Search

Cel pracyOcena związku między przyrostem masy ciała u pacjentów z pierwszorazowym epizodem psychozy (FEP), a czynnikami psycho-bio-społecznymi i socjologicznymi.MetodaW badaniu wzięło udział 25 osób z FEP w wieku 14-35 lat zbadanych w pierwszym tygodniu (P1) oraz po trzech miesiącach hospitalizacji (P3). W ciągu 3 miesięcy u wszystkich pacjentów zdiagnozowano schizofrenię. W badaniu wykorzystano: ankietę socjo-demograficzną, Skali Pozytywnych i Negatywnych Objawów Schizofrenii (PANSS), Inwentarza Stanu i Cechy Lęku (STAI), Kwestionariusza Radzenia Sobie W Sytuacjach Stresowych (CISS), Kwestionariusza Do Badania Zachowań Żywieniowych (QEB), rutynowe wyniki badań biochemicznych. Dla niektórych zmiennych obliczono różnice (zmienna_D) między wartościami w P1 i P3.WynikiWykazano zależności istotne statystycznie między masą ciała_P1, _P3 oraz _D z indeksem prozdrowotnym diety_P1 i _P3, nasileniem objawów psychotycznych mierzonych PANSS_P1 i _D, CISS skoncentrowanym na emocjach i zadaniu _P1, _P3 oraz _D, masą ciała matki w młodości i aktualną, masą ciała ojca w młodości i aktualną masą ciała oraz liczbą posiadanego przez pacjenta rodzeństwa. W analizie regresji liniowej istotnymi predyktorami masy ciała_P3 okazała się być masa ciała_P1oraz CISS skoncentrowany na emocjach_P1.WnioskiStwierdzono wieloczynnikowe uwarunkowania przyrostu masy ciała w FEP w schizofrenii. Przeciwdziałanie przyrostowi masy ciała nie powinna dotyczyć jedynie diety, ale również tego w jaki sposób nawyki żywieniowe powiązane są z towarzyszącą psychozie psychopatologią oraz funkcjonowaniem emocjonalnym pacjenta.

ECC is a significant therapeutic and social problem and a global burden on public health. The aim of this clinical trial was to test whether a 2-week daily consumption of chewing tablets containing thermally inactivated

Ischemic stroke accounts for over 80% of all strokes and is one of the leading causes of mortality and permanent disability worldwide. Intravenous administration of recombinant tissue plasminogen activator (rt-PA) is an approved treatment strategy for acute ischemic stroke of large arteries within 4.5 h of onset, and mechanical thrombectomy can be used for large arteries occlusion up to 24 h after onset. Improving diagnostic work up for acute treatment, reducing onset-to-needle time and urgent radiological access angiographic CT images (angioCT) and Magnetic Resonance Imaging (MRI) are real problems for many healthcare systems, which limits the number of patients with good prognosis in real world compared to the results of randomized controlled trials. The applied endovascular procedures demonstrated high efficacy, but some cellular mechanisms, following reperfusion, are still unknown. Changes in the morphology and function of mitochondria associated with reperfusion and ischemia-reperfusion neuronal death are still understudied research fields. Moreover, future research is needed to elucidate the relationship between continuously refined imaging techniques and the variable structure or physical properties of the clot along with vascular permeability and the pleiotropism of ischemic reperfusion lesions in the penumbra, in order to define targeted preventive procedures promoting long-term health benefits.

ECC is a significant therapeutic and social problem and a global burden on public health. The aim of this clinical trial was to test whether a 2-week daily consumption of chewing tablets containing thermally inactivated L. salivarius reduces the 12-month caries increment compared to the control group. The investigation was a single-center, randomized, controlled open-label, blinded end-point evaluation trial in two parallel groups. At baseline, 140 generally healthy children between 3 and 6 years of age with or without ECC were randomly assigned to the probiotic test group (n = 70) or to the treatment as the usual control group (n = 70). The primary outcome measure was the 1-year increment in caries incidence and prevalence. Secondary endpoints assessed were the initial, cavitated and obvious dentinal caries increment as well as the measurement of dental plaque accumulation, as an indicator of the ECC risk. Data were collected through the clinical assessment of the children’s caries (dmft and ICDAS II) and oral hygiene status (DI-S of OHI-S index). Caries incidence and prevalence were statistically significantly lower in the probiotic group versus the control group (p < 0.001 and p = 0.0075). The initial and final mean OHI-S scores in the probiotic group did not show any significant differences. In conclusion, the regular short-term intake of probiotics may reduce caries development. Our findings suggest that self-administered probiotic therapy may provide a good complement to increase the effectiveness of individual preventive home care in preschool children. This is the first clinical study evaluating the effect of a short-term probiotic intervention on reducing early childhood caries with 12 months of follow-up.

Biological therapies have changed the face of oncology by targeting cancerous cells while reducing the effect on normal tissue. This publication focuses mainly on new therapies that have contributed to the advances in treatment of certain malignancies. Immunotherapy, which has repeatedly proven to be a breakthrough therapy in melanoma, as well as B-ALL therapy with CAR T cells, are of great merit in this progress. These therapies are currently being developed by modifying bispecific antibodies and CAR T cells to improve their efficiency and bioavailability. Work on improving the therapy with oncolytic viruses is also progressing, and efforts are being made to improve the immunogenicity and stability of cancer vaccines. Combining various biological therapies, immunotherapy with oncolytic viruses or cancer vaccines is gaining importance in cancer therapy. New therapeutic targets are intensively sought among neoantigens, which are not immunocompromised, or antigens associated with tumor stroma cells. An example is fibroblast activation protein α (FAPα), the overexpression of which is observed in the case of tumor progression. Universal therapeutic targets are also sought, such as the neurotrophic receptor tyrosine kinase (NTRK) gene fusion, a key genetic driver present in many types of cancer. This review also raises the problem of the tumor microenvironment. Stromal cells can protect tumor cells from chemotherapy and contribute to relapse and progression. This publication also addresses the problem of cancer stem cells resistance to treatment and presents attempts to avoid this phenomenon. This review focuses on the most important strategies used to improve the selectivity of biological therapies.

Cel pracyZespoły kardiometaboliczne są najczęstszą przyczyną powikłań skracających oczekiwaną długość życia u pacjentów leczonych z powodu zaburzeń psychicznych, w tym schizofrenii. Jednak to, jak bardzo ryzyko kardiometaboliczne jest związane ze stylem życia, skutkami ubocznymi leczenia lub psychozą, nie jest jasne. Celem tego badania była prospektywna ocena zmian metabolicznych u młodych pacjentów, u których zdiagnozowano pierwszy ostry epizod psychozy bez wcześniejszej farmakoterapii.MetodaAnalizy zostały przeprowadzone w trakcie przyjęcia do szpitala oraz po 3 i 12 tygodniach i obejmowały morfologię krwi, profil lipidowy, glukozę, markery stanu zapalnego, ciśnienie krwi oraz wskaźnik masy ciała. Nasilenie objawów klinicznych oceniono za pomocą skali pozytywnych i negatywnych objawów (z ang. Positive and Negative Syndrome Scale, PANSS), a zdolności poznawcze oceniono za pomocą skali Montreal Cognitive Assessment (MoCA). Zmierzono również czas trwania nieleczonej psychozy (z ang. duration of untreated psychosis, DUP).WynikiStwierdzono znaczny wzrost wskaźnika masy ciała, nasilenie dyslipidemii, stanu zapalnego i skurczowego ciśnienia krwi po 12 tygodniach od rozpoczęcia leczenia, podczas gdy poziom kortyzolu spadł. Zaobserwowano ujemną korelację między pomiarami PANSS-P (skala dodatnia PANSS) a całkowitym poziomem cholesterolu, skalą całkowitą PANSS i lipoproteiną o niskiej gęstości (LDL), a także DUP i MoCA. Poziom lipoprotein o wysokiej gęstości (HDL) korelował dodatnio z DUP, kortyzolem, monocytami i leukocytami w pierwszym tygodniu.WnioskiWyniki wskazują na związek pomiędzy rozwojem i leczeniem pierwszego epizodu psychozy z wynikami badań laboratoryjnych, przyczyniając się do rozwoju stresu metabolicznego u pacjentów.

Cel pracyCelem badania była ocena związku między krótkotrwałą poprawą stanu klinicznego młodych pacjentów z pierwszym epizodem psychozy (FEP) i zmianami stężenia metabolitów tlenku azotu (NO), profilu lipidowego i markerów ogólnoustrojowego stanu zapalnego w osoczu krwi.MetodaBadanie przeprowadzono w grupie 15 młodych pacjentów z FEP (w wieku 15–35 lat), od których pobierano próbki krwi w 1, 3 i 12 tygodniu po przyjęciu do Oddziału Klinicznego Psychiatrii Dorosłych, Dzieci i Młodzieży Szpitala Uniwersyteckiego w Krakowie celem oceny metabolitów NO, morfologii, profilu lipidowego i biomarkerów stanu zapalnego. Przeanalizowano również dane demograficzne i kliniczne.WynikiW badanej grupie trzy miesiące po przyjęciu do szpitala zaobserwowano poprawę objawów klinicznych, na co wskazuje obniżenie wyników na Skali Pozytywnych i Negatywnych Objawów Schizofrenii (Positive and Negative Syndrome Scale – PANSS). Poprawa ta była związana ze spadkiem stężenia azotynów w osoczu, pogorszeniem profilu lipidowego i aktywacją ogólnoustrojowego stanu zapalnego. Zaobserwowano dodatnią korelację między stężeniem azotynów w osoczu i wynikiem PANSS oraz ujemną korelację między wynikiem podskali PANSS-P (pozytywnej) i całkowitym cholesterolem, a także całkowitym wynikiem PANSS, lipoproteiną o niskiej gęstości i liczbą białych krwinek.WnioskiUzyskane wyniki sugerują, że u młodych pacjentów z FEP stan zapalny, niekorzystne reakcje metaboliczne w tym upośledzenie dostępności NO, są wywoływane przez ciężki początek ostrej psychozy i należy je traktować jako ogólnoustrojowe objawy FEP

The aim of this study was to determine the effect of sesquiterpene lactone parthenolide on the cytotoxic and pro-oxidative effects of etoposide in HL-60 cells.Cytotoxic effects were determined by incubation of HL-60 cells with various concentrations of examined compounds and combinations thereof, which were then stained with propidium iodide and analyzed using a flow cytometer. To determine the role of oxidative stress in the action of the compounds, co-incubation with N-acetyl-l-cysteine (NAC) and parthenolide and/or etoposide was used and the level of reduced glutathione (GSH) was detected.Parthenolide significantly enhanced the cytotoxic and pro-apoptotic effects of etoposide. However, in most cases of the combinations of parthenolide and etoposide, their effect was antagonistic, as confirmed by an analysis using the CalcuSyn program. The examined compounds significantly reduced the level of GSH in HL-60 cells. Combination of etoposide at a concentration of 1.2 μM and parthenolide also significantly reduced GSH level. However, in the case of a combination of etoposide at a concentration of 2.5 μM with parthenolide, a significant increase in the level of GSH was obtained compared to compounds acting alone. This last observation seems to confirm the antagonism between the compounds tested.Parthenolide did not limit the cytotoxic effect of etoposide in HL-60 cells even in the case of antagonistic interaction. If parthenolide does increase GSH levels in combination with etoposide in the normal hematopoietic cells, it could protect them against the pro-oxidative effects of this anti-cancer drug.

Despite extensive research, there is no convincing evidence of a reliable diagnostic biomarker for schizophrenia beyond clinical observation. Disorders of glutamatergic neurotransmission associated with N-methyl-D-aspartate (NMDA) receptor insufficiency, neuroinflammation, and redox dysregulation are the principal common mechanism linking changes in the periphery with the brain, ultimately contributing to the emergence of negative symptoms of schizophrenia that underlie differential diagnosis. The aim of the study was to evaluate the influence of these systems via peripheral and cerebral biochemical indices in relation to the patient’s clinical condition. Using neuroimaging diagnostics, we were able to define endophenotypes of schizophrenia based on objective laboratory data that form the basis of a personalized approach to diagnosis and treatment. The two distinguished endophenotypes differed in terms of the quality of life, specific schizophrenia symptoms, and glutamatergic neurotransmission metabolites in the anterior cingulate gyrus. Our results, as well as further studies of the excitatory or inhibitory balance of microcircuits, relating the redox systems on the periphery with the distant regions of the brain might allow for predicting potential biomarkers of neuropsychiatric diseases, including schizophrenia. To the best of our knowledge, our study is the first to identify an objective molecular biomarker of schizophrenia outcome.

Schizophrenia is a complex mental disorder whose course varies with periods of deterioration and symptomatic improvement without diagnosis and treatment specific for the disease. So far, it has not been possible to clearly define what kinds of functional and structural changes are responsible for the onset or recurrence of acute psychotic decompensation in the course of schizophrenia, and to what extent personality disorders may precede the appearance of the appropriate symptoms. The work combines magnetic resonance spectroscopy imaging with clinical evaluation and laboratory tests to determine the likely pathway of schizophrenia development by identifying peripheral cerebral biomarkers compared to personality disorders. The relationship between the level of metabolites in the brain, the clinical status of patients according to International Statistical Classification of Diseases and Related Health Problems, 10th Revision ICD-10, duration of untreated psychosis (DUP), and biochemical indices related to redox balance (malondialdehyde), the efficiency of antioxidant systems (FRAP), and bioenergetic metabolism of mitochondria, were investigated. There was a reduction in the level of brain N-acetyl-aspartate and glutamate in the anterior cingulate gyrus of patients with schisophrenia compared to the other groups that seems more to reflect a biological etiopathological factor of psychosis. Decreased activity of brain metabolites correlated with increased peripheral oxidative stress (increased malondialdehyde MDA) associated with decreased efficiency of antioxidant systems (FRAP) and the breakdown of clinical symptoms in patients with schizophrenia in the course of psychotic decompensation compared to other groups. The period of untreated psychosis correlated negatively with glucose value in the brain of people with schizophrenia, and positively with choline level. The demonstrated differences between two psychiatric units, such as schizophrenia and personality disorders in relation to healthy people, may be used to improve the diagnosis and prognosis of schizophrenia compared to other heterogenous psychopathology in the future. The collapse of clinical symptoms of patients with schizophrenia in the course of psychotic decompensation may be associated with the occurrence of specific schizotypes, the determination of which is possible by determining common relationships between changes in metabolic activity of particular brain structures and peripheral parameters, which may be an important biological etiopathological factor of psychosis. Markers of peripheral redox imbalance associated with disturbed bioenergy metabolism in the brain may provide specific biological factors of psychosis however, they need to be confirmed in further studies.

The aim of the study was to verify the hypothesis about differences in sweet taste perception in the group of preschool children with and without caries, and to determine its relationship with cariogenic microbiota and the frequency of sweets consumption in children. The study group included of 63 children aged 2&ndash, 6 years: 32 with caries and 31 without caries. The study consisted of collecting questionnaire data and assessment of dental status using the decayed, missing, filled in primary teeth index (dmft) and the International Caries Detection and Assessment System (ICDAS II). The evaluation of sweet taste perception was carried out using a specific method that simultaneously assessed the level of taste preferences and the sensitivity threshold for a given taste. The microbiological analysis consisted of the assessment of the quantitative and qualitative compositions of the oral microbiota of the examined children. The sweet taste perception of children with caries was characterized by a lower susceptibility to sucrose (the preferred sucrose solution concentration was &gt, 4 g/L) compared to children without caries (in the range &le, 4 g/L, p = 0.0015, chi-square test). A similar relationship was also observed for frequent snacking between meals (p = 0.0038, chi-square test). The analysis of studied variables showed the existence of a strong positive correlation between the perception of sweet taste and the occurrence and intensity of the cariogenic process (p = 0.007 for dmft, and p = 0.012 for ICDAS II), as well as the frequency of consuming sweets (p &le, 0.001 for frequent and repeated consumption of sweets during the day, Spearman test) in children with caries. Additionally, children with an elevated sucrose taste threshold were more than 10-times more likely to develop S. mutans presence (OR = 10.21, 95% CI 3.11&ndash, 33.44). The results of this study suggest the future use of taste preferences in children as a diagnostic tool for the early detection of increased susceptibility to caries through microbial dysbiosis towards specific species of microorganisms.

Measurement of sperm oxidative-antioxidant indicators is widely used in the assessment and detection of biochemical causes of male infertility. The main purpose of this study was to identify biomarkers that assist in diagnostics and monitoring of male reproductive potential. We performed the assessment of oxidative-antioxidant malondialdehyde (MDA), glutathione (GSH), and total redox antioxidant potential (TRAP) indicators in seminal plasma, seminogram, clinical condition, and lifestyle of people with reproductive problems. The combined assessment of GSH and TRAP as potential biomarkers of male infertility in semen plasma was characterized by the highest total sensitivity and specificity. Furthermore, we provide evidence that male reproductive potential is significantly correlated with basic sperm parameters, sperm cell membrane integrity, their morphology, lifestyle, eating habits, occupation, and mental health. Our results provide evidence on the importance of oxidative stress and defense against free radicals in diagnosing and monitoring men with infertility that are consistent with previously conducted research. We provide an alternative approach on the possibility of interpreting the combination of the biomarkers that can bring benefits to a multi-threaded approach to the diagnosis and treatment of male infertility.

Secondary caries is a disease associated with the formation of biofilm on the border of the tooth and dental filling. Its development is strongly influenced by the dietary sweet foods and the type of dental material. The aim of the study was to assess the effect of sweeteners on the ability of clinical Streptococcus mutans strains to form biofilm on dental materials. Strains were isolated from plaque samples from 40 pediatric patients from the 3&ndash, 6 ICADS II group. The ability to form biofilm was tested on composite and glass ionomer dental materials used for milk teeth filling in the presence of sucrose, xylitol, sorbitol, and erythritol. The bacterial film mass after 12, 24, 48, and 72 h and the number of bacterial colonies significantly decreased (p &lt, 0.01) compared to the initial value for 5% erythritol and sorbitol on examined materials. A greater inhibitory effect was noted for glass ionomers compared to composites. Sucrose and xylitol supported biofilm formation, while erythritol had the best inhibitory effect. The use of fluoride-releasing glass ionomers exerted an effect synergistic to erythritol, i.e., inhibited plaque formation and the amount of cariogenic S. mutans. Selection of proper type of dental material together with replacing sucrose with polyols can significantly decrease risk of secondary caries development. Erithritol in combination with glass ionomer seems to be the most effective in secondary caries prevention.

Schizophrenia is a neurodevelopmental disorder featuring chronic, complex neuropsychiatric features. The etiology and pathogenesis of schizophrenia are not fully understood. Oxidative-antioxidant imbalance is a potential determinant of schizophrenia. Oxidative, nitrosative, or sulfuric damage to enzymes of glycolysis and tricarboxylic acid cycle, as well as calcium transport and ATP biosynthesis might cause impaired bioenergetics function in the brain. This could explain the initial symptoms, such as the first psychotic episode and mild cognitive impairment. Another concept of the etiopathogenesis of schizophrenia is associated with impaired glucose metabolism and insulin resistance with the activation of the mTOR mitochondrial pathway, which may contribute to impaired neuronal development. Consequently, cognitive processes requiring ATP are compromised and dysfunctions in synaptic transmission lead to neuronal death, preceding changes in key brain areas. This review summarizes the role and mutual interactions of oxidative damage and impaired glucose metabolism as key factors affecting metabolic complications in schizophrenia. These observations may be a premise for novel potential therapeutic targets that will delay not only the onset of first symptoms but also the progression of schizophrenia and its complications.

Thyroid abnormalities, including mild forms of hypothyroidism and hyperthyroidism, are reported as risk factors for the development of a number of neuropsychiatric disorders, including schizophrenia. The diagnostic process still takes into account the extreme ranges of the accepted reference values for serum TSH since the concentration of free thyroxine in the serum does not change by definition. TSH mU/L cut-off values in psychiatric patients are currently clinically considered in the case of extremely high serum TSH levels (>4.0 mU/L). The results obtained in this study suggest that the clinically significant value has a lower TSH cut-off point with an upper limit of 2–2.5 mU/L. The criteria for the differential diagnosis of patients with schizophrenia, however, mainly take into account statutory reference ranges without a background related to the history of thyroid diseases in the family. The results indicate the need to lower the upper cut-off values for TSH among patients with early psychosis, which is related to the potential clinical significance of the obtained values both in the field of clinical evaluation and neuroimaging and laboratory evaluation parameters. The cut-off points obtained with the prior available knowledge coincided with the values established in the unsupervised clustering method, which further confirms the legitimacy of their use in the individualized diagnosis strategy of schizophrenia.

Interactions between oral microbiota and systemic diseases have been suggested. We aimed to examine the composition of oral microbiota with reference to antioxidative defense and its correlation with clinical state in Crohn's disease (CD) in comparison to ulcerative colitis (UC).Smears were taken from the buccal and tongue mucosa of patients with CD, UC and controls, and cultured with classical microbiology methods. Bacterial colonies were identified using matrix-assisted laser desorption/ionization (MALDI) with a time-of-flight analyzer (TOF). Blood morphology and C-reactive protein (CRP) were analyzed in the hospital laboratory. Antioxidative defense potential (FRAP) was determined using spectrophotometry in saliva and serum.Oral microbiota in CD patients were characterized by lower diversity in terms of the isolated bacteria species compared to UC and this correlated with reduced FRAP in the oral cavity and intensified systemic inflammation. Oral microbiota composition in CD did not depend on the applied treatment. In CD patients, a negative correlation was observed between the FRAP value in saliva and serum and the CRP value in serum. Individual differences in the composition of oral microbiota suggest that different bacteria species may be involved in the induction of oxidative stress associated with a weakening of antioxidative defense in the oral cavity, manifested by ongoing systemic inflammation.Analysis of both the state of the microbiota and antioxidative defense of the oral cavity, as well as their referencing to systemic inflammation may potentially prove helpful in routine diagnostic applications and in aiding a better understanding of CD and UC pathogenesis associated with oral microbiota.

The diagnosis of oral lichen planus (OLP) is based on clinical examination and histopathological criteria. Noninvasive diagnostics of saliva may be considered as a confirmation of OLP diagnosis and a potential alternative to an invasive method. The objective of the present study was to evaluate the relationship between the level of tyrosine (Tyr) as well as antioxidants like uric acid (UA) and glutathione peroxidase (GPx) activity in the saliva of patients with OLP in comparison with the control group (healthy subjects without any oral changes). A total of 40 patients with OLP and 40 healthy volunteers were selected for the study based on the modified WHO diagnostic (clinical and histopathological) criteria. High-performance liquid chromatography (HPLC) was performed for Tyr concentration, while GPx activity and uric acid levels were determined by a colorimetric method. The concentrations of Tyr, UA, and GPx activity were statistically lowered in OLP patients compared to the control group. All examined parameters correlated strongly and positively with each other. Mean values of salivary UA concentrations differed between the groups of OLP patients (reticular and erosive forms) and controls (206.66 vs. 196.54 vs. 218.49 μmol/L, respectively, p=0.001). A similar trend was demonstrated in salivary Tyr concentration which differed statistically between the study and control groups (0.08 vs. 0.07 vs. 0.13 μmol/L, respectively, p=0.001). Determining of a relationship between the concentrations of Tyr, UA, and GPx activity may be useful in the prognosis of OLP. The HPLC method may be employed, as an additional noninvasive diagnostic procedure to screen OLP patients, during the routine diagnostics of salivary biochemical parameters such as aromatic amino acids.

Aim: Investigation of the influence of parthenolide (PTL) on cytarabine (Ara-C) action in an acute promyelocytic leukemia HL-60 cell line and the role of oxidative stress in its action. Methods: Cytotoxic effects and apoptosis were examined using propidium iodide (PI) or PI/Annexin-V staining, respectively. Cells were analyzed using flow cytometry. Results: PTL dose-dependently increased the percentage of dead cells. Cytotoxic and proapototic actions of PTL depend on the level of free radicals, because the addition of N-acetyl-L-cysteine (NAC) to incubation significantly reduced the effect of PTL. We did not observe a similar influence of NAC in the case of Ara-C activity. PTL significantly increased the cytotoxic and proapoptotic effects of Ara-C in comparison to the cytostatic drug alone. Interactions between the investigated compounds were mostly synergistic. NAC significantly reduced the cytotoxic effect of the combination of PTL plus Ara-C. Conclusion: PTL can significantly increase the cytotoxic and proapoptotic effects of Ara-C in an HL-60 cell line and this may warrant further research to improve the efficacy of acute promyelocytic leukemia therapy.

Lactoperoxidase (LPO) together with its (pseudo)halogenation cycle substrates, H2O2 and thiocyanate ions oxidized to hypothiocyanite ions, form one of the main systems involved in antimicrobial defense within the oral cavity. In bacterial diseases such as dental caries, lactoperoxidase is oxidized to a form known as Compound II, which is characterized by its inability to oxidize SCN–, resulting in a decreased generation of antimicrobial products. Reynoutria sp. rizome extracts, due to their high polyphenol content, have been tested as a source of compounds able to regenerate the antimicrobial activity of lactoperoxidase through converting the Compound II to the native LPO state. In the presented study, acetone extracts of R. japonica, R. sachalinensis, and R. x bohemica, together with their five fractions and four selected polyphenols dominating in the studied in extracts, were tested toward lactoperoxidase reactivating potential. For this purpose, IC50, EC50, and activation percentage were determined by Ellman’s method. Furthermore, the rate constants for the conversion of Compound I–Compound II and Compound II–native-LPO in the presence of extracts, extracts fractions, and selected polyphenols were determined. Finally, the ability to enhance the antimicrobial properties of the lactoperoxidase system was tested against Streptococcus mutans. We proved that Reynoutria sp. rhizome is the source of lactoperoxidase peroxidation cycle substrates, which can act as activators and inhibitors of the antimicrobial properties of that system. The presented study shows that the reactivation of lactoperoxidase could become a potential therapeutic target in prevention and treatment support in some infectious oral diseases.

Oxidative stress (OxS) has been implicated in the pathogenesis of Crohn's disease (CD). The aim of this study was to examine whether nonenzymatic antioxidants are associated with active CD, by using the FRAP and GSH assay in plasma. Additionally, we measured bilirubin and albumin levels as two individual components of the plasma antioxidant system. A total of 55 patients with established CD, 30 with active CD and 25 with inactive disease, and 25 healthy individuals were prospectively enrolled in this study. We evaluated CD activity index, BMI and blood morphology, platelet count, serum CRP level, and bochemical parameters of OxS: ferric reducing ability of plasma (FRAP), reduced glutathione (GSH) in plasma and bilirubin and albumin levels in serum. Plasma FRAP and GSH concentrations were decreased in both CD groups compared to controls and negatively correlated with CDAI values (FRAP: r = -0.572, p = 0.003; GSH: r = -0.761, p = 0.001), CRP and platelet count. Bilirubin and albumin levels were lower in the serum of active CD patients than inactive CD patients and controls and negatively correlated with the CD activity index (r = -0328, p = 0.036, r = -0.518, p = 0.002) and CRP (r = -0.433, p = 0.002). e decreased FRAP and GSH levels in plasma and bilirubin and albumin levels in serum of patients with active CD compared to inactive CD and controls underlines the importance of OxS in the pathophysiology and activity of CD.

Purpose In order to investigate the suitability of Streptococcus mutans species biotyping by measuring the activity of selected enzymes from a commercial test, criteria were established for biotyping clinical strains from children with dental caries. In addition, the relationships between the selected biotypes, sensitivity to commonly used antibiotics, and early childhood caries were determined. Methods A total of 142 S. mutans isolates from dental plaque of children with caries were divided into different biotypes. Patients were divided into two groups: noncavitated (1-2 in ICDAS) and cavitated (5-6 in ICDAS) lesions. Biotyping criteria were determined based on both the arbitrary method and the clusterization method. The susceptibility of the strains to amoxicillin, cefazolin, erythromycin, and teicoplanin was studied by diluting a solid medium. Results Biotype I was the most common. Mean MIC values showed that the strains belonging to biotypes II and IV were the most sensitive to amoxicillin. For predetermined biotypes, observed differences were dependent on the severity of dental caries. Conclusions The proposed method of S. mutans strains biotyping is relatively quick and simple to use, provided the application of suitable biotyping criteria, and may contribute to the effective prevention of dental caries induced by S. mutans.

Aim: The low bioavailability of curcumin, a polyphenol, limits its use as an antitumor agent. Identifying mechanisms to improve the bioavailability and effectiveness of curcumin can modify utilization of other plant-derived phenolic compounds. This study was conducted with an aim to determine the influence of some flavonoids on the effects of curcumin in an HL-60 cell line. Methods: Cells were incubated in the presence of different concentrations of curcumin and several flavonoids for 20 h. Cytotoxicity was evaluated using propidium iodide staining. The evaluation of γH2AX expression using a specific antibody, together with study of the cell cycle, was analyzed using flow cytometry. Results: A synergistic effect was obtained only using a combination of curcumin and lower concentrations of epicatechin. The low concentration of quercetin exerted an additive effect only in combination with curcumin. Moreover, incubation with curcumin and epicatechin resulted in a significant increase in the γH2AX level. Conclusion: Combination treatment with epicatechin and curcumin can potentially be considered for improving the effectiveness and bioavailability of curcumin in cell lines of myeloid leukemia.

Monika A Papież,1 Wirginia Krzyściak,2 Krzysztof Szade,3 Karolina Bukowska-Straková,3,4 Magdalena Kozakowska,3 Karolina Hajduk,3 Beata Bystrowska,5 Jozef Dulak,3,6 Alicja Jozkowicz31Department of Cytobiology, 2Department of Medical Diagnostic, Faculty of Pharmacy, Jagiellonian University Medical College, 3Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, 4Department of Clinical Immunology, Institute of Pediatrics, 5Department of Toxicology, Faculty of Pharmacy, Jagiellonian University Medical College, 6Malopolska Centre of Biotechnology, Jagiellonian University, Krakow, PolandAbstract: Curcumin may exert a more selective cytotoxic effect in tumor cells with elevated levels of free radicals. Here, we investigated whether curcumin can modulate etoposide action in myeloid leukemia cells and in normal cells of hematopoietic origin. HL-60 cell line, normal myeloid progenitor cluster of differentiation (CD)-34+ cells, and granulocytes were incubated for 4 or 24hours at different concentrations of curcumin and/or etoposide. Brown Norway rats with acute myeloid leukemia (BNML) were used to prove the influence of curcumin on etoposide action in vivo. Rats were treated with curcumin for 23days and etoposide was administered for the final 3days of the experiment. Curcumin synergistically potentiated the cytotoxic effect of etoposide, and it intensified apoptosis and phosphorylation of the histone H2AX induced by this cytostatic drug in leukemic HL-60 cells. In contrast, curcumin did not significantly modify etoposide-induced cytotoxicity and H2AX phosphorylation in normal CD34+ cells and granulocytes. Curcumin modified the cytotoxic action of etoposide in HL-60 cells through intensification of free radical production because preincubation with N-acetyl-l-cysteine (NAC) significantly reduced the cytotoxic effect of curcumin itself and a combination of two compounds. In contrast, NAC did not decrease the cytotoxic effect of etoposide. Thus, oxidative stress plays a greater role in the cytotoxic effect of curcumin than that of etoposide in HL-60 cells. In vitro results were confirmed in a BNML model. Pretreatment with curcumin enhanced the antileukemic activity of etoposide in BNML rats (1.57-fold tumor reduction versus etoposide alone; P

Many studies have shown the role of myeloperoxidase (MPO) in leukemogenic activity of etoposide. The aim of our study was to determine whether inhibition of MPO activity has influence on the formation of double-stranded DNA breaks (DSBs) that may contribute to the characteristic of leukemia translocations. Studies were carried out on HL-60 cell line, which were preincubated with the MPO inhibitor 4-aminobenzoic acid hydrazide (ABAH), or antioxidant N-acetyl-L-cysteine (NAC), followed by incubation at different concentrations of etoposide (1-10 mM) for 4 hours. Cytotoxicity was investigated using propidium iodide staining. Marker of DSBs, a phosphorylated form of histone 2AX (gH2AX) was detected using immunocytochemical methods. Cells were analyzed by flow cytometry. ABAH significantly reduced the cytotoxicity and the gH2AX level induced by lower concentrations of etoposide (1 and 1.5 mM) and did not modify the action of higher concentration (10 mM) of this cytostatic drug. NAC exerted similar impact as ABAH on the level of gH2AX induced by etoposide. The results of this study suggest that MPO contributes to increase of the DSBs level induced by low concentrations of etoposide in myeloid cells.

The effect of curcumin, a promising anticancer agent, on the action of certain cytostatic drugs, including etoposide, is not well understood. This paper examines the effect of curcumin on etoposide action in leukemic and normal bone marrow cells in vivo conditions. The experimental model used was Brown Norway rats with a transplantable acute promyelocytic leukemia. Leukemia was induced by intravenous injection of BNML (Brown Norway Myeloid Leukemia) cells. Curcumin was administered by oral gavage (200 mg/kg) for 23 consecutive days and etoposide was used intraperitoneally (50 mg/kg) for the last three days of the experiment. Control leukemic and healthy rats received the solvent for the tested compounds only. Curcumin significantly reduced the number of leukemic promyelocytes in the bone marrow of BNML rats in comparison to the leukemic control. Treatment with curcumin plus etoposide led to a decrease in the number of promyelocytes to the normal values occurring in healthy individuals. In contrast, the percentage of the normal precursors of granulocytes (p0.001) and erythrocytes (p0.001) increased significantly in comparison to the group treated with only etoposide. The results of the study indicate that curcumin may protect healthy myeloid cells against the cytotoxic effect of etoposide and potentiate the antileukemic action of this anticancer drug.

The protective action of quercetin against the pro-oxidant and apoptotic effect of etoposide was investigat ed in HL-60 cells with a high level of myeloperoxidase (MPO) activity and in cells treated with MPO inhibitor, 4-aminobenzoic acid hydrazide (ABAH). Quercetin signifi cantly protected MPO-rich cells against the pro-oxidative (p

In some diseases, a very important role is played by the ability of bacteria to form multi-dimensional complex structure known as biofilm. The most common disease of the oral cavity, known as dental caries, is a top leader. Streptococcus mutans, one of the many etiological factors of dental caries, is a microorganism which is able to acquire new properties allowing for the expression of pathogenicity determinants determining its virulence in specific environmental conditions. Through the mechanism of adhesion to a solid surface, S. mutans is capable of colonizing the oral cavity and also of forming bacterial biofilm. Additional properties enabling S. mutans to colonize the oral cavity include the ability to survive in an acidic environment and specific interaction with other microorganisms colonizing this ecosystem. This review is an attempt to establish which characteristics associated with biofilm formation--virulence determinants of S. mutans--are responsible for the development of dental caries. In order to extend the knowledge of the nature of Streptococcus infections, an attempt to face the following problems will be made: Biofilm formation as a complex process of protein-bacterium interaction. To what extent do microorganisms of the cariogenic flora exemplified by S. mutans differ in virulence determinants "expression" from microorganisms of physiological flora? How does the environment of the oral cavity and its microorganisms affect the biofilm formation of dominant species? How do selected inhibitors affect the biofilm formation of cariogenic microorganisms?

Besides their structural catalytic and diverse regulatory functions, proteins are also precursors of many important biological compounds essential for normal functioning of humans. Many of these compounds may be used as markers for identification of specific pathological states. A comprehensive knowledge about the metabolism of salivary proteins and the mechanisms of action of their metabolites allowed the development of effective treatment for many disorders. However, it should not be forgotten that in some pathological conditions, these compounds not only could be involved in the pathogenesis but also could be used as tool in the prediction of many diseases. This paper is a review of the published literature on selected salivary proteins in the context of the physiological processes of the human body and chosen chronic disorders, such as diabetes, diabetic nephropathy, mucositis, oral mycoses and caries.

Besides the structural function in proteins, aromatic amino acids are precursors of many important biological compounds essential for normal functioning of the human organism. Many of these compounds may be used as markers for identification of specific pathological states. Comprehensive knowledge about the metabolism of aromatic amino acids and mechanisms of action of their metabolites made it possible to develop effective treatments for many disorders. However, it should not be forgotten that in some pathological conditions, these compounds could not only be involved in the pathogenesis of many disease entities but could also be used as an important tool in prediction of many diseases. This paper contains a review of published literature on aromatic amino acids in the context of physiological processes of the human body and chosen social disorders, such as cancers; psychiatric disorders: depression, anxiety states, schizophrenia, bipolar affective disorders; neurodegenerative, and cardiovascular diseases; chronic kidney insufficiency or diabetes.

Ions of trace elements, zinc and copper, play a key role in a number of vital signs and metabolic processes occurring in human organism. In venous vessels, Cu and Zn ions contribute to formation of free oxygen radicals (catalysts for Habera-Weisa reaction) and may result in development of changes leading to chronic venous disease (CVD), also known as chronic venous insufficiency (CVI). These elements lead to changes occurring in cells by contributing to lipid peroxidation process. As enzyme activators, Zn and Cu ions maintain proper cell membranes functioning. In addition, these ions create the catalytic center of one of the most important enzymes of the antioxidant defence system, superoxide dismutase (SOD). THE AIM OF THE PRESENT STUDY: The aim of the present study was determination of copper and zinc ions in sufficient and insufficient vessels lyophilized and varicose veins lyophilized from patients with CVD. Further, a comparison of SOD activity in homogenates of above-mentioned tissues was done.Study material consisted of tissues lyophilized and homogenates. This material contained: - Insufficient vessels originating from area of saphenous vein ostium (VSM, vena saphe magna), where venous insufficiency with massive venous reflux was observed during ultrasonography (USG); - Sufficient vessels which fulfilled criteria of sufficient vessels during USG examination; - Varicose veins. The study group consisted of 31 patients (23 females and 8 males) and the average age was 49.9 +/- 12.5. These patients were diagnosed with the 2nd and 3rd degree of CVD according to CEAP and they underwent surgery at II Department of General Surgery UJ CM, Poland (November, 2007-March 2008). Concentration of trace elements was determined by Proton Induced X-ray Emission (PIXE) method. Activity of superoxide dismutase was determined according to method reported by Spitz and Oberley.Concentration of Zn and Cu ions was significantly higher in varicose veins in the area of insufficient valves compared to sufficient vessels. Activity of superoxide dismutase both in homogenates of varicose veins and insufficient veins was significantly higher than in homogenates of sufficient veins.Clinical changes occurring during CVD were linearly dependant on SOD activity and concentration of Zn and Cu ions, which suggested the participation of free radicals in CVD