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1.
Vascul Pharmacol ; 152: 107208, 2023 10.
Article in English | MEDLINE | ID: mdl-37572973

ABSTRACT

Here we aimed to establish an in vitro engineered heart tissue (EHT) co-morbidity mimicking model of ischemia-reperfusion injury and diabetes. EHTs were generated from primary neonatal rat cardiomyocytes. Hyperglycemic conditions or hyperosmolar controls were applied for one day to model acute hyperglycemia and for seven days to model chronic hyperglycemia. 120 min' simulated ischemia (SI) was followed by 120 min' reperfusion (R) and 1-day follow-up reperfusion (FR). Normoxic controls (N) were not subjected to SI/R. Half of the EHTs was paced, the other half was left unpaced. To assess cell injury, lactate-dehydrogenase (LDH) concentration was measured. Beating force and activity (frequency) were monitored as cardiomyocyte functional parameters. LDH-release indicated relevant cell injury after SI/N in each experimental condition, with much higher effects in the chronically hyperglycemic/hyperosmolar groups. SI stopped beating of EHTs in each condition, which returned during reperfusion, with weaker recovery in chronic conditions than in acute conditions. Acutely treated EHTs showed small LDH-release and âˆ¼80% recovery of force during reperfusion and follow-up, while chronically treated EHTs showed a marked LDH-release, only ∼30% recovery with reperfusion and complete loss of beating activity during 24 h follow-up reperfusion. We conclude that EHTs respond differently to SI/R injury in acute and chronic hyperglycemia/hyperosmolarity, and that our EHT model is a novel in vitro combination of diabetes and ischemia-reperfusion.


Subject(s)
Hyperglycemia , Myocytes, Cardiac , Rats , Animals , Ischemia , Reperfusion
2.
Phys Rev Lett ; 126(11): 113201, 2021 Mar 19.
Article in English | MEDLINE | ID: mdl-33798357

ABSTRACT

Above-threshold ionization spectra from cesium are measured as a function of the carrier-envelope phase (CEP) using laser pulses centered at 3.1 µm wavelength. The directional asymmetry in the energy spectra of backscattered electrons oscillates three times, rather than once, as the CEP is changed from 0 to 2π. Using the improved strong-field approximation, we show that the unusual behavior arises from the interference of few quantum orbits. We discuss the conditions for observing the high-order CEP dependence, and draw an analogy with time-domain holography with electron wave packets.

3.
Physiol Int ; 2021 Mar 24.
Article in English | MEDLINE | ID: mdl-33769958

ABSTRACT

OBJECTIVES: Conditions that have similar initial presentations as sepsis may make early recognition of sepsis in an emergency room (ER) difficult. We investigated whether selected physiologic and metabolic parameters can be reliably used in the emergency department to differentiate sepsis from other disease states that mimic it, such as dehydration and stroke. METHODS: Loess regression on retrospective follow-up chart data of patients with sepsis-like symptoms (N = 664) aged 18+ in a large ER in Hungary was used to visualize/identify cutoff points for sepsis risk. A multivariate logistic regression model based on standard triage data was constructed with its corresponding receiver operating characteristic (ROC) curve and compared with another model constructed based on current sepsis guidelines. RESULTS: Age, bicarbonate, HR, lactate, pH, and body temperature had U, V, W, or reverse U-shaped associations with identifiable inflexion points, but the cutoff values we identified were slightly different from guideline cutoff values. In contrast to the guidelines, no inflexion points could be observed for the association of sepsis with SBP, DPB, MAP, and RR and therefore were treated as continuous variables. Compared to the guidelines-based model, the triage data-driven final model contained additional variables (age, pH, bicarbonate) and did not include lactate. The data-driven model identified about 85% of sepsis cases correctly, while the guidelines-based model identified only about 70% of sepsis cases correctly. CONCLUSION: Our findings contribute to the growing body of evidence for the necessity of finding improved tools to identify sepsis at early time points, such as in the ER.

4.
Vascul Pharmacol ; 133-134: 106781, 2020.
Article in English | MEDLINE | ID: mdl-32827678

ABSTRACT

INTRODUCTION: Stem cell-derived cardiac myocytes are potential sources for testing cardiocytoprotective molecules against ischemia/reperfusion injury in vitro. MATERIALS AND METHODS: Here we performed a systematic analysis of two different induced pluripotent stem cell lines (iPSC 3.4 and 4.1) and an embryonic stem cell (ESC) line-derived cardiac myocytes at two different developmental stages. Cell viability in simulated ischemia/reperfusion (SI/R)-induced injury and a known cardiocytoprotective NO-donor, S-nitroso-n-acetylpenicillamine (SNAP) was tested. RESULTS: After analysis of full embryoid bodies (EBs) and cardiac marker (VCAM and cardiac troponin I) positive cells of three lines at 6 conditions (32 different conditions altogether), we found significant SI/R injury-induced cell death in both full EBs and VCAM+ cardiac cells at later stage of their differentiation. Moreover, full EBs of the iPS 4.1 cell line after oxidative stress induction by SNAP was protected at day-8 samples. CONCLUSION: We have shown that 4.1 iPS-derived cardiomyocyte line could serve as a testing platform for cardiocytoprotection.


Subject(s)
Cell Differentiation , Myocardial Reperfusion Injury/prevention & control , Myocytes, Cardiac/drug effects , Nitric Oxide Donors/pharmacology , Pluripotent Stem Cells/drug effects , S-Nitroso-N-Acetylpenicillamine/pharmacology , Cell Line , Cell Survival/drug effects , Humans , Myocardial Reperfusion Injury/metabolism , Myocardial Reperfusion Injury/pathology , Myocytes, Cardiac/metabolism , Myocytes, Cardiac/pathology , Oxidative Stress/drug effects , Phenotype , Pluripotent Stem Cells/metabolism , Pluripotent Stem Cells/pathology , Troponin I/metabolism , Vascular Cell Adhesion Molecule-1/metabolism
5.
Physiol Int ; 107(2): 349-358, 2020 Jul 17.
Article in English | MEDLINE | ID: mdl-32692716

ABSTRACT

Breast cancer is characterized by oncobiosis, the abnormal composition of the microbiome in neoplastic diseases. The biosynthetic capacity of the oncobiotic flora in breast cancer is suppressed, as suggested by metagenomic studies. The microbiome synthesizes a set of cytostatic and antimetastatic metabolites that are downregulated in breast cancer, including cadaverine, a microbiome metabolite with cytostatic properties. We set out to assess how the protein expression of constitutive lysine decarboxylase (LdcC), a key enzyme for cadaverine production, changes in the feces of human breast cancer patients (n = 35). We found that the fecal expression of Escherichia coli LdcC is downregulated in lobular cases as compared to invasive carcinoma of no special type (NST) cases. Lobular breast carcinoma is characterized by low or absent expression of E-cadherin. Fecal E. coli LdcC protein expression is downregulated in E-cadherin negative breast cancer cases as compared to positive ones. Receiver operating characteristic (ROC) analysis of LdcC expression in lobular and NST cases revealed that fecal E. coli LdcC protein expression might have predictive values. These data suggest that the oncobiotic transformation of the microbiome indeed leads to the downregulation of the production of cytostatic and antimetastatic metabolites. In E-cadherin negative lobular carcinoma that has a higher potential for metastasis formation, the protein levels of enzymes producing antimetastatic metabolites are downregulated. This finding represents a new route that renders lobular cases permissive for metastasis formation. Furthermore, our findings underline the role of oncobiosis in regulating metastasis formation in breast cancer.

6.
Phys Rev Lett ; 122(19): 193602, 2019 May 17.
Article in English | MEDLINE | ID: mdl-31144948

ABSTRACT

Electrodynamical processes induced in complex systems like semiconductors by strong electromagnetic fields have traditionally been described using semiclassical approaches. Although these approaches allowed the investigation of ultrafast dynamics in solids culminating in multipetahertz electronics, they do not provide any access to the quantum-optical nature of the interaction, as they treat the driving field classically and unaffected by the interaction. Here, using a full quantum-optical approach, we demonstrate that the subcycle electronic response in a strongly driven semiconductor crystal is imprinted in the quantum state of the driving field resulting in nonclassical light states carrying the information of the interaction. This vital step towards strong-field ultrafast quantum electrodynamics unravels information inaccessible by conventional approaches and leads to the development of a new class of nonclassical light sources.

7.
Psychopharmacology (Berl) ; 226(2): 285-93, 2013 Mar.
Article in English | MEDLINE | ID: mdl-23138433

ABSTRACT

RATIONALE: Cariprazine (RGH-188) is a D3-preferring dopamine D3/D2 receptor partial agonist antipsychotic candidate for the treatment of schizophrenia and bipolar mania. Substance abuse is a frequent comorbidity of both disorders and is associated with serious health issues. Based on preclinical efficacy, dopamine D2 and D3 receptor partial agonists and antagonists are assumed to have relapse-preventing potential in human cocaine addiction. OBJECTIVES: We investigated the anti-abuse potential of cariprazine in cocaine self-administration paradigms. Aripiprazole and bifeprunox were used as comparators because of their pharmacological similarity to cariprazine. METHODS: The effects of compounds on cocaine's rewarding effect were investigated in a continuous self-administration regimen. The relapse-preventing potential of drugs was studied in rats with a history of cocaine self-administration after a period of complete abstinence in a relapse to cocaine-seeking paradigm. RESULTS: Cariprazine, as well as aripiprazole and bifeprunox, were able to reduce the rewarding effect of cocaine (minimum effective doses were 0.17, 1, and 0.1 mg/kg, respectively) and attenuated relapse to cocaine seeking with half maximal effective dose [ED50] values of 0.2, 4.2, and 0.17 mg/kg, respectively. CONCLUSIONS: These results may predict a relapse-preventing action for cariprazine in humans in addition to its already established antipsychotic and antimanic efficacy.


Subject(s)
Antipsychotic Agents/pharmacology , Cocaine-Related Disorders/drug therapy , Dopamine Agonists/pharmacology , Piperazines/pharmacology , Animals , Aripiprazole , Benzoxazoles/pharmacology , Dose-Response Relationship, Drug , Haloperidol/pharmacology , Male , Quinolones/pharmacology , Rats , Rats, Long-Evans , Receptors, Dopamine D2/agonists , Secondary Prevention , Substance-Related Disorders/drug therapy
8.
Dermatol Res Pract ; 2010: 210150, 2010.
Article in English | MEDLINE | ID: mdl-21234359

ABSTRACT

Full-thickness burn and other types of deep skin loss will result in scar formation. For at least partial replacement of the lost dermal layer, there are several options to use biotechnologically derived extracellular matrix components or tissue scaffolds of cadaver skin origin. In a survey, we have collected data on 18 pts who have previously received acellular dermal implant Alloderm. The age of these patients at the injury varied between 16 months and 84 years. The average area of the implants was 185 cm(2). Among those, 15 implant sites of 14 patients were assessed at an average of 50 months after surgery. The scar function was assessed by using the modified Vancouver Scar Scale. We have found that the overall scar quality and function was significantly better over the implanted areas than over the surrounding skin. Also these areas received a better score for scar height and pliability. Our findings suggest that acellular dermal implants are especially useful tools in the treatment of full-thickness burns as well as postburn scar contractures.

9.
Clin Pharmacol Ther ; 87(1): 87-92, 2010 Jan.
Article in English | MEDLINE | ID: mdl-19890250

ABSTRACT

Nitric oxide (NO) plays a key role in the regulation of ocular blood flow and may be an interesting therapeutic target in ocular ischemic disease. In the present study, we hypothesized that NO-releasing drugs may increase blood flow to the head of the optic nerve and also in the choroid. The study employed a randomized, placebo-controlled, double blind, four-way crossover design. On separate study days, 12 healthy subjects received infusions of nitroglycerin, isosorbide dinitrate, sodium nitroprusside, or placebo. All three study drugs reduced the mean arterial pressure (MAP) and ocular perfusion pressure (OPP) (P < 0.001). None of the administered drugs increased the ocular hemodynamic variables. By contrast, vascular resistance decreased dose dependently during administration of the study drugs (P < 0.001). These results indicate that systemic administration of NO-donor drugs is associated with a decrease in vascular resistance in the ocular vasculature. However, because these drugs also reduce blood pressure, they do not improve perfusion to the posterior eye pole.


Subject(s)
Hemodynamics/drug effects , Nitric Oxide Donors/pharmacology , Optic Nerve/blood supply , Optic Nerve/drug effects , Vasodilator Agents/pharmacology , Adult , Cross-Over Studies , Double-Blind Method , Follow-Up Studies , Hemodynamics/physiology , Humans , Intraocular Pressure/drug effects , Intraocular Pressure/physiology , Male , Optic Nerve/physiology , Regional Blood Flow/drug effects , Regional Blood Flow/physiology , Vascular Resistance/drug effects , Vascular Resistance/physiology , Young Adult
10.
Water Sci Technol ; 58(11): 2117-25, 2008.
Article in English | MEDLINE | ID: mdl-19092187

ABSTRACT

The classification according to the Water Framework Directive (WFD) includes numerous challenges in contrast with the previously applied water qualification standards. The most important element of the ecological status, the biological one, is based on five groups of living organisms: phytoplankton, phytobenthon, macrophytes, macro-invertebrates and fish. The results of a three-year research project financed by the Ministry of Environment and Water (MoEW) and the Hungarian Academy of Sciences (HAS) are reported in this work. The objective of the project was the elaboration of a proposal for biological classification according to the WFD for the related groups of living organisms. In the course of the project the biological characteristics to be measured were selected for each of the above listed groups which served as the basic data for Biological Quality Elements (BQEs). In the BQEs we estimated the type-specific reference values for most of the Hungarian surface water types. Then we created the structure of the qualification system for these groups, including specification of class boundaries between the five classes for the Environmental Quality Ratio (EQR) values on the basis of expert estimation. A Non-Taxonomic Periphyton Index (NTPI, not included in the WFD) was also developed and tested for qualification. The elaborated classification systems were tested on the basis of existing scarce data for numerous Hungarian water types.


Subject(s)
Classification/methods , Water/standards , Animals , Diatoms/classification , Fishes/classification , Hungary , Invertebrates/classification , Phytoplankton/classification , Plants/classification , Reference Standards
11.
J Struct Biol ; 155(2): 327-39, 2006 Aug.
Article in English | MEDLINE | ID: mdl-16714122

ABSTRACT

Desmin intermediate filaments play important role in the mechanical integrity and elasticity of muscle cells. The mechanisms of how desmin contributes to cellular mechanics are little understood. Here, we explored the nanomechanics of desmin by manipulating individual filaments with atomic force microscopy. In complex, hierarchical force responses we identified recurring features which likely correspond to distinct properties and structural transitions related to desmin's extensibility and elasticity. The most frequently observed feature is an initial unbinding transition that corresponds to the removal of approximately 45-nm-long coiled-coil dimers from the filament surface with 20-60 pN forces in usually two discrete steps. In tethers longer than 60 nm we most often observed force plateaus studded with bumps spaced approximately 16 nm apart, which are likely caused by a combination of protofilament unzipping, dimer-dimer sliding and coiled-coil-domain unfolding events. At high stresses and strains non-linear, entropic elasticity was dominant, and sometimes repetitive sawtooth force transitions were seen which might arise because of slippage within the desmin protofilament. A model is proposed in which mechanical yielding is caused by coiled-coil domain unfolding and dimer-dimer sliding/slippage, and strain hardening by the entropic elasticity of partially unfolded protofilaments.


Subject(s)
Desmin/chemistry , Intermediate Filaments/chemistry , Microscopy, Atomic Force/methods , Animals , Elasticity , Models, Theoretical
12.
Eur Urol ; 48(1): 83-9; discussion 89, 2005 Jul.
Article in English | MEDLINE | ID: mdl-15967256

ABSTRACT

OBJECTIVE: Morbidity and postoperative pain after extraperitoneal (E-LRPE) and transperitoneal (T-LRPE) laparoscopic radical prostatectomy was compared to open extraperitoneal radical prostatectomy (O-RPE). MATERIAL AND METHODS: Between January 2002 and October 2003, we evaluated 41 E-LRPE, 39 T-LRPE and 41 O-RPE prospectively. All operations were performed as standard procedures by the same group of surgeons and perioperative results and complications were evaluated. Pain management was performed with tramadol 50-100 mg on demand, and no other form of anaesthesia was given. Postoperative pain was assessed daily in all patients quantifying analgesic requirement and evaluation of Visual Analogue Scale (VAS). All patients had at least a 12 month follow-up. RESULTS: Mean age, prostate volume, PSA and Gleason score were comparable between all three groups (p>0.05). Mean blood loss was lower with laparoscopy (189+/-140 and 290+/-254 ml), as compared to 385+/-410 ml for O-RPE (p=0.002). However, mean operating times were significantly longer in L-TRPE (279+/-70 min) as compared to E-LRPE (217+/-51 min) and O-RPE (195+/-72 min) (p<0.001), but E-LRPE and O-RPE showed no statistical difference (p=0.1143). Average VAS score on the 1st and 5th postoperative day for E-LRPE versus T-LRPE versus O-RPE was 4.9+/-1.0 versus 7.8+/-1.5 versus 5.8+/-1.9 and 1.6+/-0.9 versus 2.3+/-1.2 versus 2.3+/-0.9 respectively, which was significant lower (p=0.02) between E-LRPE versus T-LRPE (p<0.001) and O-RPE (p=0.008), but equal (p=0.655) between T-LRPE and O-RPE since postoperative day 3. Mean tramadol analgesic consumption within the first postoperative week was 290 versus 490 versus 300 mg respectively, which was statistical different between E-LRPE and T-LRPE (p<0.001), O-RPE and T-LRPE (p<0.001), but not between E-LRPE and O-RPE (p=0.550). Statistical analysis revealed a strong correlation of urinary leakage with increased postoperative pain (p=0.029) in all groups, especially for T-LRPE (p=0.007). Likewise, increased operating times (>240 min) were associated with increased post-operative pain (p=0.049). Full continence defined as no pads at one year was achieved in 36/41 (88%, E-LRPE) versus 33/39 (85%, T-LRPE) versus 33/41 (81%, O-RPE), respectively (p=0.2). CONCLUSION: E-LRPE resulted in a significant subjective (VAS Score, p<0.001) and objective (analgetic consumption, p<0.001) pain reduction compared to T-LRPE, but only in VAS Score compared to O-RPE (p=0.008). Analgetic consumption during first postoperative week was equal in E-LRPE (290 mg) and O-RPE (300 mg) (p=0.550). Shorter operating times, lower urinary leakage rates, lower stricture rates and lower blood loss in E-LRPE compared to T-LRPE are mainly explained due to the long learning curve in LRPE, which we did not overcome yet, and not due to the approach (extraperitoneal versus transperitoneal).


Subject(s)
Adenocarcinoma/surgery , Laparoscopy , Pain, Postoperative/epidemiology , Prostatectomy/methods , Prostatic Neoplasms/surgery , Adenocarcinoma/pathology , Follow-Up Studies , Humans , Incidence , Intraoperative Complications/epidemiology , Male , Middle Aged , Pain Measurement , Pain, Postoperative/etiology , Peritoneum , Prostatectomy/adverse effects , Prostatic Neoplasms/pathology , Retrospective Studies , Treatment Outcome
13.
Br J Ophthalmol ; 89(2): 185-8, 2005 Feb.
Article in English | MEDLINE | ID: mdl-15665350

ABSTRACT

BACKGROUND/AIM: Current evidence suggests that vascular insufficiencies in the optic nerve head play an important part in the pathogenesis of glaucomatous optic neuropathy. Trabeculectomy is the most common operative procedure for the treatment of medically uncontrolled glaucoma. This study was conducted to investigate whether trabeculectomy may improve ocular haemodynamics. METHODS: 30 patients with primary open angle glaucoma about to undergo trabeculectomy were included in the study. Patients were evaluated before surgery and at 2 and 10 weeks after trabeculectomy. Optic nerve head blood flow (OnhBF) was assessed with scanning laser Doppler flowmetry. Fundus pulsation amplitude (FPA) measurements were obtained with laser interferometry. RESULTS: Because of the decrease in intraocular pressure there was a significant increase in ocular perfusion pressure (OPP) following trabeculectomy (18.5% (SD 12.0%) and 19.0% (17.1%) at 2 and 10 weeks postoperatively; p <0.001). A significant increase in OnhBF was observed after trabeculectomy (11.6% (16.4%) and 16.2% (20.2%) for each postoperative visit, respectively; p <0.001). FPA was also significantly higher compared with baseline values (17.2% (17.3%) and 17.4% (16.3%), respectively; p <0.001). A significant association between the increase in OPP and the increase in OnhBF and FPA was observed 10 weeks after surgery (r = 0.47; p = 0.009, and r = 0.50; p = 0.005, respectively). CONCLUSION: The results of this study suggest that trabeculectomy improves ocular blood flow in patients with chronic open angle glaucoma.


Subject(s)
Glaucoma, Open-Angle/surgery , Optic Disk/blood supply , Trabeculectomy/methods , Aged , Analysis of Variance , Blood Pressure/physiology , Female , Fundus Oculi , Glaucoma, Open-Angle/physiopathology , Humans , Interferometry/methods , Intraocular Pressure/physiology , Laser-Doppler Flowmetry/methods , Male , Middle Aged , Treatment Outcome
14.
Acta Neurol Scand ; 106(6): 325-32, 2002 Dec.
Article in English | MEDLINE | ID: mdl-12460136

ABSTRACT

OBJECTIVES: Vinpocetine is a compound widely used in the prevention and treatment of cerebrovascular diseases. It is still not clear whether the drug has a direct and specific effect on neurotransmission or its effects are due to extracerebral actions, such as changes in cerebral blood flow. The main objective of the present investigation was to determine the global uptake and regional distribution of radiolabelled vinpocetine in the human brain in order to explore whether it may have direct central nervous system effects. MATERIAL AND METHODS: Three healthy subjects were examined with positron emission tomography and [11C]vinpocetine. The regional uptake was determined in anatomically defined volumes-of-interest. The fractions of [11C]vinpocetine and labelled metabolites in plasma were determined using high pressure liquid chromatography. RESULTS: The uptake of [11C]vinpocetine in brain was rapid and 3.7% (mean; n = 4) of the total radioactivity injected was in brain 2 min after radioligand administration. The uptake was heterogeneously distributed among brain regions. When compared with the cerebellum, an a priori reference region, the highest regional uptake was in the thalamus, upper brain stem, striatum and cortex. Following an initial peak, the total concentration of radioactivity in blood was relatively stable with time, whereas the concentration of the unchanged compound decreased with time in an exponential manner. CONCLUSION: Vinpocetine, administered intravenously in humans, readily passes the blood-brain barrier and enters the brain. Its regional uptake and distribution in the brain is heterogeneous, indicating binding to specific sites. The brain regions showing increased uptake in the human brain correspond to those in which vinpocetine has been shown to induce elevated metabolism and blood flow. These observations support the hypothesis that vinpocetine has direct neuronal actions in the human brain.


Subject(s)
Brain/diagnostic imaging , Carbon Radioisotopes , Neuroprotective Agents/pharmacokinetics , Tomography, Emission-Computed , Vinca Alkaloids/pharmacokinetics , Adult , Blood-Brain Barrier/drug effects , Brain/anatomy & histology , Brain/drug effects , Carbon Radioisotopes/blood , Cerebrovascular Circulation/drug effects , Chromatography, High Pressure Liquid , Humans , Magnetic Resonance Imaging , Male , Neuroprotective Agents/blood , Reference Values , Time Factors , Vinca Alkaloids/blood
15.
Diabetologia ; 45(6): 883-9, 2002 Jun.
Article in English | MEDLINE | ID: mdl-12107733

ABSTRACT

AIMS/HYPOTHESIS: It has been reported that improvement of metabolic control by intensified insulin therapy in patients with Type I (insulin-dependent) diabetes mellitus is associated with alterations in ocular blood flow. We hypothesized that these changes in ocular blood flow could be associated with alterations of plasma insulin, glucose or endothelin concentration. METHODS: In 16 patients with Type I diabetes ocular haemodynamic parameters were assessed daily during the first 5 days of institution of intensified insulin therapy and plasma concentrations of glucose, insulin, and endothelin-1 plasma were measured. Retinal white blood cell flux was estimated with the blue field entoptic technique. Pulsatile choroidal blood flow was assessed by laser interferometric measurement of fundus pulsation amplitude. RESULTS: Retinal white blood cell flux ( p=0.0015) and ocular fundus pulsation amplitude ( p<0.001) increased during institution of strict metabolic control. Changes in ocular haemodynamic variables were inversely correlated with concentrations of plasma ET-1, but not with that of insulin or glucose. CONCLUSIONS/INTERPRETATION: These data indicate that institution of improved metabolic status is paralleled by rapid changes in the production of ET-1, which could in turn affect ocular perfusion.


Subject(s)
Diabetes Mellitus, Type 1/drug therapy , Diabetes Mellitus, Type 1/physiopathology , Diabetic Retinopathy/chemically induced , Endothelin-1/blood , Insulin/therapeutic use , Adult , Albuminuria , Blood Glucose/metabolism , Blood Pressure , Cholesterol, HDL/blood , Diabetes Mellitus, Type 1/blood , Dose-Response Relationship, Drug , Female , Hemodynamics , Humans , Hypoglycemic Agents/therapeutic use , Insulin/blood , Male , Middle Aged , Pulse , Retinal Vessels/physiopathology , Triglycerides/blood
16.
J Chromatogr Sci ; 40(10): 603-8, 2002.
Article in English | MEDLINE | ID: mdl-12515365

ABSTRACT

During the discovery of metabolic routes of a drug candidate, radioactively labeled substances are administered. This study reports the multidimensional application of overpressured layer chromatography (OPLC) and high-performance liquid chromatography (HPLC) coupled with online or off-line nondestructive radioactivity detection methods in metabolism studies. Among these methods, digital autoradiography and flow-cell radioactivity detectors (RD) using solid scintillators are used. In this study, the hyphenation of OPLC with RD is reported. The application of the OPLC-RD technique is demonstrated on a metabolism study as well as the multidimensional chromatographic selectivity using normal-phase OPLC for the separation in the first dimension, followed by reversed-phase HPLC-RD, which provides additional selectivity to the separation. Information regarding the identity of radiolabeled metabolites and data obtained from spectroscopic methods could be advantageously used during structure elucidation.


Subject(s)
Chromatography, High Pressure Liquid/methods , Pharmaceutical Preparations/metabolism , Radiometry/methods , Pharmaceutical Preparations/isolation & purification
17.
Eur J Ophthalmol ; 12(6): 459-66, 2002.
Article in English | MEDLINE | ID: mdl-12510714

ABSTRACT

PURPOSE: To investigate the effect of systemic hypercapnia on retinal hemodynamics in humans. METHODS: We studied the effect of breathing a mixture of normal air with 5% CO2 for 13 minutes in ten healthy young male volunteers, using the Zeiss retinal vessel analyzer for continuous measurement of retinal vessel diameter and the blue-field entoptic technique to quantify retinal white blood cell flux. In eight other subjects the effect of hypercapnia was measured with the Zeiss retinal vessel analyzer and by laser Doppler velocimetry to establish retinal blood flow velocity. RESULTS: Retinal arterial and venous vessel diameters increased by a maximum of 4.2% and 3.2%, respectively. Peak effect was observed after 3 minutes of breathing the mixture of normal air with 5% CO2. During hypercapnia red blood cell velocity increased 11.7% and, accordingly, retinal blood flow increased 19.1%. White blood cell density and velocity rose significantly during hypercapnia, resulting in an increase in white blood cell flux (19.2%). CONCLUSIONS: Our data indicate that CO2 induces vasodilation in retinal arteries and retinal veins. Retinal blood flow and perimacular white blood cell flux increased to the same extent in subjects breathing a mixture of normal air with 5% CO2.


Subject(s)
Hypercapnia/physiopathology , Retinal Vessels/physiology , Adult , Blood Flow Velocity , Carbon Dioxide , Humans , Laser-Doppler Flowmetry , Leukocyte Count , Leukocytes/physiology , Male , Respiration , Vasodilation
18.
Am J Ophthalmol ; 132(5): 720-6, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11704033

ABSTRACT

PURPOSE: Alterations of ocular blood flow may play a role in the pathophysiology of human immunodeficiency virus (HIV) related retinal microvasculopathy. In this study ocular blood flow was investigated in patients with HIV infection. DESIGN: In a prospective, cross-sectional study ocular blood flow was measured in 37 eyes of consecutive HIV- infected persons and compared with the data of age-matched healthy controls. This sample size was calculated based on an alpha-error of 0.5 and a beta-error of 0.8. METHODS: Macular white blood cell flow, fundus pulsation amplitude, and blood flow velocities in the retrobulbar vessels were measured with blue field entoptic technique, laser interferometry, and Doppler sonography, respectively. Immunologic and ophthalmologic status was evaluated from each patient. RESULTS: Mean CD4+ cell count of the HIV-infected persons was 206.8 +/- 145.6 cells/mm(3). In five patients HIV-related retinopathy was observed. A significant reduction in leukocyte density was seen in HIV infected persons (82.2 +/- 23.4) as compared with the control group (102.0 +/- 28.4; P =.019). The resistive index in the central retinal artery was higher in HIV infected patients (0.77 +/- 0.05) as compared with the controls (0.74 +/- 0.04; P =.04). The other hemodynamic parameters were not different between groups. No correlation of flow parameters and CD4+ cell count or HIV-related retinopathy was observed. CONCLUSIONS: Decreased macular leukocyte density was detected in HIV infected persons. Our study suggests that abnormal retinal hemodynamics in individuals infected with HIV may be involved in the pathogenesis of HIV-related microvasculopathy.


Subject(s)
Ciliary Arteries/physiopathology , Eye Infections, Viral/physiopathology , HIV Infections/physiopathology , Ophthalmic Artery/physiopathology , Retinal Artery/physiopathology , Retinal Diseases/physiopathology , Adult , Aged , Blood Flow Velocity , CD4 Lymphocyte Count , Cross-Sectional Studies , Female , Humans , Laser-Doppler Flowmetry , Male , Microcirculation , Middle Aged , Prospective Studies , Ultrasonography, Doppler, Color , Vision, Entoptic
19.
Br J Clin Pharmacol ; 52(2): 210-2, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11488781

ABSTRACT

AIMS: To investigate whether nifedipine affects ocular perfusion or visual fields in open angle glaucoma patients. METHODS: In a parallel group study nifedipine or placebo was administered for 3 months (n = 30). Ocular fundus pulsation amplitude (FPA), cup blood flow (Flowcup) and visual field mean deviation (MD) were measured. RESULTS: Five patients receiving nifedipine discontinued due to adverse events. Nifedipine did not affect FPA [difference: 0.3 microm (95% CI -0.3,0.9); P = 0.70], Flowcup: [difference: -9 rel.units (95% CI -133,114); P = 0.99], or MD [difference: 0.2dB (95% CI -2.2,2.7); P = 0.51] vs placebo. CONCLUSIONS: Systemic nifedipine is not well tolerated in glaucoma patients and exerts no effect on visual fields or ocular perfusion.


Subject(s)
Calcium Channel Blockers/therapeutic use , Glaucoma, Open-Angle/drug therapy , Nifedipine/therapeutic use , Optic Nerve/drug effects , Visual Fields/drug effects , Administration, Oral , Blood Flow Velocity , Calcium Channel Blockers/adverse effects , Calcium Channel Blockers/blood , Fundus Oculi , Glaucoma, Open-Angle/physiopathology , Humans , Interferometry/methods , Intraocular Pressure , Laser-Doppler Flowmetry , Nifedipine/adverse effects , Nifedipine/blood , Optic Nerve/blood supply
20.
J Cataract Refract Surg ; 27(8): 1227-31, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11524194

ABSTRACT

PURPOSE: To evaluate the effect of brimonidine 0.2% on intraocular pressure (IOP) after small incision cataract surgery. SETTING: Department of Ophthalmology, University of Vienna, Vienna, Austria. METHODS: This prospective randomized study comprised 80 eyes of 40 patients scheduled for small incision cataract surgery in both eyes. In each patient, 1 eye was randomly assigned to receive 1 drop of brimonidine 0.2% or no treatment (control) immediately after surgery. The fellow eye received the other assigned treatment. All patients had standardized surgery by the same surgeon with sodium hyaluronate 1%, a temporal 3.5 mm sutureless posterior limbal incision, phacoemulsification, and implantation of a foldable intraocular lens. The IOP was measured preoperatively as well as 6 and 20 to 24 hours and 1 week postoperatively. RESULTS: Six hours after surgery, the mean increase in IOP was 4.7 mm Hg +/- 6.1 (SD) in the brimonidine group and 4.6 +/- 5.3 mm Hg in the control group. In each group, 17 eyes (43%) had an IOP increase of 5 mm Hg or more. Twenty to 24 hours after surgery, the mean increase in IOP was 1.5 +/- 4.2 mm Hg in the brimonidine group and 1.6 +/- 4.4 mm Hg in the control group. There were no statistically significant between-group differences at any measurement. CONCLUSIONS: In both groups, IOP significantly increased 6 hours and 20 to 24 hours after small incision cataract surgery. Brimonidine 0.2% failed to reduce the IOP increase observed after small incision cataract surgery.


Subject(s)
Adrenergic alpha-Agonists/administration & dosage , Intraocular Pressure/drug effects , Lens Implantation, Intraocular , Phacoemulsification , Quinoxalines/administration & dosage , Administration, Topical , Aged , Brimonidine Tartrate , Double-Blind Method , Female , Humans , Male , Minimally Invasive Surgical Procedures , Ocular Hypertension/prevention & control , Postoperative Complications/prevention & control , Prospective Studies
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