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Biomedical subjects

A Hoffmann

Publications and source records attributed to A Hoffmann.

At least 37 records · Page 2Linked to original sources

Light-induced decrease in DCF fluorescence of wheat leaves in the presence of salicyl hydroxamate.

5-(and-6)-Carboxy-2',7'-dichlorodihydrofluorescein diacetate (DCF-DA), a permeative indicator of oxidative stress, was loaded into dissected leaves of wheat in order to monitor the temporal development of reactive oxygen species. DCF fluorescence was found to be constant under dark conditions. Upon loading the leaves with salicyl hydroxamate, a blocker of the alternative oxidase, DCF fluorescence linearly increased in the dark. This indicates a function of alternative oxidase in preventing reactive oxygen radicals in the mitochondria. Upon illumination, the DCF signal decreased within 5 min. As illuminated chloroplasts would increase the load of reactive oxygen species, the observed decrease cannot be assigned to the production of reactive oxygen species in the chloroplasts. Three different putative mechanisms are considered which all assign an important role to light-induced delivery of NAD(P)H: (1) direct quenching of DCF fluorescence by light-generated NAD(P)H, (2) light-stimulated activation of scavenging enzymes, or (3) redirection of mitochondrial electron fluxes as caused by the delivery of excess redox equivalents (NADH) from the chloroplasts.

Chloroplasts↗

Thioflavins released from nanoparticles target fibrillar amyloid beta in the hippocampus of APP/PS1 transgenic mice.

For the delivery of drugs into the brain, the use of nanoparticles as carriers has been described as a promising approach. Here, we prepared nanoparticles as carriers for the model drugs thioflavin T and thioflavin S that bind fibrillar amyloid beta peptides (Abeta). These polymer colloids are composed of a polystyrene core and a degradable PBCA [poly(butyl-2-cyanoacrylate)] shell with a diameter of 90-100nm as shown by dynamic light scattering. Fluorescence spectrophotometric analysis revealed that encapsulated thioflavin T exhibited significantly stronger fluorescence than the free fluorophore. The enzymatic degradation of core-shell nanoparticles, as required in vivo, was shown after their treatment with porcine liver esterase, a non-specific esterase, in vitro. Shells of nanoparticles were dose-dependently degraded while their polystyrene cores remained intact. In the cortices of 7-14 months old APP/PS1 mice with age-dependent beta-amyloidosis, thioflavins selectively targeted fibrillar Abeta after biodegradation-induced release from their nanoparticulate carriers upon intracerebral injection. Collectively, our data suggest that core-shell nanoparticles with controlled degradation in vivo can become versatile tools to trace and clear Abeta in the brain.

Alzheimer Disease↗

Functional and ultrastructural neuroanatomy of interactive intratectal/tectonigral mesencephalic opioid inhibitory links and nigrotectal GABAergic pathways: involvement of GABAA and mu1-opioid receptors in the modulation of panic-like reactions elicited by electrical stimulation of the dorsal midbrain.

In the present study, the functional neuroanatomy of nigrotectal-tectonigral pathways as well as the effects of central administration of opioid antagonists on aversive stimuli-induced responses elicited by electrical stimulation of the midbrain tectum were determined. Central microinjections of naloxonazine, a selective mu(1)-opiod receptor antagonist, in the mesencephalic tectum (MT) caused a significant increase in the escape thresholds elicited by local electrical stimulation. Furthermore, either naltrexone or naloxonazine microinjected in the substantia nigra, pars reticulata (SNpr), caused a significant increase in the defensive thresholds elicited by electrical stimulation of the continuum comprised by dorsolateral aspects of the periaqueductal gray matter (dlPAG) and deep layers of the superior colliculus (dlSC), as compared with controls. These findings suggest an opioid modulation of GABAergic inhibitory inputs controlling the defensive behavior elicited by MT stimulation, in cranial aspects. In fact, iontophoretic microinjections of the neurotracer biodextran into the SNpr, a mesencephalic structure rich in GABA-containing neurons, show outputs to neural substrate of the dlSC/dlPAG involved with the generation and organization of fear- and panic-like reactions. Neurochemical lesion of the nigrotectal pathways increased the sensitivity of the MT to electrical (at alertness, freezing and escape thresholds) and chemical (blockade of GABA(A) receptors) stimulation, suggesting a tonic modulatory effect of the nigrotectal GABAergic outputs on the neural networks of the MT involved with the organization of the defensive behavior and panic-like reactions. Labeled neurons of the midbrain tectum send inputs with varicosities to ipsi and contralateral dlSC/dlPAG and ipsilateral substantia nigra, pars reticulata and compacta, in which the anterograde and retrograde tracing from a single injection indicates that the substantia nigra has reciprocal connections with the dlSC/dlPAG featuring close axo-somatic and axo-dendritic appositions in both locations. In addition, ultrastructural approaches show inhibitory axo-axonic synapses in MT and inhibitory axo-somatic/axo-axonic synapses in the SNpr. These findings, in addition to the psychopharmacological evidence for the interaction between opioid and GABAergic mechanisms in the cranial aspects of the MT as well as in the mesencephalic tegmentum, offer a neuroanatomical basis of a pre-synaptic opioid inhibition of GABAergic nigrotectal neurons modulating fear in defensive behavior-related structures of the cranial mesencephalon, in a short link, and through a major neural circuit, also in GABA-containing perikarya and axons of nigrotectal neurons.

Animals↗

Magnetization reversal in submicron disks: exchange biased vortices.

Submicron, circular, ferromagnetic-antiferromagnetic dots exhibit different magnetization reversal mechanisms depending on the direction of the magnetic applied field. Shifted, constricted hysteresis loops, typical for vortex formation, are observed for fields along the exchange bias direction. However, for fields applied close to perpendicular to the exchange bias direction, magnetization reversal occurs via coherent rotation. Magnetic force microscopy imaging together with micromagnetic simulations are used to further clarify the different magnetic switching behaviors.

Journal Article↗

Giant magnetoresistance in ferromagnet/superconductor superlattices.

We show magnetoresistance in excess of 1000% in trilayers containing highly spin-polarized La0.7Ca0.3MnO3 and high-Tc superconducting YBa2Cu3O7. This large magnetoresistance is reminiscent of the giant magnetoresistance (GMR) in metallic superlattices but with much larger values, and originates at spin imbalance due to the injection of spin-polarized carriers. Furthermore, in contrast to ordinary GMR, the magnetoresistance is intimately related to the superconductivity in the YBa2Cu3O7 layer and vanishes in the normal state. This result, aside from its fundamental importance, may be of interest for the design of novel spintronic devices based on ferromagnet/superconductor structures.

Journal Article↗

[Improved osseointegration of titanium implants after surface coating with polymers in a rabbit model].

In this study we present the first results of the investigation of polymer-coated titanium implants implanted in the proximal tibia and distal femora of New Zealand white rabbits. The results of DEXA scans, micro-CT, and histological analysis showed an increase of osseointegration. We suggest that controlled release kinetics after coupling of these polymers with BMP-2 can additionally increase osseointegration.

Animals↗

Traceability in fluorometry: Part II. Spectral fluorescence standards.

The need for the traceable characterization of fluorescence instruments is emphasized from a chemist's point of view, focusing on spectral fluorescence standards for the determination of the wavelength- and polarization-dependent relative spectral responsivity and relative spectral irradiance of fluorescence measuring systems, respectively. In a first step, major sources of error of fluorescence measurements and instrument calibration are revealed to underline the importance of this issue and to illustrate advantages and disadvantages of physical and chemical transfer standards for generation of spectral correction curves. Secondly, examples for sets of traceable chemical emission and excitation standards are shown that cover a broad spectral region and simple procedures for the determination of corrected emission spectra with acceptable uncertainties are presented. With proper consideration of the respective measurement principle and geometry, these dye-based characterization procedures can be not only applied to spectrofluorometers but also to other types of fluorescence measuring systems and even to Raman spectrometers.

Journal Article↗

Analysis and correction of ballistocardiogram contamination of EEG recordings in MR.

PURPOSE: To examine the influence of cardiac activity-related head movements and varying blood pulse frequencies on the shape of electroencephalography (EEG) recordings in a high magnetic field, and to implement a post-processing technique to eliminate cardiac activity-related artifacts. MATERIAL AND METHODS: Respiratory thoracic movements, changes of blood pulse frequency and passive head movements of 20 healthy subjects were examined outside and inside an MR magnet at rest in a simultaneously recorded 21-channel surface EEG. An electrocardiogram (ECG) was recorded simultaneously. On the basis of the correlation of the left ventricular ejection time (LVET) with the heart-rate, a post-processing heart-rate dependent subtraction of the cardiac activity-related artifacts of the EEG was developed. The quality of the post-processed EEG was tested by detecting alpha-activity in the pre- and post-processed EEGs. RESULTS: Inside the magnet, passive head motion but not respiratory thoracic movements resulted in EEG artifacts that correlated strongly with cardiac activity-related artifacts of the EEG. The blood pulse frequency influenced the appearance of the cardiac activity-related artifacts of the EEG. The removal of the cardiac activity-related artifacts of the EEG by the implemented post-processing algorithm resulted in an EEG of diagnostic quality with detected alpha-activity. CONCLUSION: When recording an EEG in MR environment, heart rate-dependent subtraction of EEG artifacts caused by ballistocardiogram contamination is essential to obtain EEG recordings of diagnostic quality and reliability.

Adult↗

Symmetry driven irreversibilities at ferromagnetic-antiferromagnetic interfaces.

The coupling between a ferromagnet and an antiferromagnet can establish a directional anisotropy called exchange bias. In many systems this exchange bias is reduced upon subsequent field cycling, which is referred to as training effects. Numerical simulations of a simple coherent rotation model suggest that the symmetry of the anisotropy in the antiferromagnet is crucial for the understanding of training effects in exchange bias systems. Namely, the existence of multiple antiferromagnetic easy anisotropy axes can initially stabilize a noncollinear arrangement of the antiferromagnetic spins, which relaxes into a collinear arrangement after the first magnetization reversal of the ferromagnet.

Journal Article↗

[Monteggia injuries in adults: Critical analysis of injury pattern, management, and results].

BACKGROUND: Complications, revision surgery, and unsatisfactory functional results after operative management of Monteggia fractures are frequent. Moreover, hardly any studies exist that deal exclusively with the therapeutic concept for adults. PATIENTS AND METHODS: Between January 1988 and December 2001, 68 patients with Monteggia fractures or equivalent injury were surgically treated. A total of 49 patients could be followed up after 83 months (25-176). Fracture type was assessed according to Bado's classification, functional results according to the Mayo elbow performance score, and the extent of osteoarthritis based on the criteria of Baird and Johnson. RESULTS: The median age of the follow-up patients was 38 years (18-89, 31 men, 18 women). Corresponding to Bado's classification the following injuries were observed: 18 cases of type 1, 22 of type 2, 5 of type 3, and 4 cases of type 4. After surgical intervention, 14 patients achieved "very good", 21 "good", 9 "satisfactory", and 5 "poor" results. Of the 14 patients with either "satisfactory" or "poor" results, 9 manifested a type 2 injury. Complications requiring revision surgery occurred in 14 patients and complications not requiring revision in another 14. Severe osteoarthritic changes in the humeral or radioulnar joint were observed in 4 cases. CONCLUSIONS: Monteggia fractures in adults are fraught with complications despite good functional results in the majority of cases. The patient should be made aware early on of the risk of residual functional deficits and the need for further surgical intervention.

Adolescent↗

A medical nutriment has supportive value in the treatment of colorectal cancer.

MSC (Avemar) is a medical nutriment of which preclinical and observational clinical studies suggested an antimetastatic activity with no toxicity. This open-label cohort trial has compared anticancer treatments plus MSC (9 g once daily) vs anticancer treatments alone in colorectal patients, enrolled from three oncosurgical centres; cohort allocation was on the basis of patients' choice. Sixty-six colorectal cancer patients received MSC supplement for more than 6 months and 104 patients served as controls (anticancer therapies alone): no statistical difference was noted in the time from diagnosis to the last visit between the two groups. End-point analysis revealed that progression-related events were significantly less frequent in the MSC group (new recurrences: 3.0 vs 17.3%, P<0.01; new metastases: 7.6 vs 23.1%, P<0.01; deaths: 12.1 vs 31.7%, P<0.01). Survival analysis showed significant improvements in the MSC group regarding progression-free (P=0.0184) and overall survivals (P=0.0278) probabilities. Survival predictors in Cox's proportional hazards were UICC stage and MSC treatment. Continuous supplementation of anticancer therapies with MSC for more than 6 months is beneficial to patients with colorectal cancer in terms of overall and progression-free survival.

Adult↗

Exchange-induced anisotropies at ferromagnetic-antiferromagnetic interfaces above and below the Néel temperature.

The exchange bias and magnetic anisotropies in a Co layer on a single-crystalline FeF2 film have been determined between 30 and 300 K. By postulating that the coupling between the ferromagnet and the antiferromagnet persists above the Néel temperature (T(N)) we develop a model that quantitatively describes the exchange bias and the anisotropies over the whole temperature range, both above and below T(N). Using only the measured low temperature exchange bias and a distribution of blocking temperatures we explain (i) the temperature dependence of the bias, (ii) the magnitude of the anisotropies, (iii) the opposite sign of the first and second order anisotropies, (iv) the observed 1/T and 1/T(3) temperature dependencies of the first and second order uniaxial anisotropies above T(N), and (v) the decrease of the anisotropies below T(N).

Journal Article↗

Determination of stale-flavor carbonyl compounds in beer by stir bar sorptive extraction with in-situ derivatization and thermal desorption-gas chromatography-mass spectrometry.

A method for the determination of stale-flavor carbonyl compounds including E-2-octenal, E-2-nonenal, E,Z-2,6-nonadienal and E,E-2,4-decadienal in beer was developed using stir bar sorptive extraction (SBSE) with in-situ derivatization followed by thermal desorption-GC-MS analysis. The derivatization conditions with O-(2,3,4,5,6-pentafluorobenzyl)hydroxylamine and the SBSE conditions--sampling mode, salt addition, sample volume, polydimethylsiloxane volume (sample/polydimethylsiloxane phase ratio) and extraction time--were examined. The method showed good linearity over the concentration range from 0.1 to 10 ng ml(-1) for all analytes and the correlation coefficients were higher than 0.9993. The limits of detection ranged from 0.021 to 0.032 ng ml(-1) for all analytes. The recoveries (98-101%) and precision (RSD 2.4-7.3%) of the method were examined by analyzing beer samples fortified at the 0.5-ng ml(-1) level. The method was successfully applied to low-level concentration samples.

Beer↗

Pregnancy in congenital cardiac disease: an increasing challenge for cardiologists and obstetricians -- a prospective multicenter study.

OBJECTIVES: Aim of this study was to assess the occurrence of pregnancy-related complications of mother and child during pregnancy, delivery and puerperium in women with CCD prospectively. STUDY DESIGN, POPULATION: This prospective multicenter study included 122 pregnancies in 106 women with CCD (72 with, 34 without previous cardiac surgery). Patient age was 17-44, median 26 years. Cardiac and non-cardiac complications, mode of delivery, abortion, and CCD of the newborn were assessed. RESULTS: Initially all women were in Functional Class I or II. Worsening during pregnancy occurred in 25.5% (n=27), mainly during the second and third trimester. Significant problems due to bleeding, hypertension, rhythm disturbances, endocarditis, liver congestion, increasing cyanosis or death, occurred in 11.3%. Twelve per cent of deliveries were premature. Five women had therapeutic abortion, nine spontaneous abortions, nine preterm births, and one intrauterine death. Seventy-nine per cent (n=85) delivered spontaneously; 21.3% (n=23) had caesarean section. Of the 111 live born children, 5.4% (n=6) had a CCD. CONCLUSIONS: Most women with CCD and a good functional class before pregnancy tolerate pregnancy without major problems. However, pregnancy may induce serious cardiac and obstetric complications. The specific risks require an individualized multidisciplinary patient-management by experienced physicians.

Adolescent↗

[Sentinel lymph node biopsy in breast cancer patients--results and experience after 500 sentinel lymph node biopsies].

INTRODUCTION: Sentinel lymph node biopsy (SLNB) is a widely used technique for axillary staging in breast cancer patients. The principle to evaluate the axillary status of a breast cancer patient with a less invasive surgery than axillary lymph node dissection (ALND) meets the new minimally invasive concept in breast cancer surgery. Some breast cancer centers proceed to SLNB without ALND in SLN-negative patients. PATIENTS AND METHODS: Between March 1998 and March 2002, 500 SLNBs were performed. After a learning period with SLNB and ALND in 75 patients with a sensitivity of 96.2% and a false-negative rate of 3.8%, SLNB alone without further ALND was performed in a group of patients. In addition, the feasibility of SLNBin patients with locally advanced breast cancer, in patients after neoadjuvant chemotherapy and in patients with multicentricity was evaluated. The combined method with blue dye and technetium-99m-labeled human albumin for identification of SLNs was applied. RESULTS: 500 SLNBs were performed. The identification rate was 86.2%. After exclusion of patients with neoadjuvant chemotherapy and patients with multicentricity, the identification rate was 94.5%. SLNs were positive in 41.3% of patients and negative in 58.7% of patients. DISCUSSION: SLNB is an excellent method for axillary stag-ing and an alternative for ALND in a certain group of breast cancer patients.

Axilla↗

Phase I clinical and pharmacokinetic study of combination chemotherapy with topotecan and ifosfamide in patients with progressive or relapsed solid tumors.

PURPOSE: Topotecan and ifosfamide are effective in the treatment of various solid tumors. Up to the time of this study, the two drugs have been combined just once (Smith et al. 1998). Due to its hematotoxicity, topotecan has been used predominantly within monochemotherapy protocols. However, the combination of topotecan and alkylating agents is supra-additive in many preclinical models. This phase-I trial was primarily performed to evaluate the maximum tolerable dose (MTD) and dose-limiting toxicity (DLT) of a combination chemotherapy with topotecan and ifosfamide using a 5-day schedule. A secondary goal was to estimate the response rate in a group of heavily pretreated patients with advanced solid tumors. METHODS: The pharmacokinetics of topotecan were preliminarily determined in some of the patients. A total of 12 patients (three female/nine male), median age 49 years (range 19-69), 11 with prior chemotherapy, received a total of 24 courses of chemotherapy at three dose-levels of topotecan. Ifosfamide was administered by intravenous infusion over 3 h immediately followed by a 30-min infusion of topotecan. Mesna (3 x 300 mg x m(2) x day) was given routinely during chemotherapy as a uroprotector. G-CSF (filgrastim) was permitted only in cases of febrile neutropenia (FN). RESULTS: The major toxicity was non-hematologic; severe liver and renal toxicity were observed in three out of 11 patients. Two treatment-related deaths occurred. No clinical remissions occurred in 11 evaluable patients. The pharmacokinetics of topotecan were relatively similar in our patients and supported findings in recent literature. The MTD of this combination was defined at dose-level 2 (1.0 mg/m(2) of topotecan and 750 mg/m(2) of ifosfamide). CONCLUSIONS: Further trials should not exceed this dose. The pharmacological causes for the pronounced toxicity have to be clarified.

Adult↗

Effects of short-term treatment with diclofenac-colestyramine on renal function and urinary prostanoid excretion in patients with type-2 diabetes.

OBJECTIVE: To determine the effect of short-term administration of diclofenac-colestyramine on glomerular filtration rate (GFR), renal plasma flow (RPF) and urinary excretion of prostanoids in patients with type-2 diabetes without and with impaired renal function. METHODS: In the randomised, single-blind, placebo-controlled, two-period crossover study, 32 patients with type-2 diabetes (group 1: 16 patients without impaired renal function, creatinine clearance > or =80 ml/min and group 2: 16 patients with impaired renal function, creatinine clearance 30-79 ml/min) received 140 mg diclofenac-colestyramine (corresponding to 75 mg diclofenac sodium) or placebo twice a day on days 1 and 2 and once on day 3 with a wash-out period of 6 days between the two periods. GFR was assessed using both measurement of creatinine clearance and calculation of inulin clearance and RPF was assessed using calculation of para-aminohippurate (PAH) clearance after the short-term administration on day 3. Urinary excretion of prostanoids (PGE(2), PGE-M, 6-keto-PGF(1alpha), 2,3-dinor-6-keto-PGF(1alpha), TxB(2), 2,3-dinor-TxB(2) and 11-dehydro-TxB(2)) were measured before and after drug intake. RESULTS: Comparison with placebo showed no effect of diclofenac-colestyramine on creatinine, inulin or PAH clearance ( P>0.05) in patients with type-2 diabetes either without or with impaired renal function. The differences in creatinine, inulin and PAH clearance between the two groups of patients were not influenced by diclofenac-colestyramine. Urinary excretion of PGE(2), PGE-M, 6-keto-PGF(1alpha), 2,3-dinor-6-keto-PGF(1alpha), TxB(2), 2,3-dinor-TxB(2) ( P=1.89) and 11-dehydro-TxB(2) was significantly reduced by diclofenac-colestyramine. CONCLUSION: These results indicate that proven non-specific cyclooxygenase inhibition by short-term administration of diclofenac-colestyramine did not affect renal haemodynamic function (GFR, RPF) in patients with type-2 diabetes either without or with impaired renal function.

Aged↗

Culture of primary human gingival fibroblasts on biodegradable membranes.

Repair and regeneration of periodontal tissues by tissue engineering is dependent on the use of biodegradable polymer scaffolds which serve as a carrier for cells or bioactive substances. There is a need to understand how a specific biomaterial may influence gene expression. The aim of this investigation was to develop and to optimize an in vitro technique for the adherance and proliferation of primary human gingivaL cells on implantable and biodegradable matrices. Square pieces of Bio-Gide matrix (BG) and slices of Ethisorb tamponade (ET) were coated with poly-L-lactide. The stability of coated and uncoated scaffolds was investigated by incubation in standard culture medium. Various concentrations of the cells were seeded onto coated and uncoated polymer matrices in tissue culture dishes without shaking ("static seeding") or continuous shaking ("agitated seeding"). Cultures were grown for 4 week and were then evaluated by light and scanning electron microscopy. After a culture period of 10 d, BG-carriers showed a delicate consistency which made histological processing difficult. Cells were grown only sparsely in coated and non-coated BG-scaffolds. Contrary. ET-specimens were stable during a 4 week culture period. After "static seeding" a significantly higher number of cells resulted in comparison to those in "agitated" cultures. The cells were evenly distributed throughout the ET-carriers and produced extracellular matrix compounds as well. Furthermore, the examination with RT-PCR (reverse transcription-polymerase chain reaction) revealed that the cells synthesized and secreted type I collagen, and expressed genes implicated in transducing bone morphogenetic protein (BMP) signals. Messenger RNAs for BMP-2, -4, -7, the BMP type I receptors Act R-1 (alk 2, activin-like kinase receptor), BMPR-IA (alk 3), -IB (alk 6), and the type II receptor BMPR-II were detected. These data reveal that static seeding favors the adherence and proliferation of primary gingival cells on polyglactin matrices. This system may serve as a valuable tool for periodontal tissue engineering.

Activin Receptors, Type I↗