Point-of-use, automated fabrication of a 3D human liver model supplemented with human adipose microvessels.

Advanced in vitro tissue models better reflect healthy and disease tissue conditions in the body. However, complex tissue models are often manufactured using custom solutions and can be challenging to manufacture to scale. Here, we describe the automated fabrication of a cell-dense, thick (≤ 1 cm), human vascularized liver tissue model using a robotic biomanufacturing platform and off-the-shelf components to build, culture, and sample liver tissues hands-free without compromising tissue health or function.

Frequency of actionable molecular drivers in lung cancer patients with precocious brain metastases.

Brain metastases frequently occur during the course of disease in patients suffering from lung cancer. Occasionally, neurological symptoms caused by brain metastases (BM) might represent the first sign of systemic tumor disease (so called precocious metastases), leading to the detection of the primary lung tumor. The biological basis of precocious BM is largely unknown, and treatment options are not well established for this subgroup of patients.

Association between orthopedic and dental findings: what level of evidence is available?

Objective: The aim of this systematic review was to provide comprehensive access to and an analysis of the specialist literature published through December 2005 describing a correlation between orthopedic (leg-length inequality, pelvis obliquity, column diseases and head posture) and dental findings (occlusion, mandibular position, temporomandibular joints, masticatory muscles).

Method: Four medical and dental internet sources (PubMed; Medpilot.de; databases of the Deutsche Arzte-Verlag and Quintessenz-Verlag) were screened for relevant articles using carefully selected retrieval strategies and keywords.

Gelation of a highly fluorescent urea-functionalized perylene bisimide dye.

[structure: see text] A urea-containing tetraphenoxy-substituted perylene bisimide has been synthesized, and its gelation ability has been studied. This functional dye forms fluorescent organogels in toluene and tetrachloromethane through self-assembly by hydrogen-bonding and pi-pi-stacking interactions. AFM and confocal laser scanning microscopy reveal the formation of fiberlike aggregates.

Serum markers of matrix turnover as predictors for the evolution of colorectal cancer metastasis under chemotherapy.

Connective tissue turnover plays a prominent role in tumour growth and metastasis. We followed serum levels of seven connective tissue parameters in 37 patients with colorectal cancer metastatic to the liver prior to and during chemotherapy. Serum samples with episodes of tumour control (n=112) showed an increase of matrix metalloproteinase-2 (MMP-2) (P View Article and Find Full Text PDF

Neoadjuvant treatment with weekly high-dose 5-Fluorouracil as 24-hour infusion, folinic acid and oxaliplatin in patients with primary resectable liver metastases of colorectal cancer.

Purpose: To evaluate the efficacy and safety of neoadjuvant treatment comprising weekly high-dose 5-fluorouracil (5-FU) as a 24-hour infusion, folinic acid (FA) and biweekly oxaliplatin (L-OHP), followed by metastatic resection in patients with primarily resectable liver metastases of colorectal cancer (CRC).

Patients And Methods: 20 patients with primarily resectable liver metastases of CRC were enrolled in a prospective phase II study. On an outpatient basis, the patients received a treatment regimen comprising biweekly 85 mg/m(2) L-OHP in the form of a 2-hour intravenous infusion and 500 mg/m(2) FA as a 1- to 2-hour intravenous infusion, followed by 2,600 mg/m(2 ) 5-FU administered as a 24-hour intravenous infusion once weekly.

Disturbance of tumor necrosis factor alpha-mediated beta interferon signaling in cervical carcinoma cells.

In the present study we show that malignant human papillomavirus (HPV)-positive cells lost their ability to synthesize endogenous beta interferon (IFN-beta) upon tumor necrosis factor alpha (TNF-alpha) treatment. IFN-beta transcription, however, was reinducible in nonmalignant HPV-positive cells, which was confirmed in functional protection assays against encephalomyocarditis virus or vesicular stomatitis virus infections. Addition of neutralizing antibodies against IFN-beta blocked the antiviral effect, excluding the possibility that other IFN types were involved.

Multicenter field trial on possible health effects of toluene. III. Evaluation of effects after long-term exposure.

In rotogravure industry, contributing considerably to mass color printing of catalogues and magazines, toluene is still extensively used as paint solvent, and many printers have been exposed to this chemical for several decades. Information on adverse health effects associated with long-term toluene exposure is still controversial. In a multi-center study, adverse health effects possibly associated with long-term toluene exposure were evaluated.

Multicenter field trial on possible health effects of toluene. II. Cross-sectional evaluation of acute low-level exposure.

Data on possible acute effects of today's relevant low-level exposure to toluene are contradictory, and information on possible effects of exposure under occupational conditions is largely lacking. In a controlled, multi-center, blinded field trial, effects possibly associated with acute toluene exposure were evaluated in workers of 12 German rotogravure factories. Medical examinations (inquiries on subjective symptoms, and standard tests of psycho-physiological and psycho-motor functions) were performed on almost 1500 volunteers, of whom 1290 were toluene-exposed (1178 men and 112 women), and about 200 participants served as references (157 men and 37 women), but the main aim of the trial was to reveal dose-response relationships.

Multicenter field trial on possible health effects of toluene. I. Toluene body burdens in workers of the rotogravure industry.

Ambient air toluene concentrations as well as corresponding individual blood toluene levels were measured under conditions of a field trial, as basis for a correlation with possible acute effects. While the results of various psycho-physiological and medical evaluations after acute (Neubert et al., 2001) and long-term toluene exposure (Gericke et al.

[Prevention and therapy of diabetic foot syndrome. Preventing complications].

Selective prevention and stage-orientated treatment of the diabetic foot syndrome helps to avoid late complications. A prerequisite is good blood sugar control, early use of ACE inhibitors, CSE inhibitors and--based on the vascular situation, with consideration given to indications--platelet aggregation inhibitors. Regular inspection of the feet must be taken seriously.

Dy-EOB-DTPA: tolerance and pharmacokinetics in healthy volunteers and preliminary liver imaging in patients.

Rationale And Objectives: To investigate the tolerance and pharmacokinetics of the new liver-specific x-ray contrast agent Dy-EOB-DTPA [(4S)-4-(4-ethoxybenzyl)-3,6,9-tris(carboxylatomethyl)-3,6,9-triazaundecanedioic acid, dysprosium (Dy) complex, disodium salt] in healthy volunteers and to obtain preliminary imaging data by abdominal spiral computed tomography (CT) in tumor patients with liver metastases.

Methods: A total of 40 healthy male volunteers received 10-minute intravenous infusions of 0.05, 0.

CEA and CA 19-9 measurement as a monitoring parameter in metastatic colorectal cancer (CRC) under palliative first-line chemotherapy with weekly 24-hour infusion of high-dose 5-fluorouracil (5-FU) and folinic acid (FA).

Background: There have been contradictory reports on the benefit of CEA and CA 19-9 measurements in patients with metastatic colorectal cancer using palliative chemotherapy. The object of this study was to examine the diagnostic accuracy of monitoring of palliative chemotherapy by means of CEA and CA 19-9.

Patients And Methods: The tumour markers CEA and CA 19-9 were subjected to serial measurement in patients with metastatic colorectal cancer (n = 90) using palliative first-line chemotherapy with weekly 24-hour infusion of high-dose 5-FU with FA and were compared with objective response according to WHO criteria.

Hypoglycemic sensorimotor polyneuropathy associated with insulinoma.

Hypoglycemia-induced peripheral neuropathy due to insulinoma is unusual and, as far as we know, has previously been reported in only 34 patients. In this case report, we describe the clinical features, electrophysiological features, and pathological findings in a 37-year-old patient with polyneuropathy from repeated hypoglycemic episodes over a 9-year period that related to an insulinoma. The literature is discussed.

In the search for specific inhibitors of human 11beta-hydroxysteroid-dehydrogenases (11beta-HSDs): chenodeoxycholic acid selectively inhibits 11beta-HSD-I.

Objective: Selective inhibitors of 11beta-hydroxysteroid-dehydrogenase type I may be of therapeutical interest for two reasons: i) 9alpha-Fluorinated 11-dehydrosteroids like 11-dehydro-dexamethasone (DH-D) are rapidly activated by human kidney 11beta-hydroxysteroid-dehydrogenase type II (11beta-HSD-II) to dexamethasone (D). If the same reaction by hepatic 11beta-HSD-I could be selectively inhibited, DH-D could be used for selective renal immunosuppressive therapy. ii) Reduction of cortisone to cortisol in the liver may increase insulin resistance in type 2 diabetes mellitus, and inhibition of the enzyme may lead to a decrease in gluconeogenesis.

Metabolism of synthetic corticosteroids by 11 beta-hydroxysteroid-dehydrogenases in man.

The presence of an 11 beta-hydroxyl group is essential for the anti-inflammatory and immunosuppressive effects of glucocorticoids. Interconversion of the 11 beta-hydroxyl into the corresponding 11 beta-keto group and vice versa by 11 beta-hydroxysteroid-dehydrogenase (11 beta-HSD) may thus play a pivotal role in the efficacy of these steroids. Therefore, we have compared the metabolism of the endogenous glucocorticoid cortisol (F) with that of synthetic 9 alpha-fluorinated steroids by 11 beta-HSDs in humans in vivo and in vitro.

Metabolism of dexamethasone in the human kidney: nicotinamide adenine dinucleotide-dependent 11beta-reduction.

Recently, two distinct isoenzymes of 11beta-hydroxysteroid-dehydrogenase (11beta-HSD) have been cloned and characterized in several species: The isoenzyme 11beta-HSD-I is widely distributed, bidirectional, prefers NADP(H) and has a low substrate affinity. The isoenzyme 11beta-HSD-II seems to exclusively oxidize physiological glucocorticoids, uses NAD as cosubstrate, has high substrate affinity, and is only found in mineralocorticoid target tissues and the placenta. Synthetic steroids fluorinated in position 9, however, are rapidly reduced by human kidney cortex slices.

Relationship between TGF alpha-induced DNA synthesis and prostaglandin synthesis in human HaCaT keratinocytes.

The relationship between transforming growth factor alpha (TGF alpha)-induced cell proliferation and prostaglandin synthesis was investigated using growth-arrested human keratinocytes of the HaCaT line. Depending on the TGF alpha concentration, the stimulation of DNA synthesis (5-fold) was found to be either insensitive (at < 10 ng/ml TGF alpha) or sensitive (at > or = 20 ng/ml TGF alpha) to inhibition by both indomethacin, an inhibitor of prostaglandin synthases (PGHS) 1 and 2 and the PGHS 2-specific inhibitor NS-398. Indomethacin-effected inhibition did not correlate with cytotoxicity and was restricted to a narrow time window after growth factor administration.

The metabolism of 9 alpha-fluorinated steroids in the human kidney.

Unlabelled: We compared the renal metabolism of 9 alpha-fluorinated steroids with that of the unfluorinated, endogenous steroid cortisol (F). By defining kinetic variables, we characterized isoenzyme activities of 11 beta-hydroxysteroid-dehydrogenase (11 beta-HSD).

Methods: I) In human kidney slices, we studied the conversion of 9 alpha-fluoro-cortisol (FF) and F to their oxo-products (and vice versa).

Stimulatory effect of thapsigargin, a non-TPA-type tumor promoter, on arachidonic acid metabolism in the murine keratinocyte line HEL30 and on epidermal cell proliferation in vivo as compared to the effects of phorbol ester TPA.

The effect of thapsigargin (Tg), a non-12-O-tetradecanoylphorbol-13-acetate (TPA) type skin tumor promoter, on arachidonic acid and prostaglandin E2 (PGE2) formation in HEL30 keratinocytes and on epidermal DNA synthesis in vitro and in vivo (mouse skin) was investigated and compared with that of the phorbol ester TPA. On a molar basis Tg was 30-fold more potent in inducing the arachidonic acid/PGE2 release than TPA. Applied together, the two agents showed a strong synergistic action.