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51.
Hansen Mads Kingo Guldberg Kjærgaard Kristoffer Eriksen Lotte Lindgreen Grønkjær Lea Ladegaard Mikkelsen Anne Catrine Daugaard Sandahl Thomas Damgaard Vilstrup Hendrik Thomsen Karen Louise Lauridsen Mette Munk Enok 《Metabolic brain disease》2022,37(3):589-605
Metabolic Brain Disease - Hepatic encephalopathy (HE) is cerebral dysfunction caused by liver failure and inflicts 30-40% of patients with liver cirrhosis during their disease course. Clinically... 相似文献
52.
Annapurna Pamreddy Sooraj Baijnath Tricia Naicker Sphamandla Ntshangase Sipho Mdanda Hlengekile Lubanyana Hendrik G. Kruger Thavendran Govender 《RSC advances》2018,8(22):11902
Bedaquiline (BDQ) is the first-in-class United States Food and Drug Administration (US FDA) approved anti-tuberculosis (anti-TB) drug, which is a novel diarylquinoline antibiotic that has recently been utilized as an effective adjunct to existing therapies for multidrug-resistant tuberculosis (MDR-TB). BDQ is especially promising due to its novel mechanism of action, activity against drug-sensitive and drug-resistant tuberculosis (TB) in addition to having the potential to shorten treatment duration. Drug delivery to the central nervous system (CNS) is a major concern in TB chemotherapy, especially with the increasing cases of CNS-TB. In this study, we investigated the CNS penetration of BDQ in healthy rodent brain. Male Sprague-Dawley rats (n = 27; 100 ± 20 g) received a single 25 mg kg−1 b.w dose of BDQ via intraperitoneal (i.p.) administration, over a 24 h period. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to determine whole tissue drug concentrations and matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) was utilized to evaluate drug distribution in the brain. BDQ reached peak concentrations (Cmax) of 134.97 ng mL−1 in the brain at a Tmax of 4 h, which is within the range required for therapeutic efficacy. BDQ was widely distributed in the brain, with a particularly high intensity in the corpus callosum and associated subcortical white matter including the striatal, globus pallidus, corticofugal pathways, ventricular system, basal forebrain region and hippocampal regions. Using MALDI MSI, this study demonstrates that due to BDQ''s distribution in the brain, it has the potential to target TB reservoirs within this organ.Bedaquiline (BDQ) was administered to healthy Sprague-Dawley rats in order to determine its localisation in the brain using mass spectrometry imaging (MSI). This study shows that BDQ has the potential for targeting TB reservoirs in the CNS. 相似文献
53.
Mark M. P. van den Dorpel Ilkka Heinonen Sanne M. Snelder Hendrik J. Vos Oana Sorop Ron T. van Domburg Daphne Merkus Dirk J. Duncker Bas M. van Dalen 《The international journal of cardiovascular imaging》2018,34(5):743-749
Left ventricular (LV) diastolic dysfunction is one of the important mechanisms responsible for symptoms in patients with heart failure. The aim of the current study was to identify parameters that may be used to detect early signs of LV diastolic dysfunction in diabetic pigs on a high fat diet, using conventional and speckle tracking echocardiography. The study population consisted of 16 healthy Göttingen minipigs and 18 minipigs with experimentally induced metabolic dysfunction. Echocardiography measurements were performed at baseline and 3-month follow-up. The ratio of peak early (E) and late filling velocity (E/A ratio) and the ratio of E and the velocity of the mitral annulus early diastolic wave (E/Em ratio) did not change significantly in both groups. Peak untwisting velocity decreased in the metabolic dysfunction group (? 30.1?±?18.5 vs. ? 23.4?±?15.5 °/ms) but not in controls (? 38.1?±?23.6 vs. ? 42.2?±?23.0 °/ms), being significantly different between the groups at the 3-month time point (p?<?0.05). In conclusion, whereas E/A ratio and E/Em ratio did not change significantly after 3 months of metabolic dysfunction, peak untwisting velocity was significantly decreased. Hence, peak untwisting velocity may serve as an important marker to detect early changes of LV diastolic dysfunction. 相似文献
54.
55.
Steen Nepper-Christensen Vibeke Backer Lawrence M DuBuske Hendrik Nolte 《Allergy and asthma proceedings》2003,24(4):253-258
For the diagnosis of allergy, presence of allergen-specific immunoglobulin E (IgE) usually is established either by allergen skin tests or by in vitro allergen-specific IgE measurements. However, in vitro assays of specific IgE often are modified as manufacturers improve allergens or change reagents to optimize test performance, affecting the diagnostic performance of in vitro allergen-specific IgE assays. This investigation compares the diagnostic outcomes of the Hitachi Chemical Diagnostics chemiluminescent assay (CLA) and Pharmacia, capsulated hydrophilic carrier polymer (CAP) in vitro allergen-specific IgE test methods in patients with inhalant allergy to a panel of selected allergens. Sera were obtained from 60 consecutive patients who had a clinical history suggesting inhalant allergy and were evaluated by allergen skin-prick test (SPT). Only patients with clinical findings of allergic asthma or rhinoconjunctivitis were included. Sera from patients with at least one positive SPT, which clinically correlated with the case history, were used for specific IgE measurements. Sensitivity and specificity were defined as conditional probabilities describing performances of the CAP system and the CLA system in reference to a standard composed of a combination of allergen-specific symptoms and a positive SPT. A test concordance of 79% was found between the CLA and CAP test results with a correlation coefficient of 0.8. Allergen-specific IgE assay sensitivity of the CLA and CAP systems was similar and allergen dependent, ranging from 67 to 100%. Assay specificity ranged from 39 to 86% for the CLA system and from 36 to 81% for the CAP system. When comparing the specific IgE results with allergen SPTs, 75% (+/- 3%) of CLApositive patients had a positive SPT, and 92% (+/- 4%) of CAPpositive patients had a positive SPT. Eighty-four percent (+/- 4%) of CLAnegative patients had a negative SPT, whereas 69% (+/- 5%) of CAPnegative patients had a negative SPT. The overall concordance between skin tests and in vitro tests was 76% for CLA and 67% for CAP. CLA and CAP score values showed good correlation and both tests may be useful when skin tests cannot be performed to identify subjects with IgE-mediated allergy. The CLA and CAP assays for allergen-specific IgE may be useful as part of an initial allergy evaluation because of the high negative predictive value of negative test results. For the majority of allergens the sensitivity was high. However, the specificity of both in vitro tests was low, indicating that positive in vitro test results should be evaluated carefully in conjunction with clinical symptoms and allergen-specific skin tests to determine the clinical relevance of the allergen sensitization. 相似文献
56.
Naujokat C Sezer O Zinke H Leclere A Hauptmann S Possinger K 《European journal of haematology》2000,65(4):221-236
The 26S proteasome is a non-lysosomal multicatalytic protease complex for degrading intracellular proteins by ATP/ubiquitin-dependent proteolysis. Tightly ordered proteasomal degradation of proteins critical for cell cycle control implies a role of the proteasome in maintaining cell proliferation and cell survival. In this study, we demonstrate that cell-permeable proteasome inhibitors, lactacystin, benzyloxycarbonyl(Z)-leucyl-leucyl-leucinal (ZLLLal; MG-132) and 4-hydroxy-5-iodo-3-nitrophenylacetyl-leucyl-leucyl-leucine vinyl sulfone (NLVS), induce apoptosis abundantly in p53-defective leukemic cell lines CCRF-CEM, U937 and K562 as well as in myelogenic and lymphatic leukemic cells obtained from adult individuals with relapsed acute leukemias. Leukemic cell apoptosis induced by the proteasome inhibitors was dependent on activation of caspase-3 and related caspase family proteases, because caspase-3 inhibitor N-acetyl-L-aspartyl-L-glutamyl-L-valyl-L-aspartal (Ac-DEVD-cho) and, more effectively, the general caspase-inhibitor N-benzyloxycarbonyl-L-valyl-L-alanyl-L-aspartate fluoromethylketone (Z-VAD-fmk) were capable of blocking apoptosis induced by lactacystin, ZLLLal or NLVS. Induction of apoptosis by lactacystin or ZLLLal was accompanied by cell cycle arrest at G2/M phase and by accumulation and stabilization of cyclin-dependent kinase inhibitor p21WAF1/Cip and tumor suppressor protein p53. A role of p53 in mediating apoptosis or induction of p21WAF1/Cip1 was ruled out since CCRF-CEM and U937 cells express non-functional mutant p53, and K562 cells lack expression of p53. Viability and hematopoietic outgrowth of human CD34+ progenitor cells treated with lactacystin were slightly reduced, whereas treatment of CD34 + cells with ZLLLal or the cytostatic drugs doxorubicin and gemcitabine resulted in markedly reduced viability and hematopoietic outgrowth. These results demonstrate a basic role of the proteasome in maintaining survival of human leukemic cells, and may define cell-permeable proteasome inhibitors as potently anti-leukemic agents which exhibit a moderate hematopoietic toxicity in vitro. 相似文献
57.
Expression profile of the telomeric complex discriminates between benign and malignant pheochromocytoma 总被引:2,自引:0,他引:2
Boltze C Mundschenk J Unger N Schneider-Stock R Peters B Mawrin C Hoang-Vu C Roessner A Lehnert H 《The Journal of clinical endocrinology and metabolism》2003,88(9):4280-4286
Telomerase, a ribonucleoprotein complex that includes the telomerase RNA component, the telomerase-associated protein (TP1), the telomerase catalytic subunit (hTERT), and the heat shock protein 90 (HSP90), is closely related to the malignant potential of human tumors. In pheochromocytomas (PC) it is very difficult to predict malignant potential by conventional histology or immunohistochemical and molecular markers. To test whether the expression of telomerase subunits is reflected in the malignant transition of PCs, we determined their mRNA and/or protein expression in 28 benign and nine malignant PCs and compared the results with telomerase activity. RT-PCR analysis revealed that TP1 was ubiquitously expressed. The telomerase RNA component was found in all malignant (100%) and in 13 of 28 (46%) benign PCs. In contrast, hTERT was clearly associated with aggressive biological behavior. All of the malignant (100%), but only two of 28 benign (7%) PCs expressed hTERT. HSP90 was increased in malignant PCs, but was also expressed at a lower level in benign tumors. High telomerase activity was measurable in hTERT-positive tissues only. Our data indicate that hTERT, HSP90, and telomerase activity are up-regulated in malignant cells of the adrenal medulla. The common expression of hTERT and telomerase activity thus represents an additional prognostic marker that may identify more aggressive tumors. 相似文献
58.
Heiko?AselmannEmail authorView authors OrcID profile Jan-Niclas?Kersebaum Alexander?Bernsmeier Jan?Henrik?Beckmann Thorben?M?ller Jan?Hendrik?Egberts Clemens?Schafmayer Christoph?R?cken Thomas?Becker 《International journal of colorectal disease》2018,33(11):1575-1581
Aim
Robotic surgery allows for a better visualization and more precise dissection especially in the narrow male pelvis and mid and lower third of the rectum. However, superiority to laparoscopic TME has yet to be proven. We therefore analyzed short-term outcomes of laparoscopic and robotic low anterior rectal resection for rectal cancer.Patients and methods
From 2011 to 2016, 44 robotic (RTME) and 41 laparoscopic (LTME) low anterior rectal resection with total mesorectal excision were performed at a single institution. Specimen quality was assessed and reported by an independent pathologist following international guidelines.Results
The groups did not differ significantly regarding gender, age, ASA stage, BMI, and distance of the lower tumor margin from the anal verge. More patients in the RTME group underwent preoperative chemoradiation (43.2 vs. 19.5%, p?=?0.019). The quality of the TME specimen was significantly better in the RTME group (complete/nearly complete/incomplete for RTME 97/0/3% and for LTME 78/17/5%, p?=?0.03). The conversion rate tended to be lower in the RTME group (7 vs. 17%, p?=?0.143). There was no difference in CRM positivity between the groups.Conclusion
Robotic surgery is safe and can improve the quality of TME for rectal cancer compared to laparoscopy. Any effect on long-term survival remains to be established.59.
Windisch W Hennings E Storre JH Matthys H Sorichter S 《Respiration; international review of thoracic diseases》2004,71(2):195-198
Untreated idiopathic congenital central hypoventilation syndrome (CCHS) is thought to cause infant death within 1-2 months. Here we present an adult patient with CCHS who survived without continuous ventilatory support, despite hypoventilation from early childhood onward. The diagnosis was confirmed at the age of 22 years, when the patient presented with hypoventilation during the night (PaCO2 60 mm Hg, PaO2 56 mm Hg, pH 7.32 HCO3- 30 mmol/l) but hyperventilation when awake (PaCO2 26 mm Hg, PaO2 81 mm Hg, pH 7.56, HCO3- 23 mmol/l). The maximal hematocrit was 77%. Despite mental retardation, noninvasive positive pressure ventilation (NPPV) could be successfully established. NPPV-supported ventilation during the night (PaCO2 36, PaO2 84 mm Hg, pH 7.47, HCO3- 25 mmol/l) reduced hematocrit values (40.6 to 36.8%) over a period of 4 years. In conclusion, long-term survival with CCHS is possible without continuous ventilatory support. Spontaneous improvement of hypoventilation during sleep throughout childhood is possible and hyperventilation during wakefulness may occur in patients with CCHS. CCHS can be managed with NPPV despite mental retardation, even over a long-term period. 相似文献
60.