The treatment of diabetes with new generation drugs

Introduction: Diabetes is a global problem, affecting nearly 422 million people around the world. Pathogenesis includes a defect in secretion or insulin activity. This results in an increase in the glucose level, which is associated with the development of complications. These include changes in peripheral vessels and nerves that lead to their damage. It is necessary to introduce appropriate treatment in the earliest stages of the disease to prevent these effects.Materials and methods: The aim of this work is to present knowledge about the treatment based on the recommendations of the Polish Diabetes Association, American Diabetes Association, as well as a literature review and analysis of publications published on PubMed and Google Scholar platforms.Results: Over the years, the recommendations and recommendations for treatment change. Recently, a greater role has been given to the latest antidiabetic drugs. This group includes SGLT-2 inhibitors as well as incremental drugs, the main representatives of which are GLP-1 analogues. These drugs affect the level of glycemia, but also have a beneficial effect on weight reduction and reduce the risk of cardiovascular events. Recently, Poland has introduced reimbursement of some new generation antidiabetic drugs such as dapaglyphosin, empaglyphosin and canaglyphosin.Conclusions: Dynamic development of diabetes treatment helps to slow down the course of the disease and postpones the introduction of insulin therapy as the final treatment method. Reimbursement of some antidiabetic drugs enables patients to have better access to drugs that have not been within their reach so far. The changes introduced are, in a way, groundbreaking in the treatment of diabetes.

The impact of coffee on human health

Introduction: Coffee is one of the most popular beverages in the world. It contains lots of biologically active ingredients. These compounds not only have aromatic properties, but many of them also have antioxidant, hepatoprotective, anti-inflammatory, antimicrobial, antiviral and relaxing smooth muscle properties. The aim of the study: The purpose of the study is to collect and review scientific publications about the impact of coffee on health. Material and method: The paper uses standard criteria as the research method. Additionally, during the literature review on PubMed and Google Scholar platforms, keywords such as coffee, caffeine, health, impact were used. Description of the state of knowledge: Numerous studies suggest that coffee impact on the long-term functioning of the organism is negligible and is associated with the consumption of coffee for a longer period of time. Chlorogenic acid, caffeine and trigoneline are primarily responsible for the positive effect. They have a hypoglycemic, bactericidal and antioxidant effect. Diterpenes, such as kahweol and cafestol may have negative influence on health. Research also suggests that coffee can reduce the risk of Parkinson's disease and type 2 diabetes. Summary: The results show that coffee ingredients can have both positive and negative effects on health. However, before these observations can be used to create nutritional advice, further research is needed. They will allow a better understanding of the mechanisms of action of the compounds responsible for reduced risk of diabetes mellitus or Parkinson's disease. Keywords: coffee, caffeine, health, cardiovascula

Does epidural analgesia modify the risk of complications after gastrectomy?

Introduction. The surgical treatment of Gastric Cancer is associated with overall complication rates as high as 50%. The intent of this study was to assess the impact of epidural analgesia (EA) on postoperative complication rates among patients undergoing gastric resections. Materials and methods. Of the 617 gastric cancer patients who between 2002 and 2010 had undergone stomach resection, 246 (39.8%) were administered EA. Groups with and without EA were compared. Results. The general rate of complications was lower in the EA group in the univariable analysis – 38.5% vs. 54.2% (odds ratio [OR]: 0.47, 95% confidence interval [CI]: 0.34–0.66, p < 0.001), intra-abdominal abscess (OR 0,28, 95% CI: 0.14–0.59, p = 0.001), pneumonia (OR 0,39, 95% CI: 0.24–0.63, p < 0.001), temperature > 38°C (OR 0.53, 95% CI: 0.37–0.74, p < 0.001) and re-operation (OR 0.53, 95% CI: 0.28–1.00, p = 0.049). These relationships were confirmed in a multivariable analysis for the general number of complications (OR 0.53, 95% CI: 0.37–0.75, p < 0.001), intra-abdominal abscess (OR 0.36, 95% CI: 0.16–0.77, p = 0.009), temperature > 38°C (OR 0.56, 95% CI: 0.39–0.82, p = 0.009), pneumonia (OR 0.42, 95% CI: 0.25–0.71, p = 0.001). Conclusions. Our findings indicate that postoperative treatment with EA for patients undergoing stomach resection is safe and contributes to a reduction in the number of postoperative complications

Depressive and anxiety symptoms among patients with inflammatory bowel diseases

Introduction. This study was conducted on a population of patients with inflammatory bowel disease (IBD) and was based on an assessment of the prevalence and severity of depression and anxiety symptoms in various clinical aspects. The psychological features of IBD patients are very important in the perception of symptoms, but crucial as triggers of IBD or as a releasing factor for IBD symptoms recurrence. Methods. The study included 130 patients with IBD, including 68 with Crohn’s disease (CD) and 62 with ulcerative colitis (UC). The severity of anxiety and depression symptoms were examined by the Hospital Anxiety and Depression Scale (HADS). Patients were also subjected to assessment of anthropometric attributes, clinical factors, quality of life, and symptoms of the disease, with dedicated clinical scales. Results. The occurrence of significant symptoms of anxiety was estimated at 45.5% in patients with CD and 30.5% in the UC patients. Significant depressive symptoms related to 20.5% of people with CD and 17.5% of patients with UC. The parameters of anxiety and depression showed significant associations with parameters of quality of life, BMI, and the scales describing the exacerbation of the diseases. Conclusions. The analyses did not reveal significant differences in the severity and prevalence of symptoms of anxiety and depression in subgroups with IBD. The expansion of relevant symptoms of anxiety and depression in this population was greater than in the general population. In addition, there was a significant correlation between parameters of HADS and clinical factors

Interleukin-1beta Promoter (−31T/C and −511C/T) Polymorphisms in Major Recurrent Depression

To elucidate a genetic predisposition to major depressive disorder, we investigated two polymorphisms (−31T/C and −511C/T) in the interleukin-1beta promoter region in patients who suffered from major recurrent depression. The aim of the current work was to compare alleles and genotype layout between patients with major recurrent depression and healthy people. We would like to indicate such combination of genotypes which corresponds with major recurrent depression. Correlations between genotypes for analyzed polymorphisms and number of episodes, number of points in Hamilton Depression Rating Scale, and age of onset were investigated as well. The study group consisted of 94 patients diagnosed with major recurrent depression. The control group included 206 healthy individuals. Both groups involved representatives of Caucasian population. Genotyping of polymorphisms was performed by using PCR-RFLP technique. A specific haplotype, composed of the C allele at −31 and the T allele at −511, has a tendency to have a statistically significant difference (p = 0.064) between patients and control group. Correspondence analysis revealed that genotype T/T at −31 and genotype C/C at −511 are associated with major recurrent depression. No association was found between genotypes for studied polymorphic sites and number of episodes, number of points in Hamilton Depression Rating Scale, and age of onset

The role of the N-terminal helix of G-protein alpha subunit in recognition of plasma membrane lipids

Heterotimeryczne Białka G pełnią ważną rolę w przekazywaniu sygnałów. Zbudowane są z podjednostek α, β, ɣ. Interakcja z błoną komórkową podjednostki α pełni ważna rolę w przekazywaniu sygnału. Jednymi z podjednostek α są Gαi1 hamujące cyklazę adenylową oraz Gαsl stymulujące cyklazę adenylową. Według badań dla podjednostek α do interakcji z błoną istotne są kotwice zbudowane z kwasów tłuszczowych oraz N-końcowa α helisa, która zawiera dodatnio naładowane reszty aminokwasowe. W czasie badań za pomocą narzędzi biologii molekularnej stworzono hybrydę Gαsl i Gαi1 z zamienioną N-końcowa α helisą Gαsl na Gαi1. Białko nie posiadało kotwic lipidowych, ponieważ było produkowane w E.coli. Następnie oczyszczono białko i wykonano liposomy zbudowane z różnych lipidów. Sprawdzono specyficzność względem lipidów hybrydy oraz czy inny obszar odpowiada za oddziaływanie białko-lipid. Doświadczenie przeprowadzono w dwóch różnych buforach, w celu sprawdzenia wpływu siły jonowej. Wyniki analiz dot-blot pokazały, że hydryda wiąże się specyficznie do błony zbudowanej z nasyconych lipidów oraz, że więcej frakcji było związane w buforze o mniejszej sile jonowej. Hybryda wykazywała cechy wiązania charakterystyczne zarówno dla podjednostki Gαi1 jak i Gαsl, co sugeruję, że w oddziaływaniu brała udział też inna cześć białka niż N-końcowa helisa. Do lepszego określenia interakcji potrzebne są dalsze badania ilościowe.Heterotrimeric G proteins are critical for cellular signaling. They are composed of α, β and ɣ subunits. Interaction α subunit-plasma membrane is crucial for signal transduction. Among Gα are Gαi1 (inhibition of adenylyl cyclase) and Gαsl (stimulation of adenylyl cyclase), which were taken into account during studies. According to a previous study presence of lipids anchors is essential for lipid-Gα subunit interaction. N-terminus helix with positively charged residues is also crucial for the interaction with the plasma membrane. In this studies, molecular biology tools and techniques were used to swap N-terminus helix Gαsl to Gαi1. The hybrid was produced in E.coli, therefore, it didn’t have lipids anchors. Then the recombinant protein was purified and liposomes (model membrane) were prepared from different lipids. The aim of the experiment was analysis of binding preferences of recombinant protein to lipids and determining another binding region within protein associated with binding to lipids. The experiments were conducted in two different buffers to check the impact of ionic strength. The dot-blot result showed that the hybrid has the preference to bind membrane with saturated chains, larger amounts of protein were bound in buffer with lower ionic strength. The hybrid has features of Gαi1 and Gαsl subunits. The result showed that the N-terminus helix and another region of the hybrid are responsible for protein-lipids interaction. Further research is needed for better determining of the hybrid-lipids interaction

Studies on the specificity of interaction of N-terminal helix of heterotrimeric G protein alpha subunit with lipids

Heterotrimeryczne białka G należą do białek podbłonowych, składają się z podjednostek α, β i γ i biorą udział w przekazie sygnału razem z receptorami sprzężonymi z białkami G (ang. GPCRs). Interakcja z błoną heterotrimerycznych białek G pełni ważną funkcję w przekazie sygnału. Do najważniejszych miejsc wiązania z błoną podjednostek Gα należy N-końcowa helisa. Za oddziaływanie odpowiadają kotwice lipidowe: mirystylacja lub palmitynacja oraz dodatnio naładowane reszty aminokwasowe. Nie jest poznane, w jaki sposób te elementy odpowiadają za specyficzne oddziaływanie z lipidami poszczególnych podjednostek Gα.Celem niniejszej pracy było zbadanie N-końcowej helisy podjednostki Gαs, nie posiadającej kotwic lipidowych. W tym celu oczyszczono i zbadano chimerę składającą się z N-końcowej helisy podjednostki Gαs związanej z mGFP. W szczególności celem było poznanie struktury drugorzędowej chimery i zmian w strukturze drugorzędowej pod wpływem: 2,2,2-trifluoroetanolu TFE (substancji naśladującej błonę komórkową) oraz składu buforu. Wykonano także badania stabilności termicznej w porównaniu do mGFP za pomocą skaningowej kalorymetrii różnicowej. Wykonano wstępną analizę wiązania chimery do wybranych lipidów za pomocą metody dot blot. Wykazano, że N-końcowy fragment Gαs-GFP przyjmuję strukturę α-helisy. W przeprowadzonych badaniach TFE nie indukowało powstania α-helisy zarówno w mGFP jak i w Gαs-GFP, skład buforu nie miał wpływu na zawartość procentową α-helisy w chimerze. Wykazano, że N-końcowa helisa jest niestabilna termicznie i nie ma wpływu na zwijanie białka mGFP. Wstępne wyniki pokazały, że chimera może specyficznie oddziaływać z lipidami. Białko preferencyjnie wiąże się do tratw lipidowych oraz ujemnie naładowanych lipidów w mieszaninie POPC/POPS.Heterotrimeric G proteins belong to peripheral proteins, consist of α, β and γ subunits and are part of the signaling pathway with G protein-coupled receptors (GPCRs). The interaction with the inner side of membrane has a pivotal function in the signal transduction. The most important membrane binding part of Gα subunits is N-terminal helix, which are anchored to the membrane by palmitoylation or myristylation. Positively charged structural motif in N-termini is second important signal for binding protein to the membrane. It is unknown how these elements are responsible for specific interaction of different Gα subunits with lipids.The aim of this study was to examine the N-terminal helix of Gαs subunit, without lipid anchors. In order to achieve this, the chimera consisting of N-terminal helix Gαs subunit fusioned with mGFP was used. Gαs-GFP was purified and examined. In particular, the aims of this study were examination of the chimera’s secondary structure and impact of: 2,2,2-trifluoroethanol (membrane mimetic and solvent), composition of buffer solution. The thermal stability of chimera compared to mGFP were also examined by differential scanning calorimetry (DSC). The preliminary analysis of the chimera binding to selected lipids was performed by dot blot method.The study has shown that the N-temini of Gαs-GFP adopts a α-helix structure. It was shown that TFE didn’t induce helix formation in mGFP and Gαs-GFP, composition of buffer solution had no effect on the α-helix content in the chimera protein. Preliminary results demonstrated that the chimera might specifically bind to lipid rafts and negatively charged POPC/POPS mixture

Production of Raw Starch-Digesting Amylolytic Preparation in Yarrowia lipolytica and Its Application in Biotechnological Synthesis of Lactic Acid and Ethanol

Sustainable economy drives increasing demand for raw biomass-decomposing enzymes. Microbial expression platforms exploited as cellular factories of such biocatalysts meet requirements of large-volume production. Previously, we developed Yarrowia lipolytica recombinant strains able to grow on raw starch of different plant origin. In the present study, we used the most efficient amylolytic strain as a microbial cell factory of raw-starch-digesting (RSD) amylolytic preparation composed of two enzymes. The RSD-preparation was produced in fed-batch bioreactor cultures. Concentrated and partly purified preparation was then tested in simultaneous saccharification and fermentation (SSF) processes with thermotolerant Kluyveromyces marxianus for ethanol production and Lactobacillus plantarum for production of lactic acid. These processes were conducted as a proof-of-concept that application of the novel RSD-preparation supports sufficient starch hydrolysis enabling microbial growth and production of targeted molecules, as the selected strains were confirmed to lack amylolytic activity. Doses of the preparation and thermal conditions were individually adjusted for the two processes. Additionally, ethanol production was tested under different aeration strategies; and lactic acid production process was tested in thermally pre-treated substrate, as well. Conducted studies demonstrated that the novel RSD-preparation provides satisfactory starch hydrolyzing activity for ethanol and lactic acid production from starch by non-amylolytic microorganisms