being fully elucidated. Assessment of Th1/Th2/Th3/Tr1 balance is an interesting approach to explain immunological disturbances in lymphomas. The aim of our study was to assess mRNA for pro- and anti-inflammatory cytokines in T-cells in 20 children with Hodgkin- and non-Hodgkin lymphomas. CD4+ and CD8+ cells were isolated from whole peripheral blood and four different cytokine mRNA levels (IFN-γ, IL-10, IL-4, TGF-β) were determined by real-time PCR technique. Comparing to the control group, we found lower expression of mRNA for IFN-gamma in CD4+ cells at the time of lymphoma diagnosis. It may be one of the pathogenetic mechanisms of impaired immunity in these patients

Relationship between asymmetric dimethylarginine, homocysteine and insulin resistance in adolescents with metabolic syndrome

WSTĘP. W ostatnich latach rozważa się znaczenie asymetrycznej dimetyloargininy (ADMA) jako nowego czynnika ryzyka miażdżycy, dysfunkcji śródbłonka oraz insulinooporności. W metabolizmie ADMA istotną rolę może odgrywać homocysteina (Hcy, homocysteine). Zwiększone stężenie ADMA wpływa na zmniejszenie biodostępności tlenku azotu (NO) przez hamowanie syntazy NO - eNOS. Celem pracy była próba poszukiwania zależności między ADMA, Hcy oraz NO u młodzieży z zespołem metabolicznym (MS, metabolic syndrome) . MATERIAŁ I METODY. Do badań zakwalifikowano 21 pacjentów z rozpoznanym MS, w wieku średnim 14,8 roku. Schorzenie rozpoznawano na podstawie kryteriów według Światowej Organizacji Zdrowia (WHO, World Health Organization) i Adult Treatment Panel III (III ATP). Grupę kontrolną stanowiło 26 zdrowych nastolatków w średnim wieku 14,6 roku. Stężenie ADMA, Hcy oraz NO (za pomocą pochodnych NOx) oznaczono metodami immunoenzymatycznymi ELISA. Ocenę stężenia wysokoczułego białka C-reaktywnego (hs-CRP, high sensitivity C-reactive protein) dokonano za pomocą metody immunoturbidymetrycznej, z użyciem odczynnika Tina-quant CRP (Latex) HS, firmy Roche. WYNIKI. U dzieci z MS stwierdzono istotnie wyższe stężenie ADMA (0,69 v. 0,46 &#956;mol/l; p < 0,001), Hcy (12,1 v. 9,4 &#956;mol/l; p = 0,003) oraz hs-CRP (0,22 v. 0,11 mg/dl; p = 0,01) w porównaniu z grupą kontrolną. Stężenie NOx było podobne w obu grupach (46,2 v. 44,8 &#956;mol/l, ns). W analizie wykazano korelację ADMA z hs-CRP (r = 0,42; p = 0,003), Hcy (r = 0,48; p = 0,01). Wskaźnik masy ciała (BMI, body mass index) (r = 0,44; p = 0,02), ciśnieniem skurczowym, rozkurczowym oraz wskaźnikiem insulinooporności HOMA (r = 0,31; p = 0,04). Dla NOx nie wykazano żadnych istotnych zależności. WNIOSKI. 1. Zespołowi metabolicznemu stwierdzanemu u nastolatków towarzyszy zwiększone stężenie ADMA, Hcy i hsCRP. 2. Stwierdzone korelacje między stężeniami ADMA, Hcy i hsCRP oraz wskaźnikiem HOMA sugerują obecność wspólnego patomechanizmu zwiększonego stężenia tych substancji i insulinooporności.INTRODUCTION. The latest research studies consider asymmetric dimethylarginine (ADMA) as a new atherosclerosis risk factor and factor for endothelial dysfunction and insulin resistance. Homocysteine (Hcy) may play significant role in ADMA metabolism Elevated ADMA results in impaired bioavailibility of nitric oxide (NO) via inhibition of nitric oxide synthase (eNOS). The aim of the study was to search the possible relationship between ADMA, Hcy and NO in teenagers with metabolic syndrome (MS). MATERIAL AND METHODS. We recruited 21 patients with MS, aged 14,8 years. Metabolic syndrome was recognized based on the WHO and ATP III criteria. Control group consisted of 26 healthy adolescents aged 14,6 years. ADMA, Hcy and NO (as NOx) concentrations were measured with immunoenzymatic (ELISA) methods. hsCRP was assessed with use of immunoturbidymetric method. RESULTS. In adolescents with MS we showed significantly elevated ADMA (0.69 v. 0.46 &#956;mol/l; p < 0.001), Hcy (12.1 v. 9.4 &#956;mol/l; p = 0.003) and hs-CRP (0.22 v. 0.11 mg/dl; p = 0.01) compared with control group. NOx concentration was similar to the control group (46.2 v. 44.8 &#956;mol/l, ns). We found significant correlations between ADMA and hs-CRP (r = 0.42; p = 0.003), Hcy (r = 0.48; p = 0.01), BMI (r = 0.44; p = 0.02), systolic blood pressure, diastolic blood pressure and insulin resistance (HOMA) (r = 0.31; p = 0.04). NOx did not correlate significantly with any of the study parameters. CONCLUSIONS. 1. In teenagers with MS we showed elevated levels of ADMA, Hcy and hs-CRP. 2. Correlations between ADMA, Hcy, hs-CRP and HOMA suggest existence of common pathomechanism of increased concentrations of these substances with insulin resistance

The mRNA expression of pro- and anti-inflammatory cytokines in T regulatory cells in children with type 1 diabetes.

Type 1 diabetes mellitus (T1DM) is caused by the autoimmune-mediated destruction of insulin-producing beta cells in the pancreas. T regulatory cells (Tregs) represent an active mechanism of suppressing autoreactive T cells that escape central tolerance. The aim of our study was to test the hypothesis that T regulatory cells express pro- and anti-inflammatory cytokines, elements of cytotoxicity and OX40/4-1BB molecules. The examined group consisted of 50 children with T1DM. Fifty two healthy individuals (control group) were enrolled into the study. A flow cytometric analysis of T-cell subpopulations was performed using the following markers: anti-CD3, anti-CD4, anti-CD25, anti-CD127, anti-CD134 and anti-CD137. Concurrently with the flow cytometric assessment of Tregs we separated CD4+CD25+CD127dim/- cells for further mRNA analysis. mRNA levels for transcription factor FoxP3, pro- and anti-inflammatory cytokines (interferon gamma, interleukin-2, interleukin-4, interleukin-10, transforming growth factor beta1 and tumor necrosis factor alpha), activatory molecules (OX40, 4-1BB) and elements of cytotoxicity (granzyme B, perforin 1) were determined by real-time PCR technique. We found no alterations in the frequency of CD4+CD25highCD127low cells between diabetic and control children. Treg cells expressed mRNA for pro- and anti-inflammatory cytokines. Lower OX40 and higher 4-1BB mRNA but not protein levels in Treg cells in diabetic patients compared to the healthy children were noted. Our observations confirm the presence of mRNA for pro- and anti-inflammatory cytokines in CD4+CD25+CD127dim/- cells in the peripheral blood of children with T1DM. Further studies with the goal of developing new strategies to potentiate Treg function in autoimmune diseases are warranted

CD40L and IL-4 stimulation of acute lymphoblastic leukemia cells results in upregulation of mRNA level of FLICE--an important component of apoptosis.

The use of cancer vaccines based on dendritic cells (DC) presenting tumor antigens can be a promising tool in the treatment of leukemia. The functional characteristics of leukemia derived DC is still to be elucidated. CD40 promotes survival, proliferation and differentiation of normal B cells. CD40 triggering was used to enhance the poor antigen-presenting capacity of leukemic B-cells. Since it is still unclear whether CD40 ligation drives neoplastic B-cells to apoptosis or not, we assessed the mRNA expression of FLICE, FAS, FADD and TRADD - important components of apoptosis machinery, using real-time PCR in acute lymphoblastic leukemia cells before and after CD40 and IL-4 stimulation. ALL cells stimulated with CD40L/IL-4 expressed dendritic cell phenotype at mRNA and protein levels (upregulation of main costimulatory and adhesion molecules noted in real-time RT PCR and flow cytometry); they also expressed higher amounts of mRNA for FLICE, TRADD and FADD after CD40L/IL-4 stimulation. However differences statistically significant comparing cells cultured with CD40L/IL-4 and medium alone regarded only FLICE. Concluding, we showed upregulation of important elements of apoptosis at mRNA level in ALL cells after CD40 ligation

Polymorphism of the FTO

The objective was to compare the impact of clinical and genetic factors on body mass index (BMI) in children with type 1 diabetes (T1DM) without severe obesity. A total of 1,119 children with T1DM (aged 4–18 years) were qualified to take part in the study. All children were genotyped for variants of FTO, MC4R, INSIG2, FASN, NPC1, PTER, SIRT1, MAF, IRT1, and CD36. Results. Variants of FTO showed significant association with BMI-SDS in the T1DM group. The main factors influencing BMI-SDS in children with T1DM included female gender (P=0.0003), poor metabolic control (P=0.0001), and carriage of the A allele of the FTO rs9939609 gene (P=0.02). Conclusion. Our research indicates, when assessing, the risk of overweight and obesity carriage of the A allele in the rs9939609 site of the FTO gene adds to that of female gender and poor metabolic control. This trial is registered with ClinicalTrials.gov (NCT01279161)

Mindfulness in healthcare professionals and medical education

Healthcare professionals are exposed not only to the ubiquitous stress, but also to the culture of perfectionism. Therefore, they need tools to achieve a balance between work and rest in order to effectively help their patients. The study objective is a review of the literature on the implementation of mindfulness in healthcare professionals and medical students. The authors searched the literature in PubMed and Google Scholar databases for publications about “mindfulness” in “healthcare professionals” and “medical students.” The search included manuscripts published to July 31, 2019. Mindfulness is a process of intentional paying attention to experiencing the present moment with curiosity, openness and acceptance of each experience without judgment. Mindfulness training leads to a better mood perception, lower stress perception, and responding to stimuli more effectively. All these features can have a potentially positive effect on healthcare service. The paper describes methods of intervention as well as their effects, which may be useful both in maintaining the well-being of healthcare professionals and in patient care. Mindfulness meditation has a beneficial effect on stress, depression, burnout, well-being and empathy among doctors, nurses and other healthcare workers. However, the method has a number of limitations, including a small number of participants, a high dropout rate in the intervention group and, above all, ceasing to practice mindfulness in the longer term after the course termination. Mindfulness can be widely implemented by healthcare professionals, thus improving their well-being and the quality of care they provide. Further standard scientific research is needed to confirm this impact

Empowerment in the Treatment of Diabetes and Obesity

As the available therapies for diabetes and obesity are not effective enough, diabetologists and educators search for new methods to collaborate with patients in order to support their health behaviors. The aim of this review is to discuss perspectives for the development of new empowerment-type therapies in the treatment of diabetes/obesity. Empowerment is a process whereby patients gain the necessary knowledge to influence their own behavior to improve the quality of their lives. It is carried out in five stages: (1) identify the problem, (2) explain the feelings and meanings, (3) build a plan, (4) act, and (5) experience and assess the execution. Although many years have passed since the advent and popularization of the concept of empowerment, the area remains controversial, mainly with regard to the methodology of therapy. Some previous studies have confirmed the positive effect of empowerment on body weight, metabolic control, and quality of life of patients with type 2 diabetes; however, few studies have been conducted in patients with type 1 diabetes. There is still a need to confirm the effectiveness of empowerment in accordance with Evidence Based Medicine by performing long-term observational studies in a large group of patients. In future, empowerment may become part of the standard of care for patients with diabetes and/or obesity

Contemporary methods of self-control and their use in children and teenagers with type 1 diabetes

Sukcesem współczesnej diabetologii jest wypracowanie kompleksowego leczenia substytucyjnego i objawowego, które jest efektywne i umożliwia normalne życie chorych na cukrzycę, pod warunkiem sumiennego przestrzegania przez pacjenta określonych reguł i obowiązków. Jest to szczególnie istotne dla pacjentów młodych, gdyż skuteczna terapia przekłada się nie tylko na ich aktualną dobrą kondycję fizyczną, ale także na prawidłowy rozwój psychofizyczny, emocjonalny i społeczny, nie naznaczony piętnem przewlekłych powikłań cukrzycowych. Jednym z takich obowiązków, a zarazem fundamentem całego procesu terapeutycznego cukrzycy jest samokontrola, czyli wszystkie działania wykonywane przez pacjenta w celu oceny wyrównania metabolicznego i ryzyka rozwoju lub też postępu powikłań, a także w celu kontroli i wpływania na własny stan zdrowia. Stanowi ona podstawę do wprowadzania zmian w leczeniu insuliną. Do elementów samokontroli należą: oznaczanie stężenia glukozy we krwi za pomocą glukometrów i/lub systemów ciągłego monitorowania glikemii, oznaczanie stężenia glukozy i ciał ketonowych w moczu, prowadzenie dzienniczka samokontroli, oznaczanie ciśnienia tętniczego, pielęgnacja stóp, a także systematyczne badania kontrolne, wysiłek fizyczny, dieta i edukacja. Wśród wymienionych elementów samokontroli najistotniejsze jest oznaczanie glikemii, gdyż na wynikach samokontroli stężenia cukru we krwi opiera się ocena wyrównania metabolicznego oraz codzienne prowadzenie modyfikacji w leczeniu, które wobec nieregularnego trybu życia dzieci i młodzieży staje się dużym wyzwaniem dla pacjentów, ich rodziców i lekarzy diabetologów. W niniejszej pracy zostały przedstawione pojęcia, metodologia, elementy i znaczenie samokontroli, rola i znaczenie wysiłku fizycznego oraz diety, jako elementów samokontroli. Omówiono również najnowsze urządzenia stosowane w samokontroli i analizie danych, a także znaczenie aspektów psychoemocjonalnych w samokontroli u młodych pacjentów z cukrzycą.The success of contemporary diabetology is the development of a comprehensive supportive care that is effective and allows for normal life with diabetes as long as the patient diligently complies with certain rules and responsibilities. This is especially important in case of young patients, as effective therapy does not only affect their current physical condition, but also the proper psychological, emotional and social development not marked by chronic diabetic complications. One of these duties, which is also the foundation of the entire therapeutic process, is self-control, namely all the actions undertaken by the patient in order to evaluate their metabolic status and risk of complications or progress, as well as to control and influence their own health. This forms the basis for making changes in an insulin therapy. The elements of self-control are: determination of blood glucose with the use of glucose meters and/or systems of continuous glucose monitoring, evaluation of glucose and ketones in the urine, keeping diabetes logbook, determination of blood pressure, foot care and regular follow-up examinations, exercise, diet and education. This article presents the concept, methodology, elements and importance of self-control, the role and importance of physical activity and diet as part of self-control. It also discusses the newest devices used in self-control and data analysis, and the importance of psychoemocional aspects in self-control among young patients with diabetes