Serum Level of MMP-3 and MMP-9 in Patients with Diabetes Mellitus Type 2 Infected with Epstein-Barr Virus.

Diabetes mellitus type 2 (DM2) has recently become one of the most important health problems in the world. Patients with DM2 with long-term glycaemia are more likely to become infected than the healthy population. Matrix metalloproteinases (MMPs) play a key role in tissue remodeling during various physiological processes. However, it has been reported that certain MMPs are overexpressed during the development of various human diseases. In this study, we analyzed the levels of MMP-3 and MMP-9 in the serum of DM2 patients with and without Epstein-Barr virus (EBV) infection. The study included 115 patients with DM2 hospitalized in the Internal Ward of the Masovian Specialist Hospital in Radom, Poland, who were divided into two groups: EBV-positive and EBV-negative. The levels of MMP-3 and MMP-9 were tested in the serum of patients using the ELISA method, while the presence of EBV in saliva was tested by polymerase chain reaction (PCR). The presented studies showed a significant difference in the concentration of both MMPs in diabetic patients additionally infected with EBV compared to the group of non-infected individuals. It seems that MMPs may be useful biomarkers in the diagnosis, prognosis, and monitoring of diabetes associated with EBV infection.

The effect of the source and dosage of dietary Cu on redox status in rat tissues.

The aim of this experiment was to investigate whether the amount of Cu added to the diet of rats can be reduced without adversely affecting the antioxidant status of tissues and growth, and whether copper nanoparticles can be used for this purpose. For four weeks, four experimental groups of rats were fed diets with two dosages of added Cu (standard-6.5 or 3.25 mg/kg) in two forms (standard-CuCO3 or copper nanoparticles). Replacing the CuCO3 supplement with CuNPs resulted in a decreased lung weight and an increased Cu content in brain, kidney and lung, intensification of lipid peroxidation processes, and weakened antioxidant defence in the lungs and kidneys. This treatment also reduced the Cu content in heart, level of lipid oxidation in the liver and testes and improved antioxidant defence in the brain. Reducing the addition of Cu to the diet from 6.5 to 3.25 mg/kg reduced lung weight and increased lipid peroxidation in the liver, heart and lungs, and also weakened antioxidant defence in the lungs and testes. This treatment also weakened the lipid peroxidation process in the spleen, small intestine and brain and strengthened the antioxidant defence of the brain and kidneys. In conclusion, replacing CuCO3 with CuNPs and reducing the level of Cu in the diet of rats has a particularly unfavourable effect on the respiratory system, causing adverse changes in the lungs. However, these treatments have a clearly positive effect on the redox status of the liver and brain.

Epstein-Barr virus in selected cancer diseases / Wirus Epsteina-Barr w wybranych chorobach nowotworowych.

Viral infections contribute to many cancers worldwide and represent a significant percentage of deaths. Oncogenic viruses include the Epstein-Barr virus, which is the main cause of infectious mononucleosis and exhibits tropism towards B lymphocytes. Due to the presence of genes responsible for latency, it can contribute to many pathological conditions. Examples of this are high-fatal malignancies located in the stomach as well as in the head and neck. Moreover, this virus poses a serious threat to immunocompromised people, which is a significant problem nowadays due to the increasing number of patients undergoing immunosuppressive therapy. Particular attention in this case is lymphoproliferative disorders after transplantation, which are a malignant neoplasm associated with EBV infection. This review focuses on the role of the Epstein-Barr virus in selected cancers.

[Morphological and molecular bases of cardiac development]. / Morfologiczne i molekularne podstawyrozwoju serca.

The heart is a mesoderm-derived organ, whose formation is regulated by various genes. Initially, the most important is expression of Nkx2.5, CR1, pitx2, anf and mhc2a, which are responsible for differentiation of cardiomyocytes. In a later phase activation of mhc2b, pitx2c, mesp1, pcmf1, vmhc, xin, mcl2v, mlc2a, mlc2a, mef2, hand1 and hand2 was revealed. Their expression is regulated by various molecules, including transcription (XIN, GATA, MEF, Tbx5, Baf60c, PECAM, tie-2, MEF2) and growth (VEGF, FGF, PDGF) factors, as well as proteins (i.e., dickkopf-1, cerberus, cytotactin, fibrillin, nodal, thrombomodulin, Wnt, bone morphometric ones - BMP2, BMP 4, BMP5, BMP7) and other substances, such as retinoid and folic acid. Crucial steps in cardiac organogenesis are development of the ventricle and atrial formation, as well as septation and valve formation. Any disturbances of such processes may lead to various congenital heart diseases and defects that could be initiated by various genetic, epigenetic or environmental factors. The most common heart malformations are: stenosis (coarctation) of the aorta and pulmonary trunk, bicuspid aortic valve, atrial and/or ventricular septal defect, persistent truncus arteriosus (Botallo duct), transposition of the great vessels, tricuspid atresia, hypoplastic left and right heart, as well as syndrome of Lutembachera, Cantrell, Ebstein, Eisenmenger and Shone and trilogy, tetralogy, pentalogy of Fallot.

Controlled Attenuation Parameter Is Associated with a Distinct Systemic Inflammatory Milieu after Clearance of HCV Infection.

Hepatitis C virus (HCV) infection is closely associated with lipid metabolism defects along with a high prevalence of hepatic steatosis. After HCV clearance, steatosis persists in many patients. However, the reasons behind this phenomenon are not completely clear. To investigate the association between 92 soluble inflammatory mediators (SIMs) and the steatosis grade, we made use of a cohort of 94 patients with chronic HCV infection who cleared HCV after direct-acting antiviral agent (DAA) treatment. Patients were classified into three groups according to their controlled attenuation parameter (CAP). CAP is associated with ALT, γ-GT and liver stiffness after HCV clearance. While stem cell factor (SCF) and tumor necrosis factor ligand superfamily member 12 (TWEAK) levels were significantly reduced in patients with CAP > 299 dB/m, the levels of fibroblast growth factor (FGF)-21 and interleukin-18 receptor 1 (IL-18R1) were higher in those patients at week 96 after virus clearance. These four markers also showed a linear correlation with CAP values. FGF-21 levels correlated with CAP only after HCV clearance. Taken together, these four biomarkers, namely SCF, TWEAK, FGF-21 and IL-18R1, are associated with CAP status after virus clearance. A potential role of these proteins in the pathogenesis of post-sustained viral response (SVR) nonalcoholic steatohepatitis requires further investigation.

[The essence of doctor-patient relationship in creating image of a medical institution]. / Istota relacji lekarz-pacjent w budowaniu wizerunku placówki medycznej.

Irrespective of changing standards and continuous reforms in health service, the patient should always remain the principal focus. The patient is a person who should be treated not only as a customer or a recipient of medical services but also as a person being in a situation which is difficult and often unacceptable. Among the factors affecting patients' satisfaction and contentment in the course of the disease it is profoundly important that he cooperates with his doctor. For years it has been attempted to create an ideal model of doctor-patient relationship which would be mutually beneficial and not violating privacy or welfare of any of them. These attempts focused on various theoretical models, among others paternalistic, informative and interpretive. However, special attention should be paid to adherence to principles which is based on respect for patient autonomy, harmlessness, charity and fairness.

[Symbolizm of medical institutions]. / Symboliczny wymiar wizerunku placówki medycznej.

Marketing in health service has become an indispensable tool for creating and maintaining a positive image of medical institutions which to a great extent determines their success on the market. This process entails not only providing professional, reliable and up-to-date patient care but also establishing good reputation among those who already use it and its potential customers. It should be recognizable also for deliverers, investors, competitors, media and particularly for society and local authorities. The key to success is professionalism of personnel and their identification with the mission of the institution and the direction of changes being implemented there. For a complete success and recognition is essential health care facilities, which affects virtually matched the name and symbol, and communication of people responsible for contact with the media.

[Marketing in health service--a necessity or a temporary whim?]. / Marketing w sluzbie zdrowia--koniecznosc czy chwilowa zachcianka?

Permanent changes occurring in economy and politics, open borders, a greater number of people with higher education as well as growing social awareness concerning taking care of health are followed by changes in healthcare sector. In response to an increased social demand, new medical institutions are being founded. They offer their patients a vast array of services ranging from therapeutic to preventive and highly specialized procedures improving their standard of living. In order to attract regular patients, and therefore receive regular income, it is necessary to stabilize such institutions on services market. It can be achieved by numerous marketing tools which, when applied appropriately, enable to create a positive image of a medical institution.

[Developmental toxicity of the over-the-counter analgetics and antypiretics]. / Toksycznosc rozwojowa leków przeciwbólowych i przeciwgoraczkowych dostepnych bez recepty.

Over-the-counter antipyretics (acetaminophen, aspirin, ibuprofen) and/or analgesics (acetaminophen, aspirin, diclofenac, ibuprofen, naproxen) are relatively safe for adults. However, data on their developmental toxicity is sparse. Moreover, experimental and clinical findings are commonly incompatible. The highest developmental toxicity was found for aspirin. However, unlike full-dose of aspirin, its low doses are compatible during pregnancy. Over-the-counter nonselective cyclooxygenase inhibitors (non-steroidal anti-inflammatory drugs, NSAID) may induce miscarriage, stillbirth, intrauterine growth retardation, preterm constriction of the ductus arteriosus with a secondary persistent pulmonary hypertension, reduced fetal renal perfusion that led to oligohydramion, prolonged pregnancy as well as an increase prevalence of intracranial bleeding in newborns. For acetaminophen and ibuprofen an increased risk of cryptorchidism was also pointed. Prenatal exposure to acetaminophen may also induce bronchial asthma during childhood, preeclampsia, preterm birth, maternal phlebothrombosis and pulmonary embolism. Furthermore, epidemiological data suggest higher risk of cardiac, abdominal wall and orofacial defects of evaluated drugs.

The association of airborne particulate matter and benzo[a]pyrene with the clinical course of COVID-19 in patients hospitalized in Poland.

Air pollution can adversely affect the immune response and increase the severity of the viral disease. The present study aimed to explore the relationship between symptomatology, clinical course, and inflammation markers of adult patients with coronavirus disease 2019 (COVID-19) hospitalized in Poland (n = 4432) and air pollution levels, i.e., mean 24 h and max 24 h level of benzo(a)pyrene (B(a)P) and particulate matter <10 µm (PM10) and <2.5 µm (PM2.5) during a week before their hospitalization. Exposures to PM2.5 and B(a)P exceeding the limits were associated with higher odds of early respiratory symptoms of COVID-19 and hyperinflammatory state: interleukin-6 > 100 pg/mL, procalcitonin >0.25 ng/mL, and white blood cells count >11 × 103/mL. Except for the mean 24 h PM10 level, the exceedance of other air pollution parameters was associated with increased odds for oxygen saturation <90%. Exposure to elevated PM2.5 and B(a)P levels increased the odds of oxygen therapy and death. This study evidences that worse air quality is related to increased severity of COVID-19 and worse outcome in hospitalized patients. Mitigating air pollution shall be an integral part of measures undertaken to decrease the disease burden during a pandemic of viral respiratory illness.

The Course of COVID-19 in Patients with Systemic Autoimmune Rheumatic Diseases.

Patients with systemic autoimmune rheumatic disease (SARD) have increased susceptibility to viral infections, including SARS-CoV-2. The aim of this study was to analyse the SARD patient population with COVID-19 (coronavirus disease 2019) in terms of baseline characteristics, severity, course and outcomes of the disease compared with the non-SARD group, and to identify factors associated with prognosis, including remdesivir therapy efficacy. Retrospective study comprised 8220 COVID-19 cases from the SARSTer database, including 185 with SARD. Length of hospitalisation, duration of oxygen therapy, mortality and the need for HFNO (high-flow nasal oxygen) and/or NIV (noninvasive ventilation) were significantly higher in the SARD versus non-SARD group. There was no difference in clinical features on admission to hospital. Patients with SARD were older and more likely to have cardiovascular, pulmonary and chronic kidney diseases. Age, the presence of cardiovascular disease, more severe conditions on admission and higher inflammatory marker values were found to be risk factors for death in the SARD group. In patients with SARD treated with remdesivir, there was a trend towards improved mortality but without statistical significance. Length of hospitalisation, 28-day mortality and the need for HFNO and/or NIV were higher in the SARD group. These patients often had other chronic diseases and were older.

Remdesivir Decreases Mortality in COVID-19 Patients with Active Malignancy.

Data on the use of remdesivir, the first antiviral agent against SARS-CoV-2, are limited in oncologic patients. We aimed to analyze contributing factors for mortality in patients with malignancies in the real-world CSOVID-19 study. In total, 222 patients with active oncological disorders were selected from a nationwide COVID-19 study of 4890 subjects. The main endpoint of the current study was the 28-day in-hospital mortality. Approximately half of the patients were male, and the majority had multimorbidity (69.8%), with a median age of 70 years. Baseline SpO2 < 85% was observed in 25%. Overall, 59 (26.6%) patients died before day 28 of hospitalization: 29% due to hematological, and 20% due to other forms of cancers. The only factor increasing the odds of death in the multivariable model was eGFR < 60 mL/min/m2 (4.621, p = 0.02), whereas SpO2 decreased the odds of death at baseline (0.479 per 5%, p = 0.002) and the use of remdesivir (0.425, p = 0.03). This study shows that patients with COVID-19 and malignancy benefit from early remdesivir therapy, resulting in a decrease in early mortality by 80%. The prognosis was worsened by low glomerular filtration rate and low peripheral oxygen saturation at baseline underlying the role of kidney protection and early hospitalization.

Ocular Involvement of SARS-CoV-2 in a Polish Cohort of COVID-19-Positive Patients.

The coronavirus SARS-CoV-2 responsible for the current human COVID-19 pandemic has shown tropism toward different organs with variable efficiency, eyes included. The purpose of this study has been to investigate the presence of detectable SARS-CoV-2 infection in ocular swabs in patients affected by COVID-19. A consecutive series of 74 COVID-19-positive patients (age 21-89) were enrolled at two Polish COVID-19 hospitals for 4 months and were characterized by PCR for the presence of the SARS-CoV-2 genetic material in nasopharyngeal (NP) and ocular swabs, while their respiratory and ocular symptoms were noted. Almost 50% of them presented with severe/critical respiratory involvement, and some degree of eye disease. No tight correlation was observed between the presence of ocular and respiratory symptoms. Three male patients presenting with severe/critical lung disease tested positive in ocular swab, however with mild/moderate ocular symptoms. In conclusion, our study lends further support to the view that overt ocular infection by the SARS-CoV-2 virus is not such a frequent occurrence.

A 56-year-old man with RT-PCR negative nasopharyngeal swabs with Coronavirus Disease 2019 (COVID-19) Pneumonia.

INTRODUCTION: Diagnostic procedure in Coronavirus Disease 2019 (COVID-19) is based mainly on performing real-time-reverse transcription-polymerase chain-reaction (RT-PCR), which has been accepted as the gold standard method. In some cases, such as mutations of the SARS-CoV-2 genome, variable viral load kinetics or laboratory errors, it can be false-negative. CASE REPORT: The case is presented of a 56-year-old man with respiratory tract symptoms, with twice negative results of real-time-reverse transcription-polymerase chain-reaction of nasopharyngeal swabs and positive chest computed tomography, with typical findings for COVID-19 pneumonia. CONCLUSIONS: Patients with negative RT-PCR results, but with positive computed tomography findings characteristic for COVID-19, should be treated as well as those infected.

Glutathione peroxidase (GPx) and superoxide dismutase (SOD) activity in patients with diabetes mellitus type 2 infected with Epstein-Barr virus.

Oxidative stress is suggested to be the crucial factor in diabetes mellitus type 2 (DM2) pathogenesis and in the development of diabetic complications. Patients with DM2 may be more susceptible to infections due to hyperglycaemia-induced virulence of various microorganisms. Several studies pointed that Epstein-Barr virus (EBV) infection is associated with reactive oxygen species (ROS) production and/or activation of signalling pathways connected with ROS. The present study analyzed serum activity of glutathione peroxidase (GPx) and superoxide dismutase (SOD) in DM2 patients with and without EBV infection. Blood and saliva were collected from 120 patients with DM2. EBV DNA was detected in the saliva using nested-PCR technique. Spectrophotometric methods were implemented to determine serum GPx and SOD activity with the use of diagnostic kits produced by Randox Laboratories. GPx and SOD activity was decreased in diabetic patients, with the lowest values in DM2 EBV-positive patients. There was correlation between GPx and SOD activity-with increased value of GPx, SOD activity was also rised. In patients with DM2 history longer than 10 years as well as in DM2 patients with obesity, antioxidant enzymes activity was decreased. Determination of examined parameters may be useful in diabetic patients with EBV infection and could be important prognostic factor.

Convalescent Plasma Transfusion for the Treatment of COVID-19-Experience from Poland: A Multicenter Study.

Because the optimal treatment for COVID-19 is still unknown, it is important to explore every potential way of improving the chances of survival for COVID-19 patients. The aim of the study was to analyze the effectiveness of convalescent plasma on COVID-19 patients. The study population consisted of 78 patients diagnosed with COVID-19, selected from the SARSTer national database, who received convalescent plasma. The impact on clinical and laboratory parameters was assessed. A clinical improvement was observed in 62 (79%) patients, and 10 (13%) patients died from COVID-19. No side effects of the convalescent plasma treatment were observed. When plasma was administered earlier than 7 days from diagnosis, the total hospitalization time was shorter (p < 0.05). Plasma efficacy was inferior to remdesivir in endpoints such as the necessity and duration of oxygen therapy, the duration of hospitalization, and mortality rate, and inferior to other drugs in the case of the duration of hospitalization and the necessity of constant oxygen therapy, but comparable in most other measured endpoints. A comparison of a 30-day mortality rate in patients who received plasma and remdesivir (4/25, 16%) and who received only plasma (6/53, 11%) showed no significant difference. Convalescent plasma efficacy is inferior to remdesivir when treating COVID-19 patients but the addition of remdesivir to plasma does not improve the treatment effectiveness. In most endpoints, plasma was comparable to other treatment options. In our opinion, convalescent plasma may be used as a supportive treatment in COVID-19 patients because of the low frequency of adverse effects and availability, but must be given as early from the diagnosis as possible.

Transforming Growth Factor-ß, Interleukin-10, and Serological Markers in EBV-associated Gastric Carcinoma.

BACKGROUND/AIM: The association between Epstein-Barr virus (EBV) and gastric cancer (GC) has been reported by many researchers. Immunosuppressive cytokines, such as interleukin-10 (IL-10) and transforming growth factor ß (TGFß), play an important role in the tumor process. The aim of the present study was to detect antibodies against EBV and explore the levels of TGFß and IL-10 in Polish GC patients. PATIENTS AND METHODS: Fifty patients with GC and 50 hospitalized individuals without GC (control group) were enrolled in the study. Frozen tumor tissue fragments were tested using nested PCR assay for EBV DNA detection. ELISA test was used to detect the presence of anti-VCA IgG, anti-EBNA IgG, anti-EA IgG, TGFß and Il-10 in sera from all individuals. RESULTS: EBVCA was detected in 88.0%, EBNA in 90.0%, and EA in 72.0% of patients. Levels of TGFß and IL-10 were significantly higher in patients with high levels of anti-EA antibodies (25.4 ng/ml; 7.8 pg/ml) compared to patients with low levels of anti-EA antibodies (12.61 ng/ml; 4.29 pg/ml). CONCLUSION: The significantly higher level of EA in patients' sera indicates EBV reactivation. TGFß level was significantly higher in GC than in the control group, especially in EA-positive patients, indicating its possible role in gastric carcinogenesis.