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Biomedical subjects

E Farkas

Publications and source records attributed to E Farkas.

At least 19 recordsLinked to original sources

Influence of chlorhexidine species on the liquid crystalline structure of vehicle.

The aim of this study was to investigate the influence of three chlorhexidine species, chlorhexidine base and its salts (diacetate and digluconate), on the physico-chemical features of liquid crystalline systems and on drug transport through lipophilic membranes. Nonionic surfactant, Synperonic A7 (PEG(7)-C(13--15)) was selected for the preparation of the liquid crystalline systems. Mixtures of different ratios of Synperonic A7 and water were prepared. The liquid crystalline systems were characterized using polarizing microscopy, small-angle neutron scattering and transmission electron microscopy. Membrane transport was also examined. The addition of chlorhexidine species to the liquid crystalline system modified the structure of the liquid crystalline system. As a result of liquid crystal--drug interaction, the solubility of chlorhexidine base and its diffusion through lipophilic membranes increased in comparison with those of the chlorhexidine salts.

Chemical Phenomena↗

Interaction between iron(II) and hydroxamic acids: oxidation of iron(II) to iron(III) by desferrioxamine B under anaerobic conditions.

Interaction between iron(II) and acetohydroxamic acid (Aha), alpha-alaninehydroxamic acid (alpha-Alaha), beta-alaninehydroxamic acid (beta-Alaha), hexanedioic acid bis(3-hydroxycarbamoyl-methyl)amide (Dha) or desferrioxamine B (DFB) under anaerobic conditions was studied by pH-metric and UV-Visible spectrophotometric methods. The stability constants of complexes formed with Aha, alpha-Alaha, beta-Alaha and Dha were calculated and turned out to be much lower than those of the corresponding iron(II) complexes. Stability constants of the iron(II)-hydroxamate complexes are compared with those of other divalent 3d-block metal ions and the Irving-Williams series of stabilities was found to be observed. Above pH 4, in the reactions between iron(II) and desferrioxamine B, the oxidation of the metal ion to iron(III) by the ligand was found. The overall reaction that resulted in the formation of the tris-hydroxamato complex [Fe(HDFB)]+ and monoamide derivative of DFB at pH 6 is: 2Fe2+ + 3H4DFB+ = 2[Fe(HDFB)]+ + H3DFB-monoamide+ + H2O + 4H+. Based on these results, the conclusion is that desferrioxamine B can uptake iron in iron(III) form under anaerobic conditions.

Journal Article↗

Penicillin productivity and glutathione-dependent detoxification of phenylacetic and phenoxyacetic acids in Penicillium chrysogenum.

Both toxicity and penicillin productivity of the hydroxylated derivatives of phenylacetic acid (PA) and phenoxyacetic acid (POA) were highly dependent on the position of hydroxylation on the aromatic ring in Penicillium chrysogenum. Hydroxylation at position 2 diminished penicillin production but the compounds retained most of their toxicity. On the other hand, hydroxylation at position 4 resulted in barely toxic derivatives with still significant penicillin productivity. 3-Hydroxy-PA was a weak side-chain precursor with considerably reduced toxicity. The activity of the glutathione-dependent detoxification pathway correlated well with the toxicity of the compounds but there was no correlation between acidity, toxicity and penicillin productivity.

Acetates↗

Cerebral microvascular pathology in aging and Alzheimer's disease.

The aging of the central nervous system and the development of incapacitating neurological diseases like Alzheimer's disease (AD) are generally associated with a wide range of histological and pathophysiological changes eventually leading to a compromised cognitive status. Although the diverse triggers of the neurodegenerative processes and their interactions are still the topic of extensive debate, the possible contribution of cerebrovascular deficiencies has been vigorously promoted in recent years. Various forms of cerebrovascular insufficiency such as reduced blood supply to the brain or disrupted microvascular integrity in cortical regions may occupy an initiating or intermediate position in the chain of events ending with cognitive failure. When, for example, vasoconstriction takes over a dominating role in the cerebral vessels, the perfusion rate of the brain can considerably decrease causing directly or through structural vascular damage a drop in cerebral glucose utilization. Consequently, cerebral metabolism can suffer a setback leading to neuronal damage and a concomitant suboptimal cognitive capacity. The present review focuses on the microvascular aspects of neurodegenerative processes in aging and AD with special attention to cerebral blood flow, neural metabolic changes and the abnormalities in microvascular ultrastructure. In this context, a few of the specific triggers leading to the prominent cerebrovascular pathology, as well as the potential neurological outcome of the compromised cerebral microvascular system are also going to be touched upon to a certain extent, without aiming at total comprehensiveness. Finally, a set of animal models are going to be presented that are frequently used to uncover the functional relationship between cerebrovascular factors and the damage to neural networks.

Aging↗

[Oncocytic carcinoid tumor of the lung].

An elderly female patient was admitted and operated on for a lesion in the upper lobe of the right lung. After lobectomy the patient has recovered without complications. Histology proved oncocyter carcinoid tumour. This neuro-endocrine tumour is a rarity in the lungs with less than forty cases reported in the reviewed literature. This is the first case reported in Hungary.

Aged↗

[Laparoscopic resection of the rectum].

Improving the laparoscopic equipments and the techniques have spreaded the repertoire of the laparoscopic procedures. In the beginning, it was performed the laparoscopic-assisted resection of the rectum, and later was performed the entire laparoscopic procedures on the colon. It had presented a patient, 71 years old man with diagnosis of the adenocarcinoma recti. After preoperately prepare carried out the laparoscopic procedure with T-T anastomosis by EEA stapler. We presented the first case of the laparoscopical performed resection of the rectum with desire to show possibilities and advantages of the laparoscopic surgery in the relation with conventional surgery and with hope that this techniques would be found the application in our land.

Adenocarcinoma↗

Enzymatic synthesis of fucose-containing disaccharides employing the partially purified alpha-L-fucosidase from Penicillium multicolor.

The alpha-L-Fucp-(1 --> 3)-D-GlcpNAc disaccharide structure is a vital core unit of the oligosaccharide components of glycoconjugates isolated from human milk and blood group substances. Alpha-L-Fucosidase from Penicillium multicolor catalyses the transfer of L-fucose from donor structures such as alpha-L-FucpOpNP and alpha-L-FucpF to various GlcpNAc derivatives and Glcp, forming alpha-(1 --> 3) linkages. The synthesis of several biologically relevant disaccharides including alpha-L-Fucp-(1 --> 3)-alpha-D-GlcpNAcOMe, alpha-L-Fucp-(1 --> 3)-alpha-D-GlcpNAcOAll, alpha-L-Fucp-(1 --> 3)-beta-D-GlcpNAcOAll, alpha-L-Fucp-(1 --> 3)-D-GlcpNAc and alpha-L-Fucp-(1 --> 3)-D-Glcp has been achieved in up to 34% yields by application of this enzyme.

Animals↗

The effect of liquid crystalline structure on chlorhexidine diacetate release.

The aim of this study was to examine different liquid crystalline preparations containing chlorhexidine diacetate and to find connection between their structure and the kinetic of drug release. Nonionic surfactant, Synperonic A7 (PEG(7)-C(13-15)) was selected for the preparation of the examined liquid crystalline systems. Mixtures of different ratios of Synperonic A7 and water were produced. By increasing the water content of the systems, lamellar and hexagonal liquid crystal structures were observed. For the analysis of the prepared liquid crystalline systems polarising microscopy, rheology study, differential scanning calorimetry and dynamic swelling tests were carried out. The chlorhexidine diacetate release was examined by Franz-type vertical diffusion cell apparatus. The chlorhexidine diacetate release from hexagonal liquid crystalline preparations was characterised by zero-order release kinetics, while the drug release from lamellar liquid crystalline systems was described by anomalous (non-Fickian) transport. The results indicate that the drug release kinetic is strongly dependent on the liquid crystalline structure.

Anti-Infective Agents, Local↗

Pathological features of cerebral cortical capillaries are doubled in Alzheimer's disease and Parkinson's disease.

Cerebral capillaries represent a major interface between the general circulation and the central nervous system and are responsible for sufficient and selective nutrient transport to the brain. Structural damage or dysfunctioning carrier systems of such an active barrier leads to compromised nutrient trafficking. Subsequently, a decreased nutrient availability in the neural tissue may contribute to hampered neuronal metabolism, hence to behavioral and cognitive functional deficiencies. Here we focus on the ultrastructural abnormalities of cerebral microvessels in Alzheimer's disease (AD: n = 5) and Parkinson's disease (PD; n = 10). The capillary microanatomy in samples from the cingulate cortex was investigated by electron microscopy and severe damage to the vessel walls was observed. Characteristic pathological changes including capillary basement membrane thickening and collagen accumulation in the basement membrane were enhanced in both AD and PD. The incidence of capillaries with basement membrane deposits was two times higher in AD and PD than in age-matched controls. Degenerative pericytes in all groups appeared at a similar frequency. The data indicate that basement membrane deposits, as opposed to pericytic degeneration, represent an important pathological feature of AD and PD and suggest that capillary dysfunction may play a causal role in the development of these two major neurodegenerative diseases.

Aged↗

Some factors affecting metal ion-monohydroxamate interactions in aqueous solution.

The chelating properties exhibited by a series of monohydroxamic acids (propanohydroxamic acid (Pha), hexanohydroxamic acid (Hha), benzohydroxamic acid (Bha), N-methyl-acetohydroxamic acid (MAha), N-phenyl-acetohydroxamic acid (PhAha) and 2-hydroxypyridine-N-oxide (PYRha)) towards copper(II), nickel(II), zinc(II), calcium(II), magnesium(II) and aluminium(III) ions were studied by pH-metric, spectrophotometric and, in one case, by 27Al NMR methods. The results were compared with the corresponding data for metal ion-acetohydroxamate (Aha) and metal ion-desferrioxamine B (DFB) complexes. Changes of the substituents either on the carbon or on the nitrogen of the hydroxamate moiety caused a measurable effect on the chelate stability only in the case of aluminium(III) complexes. The aromatic derivative, PYRha, formed significantly more stable complexes than expected on the basis of the ligand basicity. The higher complex-forming ability of DFB compared to monohydroxamic acids diminishes in the case of the largest calcium(II) ion.

Aluminum↗

Metal complexes of salicylhydroxamic acid (H2Sha), anthranilic hydroxamic acid and benzohydroxamic acid. Crystal and molecular structure of [Cu(phen)2(Cl)]Cl x H2Sha, a model for a peroxidase-inhibitor complex.

Stability constants of iron(III), copper(II), nickel(II) and zinc(II) complexes of salicylhydroxamic acid (H2Sha), anthranilic hydroxamic acid (HAha) and benzohydroxamic acid (HBha) have been determined at 25.0 degrees C, I=0.2 mol dm(-3) KCl in aqueous solution. The complex stability order, iron(III) >> copper(II) > nickel(II) approximately = zinc(II) was observed whilst complexes of H2Sha were found to be more stable than those of the other two ligands. In the preparation of ternary metal ion complexes of these ligands and 1,10-phenanthroline (phen) the crystalline complex [Cu(phen)2(Cl)]Cl x H2Sha was obtained and its crystal structure determined. This complex is a model for hydroxamate-peroxidase inhibitor interactions.

Copper↗

Similar ultrastructural breakdown of cerebrocortical capillaries in Alzheimer's disease, Parkinson's disease, and experimental hypertension. What is the functional link?

The brain, as an intensely active organ, is highly dependent on a sufficient nutrient and oxygen availability in order to reach its optimal working capacity. It is well known that the vital supply of energy substrates is provided by the circulatory system, which splits up into a fine, terminal capillary network in target tissues. These capillaries are considered as important sites, since the actual nutrient trafficking takes place through their walls. That is why an intact, preserved structure of the microvessels is crucial to fulfill their function. Since the brain is known to be particularly vulnerable to suboptimal oxygen and glucose delivery, the intact morphology of capillaries is of paramount importance. Several observations have indicated that the cerebral capillary ultrastructure is damaged in Alzheimer's disease (AD). Curiously, the regional cerebral blood flow of AD patients is also significantly lower than in age-matched control individuals. Based on these data, it has been suggested that the decreased blood supply and the cerebrovascular alterations contribute to the development of dementia. However, we have observed similar capillary damage in Parkinson's disease patients and chronically hypertensive rats in addition to AD cases, as presented here. These findings indicate that cerebral capillary damage is not exclusive for AD but occurs under other neurodegenerative disorders and hypertension, as well. We hypothesize that ultrastructural abnormalities of cerebral capillaries are causally related to decreased cerebral blood flow and create a condition that favors neurodegenerative mechanisms including the development of dementia.

Alzheimer Disease↗

[Feasibility and accuracy of the combined radioisotope and blue-dye guided sentinel lymph node biopsy in breast cancer].

Sentinel lymph node biopsy is a minimally invasive operation for staging regional lymph nodes in breast cancer. This method was introduced in the last decade. However there are some remaining questions regarding labelling, surgical technique, indications, and the pathological examination of the removed sentinel lymph nodes which have to be answered before can be introduced as the routine clinical practice. 98 patients with primary breast cancer underwent double guided (radioisotope and blue-dye) sentinel lymph node biopsy in our department during a surgical feasibility study between December 1997 and February 2000. The operation was successful in 92 patients (94%). False negative rate, sensitivity and accuracy were 15%, 85% and 95% retrospectively. During the learning curve the success rate improved from 83% to 99%, the sensitivity from 79% to 89% and the accuracy from 88% to 97% and the false negative rate decreased from 21% to 11%. In T1 tumors the false negative rate and accuracy were 6% and 98%, while in T2 tumors these were 24% and 86%. Application of a larger particle sized colloid (200-600 nm), subareolar injection and next day operation technique had no effects on the results. Double guided sentinel lymph node biopsy is a sensitive surgical staging procedure which accurately predicts the lymph node status in T1 breast tumors. The technique used by us is easy to reproduce, and learn and is beneficial in technical and radiation protection aspects.

Adult↗

[Initial experiences with sentinel lymph node biopsy in malignant melanoma].

Elective versus therapeutic lymph node dissection has been a controversial field of the surgical treatment of cutaneous malignant melanoma for more than two decades. The identification and biopsy of the sentinel lymph node in different solid malignancies has become feasible by the method described by Morton in 1992. The sentinel lymph node is the first tumor draining lymph node in the regional lymph node basin. If metastasis is not proven in the sentinel node by detailed histological study those are unlikely in other regional lymph nodes and formal lymph node dissection can be omitted. Patients undergoing surgery for primary cutaneous (intermediate or high risk) melanoma have been initiated in this feasibility study. Of the 40 patients the sentinel lymph node biopsy was unsuccessful in two and at least one positive sentinel lymph node was found in nine patients. The duration of the procedure is between five and 15 minutes. After this feasibility study further prospective and randomized studies are projected.

Adult↗

[The role of intraoperative gamma-probe-guided sentinel lymph node biopsy in the treatment of malignant melanoma and breast cancer].

In the treatment of malignant tumors regional lymphadenectomy is used for two purposes. It is used partly for staging the regional lymph nodes which is a significant and independent prognostic factor and determines the need for adjuvant oncologic treatment and partly for achieving locoregional disease control. Removal of tumor-free lymph nodes by regional lymph node clearance is unnecessary according to our current knowledge. Since the sensitivity and specificity of non-invasive clinical examinations are insufficient in predicting the nodal status the histological study of the regional lymph nodes cannot be abandoned. A new and minimally invasive surgical procedure, the mapping and removal of the first tumor draining lymph node, the sentinel node provides the possibility of pathological nodal staging without performing formal lymphadenectomy. Mapping of the sentinel node can be performed by the use of a radioisotope and intraoperative hand-held gamma-probe or a vital blue dye or a combination of these two. This latter method was used by the authors in 73 patients (25 with malignant melanoma and 48 with breast cancer). Sentinel lymph node biopsy was performed successfully in 92% of patients with melanoma and 90% of patients with breast cancer. In three breast cancer patients the sentinel node inaccurately predicted the axillary status as negative, but is was in 93% accurate in predicting the histologic nodal state. According to our preliminary experiences intraoperative gamma-probe guided sentinel lymph node biopsy is considered a feasible procedure in both malignant melanoma and breast cancer. More experiences are needed before introducing this method in the routine clinical practice.

Biopsy↗

Cerebral hypoperfusion yields capillary damage in the hippocampal CA1 area that correlates with spatial memory impairment.

The impact of chronic cerebral hypoperfusion on cognitive function and cerebral capillary morphology in the hippocampus was examined. Young adult Wistar rats were subjected to permanent ligation of both common carotid arteries (two-vessel occlusion). One month after vascular occlusion, a small but non-significant impairment in the acquisition of spatial information was registered compared with sham-operated controls. Two months after surgery, the occluded animals displayed an impaired performance throughout the training period. One year after surgery, the acquisition curves demonstrated a significant attenuation of the learning rate in the occluded rats group, whereas no significant differences in long-term retention were observed. Thus, chronic hypoperfusion induced by two-vessel occlusion gave rise to impairment of spatial memory. Following behavioural testing, the rats were killed at the age of 17 months, and capillaries in the CA1 and dentate gyrus were examined using transmission electron microscopy. Typical age-related capillary abnormalities such as degenerative pericytes and thickened basement membranes (with or without fibrosis) were detected in the hippocampus of sham animals. In occluded rats, the occurrence of capillaries displaying such abnormalities almost doubled in the CA1 region, but was similar in the dentate gyrus, compared with sham controls. A highly significant correlation was found between the last Morris maze performance and the percentage of capillaries with deposits in the basement membrane in the hippocampal CA1 area of occluded rats, which was not present in the sham animals. We conclude that a long-term hypoperfusion accelerated the development of age-related ultrastructural aberrations of capillaries in the hippocampal CA1 area, but not in the dentate gyrus. Thus, not only neurons, but also capillaries in the hippocampal CA1 area are sensitive to an impaired microcirculation. Moreover, the cognitive performance of hypoperfused rats correlated closely with the condition of the capillaries in the CA1 area, suggesting that capillary integrity is one of the important determinants of brain function in conditions that compromise cerebral microcirculation.

Animals↗