Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 35
Filter
1.
J Vasc Surg Cases Innov Tech ; 9(4): 101354, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38078283

ABSTRACT

An aorto-esophageal fistula (AEF) is a rare complication of aortic surgery but can cause potentially lethal upper gastrointestinal tract bleeding. A patient presented with an AEF secondary to emergency endovascular repair of a contained penetrating atherosclerotic ulcer rupture of the thoracic aorta and was successfully treated with endoscopic closure using fibrin glue. As endovascular repair becomes increasingly common, a greater incidence of AEFs should be anticipated and the treatment options better described.

2.
Sci Rep ; 13(1): 9158, 2023 06 06.
Article in English | MEDLINE | ID: mdl-37280241

ABSTRACT

The prevalence of metabolic risk factors and non-alcoholic fatty liver disease (NAFLD) is high among people living with HIV (PLWH). Data on the recently proposed definition of metabolic dysfunction-associated fatty liver disease (MAFLD) in PLWH receiving antiretroviral therapy (ART) remains unknown. A total of 282 PLWH were included in this cross-sectional cohort study. Vibration-controlled transient elastography (VCTE) was used to assess hepatic steatosis and fibrosis. MAFLD and its subgroups (overweight/obese, lean/normal weight, and type 2 diabetes) were defined according to a recently published international consensus statement. The majority of this cohort was male (n = 198, 70.2%), and the median age was 51.5 years. The median BMI was 25 kg/m2, and obesity was prevalent in 16.2% (n = 44). A total of 207 (73.4%) PLWH were classified as non-MAFLD while 75 (26.6%) qualified as MAFLD. The median CAP in the MAFLD group was 320 dB/m. PLWH with MAFLD showed a higher median LSM (p < 0.008) and were older (p < 0.005) compared to the non-MAFLD group. Overall, the metabolic risk profile was comparable between MAFLD and NAFLD. The majority of PLWH and MAFLD were overweight or obese (n = 58, 77.3%). The highest median LSM values were observed in the subgroup with MAFLD and type 2 diabetes. HIV-related parameters did not differ between non-MAFLD and MAFLD. The prevalence of MAFLD in PLWH is high and comparable to NAFLD. PLWH may be characterized according to the novel MAFLD criteria and its subgroups to identify patients at risk for chronic liver disease.


Subject(s)
Diabetes Mellitus, Type 2 , Non-alcoholic Fatty Liver Disease , Humans , Male , Middle Aged , Non-alcoholic Fatty Liver Disease/complications , Non-alcoholic Fatty Liver Disease/epidemiology , Cross-Sectional Studies , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/epidemiology , Overweight , Obesity/complications , Obesity/epidemiology , Liver Cirrhosis
3.
World Neurosurg ; 173: e306-e320, 2023 May.
Article in English | MEDLINE | ID: mdl-36804433

ABSTRACT

BACKGROUND: Decompressive hemicraniectomy (DHC) is performed to relieve life-threatening intracranial pressure elevations. After swelling abates, a cranioplasty is performed for mechanical integrity and cosmesis. Cranioplasty is costly with high complication rates. Prior attempts to obviate second-stage cranioplasty have been unsuccessful. The Adjustable Cranial Plate (ACP) is designed for implantation during DHC to afford maximal volumetric expansion with later repositioning without requiring a second major operation. METHODS: The ACP has a mobile section held by a tripod fixation mechanism. Centrally located gears adjust the implant between the up and down positions. Cadaveric ACP implantation was performed. Virtual DHC and ACP placement were done using imaging data from 94 patients who had previously undergone DHC to corroborate our cadaveric results. Imaging analysis methods were used to calculate volumes of cranial expansion. RESULTS: The ACP implantation and adjustment procedures are feasible in cadaveric testing without wound closure difficulties. Results of the cadaveric study showed total volumetric expansion achieved was 222 cm3. Results of the virtual DHC procedure showed the volume of cranial expansion achieved by removing a standardized bone flap was 132 cm3 (range, 89-171 cm3). Applied to virtual craniectomy patients, the total volume of expansion achieved with the ACP implantation operation was 222 cm3 (range, 181-263 cm3). CONCLUSIONS: ACP implantation during DHC is technically feasible. It achieves a volume of cranial expansion that will accommodate that observed following survivable hemicraniectomy operations. Moving the implant from the up to the down position can easily be performed as a simple outpatient or inpatient bedside procedure, thus potentially eliminating second-stage cranioplasty procedures.


Subject(s)
Decompressive Craniectomy , Plastic Surgery Procedures , Humans , Decompressive Craniectomy/methods , Postoperative Complications/surgery , Skull/diagnostic imaging , Skull/surgery , Cadaver , Retrospective Studies
4.
Z Gastroenterol ; 61(3): 275-279, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36379462

ABSTRACT

Gastric antral vascular ectasia (GAVE) syndrome is a rare but often challenging etiology of upper gastrointestinal bleeding (UGIB).We report on a 60-year-old patient with liver cirrhosis, GAVE syndrome and recurrent and refractory GAVE-related UGIB. During a 5-month hospital stay, the patient required a total of 82 packed red blood cells (pRBCs) and 23 gastroscopies. All endoscopic approaches, including multiple argon plasma coagulation and band ligation sessions, remained unsuccessful. Antrectomy was waived because of the high perioperative mortality risk in Child-Pugh B liver cirrhosis. TIPS insertion also failed to control the bleeding. Only continuous intravenous octreotide infusion slowed the bleeding, but this forced the patient to be hospitalized. After 144 inpatient days, administration of subcutaneous octreotide allowed the patient to be discharged. However, the patient continued to require two pRBCs every 2-3 weeks. Based on recently published data, we treated the patient with bevacizumab (anti-VEGF antibody) off-label at a dose of 7.5 mg/kg body weight every three weeks in nine single doses over six months. Since the first administration, the patient has remained transfusion-free, has not required hospitalization, and leads an active life, working full-time. He remains on octreotide, which has been reduced but not yet discontinued. Additionally, no adverse events were observed.Thus, in patients with liver cirrhosis and refractory GAVE-related hemorrhage, bevacizumab combined with subcutaneous octreotide should be considered as an effective and durable pharmacological treatment option.


Subject(s)
Gastric Antral Vascular Ectasia , Male , Humans , Middle Aged , Gastric Antral Vascular Ectasia/complications , Gastric Antral Vascular Ectasia/surgery , Octreotide/therapeutic use , Bevacizumab , Treatment Outcome , Liver Cirrhosis/complications , Liver Cirrhosis/diagnosis , Liver Cirrhosis/drug therapy , Gastrointestinal Hemorrhage/diagnosis , Gastrointestinal Hemorrhage/drug therapy , Gastrointestinal Hemorrhage/etiology
5.
Qual Life Res ; 32(2): 401-411, 2023 Feb.
Article in English | MEDLINE | ID: mdl-35996039

ABSTRACT

PURPOSE: Liver-related comorbidities can impair the health-related quality of life (HRQL) in people living with human immunodeficiency virus (HIV) (PLWH). However, the role of hepatic steatosis and significant fibrosis in PLWH remains incompletely characterized. Therefore, the aim of this study was to explore the association of hepatic steatosis and significant fibrosis on the HRQL using the medical outcomes study HIV health survey (MOS-HIV) in PLWH. METHODS: A total of 222 PLWH were included in the final analysis of this cohort study. Metabolic comorbidities, socioeconomic factors, and HIV-related parameters were assessed. Hepatic steatosis and fibrosis were measured using vibration-controlled transient elastography (VCTE). The MOS-HIV survey, containing two summary scores (physical health summary (PHS) and mental health summary (MHS)) and ten domains, was used to assess the HRQL. Clinical predictors were identified using multivariable linear regression models. RESULTS: The majority of this cohort was male, and the median age was 52 years, with a high prevalence of hepatic steatosis (n = 81, 36.5%). Significant fibrosis was present in 7.7% (n = 17). The mean PHS and MHS scores were 52.7 ± 9.5 and 51.4 ± 10.5, respectively. The lowest scores were in the general health perception (GHP) and energy/fatigue (EF) domains. A high BMI and waist circumference were associated with a poor PHS score. Lower education, unemployment, arterial hypertension, and significant fibrosis remained independent predictors of an impaired HRQL. CONCLUSION: Metabolic comorbidities, significant fibrosis, and a lower socioeconomic status may negatively affect the HRQL in PLWH. Considering the negative impact of significant fibrosis on the outcome, counseling and preventive measures according to current guidelines are recommended in this subgroup of PLWH.


Subject(s)
HIV Infections , Quality of Life , Humans , Male , Middle Aged , Quality of Life/psychology , HIV Infections/drug therapy , HIV , Cohort Studies , Liver Cirrhosis
6.
Clin Case Rep ; 8(12): 2990-2994, 2020 Dec.
Article in English | MEDLINE | ID: mdl-33363865

ABSTRACT

The biological anakinra appears promising to halt cytokine storm syndrome seen in severe courses of COVID-19. However, immunosuppression with anakinra may facilitate sepsis, necessitating continuous screening for bacterial superinfections.

7.
Z Gastroenterol ; 58(1): 30-38, 2020 Jan.
Article in English | MEDLINE | ID: mdl-31931538

ABSTRACT

BACKGROUND: In order to reduce alcohol relapse after liver transplantation (LT), the German national guidelines for waiting-list maintenance and organ allocation demand a minimum 6-month period of alcohol abstinence pre-LT, confirmed by measuring urinary ethyl glucuronide (uEtG). METHODS: Between January 2015 and June 2016, uEtG was measured at least once in 339 cirrhotic patients with an indication for LT at the University Medical Center Mainz. uEtG was measured with an enzyme-linked immunosorbent assay (ELISA) screening test (cutoff value: 500 µg/L). For uEtG values ≥ 500 µg/L, liquid chromatography-mass spectrometry (LC-MS/MS) was performed as a confirmatory assay. Data were collected prospectively in a transplant database. RESULTS: Of the 339 potential liver transplant candidates, uEtG was negative in 86.4 %. Most patients were male (64.3 %), with an average age of 56.42 ±â€Š10.1 years. In the multivariate analysis, mean corpuscular volume (p = 0.001), urinary creatinine (p = 0.001), gamma-glutamyl transferase (p = 0.001), and hemoglobin (p = 0.003) were significantly associated with a positive uEtG test result. The sensitivity of the ELISA screening test was 100 % for uEtG values > 2000 µg/L, as confirmed by LC-MS/MS. CONCLUSION: uEtG is an effective parameter to reveal alcohol consumption by patients on the waiting list for LT. The sensitivity of the ELISA is excellent for uEtG values > 2000 µg/L, for which LC-MS/MS confirmation could be omitted.


Subject(s)
Alcohol Drinking , Glucuronates/urine , Liver Cirrhosis, Alcoholic/surgery , Liver Cirrhosis, Alcoholic/urine , Liver Transplantation , Mass Screening/methods , Aged , Biomarkers/urine , Chromatography, Liquid , Cohort Studies , Enzyme-Linked Immunosorbent Assay , Ethanol/blood , Ethanol/urine , Female , Humans , Liver Cirrhosis, Alcoholic/diagnosis , Male , Middle Aged , Predictive Value of Tests , Prospective Studies , Sensitivity and Specificity , Tandem Mass Spectrometry , Waiting Lists
8.
Cell Physiol Biochem ; 52(5): 1039-1060, 2019.
Article in English | MEDLINE | ID: mdl-30977987

ABSTRACT

BACKGROUND/AIMS: Endothelial cells exposed to the Random Positioning Machine (RPM) reveal three different phenotypes. They grow as a two-dimensional monolayer and form three-dimensional (3D) structures such as spheroids and tubular constructs. As part of the ESA-SPHEROIDS project we want to understand how endothelial cells (ECs) react and adapt to long-term microgravity. METHODS: During a spaceflight to the International Space Station (ISS) and a subsequent stay onboard, human ECs (EA.hy926 cell line) were cultured for 12 days in real microgravity inside an automatic flight hardware, specially designed for use in space. ECs were cultivated in the absence or presence of vascular endothelial growth factor, which had demonstrated a cell-protective effect on ECs exposed to an RPM simulating microgravity. After cell fixation in space and return of the samples, we examined cell morphology and analyzed supernatants by Multianalyte Profiling technology. RESULTS: The fixed samples comprised 3D multicellular spheroids and tube-like structures in addition to monolayer cells, which are exclusively observed during growth under Earth gravity (1g). Within the 3D aggregates we detected enhanced collagen and laminin. The supernatant analysis unveiled alterations in secretion of several growth factors, cytokines, and extracellular matrix components as compared to cells cultivated at 1g or on the RPM. This confirmed an influence of gravity on interacting key proteins and genes and demonstrated a flight hardware impact on the endothelial secretome. CONCLUSION: Since formation of tube-like aggregates was observed only on the RPM and during spaceflight, we conclude that microgravity may be the major cause for ECs' 3D aggregation.


Subject(s)
Epithelial Cells/metabolism , Gene Expression Regulation , Space Flight , Spheroids, Cellular/metabolism , Weightlessness , Cell Line , Epithelial Cells/cytology , Humans , Spheroids, Cellular/cytology
9.
J Gastrointestin Liver Dis ; 28(1): 53-61, 2019 Mar.
Article in English | MEDLINE | ID: mdl-30851173

ABSTRACT

BACKGROUND AND AIMS: Fibrosis progression (FP) after liver transplantation (LT) increases morbidity and mortality. Biomarkers are needed for early prediction of FP. A recipient's seven-gene cirrhosis risk score (CRS) has been associated with FP, especially in non-transplant cohorts. A broader validation of CRS, including the genotype of the donor-organ and HCV-negative patients is lacking. We therefore analyzed the impact of donor- and recipient-specific genotypes on FP after LT in a large cohort of HCV-positive and -negative patients. METHOD: Genotyping from liver biopsies (n=201 donors) and peripheral blood (n=442 recipients) was performed. Cirrhosis risk score was correlated with FP at 1 and 5 years after LT. RESULTS: Fibrosis >/=F2 was documented in 26.5% of the recipients' CRS group (R-CRS) (defined by recipient's genotype) and in 23.4% of the donors' CRS- group (D-CRS) (defined by donor's genotype). Cumulative incidence for fibrosis >/=F2 was higher in patients with D-CRS >0.7 (p=0.03). While the R-CRS showed no prognostic relevance, D-CRS >0.7 was associated with higher hazard ratios (HRs) for fibrosis >/=F2 (HR=2.04; p=0.01), especially in HCV-negative patients (HR=2.59, p=0.03). Donors' CRS >0.7 was associated with higher risk for >/=F2 in 1-year protocol biopsies (p<0.001). Among the patients in whom both the recipient's and donor's CRS were available, fibrosis >/=F2 was encountered more frequently in patients with a D-CRS >0.7, in combination with any R-CRS, compared to patients with D-CRS scores /=F2 in subgroups. CONCLUSION: High D-CRS >0.7 predicted early FP after LT, especially in HCV negative patients.


Subject(s)
Liver Cirrhosis/genetics , Liver Transplantation/adverse effects , Tissue Donors , Disease Progression , Female , Genetic Markers , Genetic Predisposition to Disease , Humans , Liver Cirrhosis/pathology , Liver Transplantation/methods , Male , Middle Aged , Phenotype , Risk Assessment , Risk Factors , Time Factors , Treatment Outcome
10.
Am Univ Law Rev ; 68(3): 761-821, 2019.
Article in English | MEDLINE | ID: mdl-30919611

ABSTRACT

The digital universe remains a black box. Despite attaining high-technology capabilities like artificial intelligence and cognitive computing, "Big Data" analytics have failed to keep pace with surging data production. At the same time, the falling costs of cloud storage and distributed systems have made mass data storage cheaper and more accessible. These effects have produced a chasm between data that is stored and data that can be readily analyzed and understood. Enticed by the promise of extracting future value from rising data stockpiles, organizations now retain massive quantities of data that they cannot presently know or effectively manage. This rising sea of "dark data" now represents the vast majority of the digital universe. Dark data presents a quandary for organizations and the judicial system. For organizations, the inability to know the contents of retained dark data produces invisible risk under a spreading patchwork of digital privacy and data governance laws, most notably in the medical and consumer protection areas. For courts increasingly confronted with Big Data-derived evidence, dark data may shield critical information from judicial view while embedding subjective influences within seemingly objective methods. To avoid obscuring organizational risk and producing erroneous outcomes in the courtroom, decision-makers must achieve a new awareness of dark data's presence and its ability to undermine Big Data's vaunted advantages.


Subject(s)
Big Data , Computer Security/legislation & jurisprudence , Data Collection/legislation & jurisprudence , Privacy/legislation & jurisprudence , Health Insurance Portability and Accountability Act/legislation & jurisprudence , Humans , United States , United States Federal Trade Commission/legislation & jurisprudence
11.
Appl Microbiol Biotechnol ; 102(18): 7795-7803, 2018 Sep.
Article in English | MEDLINE | ID: mdl-30027491

ABSTRACT

Commercial mushrooms are produced on lignocellulose such as straw, saw dust, and wood chips. As such, mushroom-forming fungi convert low-quality waste streams into high-quality food. Spent mushroom substrate (SMS) is usually considered a waste product. This review discusses the applications of SMS to promote the transition to a circular economy. SMS can be used as compost, as a substrate for other mushroom-forming fungi, as animal feed, to promote health of animals, and to produce packaging and construction materials, biofuels, and enzymes. This range of applications can make agricultural production more sustainable and efficient, especially if the CO2 emission and heat from mushroom cultivation can be used to promote plant growth in greenhouses.


Subject(s)
Agaricales/growth & development , Agriculture/economics , Lignin/economics , Agaricales/metabolism , Agriculture/instrumentation , Culture Media/analysis , Culture Media/economics , Culture Media/metabolism , Lignin/analysis , Lignin/metabolism , Waste Products/analysis , Waste Products/economics
12.
Beilstein J Nanotechnol ; 8: 1375-1387, 2017.
Article in English | MEDLINE | ID: mdl-28900593

ABSTRACT

The chemisorption of magnetically bistable transition metal complexes on planar surfaces has recently attracted increased scientific interest due to its potential application in various fields, including molecular spintronics. In this work, the synthesis of mixed-ligand complexes of the type [NiII2L(L')](ClO4), where L represents a 24-membered macrocyclic hexaazadithiophenolate ligand and L' is a ω-mercapto-carboxylato ligand (L' = HS(CH2)5CO2- (6), HS(CH2)10CO2- (7), or HS(C6H4)2CO2- (8)), and their ability to adsorb on gold surfaces is reported. Besides elemental analysis, IR spectroscopy, electrospray ionization mass spectrometry (ESIMS), UV-vis spectroscopy, and X-ray crystallography (for 6 and 7), the compounds were also studied by temperature-dependent magnetic susceptibility measurements (for 7 and 8) and (broken symmetry) density functional theory (DFT) calculations. An S = 2 ground state is demonstrated by temperature-dependent susceptibility and magnetization measurements, achieved by ferromagnetic coupling between the spins of the Ni(II) ions in 7 (J = +22.3 cm-1) and 8 (J = +20.8 cm-1; H = -2JS1S2). The reactivity of complexes 6-8 is reminiscent of that of pure thiolato ligands, which readily chemisorb on Au surfaces as verified by contact angle, atomic force microscopy (AFM) and spectroscopic ellipsometry measurements. The large [Ni2L] tail groups, however, prevent the packing and self-assembly of the hydrocarbon chains. The smaller film thickness of 7 is attributed to the specific coordination mode of the coligand. Results of preliminary transport measurements utilizing rolled-up devices are also reported.

13.
Drug Des Devel Ther ; 11: 2131-2138, 2017.
Article in English | MEDLINE | ID: mdl-28744104

ABSTRACT

BACKGROUND: Recurrent hepatitis C virus (HCV) infection after liver transplantation (LT) has been a frequent and relevant problem in the past two decades. This analysis evaluated the efficacy and safety of new interferon (IFN)-free direct-acting antiviral (DAA) therapies in a large real-world cohort of HCV patients after LT. METHODS: We retrospectively analyzed a cohort of 157 patients infected with HCV who underwent deceased donor LT between 1997 and 2014. Patient survival, outcome, and side effects of antiviral therapy were assessed. RESULTS: Survival with recurrent HCV genotype 1 (GT1) infection was inferior to other HCV GTs (P=0.01). The overall sustained virological response (SVR) rate with new DAA therapy was 94.6% (n=37). Patients with both GT1 and other GTs reached SVR rates >90%. We noticed a few side effects, mainly caused by ribavirin, and only one discontinuation in DAA-treated patients. CONCLUSION: DAA therapy was effective and safe in previous hard-to-treat patients after LT in this real-world cohort.


Subject(s)
Antiviral Agents/therapeutic use , Hepatitis C, Chronic/drug therapy , Liver Transplantation/methods , Aged , Antiviral Agents/adverse effects , Cohort Studies , Drug Therapy, Combination , Female , Hepacivirus/drug effects , Hepatitis C, Chronic/virology , Humans , Liver Cirrhosis/etiology , Liver Cirrhosis/prevention & control , Male , Middle Aged , Recurrence , Retrospective Studies , Survival Analysis , Treatment Outcome
14.
J Phys Condens Matter ; 29(39): 395301, 2017 Oct 04.
Article in English | MEDLINE | ID: mdl-28677599

ABSTRACT

Superconducting micro- and nanohelices are proposed for the first time. A theoretical investigation of the superconducting state in the helical coils at the micro- and nanoscale is performed within the time-dependent Ginzburg-Landau approach. The pattern and number of vortices in a stationary distribution are determined by their confinement to the ultrathin helical coil and can therefore be efficiently controlled by the spiral stripe width and the spiral pitch distance for both dense and sparse coils. Quasi-degeneracy of vortex patterns is manifested in the helical coil when the number of vortices is incommensurable with the total number of half-turns. With increasing radius, superconducting helical coils provide a physical realization of a transition from the vortex pattern peculiar to an open tube to that of a planar stripe.

15.
J Thorac Oncol ; 12(10): 1561-1570, 2017 10.
Article in English | MEDLINE | ID: mdl-28648948

ABSTRACT

INTRODUCTION: NRG Oncology RTOG 0937 is a randomized phase II trial evaluating 1-year overall survival (OS) with prophylactic cranial irradiation (PCI) or PCI plus consolidative radiation therapy (PCI+cRT) to intrathoracic disease and extracranial metastases for extensive-disease SCLC. METHODS: Patients with one to four extracranial metastases were eligible after a complete response or partial response to chemotherapy. Randomization was to PCI or PCI+cRT to the thorax and metastases. Original stratification included partial response versus complete response after chemotherapy and one versus two to four metastases; age younger than 65 years versus 65 years or older was added after an observed imbalance. PCI consisted of 25 Gy in 10 fractions. cRT consisted of 45 Gy in 15 fractions. To detect an improvement in OS from 30% to 45% with a 34% hazard reduction (hazard ratio = 0.66) under a 0.1 type 1 error (one sided) and 80% power, 154 patients were required. RESULTS: A total of 97 patients were randomized between March 2010 and February 2015. Eleven patients were ineligible (nine in the PCI group and two in the PCI+cRT group), leaving 42 randomized to receive PCI and 44 to receive PCI+cRT. At planned interim analysis, the study crossed the futility boundary for OS and was closed before meeting the accrual target. Median follow-up was 9 months. The 1-year OS was not different between the groups: 60.1% (95% confidence interval [CI]: 41.2-74.7) for PCI and 50.8% (95% CI: 34.0-65.3) for PCI+cRT (p = 0.21). The 3- and 12-month rates of progression were 53.3% and 79.6% for PCI and 14.5% and 75% for PCI+cRT, respectively. Time to progression favored PCI+cRT (hazard ratio = 0.53, 95% CI: 0.32-0.87, p = 0.01). One patient in each arm had grade 4 therapy-related toxicity and one had grade 5 therapy-related pneumonitis with PCI+cRT. CONCLUSIONS: OS exceeded predictions for both arms. cRT delayed progression but did not improve 1-year OS.


Subject(s)
Cranial Irradiation/methods , Lung Neoplasms/complications , Small Cell Lung Carcinoma/complications , Adult , Aged , Aged, 80 and over , Brain Neoplasms/secondary , Female , Humans , Lung Neoplasms/mortality , Lung Neoplasms/pathology , Male , Middle Aged , Small Cell Lung Carcinoma/mortality , Small Cell Lung Carcinoma/pathology , Survival Rate
16.
Oncotarget ; 8(70): 115667-115680, 2017 Dec 29.
Article in English | MEDLINE | ID: mdl-29383190

ABSTRACT

BACKGROUND: Organic cation transporters (OCT) are responsible for the uptake of a broad spectrum of endogenous and exogenous substrates. Downregulation of OCT is frequently observed in human hepatocellular carcinoma (HCC) and is associated with a poor outcome. The aim of our current study was to elucidate the impact of OCT3 on hepatocarcinogenesis. METHODS: Transcriptional and functional loss of OCT was investigated in primary murine hepatocytes, derived from Oct3-knockout (Oct3-/-; FVB.Slc22a3tm1Dpb ) and wildtype (WT) mice. Liver tumors were induced in Oct3-/- and WT mice with Diethylnitrosamine and Phenobarbital over 10 months and characterized macroscopically and microscopically. Key survival pathways were investigated by Western Blot analysis. RESULTS: Loss of Oct3-/- in primary hepatocytes resulted in significantly reduced OCT activity determined by [3H]MPP+ uptake in vivo. Furthermore, tumor size and quantity were markedly enhanced in Oct3-/- mice (p<0.0001). Oct3-/- tumors showed significant higher proliferation (p<0.0001). Ki-67 and Cyclin D expression were significantly increased in primary Oct3-/- hepatocytes after treatment with the OCT inhibitors quinine or verapamil (p<0.05). Functional inhibition of OCT by quinine resulted in an activation of c-Jun N-terminal kinase (Jnk), especially in Oct3-/- hepatocytes. CONCLUSION: Loss of Oct3 leads to enhanced proliferation and hepatocarcinogenesis in vivo.

17.
J Gastrointestin Liver Dis ; 25(1): 15-24, 2016 Mar.
Article in English | MEDLINE | ID: mdl-27014750

ABSTRACT

BACKGROUND AND AIMS: Smoking has multiple effects on factors influencing hepatitis C and antiviral therapy, including lipid metabolism, fibrosis, platelet count and adherence aspects. The aim of this analysis was to determine the impact of smoking on hepatitis C virus antiviral therapy. METHODS: Data of two cohorts of an observational multicenter study including therapy-naïve patients infected with genotype 1 hepatitis C virus (HCV) treated with dual antiviral therapy (n=7,796) with pegylated interferon alpha 2a in combination with ribavirin, or triple antiviral therapy (n=1,122) containing telaprevir or boceprevir, were analysed. RESULTS: In the univariate matched pair analysis of dual antiviral therapy patients (n=584), smoking was significantly associated with lower sustained viral response rates (p=0.026, OR 0.69 CI: 0.50 - 0.96). The effect of smoking on sustained viral response remained significant (p=0.028, OR 0.67 CI: 0.47 - 0.96) in the multivariate analysis when adjusting for all other baseline parameters with a significant association in the univariate analysis, i.e. diabetes, fibrosis, body mass index, transaminases and baseline viral load. Under protease inhibitors the influence of smoking on virological response did not arise. CONCLUSIONS: Smoking has a negative impact on antiviral therapy in naïve patients infected with HCV genotype 1 independently of age, gender, history of drug use or alcoholic liver disease. The effects of smoking might be overcome by the new antiviral agents.


Subject(s)
Antiviral Agents/therapeutic use , Hepacivirus/drug effects , Hepatitis C/drug therapy , Interferon-alpha/therapeutic use , Oligopeptides/therapeutic use , Polyethylene Glycols/therapeutic use , Proline/analogs & derivatives , Protease Inhibitors/therapeutic use , Smoking/adverse effects , Adolescent , Adult , Aged , Aged, 80 and over , Antiviral Agents/adverse effects , Drug Therapy, Combination , Female , Genotype , Germany , Hepacivirus/enzymology , Hepacivirus/genetics , Hepatitis C/diagnosis , Hepatitis C/virology , Humans , Interferon-alpha/adverse effects , Logistic Models , Male , Middle Aged , Multivariate Analysis , Odds Ratio , Oligopeptides/adverse effects , Polyethylene Glycols/adverse effects , Proline/adverse effects , Proline/therapeutic use , Protease Inhibitors/adverse effects , Recombinant Proteins/adverse effects , Recombinant Proteins/therapeutic use , Ribavirin/therapeutic use , Risk Factors , Time Factors , Treatment Outcome , Viral Load , Young Adult
18.
BMC Cancer ; 16: 94, 2016 Feb 12.
Article in English | MEDLINE | ID: mdl-26872727

ABSTRACT

BACKGROUND: The polyspecific organ cation transporter 1 (OCT1) is one of the most important active influx pumps for drugs like the kinase inhibitor sorafenib. The aim of this retrospective study was the definition of the role of intratumoral OCT1 mRNA expression in hepatocellular carcinoma (HCC) as a biomarker in systemic treatment with sorafenib. METHODS: OCT1 mRNA expression levels were determined in biopsies from 60 primary human HCC by real time PCR. The data was retrospectively correlated with clinical parameters. RESULTS: Intratumoral OCT1 mRNA expression is a significant positive prognostic factor for patients treated with sorafenib according to Cox regression analysis (HR 0.653, 95%-CI 0.430-0.992; p = 0.046). Under treatment with sorafenib, a survival benefit could be shown using the lower quartile of intratumoral OCT1 expression as a cut-off. Macrovascular invasion (MVI) was slightly more frequent in patients with low OCT1 mRNA expression (p = 0.037). Treatment-induced AFP response was not associated with intratumoral OCT1 mRNA expression levels (p = 0.633). CONCLUSIONS: This study indicates a promising role for intratumoral OCT1 mRNA expression as a prognostic biomarker in therapeutic algorithms in HCC. Further prospective studies are warranted on this topic.


Subject(s)
Biomarkers, Tumor/biosynthesis , Carcinoma, Hepatocellular/genetics , Liver Neoplasms/drug therapy , Organic Cation Transporter 1/biosynthesis , Aged , Biomarkers, Tumor/genetics , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/pathology , Cation Transport Proteins/biosynthesis , Cation Transport Proteins/genetics , Female , Gene Expression Regulation, Neoplastic/drug effects , Humans , Kaplan-Meier Estimate , Liver Neoplasms/genetics , Liver Neoplasms/pathology , Male , Middle Aged , Niacinamide/administration & dosage , Niacinamide/analogs & derivatives , Organic Cation Transporter 1/genetics , Phenylurea Compounds/administration & dosage , RNA, Messenger/biosynthesis , Sorafenib
19.
Adv Mater ; 28(15): 2971-7, 2016 Apr 20.
Article in English | MEDLINE | ID: mdl-26890153

ABSTRACT

Organic diodes consisting of molecular nano-pyramid structures sandwiched between metal and strained nano-membrane electrodes are created. The robust and smooth contacts provided by self-curled metal layers render the molecular nano-pyramids efficent channels for detecting nitrogen dioxide airflow.

20.
Nano Lett ; 14(5): 2387-93, 2014 May 14.
Article in English | MEDLINE | ID: mdl-24738656

ABSTRACT

The decrease of thermal conductivity is crucial for the development of efficient thermal energy converters. Systems composed of a periodic set of very thin layers show among the smallest thermal conductivities reported to-date. Here, we fabricate in an unconventional but straightforward way hybrid superlattices consisting of a large number of nanomembranes mechanically stacked on top of each other. The superlattices can consist of an arbitrary composition of n- or p-type doped single-crystalline semiconductors and a polycrystalline metal layer. These hybrid multilayered systems are fabricated by taking advantage of the self-rolling technique. First, differentially strained nanomembranes are rolled into three-dimensional microtubes with multiple windings. By applying vertical pressure, the tubes are then compressed and converted into a planar hybrid superlattice. The thermal measurements show a substantial reduction of the cross-sectional heat transport through the nanomembrane superlattice compared to a single nanomembrane layer. Time-domain thermoreflectance measurements yield thermal conductivity values below 2 W m(-1) K(-1). Compared to bulk values, this represents a reduction of 2 orders of magnitude by the incorporation of the mechanically joined interfaces. The scanning thermal atomic force microscopy measurements support the observation of reduced thermal transport on top of the superlattices. In addition, small defects with a spatial resolution of ∼100 nm can be resolved in the thermal maps. The low thermal conductivity reveals the potential of this approach to fabricate miniaturized on-chip solutions for energy harvesters in, e.g., microautonomous systems.

SELECTION OF CITATIONS
SEARCH DETAIL
...