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Pseudohypericin and Hyperforin in Hypericum perforatum from Northern Turkey:Variation among Populations,Plant Parts and Phenological Stages

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Journal of Integrative Plant Biology 2008年第5期50卷 575-580页

作者： Cüneyt irak Jolita Radusiene Valdimaras Janulis Liudas Ivanauskas Faculty of Agriculture Department of Agronomy University of Ondokuz Mayis55139 KurupelitSamsunTurkey Institute of Botany VilniusLT-08406Lithuania kaunas university of medicine KaunasLT-44307Lithuania

Hypericum perforatum is a perennial medicinal plant known as ＂St. John＇s wort＂ in Western Europe and has been used in the treatment of several diseases for centuries. In the present study, morphologic, phenologic and population variability in pseudohypericin and hyperforin concentrations among H. perforatum populations from Northern Turkey was investigated for the first time. The aerial parts of H. perforatum plants representing a total of 30 individuals were collected at full flowering from 10 sites of Northern Turkey to search the regional variation in the secondary metabolite concentrations. For morphologic and phenologic sampling, plants from one site were gathered in five phenological stages： vegetative, floral budding, full flowering, fresh fruiting and mature fruiting. The plant materials were air-dried at room temperature and subsequently assayed for chemical concentrations by high performance liquid chromatography. Secondary metabolite concentrations ranged from traces to 2.94mg/g dry weight （DW） for pseudohypericin and traces -6.29mg/g DW for hyperforin. The differences in the secondary metabolite concentrations among populations of H. perforatum were found to be significant. The populations varied greatly in hyperforin concentrations, whereas they produced a similar amount of pseudohypericin. Concentrations of both secondary metabolites in all tissues increased with advancing of plant development and higher accumulation levels were reached at flowering. Among different tissues, full opened flowers were found to be superior to stems, leaves and the other reproductive parts with regard to pseudohypericin and hyperforin accumulations. The present findings might be useful to optimize the processing methodology of wild-harvested plant material and obtain increased concentrations of these secondary metabolites.

关键词： hyperforin Hypericum perforatum morphologic and phenologic variations population variability pseudohypericin.

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Variation of Bioactive Compounds in Hypericum perforatum Growing in Turkey During Its Phenological Cycle

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Journal of Integrative Plant Biology 2007年第5期49卷 615-620页

作者： Cüneyt Cirak Jolita Radusiěne Birsen (Saglam) Karabük Valdimaras Janulis Liudas Ivanauskas Faculty of Agriculture Department of Agronomy University of Ondokuz Mayis Samsun 55139 Turkey Institute of Botany Zaliuju ezeru Vilnius LT-08406 Lithuania kaunas university of medicine Kaunas LT-44307 Lithuania

The present study was conducted to determine phenologic and morphogeneUc variation of hyperlcln, chlorogenlc acid and flavonoids, as rutin, hyperoside, apigenin-7-O-glucoside, quercitrin, quercetin content of Hypericum perforatum L. growing in Turkey. Wild growing plants were harvested at vegetative, floral budding, full flowering, fresh frulUng and mature fruiting stages and dissected into stem, leaf and reproductive tissues and assayed for bioacUve compounds by the High performance liquid chromatography （HPLC） method. Hypericin concentration ranged between 0 and 2.73 mg/g DW, chlorogenic acid 0.00-3.64 mg/g DW, rutin 0.00-3.36 mg/g DW, hyperoside 0.04- 22.42 mg/g DW, quercitrin 0.03-3.46 mg/g DW and quercetin 0.04-1.02 mg/g DW depending on ontogenetic and morphogenetic sampling. Leaves were found to be superior to stems and reproductive parts with regard to phenolic accumulation for all compounds tested while flowers accumulated the highest levels of hypericln. Quercltrln, quercetln and hypericin content in all tissues increased with advancing of developmental stages and reached their highest level during flower ontogenesis. Similarly, chlorogenic acid, hyperoside and apigenin-7-O-glucoside content in different plant parts increased during plant development, however, the highest level was observed at different stages of plant phenology for each tissue. Chlorogenic acid was not detected in stems, leaves and reproductive parts in several stages of plant phenology and its variation during plant growth showed inconsistent manner. In contrast to the other compounds examined, rutin content of stems and leaves decreased with advanc- ing of plant development and the highest level for both tissues was observed at the vegetative stage. However, content of the same compound in reproductive parts was the highest at mature fruiting. The present findings might be useful to obtain increased concentration of these natural compounds.

关键词： chiorogenic acid flavonoids hypericin Hypericum perforatum morphogenetic variation phenologic variation.

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Intrahepatic cholestasis of pregnancy-current achievements and unsolved problems

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World Journal of Gastroenterology 2008年第38期14卷 5781-5788页

作者： Jurate Kondrackiene Limas Kupcinskas Department of Gastroenterology Kaunas University of MedicineKaunas 50009 Lithuania

Intrahepatic cholestasis of pregnancy （ICP） is the most common pregnancy-related liver disorder. Maternal effects of ICP are mild; however, there is a clear association between ICP and higher frequency of fetal distress, preterm delivery, and sudden intrauterine fetal death. The cause of ICP remains elusive, but there is evidence that mutations in genes encoding hepatobiliary transport proteins can predispose for the development of ICP. Recent data suggest that ursodeoxycholic acid is currently the most effective pharmacologic treatment, whereas obstetric management is still debated. Clinical trials are required to identify the most suitable monitoring modalities that can specifically predict poor perinatal outcome. This article aims to review current achievements and unsolved problems of ICR

关键词： Cholestasis of pregnancy Canalicular ABC transporters Pruritus Fetal outcome Ursodeoxycholic acid

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Predictors of premature delivery in patients with intrahepatic cholestasis of pregnancy

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World Journal of Gastroenterology 2007年第46期13卷 6226-6230页

作者： Jurate Kondrackiene Ulrich Beuers Rimantas Zalinkevicius Horst-Dietmar Tauschel Vladas Gintautas Limas Kupcinskas Department of Gastroenterology Kaunas University of MedicineKaunasLithuania Department of Gastroenterology and Hepatology Academic Medical CenterUniversity of AmsterdamAmsterdamThe Netherlands Institute of Endocrinology Kaunas University of MedicineKaunasLithuania Dr.Falk Pharma GmbH FreiburgGermany Department of Obstetrics and Gynecology Kaunas University of MedicineKaunasLithuania

AIM： To evaluate the predictive value of clinical symptoms and biochemical parameters for prematurity in intrahepatic cholestasis of pregnancy （ICP）. METHODS： Sixty symptomatic patients with ICP were included in this retrospective analysis. Preterm delivery was defined as delivery before 37 wk gestation. Predictors of preterm delivery were disclosed by binary multivariate logistic regression analysis. RESULTS： Mean time of delivery was 38.1 ± 1.7 wk. No stillbirths occurred. Premature delivery was observed in eight （13.3%） patients. Total fasting serum bile acids were higher （47.8 ±15.2 vs 41.0 ± 10.0 μmol/L, P 〈 0.05）, and pruritus tended to start earlier （29.0 ± 3.9 vs 31.6 ± 3.3 wk, P = 0.057） in patients with premature delivery when compared to those with term delivery. Binary multivariate logistic regression analysis revealed that early onset of pruritus （OR 1.70, 95% CI 1.23-2.95, P = 0.038） and serum bile acid （OR 2.13, 95% CI 1.13-3.25, P = 0.013） were independent predictors of preterm delivery. CONCLUSION： Early onset of pruritus and high levels of serum bile acids predict preterm delivery in ICP, and define a subgroup of patients at risk for poor neonatal outcome.

关键词： Intrahepatic cholestasis Delivery Pregnancy

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Atrophic gastritis and gastric cancer tissue miRNome analysis reveals hsa-miR-129-1 and hsa-miR-196a as potential early diagnostic biomarkers

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World Journal of Gastroenterology 2022年第6期28卷 653-664页

作者： Greta Varkalaite Evelina Vaitkeviciute Ruta Inciuraite Violeta Salteniene Simonas Juzenas Vytenis Petkevicius Rita Gudaityte Antanas Mickevicius Alexander Link Limas Kupcinskas Marcis Leja Juozas Kupcinskas Jurgita Skieceviciene Institute for Digestive Research Lithuanian University of Health SciencesKaunas 44307Lithuania Department of Gastroenterology Lithuanian University of Health SciencesKaunas 44307Lithuania Department of Surgery Lithuanian University of Health SciencesKaunas 44307Lithuania Department of Gastroenterology Hepatology and Infectious DiseasesOttovon-Guericke University HospitalMagdeburg 39120Germany Institute of Clinical and Preventive medicine&Faculty of medicine University of LatviaRiga 1586Latvia

BACKGROUND Gastric cancer(GC)is one of the most frequently diagnosed tumor *** most cases,GC develops in a stepwise manner from chronic gastritis or atrophic gastritis(AG)to *** of the major issues in clinical settings of GC is diagnosis at advanced disease stages resulting in poor *** RNAs(mi RNAs)are small noncoding molecules that play an essential role in a variety of fundamental biological ***,clinical potential of mi RNA profiling in the gastric cancerogenesis,especially in premalignant GC cases,remains *** To evaluate the AG and GC tissue mi RNomes and identify specific mi RNAs’potential for clinical applications(e.g.,non-invasive diagnostics).METHODS Study included a total of 125 subjects:Controls(CON),AG,and GC *** study subjects were recruited at the Departments of Surgery or Gastroenterology,Hospital of Lithuanian university of Health Sciences and divided into the profiling(n=60)and validation(n=65)*** RNA isolated from tissue samples was used for preparation of small RNA sequencing libraries and profiled using next-generation sequencing(NGS).Based on NGS data,deregulated mi RNAs hsa-mi R-129-1-3 p and hsa-mi R-196 a-5 p were analyzed in plasma samples of independent cohort consisting of CON,AG,and GC *** level of hsa-mi R-129-1-3 p and hsa-mi R-196 a-5 p was determined using the quantitative real-time polymerase chain reaction and 2-ΔΔCt *** Results of tissue analysis revealed 20 differentially expressed mi RNAs in AG group compared to CON group,129 deregulated mi RNAs in GC compared to CON,and 99 altered mi RNAs comparing GC and AG *** 2 mi RNAs(hsa-mi R-129-1-3 p and hsa-mi R-196 a-5 p)were identified to be step-wise deregulated in healthy-premalignant-malignant *** under the curve(AUC)-receiver operating characteristic analysis revealed that expression level of hsa-mi R-196 a-5 p is significant for discrimination of CON vs AG,CON vs GC and A

关键词： Gastric cancer Atrophic gastritis Tumorigenesis Helicobacter pylori MicroRNAs Biomarkers

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Disease-specific health-related quality of life and its determinants in liver cirrhosis patients in Lithuania

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World Journal of Gastroenterology 2006年第48期12卷 7792-7797页

作者： Jolanta Sumskiene Linas Sumskas Dalius Petrauskas Limas Kupcinskas Department of Gastroenterology Kaunas University of Medicine A.Mickeviciaus street 9 Kaunas LT-44307 Lithuania Institute for Biomedical Research of kaunas university of medicine Eiveniu street 4 Kaunas LT-50009 Lithuania

AIM: To evaluate disease-specific quality of life (QOL) in liver cirrhosis patients and to compare it with those of a healthy population. Also an important objective was to assess whether QOL in liver cirrhosis patients differs by age and gender, by type and severity of disease. METHODS: The case group of 131 liver cirrhosis patients was selected. The control group of 262 was enrolled from a healthy population according to the scheme of case-control study. Clinical, demographic, laboratory data were collected. QOL was measured with a specific chronic liver disease questionnaire (CLDQ), which was translated and validated in Lithuanian. QOL scores were compared between groups by age, gender, type and severity of disease. Cronbach’s alpha statistics calculation was used for evaluation of internal consistency reliability. Student’s t test or ANOVA were used for evaluation hypothesis about probability equation. RESULTS: QOL was significantly lower in liver cirrhosis patients than in healthy population (59.5 ± 18.3 vs 85.3 ± 12.3, P < 0.001). The significant QOL differences between case and control groups were observed in domains of worry and abdominal symptoms, the smaller differences-in emotional functions and systematic symptom domains. Significantly worse QOL was in observed patients with increased clinical severity of the disease measured by Child-Pugh class. Age, gender and etiology of disease had an insignificant effect on QOL in cirrhotic patients. CONCLUSION: QOL was significantly impaired in all CLDQ domains in liver cirrhosis patients. Increase in severity of disease was the major factor associated with poorer QOL.

关键词： Liver cirrhosis Quality of life Chronic liverdisease questionnaire Case and control patients

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High frequency of the c.3207C>A (p.H1069Q) mutation in ATP7B gene of Lithuanian patients with hepatic presentation of Wilson's disease

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World Journal of Gastroenterology 2008年第38期14卷 5876-5879页

作者： Laimutis Kucinskas Jolanta Jeroch Astra Vitkauskiene Raimundas Sakalauskas Vitalija Petrenkiene Vaidutis Kucinskas Rima Naginiene Hartmut Schmidt Limas Kupcinskas Institute of Biology of kaunas university of medicine Mickeviiaus 9 Kaunas LT-44307 Lithuania Institute of Biomedical Research of kaunas university of medicine Eiveniu 4 Kaunas LT-50009 Lithuania Laboratory of Immunology and Genetics Kaunas University of Medicine Eiveniu 2 Kaunas LT-50009 Lithuania Department of Pulmonology and Immunology Kaunas University of Medicine Eiveniu 2Kaunas LT-50009 Lithuania Department of Gastroenterology Kaunas University of Medicine Eiveniu 2Kaunas LT-50009 Lithuania Department of Human and Medical Genetics Faculty of Medicine Vilnius University Santariskiu 2Vilnius LT-08661 Lithuania Institute of Biomedical Research of kaunas university of medicine Eiveniu 4Kaunas LT-50009 Lithuania Department of Hepatotransplanthology University of Munster Schlossplatz 2Munster D-48149 Germany Department of Gastroenterology Kaunas University of Medicine Eiveniu 2 Kaunas LT-50009 Lithuania

AIM： To investigate the prevalence of the ATP7B gene mutation in patients with hepatic presentation of Wilson＇s disease （WD） in Lithuania. METHODS： Eleven unrelated Lithuanian families, including 13 WD patients were tested. Clinically WD diagnosis was established in accordance to the Leipzig scoring system. Genomic DNA was extracted from whole venous blood using a salt precipitation method. Firstly, the semi-nested polymerase chain reaction （PCR） technique was used to detect the c.3207C〉A （p.H1069Q） mutation. Patients not homozygous for the c.3207C〉A （p.H1069Q） mutation were further analyzed. The 21 exons of the WD gene were amplified in a thermal cycler （Biometra T3 Thermocycler, G0ttingen, Germany）. Direct sequencing of the amplified PCR products was performed by cycle sequencing using fluorescent dye terminators in an automatic sequencer （Applied Biosystems, Darmstadt, Germany）. RESULTS： Total of 13 WD patients （mean age 26.4 years; range 17-40; male/female 3/10） presented with hepatic disorders and 16 their first degree relatives （including 12 siblings） were studied. Some of WD patients, in addition to hepatic symptoms, have had extrahepatic disorders （hemolytic anemia 3; Fanconi syndrome 1; neurophsychiatric and behavioural disorder 2）. Liver biopsy specimens were available in all of 13 WD patients （8 had cirrhosis; 1-chronic hepatitis; 3-acute liver failure, 1-1iver steatosis）. Twelve of 13 （92.3%） WD patients had the c.3207C〉A （***069Q） mutation, 6 of them in both chromosomes, 6 were presented as compound heterozygotes with additional c.3472-82delGGTTTAACCAT, c.3402delC, c.3121C〉T （***041W） or unknown mutations. For one patient with liver cirrhosis and psychiatric disorder （Leipzig score 6）, no mutations were found. Out of 16 first degree WD relatives, 11 （68.7%） were heterozygous for the c.3207C〉A （p.H1069Q） mutation. Two patients with fulminant WD died from acute liver failure and ii are in full remission under peniciilamine or zinc acetate treatment. Thr

关键词： Wilson disease ATP7B gene c.3207C〉A(p.H1069Q) mutation Cirrhosis Urine copper Copper in liver biopsies

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Crohn’s disease in human immunodeficiency virus-infected patient:A case report

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World Journal of Clinical Cases 2023年第17期11卷 4202-4209页

作者： Ausra Vinikaite Benediktas Kurlinkus Dominyka Jasinskaite Sandra Strainiene Audrone Buineviciute Goda Sadauskaite Vytautas Kiudelis Edita Kazenaite Lithuanian university of Health Sciences Faculty of MedicineKaunas 44307Lithuania Clinic of Gastroenterology Nephrourology and SurgeryInstitute of Clinical MedicineFaculty of MedicineVilnius UniversityVilnius 01513Lithuania Center of Hepatology Gastroenterology and DietologyVilnius University Hospital Santaros ClinicsVilnius 08661Lithuania Department of Internal medicine and Surgery Antakalnis ClinicVilnius 10207Lithuania Department of Gastroenterology Lithuanian University of Health SciencesKaunas 44307Lithuania

BACKGROUND Inflammatory bowel disease(IBD)is an autoimmune condition treated with immunosuppressive ***,the need for immune system suppression becomes questionable when infection with the human immunodeficiency virus(HIV)occurs simultaneously and impacts the course of *** reported case represents the clinical course,prescribed treatment and its effect,as well as clinical challenges faced by physicians in a combination of such *** also present a comprehensive literature review of similar *** SUMMARY A 49-year-old woman suffering from a newly diagnosed Crohn’s disease was hospitalized due to exacerbated symptoms(abdominal pain,fever,and weight loss).During her hospital stay,she tested positive for *** conservative treatment,the patient improved and was *** the outpatient clinic,her HIV infection was confirmed as stage C3,and antiretroviral treatment was initiated *** notwithstanding,soon the patient was rehospitalized with pulmonary embolism and developed a series of complications because of the subsequent coexistence of IBD and *** intensive and meticulous treatment,the patient’s condition has improved and she remains in *** The paucity of studies and data on the coexistence of HIV and IBD leaves clinicians doubting the optimal treatment options.

关键词： Crohn’s disease Inflammatory bowel disease Human immunodeficiency virus Immunocompromised patient Case report

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Early recognition of abdominal compartment syndrome in patients with acute pancreatitis

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World Journal of Gastroenterology 2009年第6期15卷 717-721页

作者： Zilvinas Dambrauskas Audrius Parseliunas Antanas Gulbinas Juozas Pundzius Giedrius Barauskas Laboratory for Research of Digestive System Institute for Biomedical Research and Department of SurgeryKaunas University of MedicineEiveniu Str.250009 KaunasLithuania Department of Surgery Kaunas University of MedicineEiveniu Str.250009 KaunasLithuania

AIM： To assess the value of widely used clinical scores in the early identification of acute pancreatitis （AP） patients who are likely to suffer from intra-abdominal hypertension （IAH） and abdominal compartment syndrome （ACS）.METHODS： Patients （η = 44） with AP recruited in this study were divided into two groups （ACS and non-ACS） according to intra-abdominal pressure （IAP） determined by indirect measurement using the transvesical route via Foley bladder catheter. On admission and at regular intervals, the severity of the AP and presence of organ dysfunction were assessed utilizing different multifactorial prognostic systems： Glasgow-Imrie score, Acute Physiology and Chronic Health Evaluation Ⅱ （APACHE-Ⅱ） score, and Multiorgan Dysfunction Score （MODS）. The diagnostic performance of scores predicting ACS development, cut-off values and specificity and sensitivity were established using receiver operating characteristic （ROC） curve analysis.RESULTS： The incidence of ACS in our study population was 19.35%. IAP at admission in the ACS group was 22.0 （18.5-25.0） mmHg and 9.25 （3.0-12.4） mmHg in the non-ACS group （P 〈 0.01）. Univariate statistical analysis revealed that patients in the ACS group had significantly higher multifactorial clinical scores （APACHE Ⅱ, Glasgow-Imrie and MODS） on admission and higher maximal scores during hospitalization （P 〈 0.01）. ROC curve analysis revealed that APACHE Ⅱ, Glasgow-Imrie, and MODS are valuable tools for early prediction of ACS with high sensitivity and specificity, and that cut-off values are similar to those used for stratification of patients with severe acute pancreatitis （SAP）.CONCLUSION： IAH and ACS are rare findings in patients with mild AR Based on the results of our study we recommend measuring the IAP in cases when patients present with SAP （APACHE Ⅱ 〉 7; MODS 〉 2 or Glasgow-Imrie score 〉 3）.

关键词： Acute pancreatitis Abdominal compartment syndrome Intra-abdominal pressure Intra-abdominal hypertension Organ dysfunction

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Clinical Significance Of High Risk Hpv Test For The Diagnostics Of Cervical Intraepithelial Neoplasia （CIN）

Clinical Significance Of High Risk Hpv Test For The Diagnost...

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24th International Papillomavirus Conference and Clinical Workshop

作者： Kristina Jariene mindaugas Kliucinskas ruta Nadisauskiene meile Minkauskiene daiva Vaitkiene knstina Ramonaitiene ramune Galvanauskaite Department of Obstetrics and Gynaecology Kaunas University of MedicineLithuania Department of Obstetrics and Gynaecology Kaunas University of MedicineLithuania Department of Obstetrics and Gynaecology Kaunas University of MedicineLithuania Department of Obstetrics and Gynaecology Kaunas University of MedicineLithuania Department of Obstetrics and Gynaecology Kaunas University of MedicineLithuania Department of Obstetrics and Gynaecology Kaunas University of MedicineLithuania Department of Obstetrics and Gynaecology Kaunas University of MedicineLithuania

＜正＞*** evaluate the sensitivity and the specificity of the HPV test and Papanicolaou smear for the diagnosis of high grade cervical intraepithelial neoplasia（CIN2/3,CIS）. Methods.A prospective study of women with either mild or borderline dyskaryosis on Pap smear（HSIL,LSIL,ASC-US,ASC-H or AGUS）referred to the Outpatient OB/GYN Department of kaunas university of medicine from October 1,2006 to June 30,

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