Does a melatonin supplement alter the course of gastro-esophageal reflux disease?

Symptomatic gastro-esophageal reflux disease(GERD) is a very common disease.The consequence of GERD is not only erosive esophagitis,but also esophageal stricture,Barrett’s esophagus and extra-esophageal damage(including the lungs,throat,sinuses,middle ear and teeth).GERD and Barrett’s esophagus are also identif ied as major risk factors for esophageal carcinoma.Therapy with melatonin prevents esophageal injury from acid-pepsin and acid-pepsin-bile exposure in animals,then further studies are required in humans to establish whether a melatonin supplement is able to protect the patients with GERD from erosions,Barrett’s and neoplasia.     

Pharmacogenetics of the local thrombolysis in patients with deep vein thrombosis

Thrombophilia, the state of increased tendency for blood clotting, is considered the disorder of a complex etiology, caused by both environmental and genetic factors. As gene variants predisposing to thrombophilia and influencing the increased risk of vein thrombosis might influence response to local thrombolysis, the aim of the work was to characterize the pharmacogenetic conditions for local streptokinase treatment in patients with a deep vein thrombosis (DVT) of lower extremities based on the following polymorphism analyses: G1691A polymorphism of factor V (FV), G20210A polymorphism of prothrombin (PT), A4250G (Thr312Ala) polymorphism of fibrinogen-alpha (FGA), G(-455)A polymorphism of fibrinogen-beta (FGB), 4G/5G polymorphism of plasminogen activator inhibitor type 1(PAI-1) and insertion/deletion (I/D) polymorphism of tissue plasminogen activator (t-PA). The study included 40 DVT patients who underwent a local thrombolytic treatment within 14-day period from diagnosis. Full recanalization was achieved in 20 subjects (50%) [group R(+)], whereas incomplete or total lack of recanalization was identified in the remaining 20 patients [group R(-)]. No major complications of thrombolytic treatment occurred in the studied group. In the case of prothrombin gene all individuals carried homozygous wild type genotype (GG). Prevalence of the genotypes and alleles of the remaining five polymorphisms did not differ significantly between the groups R(+) and R(-). Neither sex nor age, smoking or time period from diagnosis to introduction of the thrombolytic treatment significantly influenced treatment efficacy. The results of the study suggest that a local thrombolysis with streptokinase introduced within two week period from the diagnosis is a safe and efficient method of treatment for deep vein thrombosis of lower extremities. However, size of the group is insufficient to clearly determine the association between investigated polymorphisms and efficacy of local treatment with streptokinase.     

RNA-mediated epigenetic regulation of DNA copy number

Increasing evidence suggests that parentally supplied RNA plays crucial roles during eukaryotic development. This epigenetic contribution may regulate gene expression from the earliest stages. Although present in a variety of eukaryotes, maternally inherited characters are especially prominent in ciliated protozoa, in which parental noncoding RNA molecules instruct whole-genome reorganization. This includes removal of nearly all noncoding DNA and sorting the remaining fragments, producing extremely gene-rich somatic genomes. Chromosome fragmentation and extensive replication produce variable DNA copy numbers in the somatic genome. Understanding the forces that drive and regulate copy number change is fundamental. We show that RNA molecules present in parental cells during sexual reproduction can regulate chromosome copy number in the developing nucleus of the ciliate Oxytricha. Experimentally induced changes in RNA abundance can both increase and decrease the levels of corresponding DNA molecules in progeny, demonstrating epigenetic inheritance of chromosome copy number. These results suggest that maternal RNA, in addition to controlling gene expression or DNA processing, can also program DNA amplification levels.     

Congestive heart failure and continuous murmur in patient after lumbar disc surgery--a case report

We present a case of a 61-year-old female who was admitted to the hospital with symptoms of congestive heart failure. Diagnosis of arteriovenous fistula was suggested by the echocardiographic signs of high-output state and a continuous murmur heard especially close to the surgical scar from an intervention on the L4-L5 disc that the patient had undergone eight months before. Aortography confirmed arteriovenous fistula between the right common iliac artery and inferior vena cava. After surgical closure of the fistula, normal cardiac function was restored.     

Teat tablet with sodium ibuprofen: the effect of sorbitol on therapeutic agent pharmaceutical availability and on physicochemical parameters of a drug form

Dosing pediatric drugs available on pharmaceutical markets of analgesic, antifebrile and anti-inflammatory activity to children up to 3 years of age is not precise and frequently causes problems. The aim of the study was to work out a pediatric teat form of a drug with sodium ibuprofen and to determine the effect of sorbitol content on pharmaceutical availability of the therapeutic agent. Three variants of tablets containing 50 mg of sodium ibuprofen differing in the percentage content of sorbitol (from 37% - batch I to 79% - batch III) were produced. Quality tests of the produced forms of drugs (PPVI) were performed and the tests of therapeutic agent pharmaceutical availability by spatula method and by a method with a teat. Tablets of all batches had a smooth surface and same shape. The content of the therapeutic agent was within the limit of 95-105% of the declared value. The highest value of Q coefficient in the release test by pharmacopeal method and the shortest disintegration time (12 minutes) were obtained for tablets with 79% content of sorbitol. In conclusion, teat tablets with sodium ibuprofen of the highest sorbitol content (79%) demonstrated the expected physicochemical parameters and high pharmaceutical availability.     

ERα and ERβ expression in correlation with Ki-67, Bcl-2 and Bak in primary tumors and lymph node metastases of breast cancer: The effect of pre-operative chemotherapy

This study aimed to assess the pre-operative chemotherapy impact on the relationship between estrogen receptor (ER) expression and markers of proliferation and apoptosis in primary and metastatic breast cancer. Immunohistochemical examinations were conducted on surgically removed ductal invasive breast cancers and their lymph node metastases in 135 patients. A total of 64 patients from this group underwent pre-operative chemotherapy and in 71 cases the surgery was performed without primary chemotherapy. A negative correlation between ERα and Ki-67 was found in primary tumors and lymph node metastases. A positive correlation was observed between ERα and Bcl-2. A positive correlation was also noted between ERβ and Bak, suggesting that the two ERs were involved in the regulation of proteins responsible for the control of the apoptotic process. Assessment of the expression of the proteins conducted separately in primary tumors and lymph node metastases did not reveal a significant effect of pre-operative chemotherapy on the correlations of ERs with Ki-67, Bcl-2 and Bak. However, the analysis of the correlations between the receptor expression in primary tumors and Ki-67, Bcl-2 and Bak in lymph node metastases showed a statistically significant impact of pre-operative chemotherapy on the correlations of ERα and Bcl-2 with ERβ and Bak, confirming involvement of the two ERs in the regulation of apoptosis during breast carcinogenesis.     

Management of rheumatoid arthritis in Poland – where daily practice might not always meet evidence-based guidelines

IntroductionInternational recommendations are intended to help rheumatologists in the effective management of rheumatoid arthritis (RA) through an evidence-based approach. This research aimed to evaluate management patterns and associated difficulties encountered by rheumatologists in daily practice.Material and methodsInterviewers recruited 101 Polish rheumatologists in a random quota-based, nationwide sample of outpatient clinics. Quantitative data were input online using a computer-assisted web interview tool.ResultsDisease-modifying antirheumatic drugs (DMARDs) are not initiated at the time of diagnosis in 15% of RA patients, most often due to difficulties in patient-provider communication. The RA activity is assessed every 4 to 6 months by 30% of rheumatologists, and 64% of patients are reported to never achieve remission. Composite indices are the most reliable indicators of remission only for 38% of responders. Despite inadequate disease control with ≥ 2 treatment schedules with synthetic DMARDs, 34% of these patients are not considered for biological DMARDs (bDMARDs). Contraindications and reimbursement barriers are the most frequently stated reasons. Therapy with glucocorticoid (GC) lasting over 3 months is reported by 70% of rheumatologists. International recommendations are stated as the most common basis for treatment decisions.ConclusionsAwareness of recommendations is not sufficient to ensure their application in clinical practice. Inadequate management of RA is quite prevalent, with a substantial contribution of non-medical factors. Daily practice mainly deviates from guidelines regarding frequency and mode of monitoring measures, time to DMARD initiation, and duration of GC treatment. Education programs and policy changes may significantly narrow the gap between evidence and practice.     

Coordinated medical care for children with neurofibromatosis type 1 and related RASopathies in Poland

Coordinated medical care offered in Poland for patients suffering from neurofibromatosis type 1 and related RASopathies combines complex multispecialty consultation with permanent supervision and the patient’s oriented longitudinal care. Neurofibromatosis type 1 is one of the most common single gene disorders in the global population, observed in 1 out of 2500–3000 live births. It is a primary neoplasia disease with 100% penetration of the gene mutation but remarkable age-dependent onset of different disease signs and symptoms, outstanding clinical heterogeneity between patients even in one family and lack of genotype-phenotype correlation, a high rate of spontaneous mutation exceeding 50%, and multiple comorbidities among which increased risk of malignancy is the most important. Medical practice proved that not only patient-oriented complex but also coordinated care provided in centers of competence is indispensable for patients and the families and provides a sense of medical security to them in conjunction with public health costs rationalization.     

What Is the Role of Therapeutic Plasma Exchange as an Adjunctive Treatment in Severe COVID-19: A Systematic Review

Introduction: Since the COVID-19 pandemic outbreak, multiple promising treatment modalities have been tested, however, only several of them were proven to be effective. Therapeutic plasma exchange (TPE) has been recently discussed as a possible supportive treatment for severe cases. Methods: To investigate a possible role of TPE in severe COVID-19 we used a structured systematic search strategy to retrieve all relevant publications in the field. We screened in PubMed, EMBASE, Web of Science, Cochrane Library and clinicaltrials.gov for data published until the 4 June 2021. Results: We identified 18 papers, enrolling 384 patients, 220 of whom received TPE. The number of TPE sessions ranged from 1 to 9 and the type of replacement fluid varied markedly between studies (fresh frozen plasma or 5% albumin solution, or convalescent plasma). Biochemical improvement was observed in majority of studies as far as C-reactive protein (CRP), interleukin-6 (IL-6), ferritin, lactate dehydrogenase (LDH), D-dimer concentrations and lymphocyte count are concerned. The improvement at a laboratory level was associated with enhancement of respiratory function. Adverse effects were limited to five episodes of transient hypotension and one femoral artery puncture and thrombophlebitis. Conclusions: Although the effect of therapeutic plasma exchange on mortality remains unclarified, the procedure seems to improve various secondary end-points such as PaO₂/FiO₂ ratio or biomarkers of inflammation. Therapeutic plasma exchange appears to be a safe treatment modality in COVID-19 patients in terms of side effects.