Hepatomegalija i povišene aminotransferaze u bolesnice s loše reguliranom šećernom bolešću

Elevated liver function tests, right upper quadrant abdominal pain, and hepatomegaly occurring in a diabetic patient treated with high doses of insulin may point to the presence of pathologic glycogen accumulation in the liver parenchymal cells. The condition was first described in children, however, studies performed in adults have shown a condition that is similar in many aspects. A case is presented of a 41-year-old female diabetic patient with abnormal liver tests and hepatomegaly. Abdominal ultrasound confirmed liver enlargement without any signs of fatty liver. Liver biopsy revealed a picture compatible with glycogenosis. As excessive hepatic glycogen deposition occurred at an adult age and without a related family history, while the patient presented with normal mental and motor development, the diagnoses of Mauriac syndrome and hereditary were ruled out. The condition was attributed to insulin hyperdosage. The patient was recommended improved glycemic control, more appropriate diet and physical exercise. On follow-up visit 3 months of discharge from the hospital, significant hepatomegaly regression was demonstrated by palpation and ultrasonography, and was accompanied by normalization of serum aminotransferases, blood glucose and glycosylated hemoglobin. Elevated serum aminotransferases and alkaline phosphatase with hepatomegaly as a consequence of hepatocellular glycogen accumulation can occur in diabetic patients of any age who are treated with high doses of insulin, and should therefore be included in the differential diagnosis.Pojava povišenih jetrenih enzima, bolova u desnom gornjem abdominalnom kvadrantu i hepatomegalije u bolesnika sa šećernom bolešću liječenih visokim dozama inzulina može ukazivati na patološko nakupljanje glikogena u stanicama jetrenog parenhima. Ovo je stanje prvotno opisano u djece, a kasnije studije provedene na odraslima pokazale su jednaku kliničku sliku. Prikazan je slučaj 41-godišnje žene oboljele od šećerne bolesti s poremećenim jetrenim nalazima i hepatomegalijom, kod koje je ultrazvuk potvrdio povećanje jetre bez znakova steatoze, a biopsijom je postavljena dijagnoza glikogenoze. S obzirom na to da je izrazito nakupljanje glikogena u ovom slučaju nastupilo u odrasloj dobi, bez pozitivne obiteljske anamneze, a bolesnica je imala uredan psihički i tjelesni razvoj, iz diferencijalne dijagnoze se je mogao isključiti Mauriacov sindrom i nasljedna glikogenoza. Uzrok ovoga stanja u ove bolesnice bilo je liječenje osnovne bolesti visokim dozama inzulina. Stoga joj je preporučena poboljšana kontrola glikemije praćena ispravnom dijetom i tjelesnom aktivnošću. Na kontrolnom pregledu nakon tri mjeseca došlo je do regresije hepatomegalije potvrđene palpacijom i ultrazvukom, te do normaliziranja serumskih aminotransferaza, glukoze u krvi i glikoziliranog hemoglobina. Povišene aminotransferaze i alkalna fosfataza uz hepatomegaliju mogu se naći kod bolesnika dijabetičara liječenih visokim dozama inzulina, kao posljedica nakupljanja glikogena u jetrenim stanicama, pa ovo stanje treba uključiti u diferencijalnu dijagnozu

Adjusted Blood Requirement Index as Indicator of Failure to Control Acute Variceal Bleeding

Aim: To estimate the clinical value of adjusted blood requirement index (ABRI) in relation to other criteria for failure of variceal bleeding control proposed at Baveno consensus workshops and to evaluate ABRI as an early predictor of occurrence of other Baveno criteria and identification of possible predictors of unfavorable ABRI. Methods: We retrospectively analyzed the data on 60 patients admitted to the hospital due to acute variceal bleeding. Number of treatment failures according to Baveno II-III and Baveno IV definitions and criteria was compared. We tested the ABRI’s predictability of other Baveno IV and Baveno II-III criteria. Logistic regression analysis was performed to ascertain independent variables that predict ABRI≥0.75. Results: Failure to control variceal bleeding occurred in 40 of 60 patients according to Baveno II-III criteria, and in 35 of 60 patients according to Baveno IV criteria. Excluding the criterion of “transfusion of 2 units of blood or more (over and above the previous transfusions)”and ABRI criterion, failure to control variceal bleeding was observed in 17 and 14 of 60 patients, respectively. Congruence of ABRI with other criteria was present in about two-thirds of the cases. ABRI≥0.75 was associated with increased risk of positive other Baveno criteria,particularly modified Baveno II-III (odds ratio [OR] 4.10; 95% confidence interval [CI], 1.11-15.05) and Baveno IV without ABRI (OR 4.37; 95% CI, 1.04-18.28). Independent predictors of ABRI≥0.75 identified in logistic regression analysis were male sex (P<0.001) and higher hematocrit values (P=0.004). Conclusion: We found low congruence between ABRI and other Baveno criteria. It seems that criteria related to the quantity of blood transfusions are not reliable indicators of treatment failure

Proliferative advantage of specific aneuploid cells drives evolution of tumor karyotypes

Most tumors have abnormal karyotypes, which arise from mistakes during mitotic division of healthy euploid cells and evolve through numerous complex mechanisms. In a recent mouse model with increased chromosome missegregation, chromosome gains dominate over losses both in pretumor and tumor tissues, whereas T-cell lymphomas are characterized by gains of chromosomes 14 and 15. However, the quantitative understanding of clonal selection leading to tumor karyotype evolution remains unknown. Here we show, by introducing a mathematical model based on a concept of a macro-karyotype, that tumor karyotypes can be explained by proliferation-driven evolution of aneuploid cells. In pretumor cells, increased apoptosis and slower proliferation of cells with monosomies lead to predominant chromosome gains over losses. Tumor karyotypes with gain of one chromosome can be explained by karyotype-dependent proliferation, whereas, for those with two chromosomes, an interplay with karyotype-dependent apoptosis is an additional possible pathway. Thus, evolution of tumor-specific karyotypes requires proliferative advantage of specific aneuploid karyotypes

Hepatomegalija i povišene aminotransferaze u bolesnice s loše reguliranom šećernom bolešću

Elevated liver function tests, right upper quadrant abdominal pain, and hepatomegaly occurring in a diabetic patient treated with high doses of insulin may point to the presence of pathologic glycogen accumulation in the liver parenchymal cells. The condition was first described in children, however, studies performed in adults have shown a condition that is similar in many aspects. A case is presented of a 41-year-old female diabetic patient with abnormal liver tests and hepatomegaly. Abdominal ultrasound confirmed liver enlargement without any signs of fatty liver. Liver biopsy revealed a picture compatible with glycogenosis. As excessive hepatic glycogen deposition occurred at an adult age and without a related family history, while the patient presented with normal mental and motor development, the diagnoses of Mauriac syndrome and hereditary were ruled out. The condition was attributed to insulin hyperdosage. The patient was recommended improved glycemic control, more appropriate diet and physical exercise. On follow-up visit 3 months of discharge from the hospital, significant hepatomegaly regression was demonstrated by palpation and ultrasonography, and was accompanied by normalization of serum aminotransferases, blood glucose and glycosylated hemoglobin. Elevated serum aminotransferases and alkaline phosphatase with hepatomegaly as a consequence of hepatocellular glycogen accumulation can occur in diabetic patients of any age who are treated with high doses of insulin, and should therefore be included in the differential diagnosis.Pojava povišenih jetrenih enzima, bolova u desnom gornjem abdominalnom kvadrantu i hepatomegalije u bolesnika sa šećernom bolešću liječenih visokim dozama inzulina može ukazivati na patološko nakupljanje glikogena u stanicama jetrenog parenhima. Ovo je stanje prvotno opisano u djece, a kasnije studije provedene na odraslima pokazale su jednaku kliničku sliku. Prikazan je slučaj 41-godišnje žene oboljele od šećerne bolesti s poremećenim jetrenim nalazima i hepatomegalijom, kod koje je ultrazvuk potvrdio povećanje jetre bez znakova steatoze, a biopsijom je postavljena dijagnoza glikogenoze. S obzirom na to da je izrazito nakupljanje glikogena u ovom slučaju nastupilo u odrasloj dobi, bez pozitivne obiteljske anamneze, a bolesnica je imala uredan psihički i tjelesni razvoj, iz diferencijalne dijagnoze se je mogao isključiti Mauriacov sindrom i nasljedna glikogenoza. Uzrok ovoga stanja u ove bolesnice bilo je liječenje osnovne bolesti visokim dozama inzulina. Stoga joj je preporučena poboljšana kontrola glikemije praćena ispravnom dijetom i tjelesnom aktivnošću. Na kontrolnom pregledu nakon tri mjeseca došlo je do regresije hepatomegalije potvrđene palpacijom i ultrazvukom, te do normaliziranja serumskih aminotransferaza, glukoze u krvi i glikoziliranog hemoglobina. Povišene aminotransferaze i alkalna fosfataza uz hepatomegaliju mogu se naći kod bolesnika dijabetičara liječenih visokim dozama inzulina, kao posljedica nakupljanja glikogena u jetrenim stanicama, pa ovo stanje treba uključiti u diferencijalnu dijagnozu

High-performance liquid chromatography evaluation of lipophilicity and QSRR modeling of a series of dual DNA gyrase and topoisomerase IV inhibitors

Bacterial DNA gyrase and topoisomerase IV control the topological state of DNA during replication and represent important antibacterial drug targets. To be successful as drug candidates, newly synthesized compounds must possess optimal lipophilicity, which enables efficient delivery to the site of action. In this study, retention behavior of twenty-three previously synthesized dual DNA gyrase and topoisomerase IV inhibitors was tested in RP-HPLC system, consisting of C8 column and acetonitrile/phosphate buffer (pH 5.5 and pH 7.4) mobile phase. logD was calculated at both pH values and the best correlation with logD was obtained for retention parameter φ0, indicating that this RP-HPLC system could be used as an alternative to the shake-flask determination of lipophilicity. Subsequent QSRR analysis revealed that intrinsic lipophilicity (logP) and molecular weight (bcutm13) have a positive, while solubility (bcutp3) has a negative influence on this retention parameter

Subcellular distribution of glutathione and its dynamic changes under oxidative stress in the yeast Saccharomyces cerevisiae

Glutathione is an important antioxidant in most prokaryotes and eukaryotes. It detoxifies reactive oxygen species and is also involved in the modulation of gene expression, in redox signaling, and in the regulation of enzymatic activities. In this study, the subcellular distribution of glutathione was studied in Saccharomyces cerevisiae by quantitative immunoelectron microscopy. Highest glutathione contents were detected in mitochondria and subsequently in the cytosol, nuclei, cell walls, and vacuoles. The induction of oxidative stress by hydrogen peroxide (H2O2) led to changes in glutathione-specific labeling. Three cell types were identified. Cell types I and II contained more glutathione than control cells. Cell type II differed from cell type I in showing a decrease in glutathione-specific labeling solely in mitochondria. Cell type III contained much less glutathione contents than the control and showed the strongest decrease in mitochondria, suggesting that high and stable levels of glutathione in mitochondria are important for the protection and survival of the cells during oxidative stress. Additionally, large amounts of glutathione were relocated and stored in vacuoles in cell type III, suggesting the importance of the sequestration of glutathione in vacuoles under oxidative stress

Subcellular distribution of glutathione and cysteine in cyanobacteria

Glutathione plays numerous important functions in eukaryotic and prokaryotic cells. Whereas it can be found in virtually all eukaryotic cells, its production in prokaryotes is restricted to cyanobacteria and proteobacteria and a few strains of gram-positive bacteria. In bacteria, it is involved in the protection against reactive oxygen species (ROS), osmotic shock, acidic conditions, toxic chemicals, and heavy metals. Glutathione synthesis in bacteria takes place in two steps out of cysteine, glutamate, and glycine. Cysteine is the limiting factor for glutathione biosynthesis which can be especially crucial for cyanobacteria, which rely on both the sufficient sulfur supply from the growth media and on the protection of glutathione against ROS that are produced during photosynthesis. In this study, we report a method that allows detection and visualization of the subcellular distribution of glutathione in Synechocystis sp. This method is based on immunogold cytochemistry with glutathione and cysteine antisera and computer-supported transmission electron microscopy. Labeling of glutathione and cysteine was restricted to the cytosol and interthylakoidal spaces. Glutathione and cysteine could not be detected in carboxysomes, cyanophycin granules, cell walls, intrathylakoidal spaces, periplasm, and vacuoles. The accuracy of the glutathione and cysteine labeling is supported by two observations. First, preadsorption of the antiglutathione and anticysteine antisera with glutathione and cysteine, respectively, reduced the density of the gold particles to background levels. Second, labeling of glutathione and cysteine was strongly decreased by 98.5% and 100%, respectively, in Synechocystis sp. cells grown on media without sulfur. This study indicates a strong similarity of the subcellular distribution of glutathione and cysteine in cyanobacteria and plastids of plants and provides a deeper insight into glutathione metabolism in bacteria

Problems of translating polite expressions from English to Croatian

Kao što naslov govori, ovaj rad bavi se problemima prevođenja uljudnih izraza s japanskog na hrvatski jezik. Nastoji se predstaviti razlike, ali i sličnosti, između hrvatske i japanske uljudnosti te prikazati neke češće probleme u prijevodu uljudnosti između ta dva jezika i primjeri rješenja. Za početak rada se predstavljaju i objašnjavaju osnovne teorije uljudnosti u zapadnjačkom društvu i u Japanu, a zatim se pojedinačno predstavljaju iskazivanja uljudnosti u hrvatskom te japanskom jeziku, da bi se na kraju iz konkretnog primjera japanskog e-maila prevedenog na hrvatski od strane više prevoditelja, na različite načine, prikazalo neke od problema u prijevodu i kako različiti prevoditelji drugačije interpretiraju tekst te kako se u pojedinom prijevodu prevoditelj suočio sa svakim problemom, kako ga je riješio, a što se u prijevodu izgubilo. Za prijevod između ova dva jezika potrebno je dobro poznavanje japanskog jezika, posebice gramatičkih struktura i keiga, ali i dobro poznavanje hrvatskog jezika za uspješno stvaranje ekvivalentnih izraza i za uspješan prijevod koji izgleda prirodno. U japanskom jeziku primjećuje se više jasno određenih razina uljudnosti, što omogućava specifičnost i prikazuje govornikov položaj u odnosu na sugovornika i situaciju, dok u hrvatskom jeziku ne postoje toliko jasne razine uljudnog obraćanja, što omogućava veću slobodu u načinu izražavanja, jer je govornik manje ograničen društvenim i jezičnim normama pri izboru prikladnog uljudnog izraza. Međutim, ova dva različita načina izražavanja uljudnosti predstavljaju problem u prijevodu jer se prevođenjem na hrvatski riskira gubitak specifičnosti koja se vidi u japanskom uljudnom izražavanju, ali s druge strane povećava se specifičnost u nekim drugim elementima poput roda ili broja koji u japanskom izvorniku nisu uvijek eksplicitno izraženi.As the title implies, this thesis observes problems that occur when translating polite expressions from Japanese to Croatian language. The aim is to present the differences, but also similarities, between Croatian and Japanese politeness and to show some common problems when translating politeness between the two languages, along with examples of solutions. In the first part of the thesis, basic politeness theories in the West and Japan are presented and explained, followed by a short explanation of politeness strategies in Croatian and Japanese, respectively. Finally, some common problems in translation were shown on the example of a Japanese e-mail translated into Croatian by several different translators, and the thesis demonstrates how different translators interpret the text differently, how each translator faced the problems in the text, how they solved it and what was lost in the translation. Translation between these two languages requires not only a solid knowledge of the Japanese language, especially grammatical structures and keigo but also a good knowledge of the Croatian language to successfully use equivalent terms for a successful and natural-sounding translation. The Japanese language has more clearly defined levels of politeness, allowing specificity and shows the speaker's position in relation to the hearer and the situation, while Croatian doesn't have as clearly defined politeness levels, allowing greater freedom of expression, less limited by societal and language norms for expressing politeness. Naturally, these two different and in a way conflicting ways of expressing politeness cause problems in translation because translating into Croatian risks losing specificity shown in Japanese polite expression, but on the other hand increases specificity in other situations like gender or number, which are not always explicit in the Japanese original