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The occurrence of a periosteal chondroma (juxtacortical chondroma) in an adult male Uromastyx maliensis is documented for the first time. The chondroma developed near the right shoulder joint from the periosteal membrane, causing partial atrophy in the surrounding skeletal muscles. In the chondroma tissues widespread central necrosis and secondary calcium salt deposition were observed. Monomorphic chondrocytes were irregularly spread in the chondromucin matrix. The lizard had locomotor problems due to irritation of the periosteum and reduced movement of the bones constituting the shoulder joint caused by the chondroma.

The interaction of laser light with a metal surface yields a complex configuration of point defects, e.g., droplets and holes and vortex microfilaments. When a single filament interacts with a defect it "winds" around the defect and can form loops, and rings. Interaction of a single filament with a single defect gives rise to arc deformation bending, formation of loops and rings, while its interaction with a two-dimensional (2D) random lattice of defects gives rise to the vortex filament splitting and breaking which occur at nodal points of the Voronoi lattice. Interaction of one-dimensional (1D) vortex filament lattice with 2D lattice of defects results in the formation of knotted structures such as the Hopf links as well as 1D and 2D Hopf link crystals, knotted along the sides of the Voronoi lattice. We observed that configurations of vortex filaments are organized at three hierarchical levels of growing complexity. Every level is comprised of the elements of the lower complexity one, indicating the presence of a supercomplexity.

Background: Although postoperative heart failure is a major determinant of operative mortality in cardiac surgery it has received little attention in the literature, and long-term consequences remain to be addressed. Therefore, the impact of postoperative heart failure on long-term survival in relation to other risk factors was studied., Methods: All patients undergoing aortic valve replacement (AVR) for aortic stenosis from 1995 through 2000 in the southeast region of Sweden (n = 398) were compared with a cohort, matched for age and sex, undergoing coronary artery bypass grafting (CABG [n = 398]). Risk factors for 5-year mortality were analyzed., Results: Forty-five AVR and 47 CABG patients required treatment for postoperative heart failure. Thirty-day, 1-year, and 5-year mortality in patients with and without postoperative heart failure after AVR were 6.7% versus 1.4% (p = 0.05), 8.9% versus 4.0% (p = 0.13), and 42.2% versus 14.2% (p < 0.0001) respectively. Corresponding results in the CABG group were 21.3% versus 1.1% (p < 0.0001), 25.5% versus 3.1% (p < 0.0001), and 36.2% versus 11.1% (p = 0.0015). Postoperative heart failure, preoperative renal dysfunction, procedure-associated stroke, body mass index less than 19 kg/m2, older age, preoperative atrial fibrillation, and preoperative anemia turned out as independent risk factors for 5-year mortality after AVR. In the CABG group, postoperative heart failure, diabetes mellitus, older age, and procedure-associated stroke emerged as independent risk factor for 5-year mortality., Conclusions: Postoperative heart failure was associated with high early mortality after CABG whereas the grave consequences of postoperative heart failure after AVR for aortic stenosis became evident only with time.

The aim of this work was to develop a simple, economic procedure for the manufacturing of coated iron(II) sulfate particles by using a crystallization technique for the development of round particles, followed by coating with a lipophilic material. Several batches of iron(II) sulfate heptahydrate were produced by a cooling crystallization, with variation of the crystallization parameters. The spherical crystals were coated with stearin. The products were characterized for particle size, roundness, bulk density and in vitro drug dissolution. Crystallization was performed from deionized water with no addition of seed crystals and by cooling by applying a linear cooling rate. The developed iron(II) sulfate crystals were round with average diameter of 729+/-165 microm. The best form for the sustained release of iron(II) sulfate was the sample HTP-2 which contained 11% of stearin relative to the iron(II) sulfate. The spherical crystallization of iron(II) sulfate is simple and fast, and does not require a dangerous, expensive solvent. The round particles can coat directly with lipophilic material which results in slow release of iron(II) sulfate and protects the iron(II) from oxidation and inhibits the loss of crystal water. The coated crystals can be filled into capsules to yield the final dosage form.

Chronic pain states and epilepsies are common therapeutic targets of voltage-gated sodium channel blockers. Inhibition of sodium channels results in central muscle relaxant activity as well. Selective serotonin reuptake inhibitors are also applied in the treatment of pain syndromes. Here, we investigate the pharmacodynamic interaction between these two types of drugs on spinal neurotransmission in vitro and in vivo. Furthermore, the ability of serotonin reuptake inhibitors to modulate the anticonvulsant and windup inhibitory actions and motor side effect of the sodium channel blocker lamotrigine was investigated. In the hemisected spinal cord model, we found that serotonin reuptake inhibitors increased the reflex inhibitory action of sodium channel blockers. The interaction was clearly more than additive. The potentiation was prevented by blocking 5-HT(2) receptors and PKC, and mimicked by activation of these targets by selective pharmacological tools, suggesting the involvement of 5-HT(2) receptors and PKC in the modulation of sodium channel function. The increase of sodium current blocking potency of lamotrigine by PKC activation was also demonstrated at cellular level, using the whole-cell patch clamp method. Similar synergism was found in vivo, in spinal reflex, windup, and maximal electroshock seizure models, but not in the rotarod test, which indicate enhanced muscle relaxant, anticonvulsant and analgesic activities with improved side effect profile. Our findings are in agreement with clinical observations suggesting that sodium channel blocking drugs, such as lamotrigine, can be advantageously combined with selective serotonin reuptake inhibitors in some therapeutic fields, and may help to understand the molecular mechanisms underlying the interaction.

Background & Aims: Glutamate plays an important role for myocardial metabolism in association with ischaemia. Patients with coronary artery disease characteristically demonstrate increased uptake of glutamate. Improved recovery of myocardial metabolism and haemodynamic state after coronary surgery has been reported in patients treated with glutamate infusion. However, the effect of glutamate has not been studied after other cardiac surgical procedures. In addition, the effects of glutamate on peripheral tissue metabolism remain to be described., Methods: Twenty patients undergoing surgery for aortic stenosis were studied after randomisation to blinded infusion of glutamate or saline during 1h immediately after skin closure. Myocardial and leg tissue metabolism were assessed with organ balance techniques., Results: Postoperative glutamate infusion induced a marked increase in myocardial and leg tissue uptake of glutamate. This was associated with a significant uptake of lactate in the heart. The negative arterial-venous differences of amino acids and free fatty acids across the leg were significantly smaller in the glutamate group. Haemodynamic state remained stable and did not differ between groups., Conclusion: The heart and peripheral tissues consumed the exogenously administered glutamate after surgery for aortic stenosis. Potentially favourable effects of glutamate on myocardial and peripheral tissue metabolism are suggested.

The effects of heavy metal pollutants on aquatic birds have been widely studied in ecotoxicological investigations; however, the predominant focus has been on the postnatal period of life. Limited information on the adverse effects of metals to bird eggs is available. The possible toxic effects of lead and copper were studied in mallard eggs. After the accidental severe heavy metal pollution of the Tisa river (Hungary) in March 2000, these metals were detected in the highest concentration in both the water and the sediment, reaching far beyond acceptable concentrations. Pb treatment (2.9 mg/L) significantly increased the rate of mortality after a single immersion of the eggs into polluted water for 30 min. The rate of dead embryos significantly increased after the combined exposure to Cu and Pb (0.86 and 2.9 mg/L, respectively) both in the single- (once for 30 min) and in the multiple- (10s daily during first trimester of incubation) immersion groups. It was concluded that elevated metal concentrations similar to those found in the Tisa river after the tailing dam failure may cause toxic effects (mortality and teratogenicity) upon exposure of mallard eggs.

Aspergillus terreus is a ubiquitous fungus in our environment. It is an opportunistic human pathogen and economically important as the main producer of lovastatin, a cholesterol lowering drug. Our aim was to examine the genetic variability of A. terreus and closely related species using molecular and analytical techniques. Lovastatin production was examined by HPLC. Lovastatin was produced by seven isolates belonging to the species A. terreus. RAPD analyses were carried out using 25 different random primers. Neighbor-joining analysis of RAPD data (120 characters) resulted in clustering of the A. terreus isolates into distinct groups. Some correlation was observed between lovastatin producing abilities of the isolates and their position on the dendrogram based on RAPD profiles. The internal transcribed spacer region and the 5.8S rRNA gene of A. terreus and related isolates was also sequenced. Phylogenetic analysis of sequence data let us classify the isolates into different clades which mostly correspond to the species Aspergillus terreus, Aspergillus flavipes, Aspergillus niveus, Aspergillus carneus and Aspergillus janus/A. janus var. brevis. Aspergillus allahabadii, A. terreus var. aureus and A. niveus var. indicus belonged to the A. niveus clade, while an Aspergillus isolate previously classified as A. niveus was most closely related to A. flavipes isolates. Aspergillus anthodesmis formed a distinct branch on the tree. Although it was previously suggested based on 28S rDNA sequence data that Aspergillus section Terrei should include A. carneus and A. niveus isolates, phylogenetic analysis of ITS sequences indicate that A. flavipes isolates are more closely related to A. terreus than A. carneus isolates. Our data suggest that sections Terrei and Flavipedes should be merged. However, further loci should be analysed to draw more definite conclusions.

In the present study, the effect of specific, membrane-permeable calpain inhibitor, PD150606, was analysed on synaptic efficacy in in vitro brain slices experiments after ischemic insult of rats in vivo, and on cell viability in a glutamate excitotoxicity test in mouse cell culture. Bilateral common carotid artery ligation (BCCL) for 24 h markedly increased calpain activity and enhanced LTP induction in rat hippocampus, although the CA1 layer significantly shrank. The enhancement of LTP could be diminished by short-term application of PD150606 (40 microM) into the perfusion solution. Intracerebroventricular administration of PD150606 (100 microM) parallel with ischemic insult prevented LTP and effectively inhibited hippocampal calpain activity. Intracerebroventricularly applied PD150606 inhibited the CA1 layer shrinkage after common carotid ligation. High level of exogenous glutamate caused marked decrease of cell viability in mouse cerebellar granule cell cultures, which could be partly warded off by 20 microM PD150606. Our data witness that calpain action is intricately involved in the regulation of synaptic efficacy.

Objectives: To identify characteristics of older primary care patients who were cognitively impaired and who underwent mental status testing by their physicians., Design: Cross-sectional and retrospective analysis., Setting: Seven small-town primary care practices., Participants: A total of 1,107 patients with a mean+/-standard deviation age of 76.3+/-6.6, screened using the Mini-Mental State Examination (MMSE); medical records reviewed., Measurements: Demographics, MMSE, medical record information. Odds ratios (OR) with 95% confidence intervals (CI), adjusted for age, sex, and education., Results: Thirty-one percent of the sample had MMSE scores of less than 25. Among these patients, physicians documented memory loss in only 23% which was significantly more often than in the higher scoring group (OR=1.9, 95% CI=1.3-2.8), basic activity of daily living (ADL) impairment in 7.9% (OR=2.4, 95% CI=1.3-4.4), instrumental ADL (IADL) impairment in 6.7% (OR=2.2, 95% CI=1.1=4.2), dementia in 12.2% (OR=3.7, 95% CI=2.0-6.8), and prescription of cholinesterase inhibitors in 7.6% (OR=4.4, 95% CI=1.9-10.2). Physicians recorded mental status testing largely in patients with research MMSE scores of 24 to 28, significantly more often when they also documented memory loss (OR=3.8, 95% CI=2.5-5.6) or impaired IADLs (OR=2.7, 95% CI=1.4-5.2), diagnosed dementia (OR=4.9, 95% CI=2.8-8.6), referred to specialists (OR=6.3, 95% CI=2.5-16.2) or social services (OR=3.6, 95% CI=1.8-7.3), or prescribed cholinesterase inhibitors (OR=8.5, 95% CI=4.2-17.5)., Conclusion: Physicians noted impairment in a minority of impaired patients. They tested mental status in those with documented cognitive and functional difficulties, in very mildly impaired patients, and in those for whom they intervened.

Introduction: The authors report their in vivo and in vitro results of the elution characteristics of gentamycin sulfate from bone cement, which is the most commonly used way of local antibiotic prophylaxis in Europe in the field of orthopedic surgery., Aim: The aim of this study was to investigate the elution of the gentamycin sulfate from bone cement, describe the dynamics of the emission in time and evaluate the relationship between the minimal inhibitory concentration (MIC) and the eluted concentration of the antibiotic., Methods: The in vivo investigation samples were taken from 9 patient from drain fluids to evaluate the eluted antibiotic concentration by fluorescent polarisation immunoassay method (FPI). The in vitro emission-dynamics of two different bone cement-Gentamycin sulphate complex were analysed by plate diffusion method during one-year period after mixing., Results: Their results showed that 24 hours after the operation the gentamycin concentrations in the drain fluid taken from around the endoprosthesis implanted with Palacos-R bone cement diminished, yet remained above the MIC level. High but rapidly decreasing antibiotic level was detected by the in vitro method within the first week, reading an almost steadily low concentration by the end of the first month. Surprisingly, after one year it was still possible to demonstrate the inhibitory effect of the drug from both tested types of cements., Conclusions: It is concluded that the gentamycin is able to elute from the bone cement in useful concentration after the implantation of endoprosthesis. However, this in vitro method is a useful and reproducible technique for the measurement of the efficacy of antibiotic emission from bone cement, the conversation of the results to the in vivo remains to be obscured. Nevertheless, the usage of local antibiotic prophylaxis seems to be useful during orthopaedic major intervention.

Calpains, the Ca(2+)-dependent thiol proteases, are abundant in the nervous tissue. The ubiquitous enzyme forms in mammals are heterodimers consisting of a specific, micro or m, large (catalytic) subunit and, apparently, a common small (regulatory) subunit (CSS1). Recently, however, we described a second form of small subunit (CSS2), which is of restricted occurrence [Schád, E., Farkas, A., Jékely, G., Tompa, P. & Friedrich, P. (2002) Biochem. J., 362, 383-388]. Here we analysed the distribution of immunoreactivity in various parts of rat brain against two anti-CSS1 and two anti-CSS2 antibodies by correlated light and electron microscopy. Remarkably, the antibodies showed differential distribution in various parts of rat cortex: anti-CSS1 reacted mainly with perikarya and dendrites, whereas anti-CSS2 was more prominent in axons. In serial sections CSS2 and synaptophysin gave very similar patterns, i.e. these epitopes seem to colocalize. Electron microscopy confirmed that CSS1 was mainly localized postsynaptically in dendrites and somata, whereas CSS2 was found presynaptically. The hypothesis is advanced that these distinct distributions of calpain subunits may be related to the transport of these enzymes in nerve cells.

The heat-shock protein Hsp90 has been shown to be essential for the functional integrity of the telomerase complex. The telomerase activity is enhanced in melanoma and stabilizes the chromosomal integrity in proliferating cells. Furthermore, overexpression of Hsp90 induces silencing of point mutations in transcription factors which, otherwise, would result in a loss-of-function phenotype. In melanocytic lesions there is a higher risk of mutations caused by the enhanced proliferation in melanocytic cells. By analyzing microdissected melanocytic tumors by semiquantitative PCR, we demonstrate an overexpression of Hsp90 mRNA in malignant melanomas (10/14) and in melanoma metastases (6/6) as well as in melanoma cell lines (9/9) when compared with melanocytic nevi (2/9). These results could be confirmed on protein level by immunohistochemistry. While melanocytic nevi show discrete Hsp90 expression only in a minor fraction (2/9), malignant melanomas and metastases show a positive Hsp90 immunohistochemistry in the majority of cases; (7/9) and (13/14), respectively. In addition, by analyzing melanoma metastases by flow cytometry we show that Hsp90 is expressed on the surface of tumor cells (7/8). From these data we conclude that Hsp90 is present in advanced malignant melanomas and may have a stabilizing effect on the cellular functions in proliferating cells of melanocytic lesions and could thereby be a prerequisite for the tumor progression. As Hsp90 is expressed on the cell surface, it might also be a potential immunorelevant target structure for immunotherapy of melanoma.

Fungal polyketide synthases are responsible for the biosynthesis of several mycotoxins and other secondary metabolites. The aim of our work was to investigate the diversity of polyketide synthases in Aspergillus species using two approaches: PCR amplification using oligonucleotide primers, and bioinformatics. Ketosynthase domain probes amplified DNA fragments of about 700 bp in each examined isolate. Sequences of these domains were aligned and analyzed by phylogenetic methods. The ketosynthase domain sequences were highly diverse indicating that they most probably represent polyketide synthases responsible for different functions. A. albertensis and A. niger ketosynthase domain sequences clustered together with sequences of genes required for pigment biosynthesis (wA) in A. nidulans and P. patulum, while the ketosynthase domain sequence of A. muricatus was most closely related to an A. parasiticus wA type domain sequence, and those of the A. ochraceus isolates formed a distinct clade on the tree. These sequences were highly homologous to an A. terreus naphthopyrone synthase gene. An Aspergillus fumigatus genomic database was also searched for ketosynthase domain sequences, which have been included in the phylogenetic analysis. Altogether 14 putative ketosynthase domain sequences were identified. Clustering of the ketosynthase domain sequences correlated well with the type of metabolites produced by the corresponding polyketide synthases. At least 8 clusters with putative ketosynthase domain sequences of unknown function have been identified. Further studies are in progress to clarify the role of some of the identified polyketide synthase genes.

The neuroprotective effect of BGP-15 against peripheral sensory neuropathy was studied in rats that were exposed to short-term cisplatin or taxol administration. The changes of nerve conduction velocity were determined in situ after treating the Wistar rats with BGP-15 (50, 100, and 200 mg/kg po daily doses throughout the experiment), cisplatin (1.5 mg/kg ip daily dose for 5 days), or taxol (5.0 mg/kg ip daily dose every other day in a 10-day interval) alone or giving the test compound in combination with cisplatin or taxol. Electrophysiological recordings were carried out in vivo by stimulating the sciatic nerve at both sciatic notch and ankle site. Neither motor nor sensory nerve conduction velocity was altered by any dose level of BGP-15 tested. Both anticancer drugs decreased the sensory nerve conduction velocity (SNCV). BGP-15 treatment prevented the impairment of SNCV either in part or totally in the cisplatin- or taxol-treated groups. This neuroprotective potential of BGP-15 could be well correlated with its recently described poly(ADP-ribose) polymerase- inhibitory effect and its ability to protect against the damages induced by the increased level of reactive oxygen species in response to anticancer treatment.

Cell membrane localization of the 72 kDa heat shock protein 70 (Hsp70) has been found on different tumour cell lines, on biopsy material from solid tumours and metastases and on leukaemic blasts from acute myelogenous leukaemia patients, but not on the corresponding normal tissues, as determined by flow cytometry using the Hsp70-specific monoclonal antibody C92F3B1. In the present study Hsp70 membrane expression was studied on primary malignant melanomas, melanoma metastases, melanocytes, human skin fibroblasts and peripheral blood lymphocytes, together with expression of the melanoma-associated markers Mel-1, Mel-2 and Mel-5, major histocompatibility complex class I and the fibroblast-specific marker ASO2. As previously shown, fibroblasts and peripheral blood lymphocytes from healthy human volunteers were found to be negative for Hsp70 and for the melanoma-associated markers Mel-1, Mel-2 and Mel-5. Human melanocytes from healthy human donors were also negative for Hsp70, but were positive for Mel-1 and Mel-5. Independent of the Clark's level, all the malignant melanomas (n = 9) and metastases (n = 11) exhibited were positive for both Mel-1 and Mel-2. The primary melanomas could be divided into two groups according to their Hsp70 and Mel-5 expression pattern: those with an Hsp70-negative and a Mel-5-positive phenotype (-/+) (five out of nine), and those with an Hsp70-positive and a Mel-5-negative phenotype (+/-) (four out of nine). All the melanoma metastases (n = 11) had an Hsp70-positive, Mel-5-negative phenotype (+/-). These data provide the first hint that the marker combination Hsp70 positive/Mel-5 negative might be useful in estimating the metastatic potential of a melanoma. Investigations on changes in the marker combination Hsp70/Mel-5 during onset of melanoma disease and progression will clarify its potential as a prognostic risk factor.

The purpose of the presentation was to draw attention to a possible complication of a minimally invasive therapy outlining the complex role of the systemic etiologic factors. A patient with dermal pressure urticaria and polyvalent anaphylactic reactions showed up at our Dental Clinic. Urticaria was also present in the oral cavity. The main objective of the treatment plan was to find out how the edentulous alveolar ridge can be loaded and the selective support haw can be distributed on the abutment teeth. After the preventive and conservative phase of our comprehensive treatment lower and upper removable partial dentures were designed based on the selective support principles. In the maxilla a full denture while in the mandible a partial metal plate was made. After the metal framework having been tried in a second functional impression was taken to maximally utilize the advantages of the mixed (dental and mucogingival) support. The upper and lower alveolar mucosa could tolerate the denture plates after the insertion and only minute oedema occurred on the upper jaw along the post dam region which could be eliminated by small adjustments. It was concluded that in case of a known pressure urticaria the occlusal load of the edentulous mucosa can be kept on a tolerable level. Especially on the soft tissues with thick submucous layer can developed sever oedema (giant oedema, Quincke--oedema) that can lead to breathing difficulties, suffocation or even death.

Parametric analysis of cryogenic cooling of shell eggs was performed using finite element analysis. Two cooling temperatures (-50 and -70 C), three cooling convective heat transfer coefficients (20, 50, and 100 W/ m2K), two equilibration temperatures (7 and 25 C), and two equilibration heat transfer coefficients (0 and 20 W/ m2K) were considered in the analysis. Lower temperatures and higher cooling convective heat transfer coefficients resulted in higher cooling rates and lower final egg temperatures. A chart and equation were developed to identify combinations of processing parameters to yield the desired egg temperature (7 C) at the end of adiabatic equilibration. Results show that a cooling time of 8.2 min was required to reach a final egg temperature of 7 C for a cooling temperature of -50 C and a convective heat transfer coefficient of 20 W/m2K. The cooling time decreased to 2 min when the convective heat transfer coefficient increased to 100 W/m2K, at a cooling temperature of -50 C. Processing at -70 C and 20 W/m2K, required 5.3 min to reach a final temperature of 7 C. At a higher convective heat transfer coefficient (100 W/m2K) and -70 C, a processing time of 1.3 min was sufficient to reach the target temperature of 7 C. The results may be used as a reference in process or equipment design for shell egg cooling in cryogenic CO2.

The ultraviolet (UV) components of sunlight induce damage to the DNA in skin cells, which is considered to be the initiating step in the harmful biological effects of UV radiation. Repair of DNA damage results in the formation of single-strand DNA breaks, which activate the nuclear poly(ADP-ribose) polymerase (PARP). Overactivation of PARP worsens the oxidative cell damage and impairs the energy metabolism, raising the possibility that moderation of PARP activation following DNA damage may protect skin cells from UV radiation. The topical effects of the novel PARP inhibitor O-(3-pyperidino-2-hydroxy-1-propyl) pyridine-3-carboxylic acid amidoxime monohydrochloride (BGP-15M) were investigated on UV-induced skin damage in a hairless mouse model. For evaluation of the UV-induced acute photodamage to the skin and the potential protective effect of BGP-15M, DNA injury was detected by measuring the formation of single-strand DNA breaks and counting the resulting sunburn (apoptotic) cells. The ADP-ribosylation of PARP was assessed by Western blot analysis and then quantified. In addition, the UV-induced immunosuppression was investigated by the immunostaining of tumor necrosis factor alpha and interleukin-10 expressions in epidermal cells. The signs of inflammation were examined clinically and histochemically. Besides its primary effect in decreasing the activity of nuclear PARP, topically applied BGP-15M proved to be protective against solar and artificial UV radiation-induced acute skin damage. The DNA injury was decreased (P<0.01). An inhibition of immunosuppression was observed by down-regulation of the epidermal production of cytokines IL-10 and TNFalpha. In the mouse skin, clinical or histological signs of UV-induced inflammation could not be observed. These data suggest that BGP-15M directly interferes with UV-induced cellular processes and modifies the activity of PARP. The effects provided by topical application of the new PARP-regulator BGP-15M indicate that it may be a novel type of agent in photoprotection of the skin.

The suprachiasmatic nuclei (SCN) constitute the principal pacemaker of the circadian timing system in mammals. The generated rhythm is forwarded mostly through projections to various hypothalamic nuclei. On the other hand, the regulated processes feedback to the SCN. One of the possible feedback pathways is the orexinergic projection from the lateral hypothalamus. Orexins are recently identified neuropeptides with an overall facilitatory effect on waking behaviors. Orexinergic fibers are widely distributed throughout the brain and are also present in the SCN. In this study we examined the effect of orexin-A on the spontaneous activity of rat SCN cell in vitro. Neurons showed 2 different firing pattern (continuous-regular, intermittent-irregular). Orexin-A increased firing rate in both cell types at 10(-8) M concentration, but caused a clear suppression of neuronal activity at 10(-7) M. Continuously firing neurons were less responsive than those firing intermittently. These results show that orexin-A may play a role in the modulation of the circadian pacemaker function. The neuropeptide might exert both direct, postsynaptic effects on SCN neurons and indirect, presynaptic effects on excitatory and inhibitory terminals. The dose-dependent modification of the firing rate indicate that the weight of these factors changes with the concentration of orexin-A.

The aim of the study was to investigate the role of circulating (i.e., present in the serum) and locally produced (i.e., in the lamina propria of mucous membranes) immunoglobulins including IgE. The IgG, IgA, IgM immunoglobulins, and IgE (total and specific) were measured in patients' sera with atopic dermatitis (AD) (n = 93). As control subjects 83 healthy volunteers, matched for sex and age, were included. The IgG and IgM levels were within the normal range. Mean value of the total IgA (2.55 +/- 0.26 g/L, in controls 1.49 +/- 0.32 g/L) and IgE (609 IU/mL, in controls below 40 IU/mL) levels were significantly elevated (p < 0.05) in sera of AD patients. Based on the serum total IgE levels (above or below 40 IU/mL) the patients were divided into RAST-positive and RAST-negative types of allergy, respectively. RAST-positive AD (n = 79) showed hypersensitivity to inhalant and food allergens determined by the specific IgE test. The majority of RAST-positive AD cases (n = 68) presented only skin manifestations, while the rest of the patients (n = 11) had rhinoconjunctivitis as well. RAST-positive AD patients with rhinoconjunctivitis showed an increased IgE level in tears (above 10 IU/mL). The specific IgE test positivity in tears correlated with elevated serum total IgE levels and specific IgE positivity (r = 0.925). Total and allergen-specific IgE in the tears can be used to diagnose allergy in vitro. It is believed that the mucosal permeability is enhanced in the atopic inflammatory process, and this may facilitate the transmission of environmental allergens.

The production of spherical crystals has recently gained great attention due to the fact that the crystal habit (form, surface, size, etc.) can be modified during the crystallization process. Spherical crystals of ASA were developed by non-typical and typical spherical crystallization techniques. The non-typical spherical crystallization process (conventional stirred tank method) resulted in few monocrystals and non-spherical crystal agglomerates. The typical spherical crystallization process was carried out by the three solvent-system (ethanol-water-carbon tetrachloride). The products were qualified by morphological study, NIR investigation, salicylic acid content, dissolution rate, studies on flowability, compactibility, cohesivity and tablettability. The results demonstrate that only typical spherical crystallization can be recommended for the production of spherical crystals of ASA. Only product made by this technique shows excellent flow properties and favourable compactibility, cohesiveness and tablettability values.

This study examined the effect of rapid cooling with air and CO2 on shell egg quality over 14 wk. The 240 fresh eggs were initially heated to 47 C for 24 h in an incubator, cooled using rapid air cooling or CO2 cooling, and then stored in air or CO2 in 250-mL jars for 14 wk. The CO2 levels were recorded of the jar atmosphere, of the egg air cell, and of the egg albumen. The Haugh units of each egg, pH, and of albumen from five eggs per group were also recorded. Haugh units are a logarithmic, empirical relationship between albumen height and egg weight (Stadelman, 1995). Haugh units for the control eggs averaged 70.8 over 10 wk of the study. The control eggs were of such poor quality that they could not be sampled after 10 wk. The air-cooled and CO2-stored eggs averaged 70.3 Haugh units over the 14-wk storage period; however, the egg quality significantly deteriorated after 10 wk. The CO2-cooled and CO2-stored eggs averaged 75.9 Haugh units over the 14 wk study, with no observable decrease in quality. Rapid air-cooling produces a lower quality egg than rapid cooling with CO2. Subsequent storage of rapidly air-cooled eggs in C02 may increase shelf life, but Haugh units were not statistically different from rapid air-cooled eggs. CO2-cooling and subsequent storage in CO2 increased Haugh units. The shelf life of shell eggs could be extended to greater than 14 wk when the eggs were CO2-cooled and CO2-stored.

The gas composition of the air cell in a shell egg is influenced by heating from egg washing and candling and the method of cooling and storage. This study found that N2 gas (-122 C), CO2 gas (-45 C), and cold air (-15 C) could be used to rapidly cool shell eggs from 47.7 C to 7 C in 30 min or less. These results suggest that the gas composition of the air cell in shell eggs can be significantly modified using N2 cooling and CO2 cooling. Commercial field studies have shown that these modifications, which take place during cryogenic cooling, can significantly reduce microbial levels and increase shelf life of shell eggs. Storage in a modified atmosphere environment further enhanced these changes. It was found that the CO2 concentration in the air cell of a shell egg can be increased from 0.04 to 48% by CO2 cooling and storage in a CO2 environment.

Background: The presence of lymphangiectasis without the characteristic spindle cell proliferation may lead to diagnostic difficulties in Kaposi's sarcoma. Although the literary data mention that the lymphangioma-like tumors may occur in Kaposi's sarcoma, there have been few specific reports and case presentations published., Observations: A case of lymphangioma-like Kaposi's sarcoma in association with IgG/lambda type paraproteinaemia is reported in a 60-year-old man. The HSV8 DNA sequence could be detected by PCR analysis from lesional skin., Conclusion: The beneficial effect of alpha-2 interferon (4.5 million units per week) combined with retinoic treatment (0.5 mg/body weight of isotretinoin) caused the regression of the skin rashes while improving the values of immunological tests (T cell function, quantity of paraproteins). The patient's improved general condition and the ameliorating immunological parameters were due to the combination of two regimens applied in a low-dose the alpha-2 interferon (tumor regression) and the oral isotretinoid (antitumor activity, reduction of IL-6 receptor display) treatment.

Vibrio vulnificus is a ubiquitous marine bacterium frequently isolated from shellfish and associated with severe and often fatal disease in humans. Various control strategies to reduce the disease risk associated with V. vulnificus contamination in shellfish have been proposed. However, evaluating the efficacy of these control strategies is complicated because of the difficulty in distinguishing V. vulnificus from the high levels of background environmental Vibrio spp. The purpose of this research was to develop a model indicator V. vulnificus strain that could be readily differentiated from background microflora and used to facilitate the evaluation of processing efficacy. A spontaneous nalidixic acid-resistant strain of V. vulnificus (Vv-NA) was prepared from a wild-type parent (Vv-WT) using selective plating techniques. Vv-NA was very similar to Vv-WT with respect to biochemical characteristics, appearance on selective plating media, detection limits using most probable number and polymerase chain reaction, and growth rate. In comparative freeze inactivation studies on pure cultures, Vv-WT and Vv-NA had similar freeze inactivation profiles at -20 degrees C (conventional freezing), at -85 degrees C (cold blast freezing), and in liquid nitrogen (cryogenic freezing). In oyster homogenates artificially inoculated with Vv-NA, the organism was inactivated 95 to 99% after freezing, irrespective of freezing temperature. Thermal inactivation comparisons of pure cultures of Vv-WT and Vv-NA using the capillary tube method revealed statistically significant differences in D values at 47 degrees C (2.2 versus 3.0 min, respectively) and 50 degrees C (0.83 versus 0.56 min, respectively), but nearly identical values at 52 degrees C (0.21 versus 0.22 min, respectively). However, these D values were notably higher than those reported by other investigators and hence provided a conservative means by which to evaluate thermal inactivation. In oyster homogenates seeded with Vv-NA, D values of 1.3+/-0.09 min and 0.41+/-0.01 min were obtained at 46 degrees C and 48 degrees C, respectively. This study demonstrated that Vv-NA is readily enumerated and could be used as a surrogate for evaluating the degree of V. vulnificus inactivation provided by freezing and thermal treatments of oyster homogenates.

We describe herein a brother and sister diagnosed with xeroderma pigmentosum variant (XP-V) in early adult life, who presented with increased sensitivity to sunlight and with cutaneous carcinomas on sun-damaged skin. The 27-year-old male farmer (Case 1.) was diagnosed with advanced squamous cell carcinoma (SCC) and multiple actinic lesions. Surgical removal of these lesions was performed. Three months later he died of multiple pelvic metastases of SCC. His 29-year-old sister (Case 2.) was operated on for different tumors, histologically SCC-s or basal cell carcinomas (BCC), or praecancerous conditions many times. After a two year interval she was treated with low dose isotretinoin (2 mg/body weight). Diagnosis of XP-V was based on unscheduled DNA analysis (USD) and on clinical symptoms. We observed that during the long lasting isotretinoin treatment the tumor frequency dropped to a quarter. Therefore, the isotretinoin treatment seems to be a good approach for cancer prevention in conditions with high predisposition to skin cancer, such as in XP-V.

In the present work we report the development of a new radioimmunoassay method for measuring the substance P content liberated from isolated rat tracheae in response to electrical or chemical (capsaicin, resiniferatoxin, piperine) stimulation. The amount of substance P released by electrical stimulation has been found to be dependent on the number of pulses and chemically elicited substance P release also proved to be dose-dependent. Our findings reinforce previous data that resiniferatoxin is approximately 100 times more potent than capsaicin and the potency ratio between piperine and capsaicin is 1/50.

Physical properties of crystals, such as size, crystal size distribution and morphology, may predetermine the usefulness of crystalline materials in many pharmaceutical application. The above properties can be regulated with the crystallization process. The spherical crystals are suitable for direct tablet-making because of their better flowability and compressibility properties. These crystals can be used in the filling of the capsule. In this work, the spherical crystals such as "single crystal", "poly-crystals" and agglomerates with other excipients are collected from the literature and the experimental results of the authors. A close cooperation between chemists and the pharmaceutical technologists can help for doing steps in this field.

Between 1991 and 1993, 32 cases of fingernail mycosis and 20 cases of toenail mycosis caused by dermatophytes were treated with terbinafine. For 8 weeks, 250 mg of terbinafine was given daily for fingernail infections, and for 12 weeks the same dose was given for toenail involvement; the short-term follow-up was 24 and 48 weeks respectively. A long-term follow-up was performed twice, initially at 24 and then at 48 months after the end of the treatment. For fingernail mycosis, the mycological cure rate was 100% at the end of month 24 and 91% at the end of month 48. Mycological cultures gave negative results in toenail infections in 90% after 24 months and in 86% after 48 months. After 24 months, 23 out of 26 patients (88%) with fingernail and 17 out of 20 patients (95%) with toenail mycosis were clinically cured. After 48 months, 20 out of 22 cases (91%) with fingernail and 10 out of 14 cases (71%) with toenail involvement showed a complete cure.

Preservation of the chemical architecture of a cell or of an organism under changing and perhaps stressful conditions is termed homeostasis. An integral feature of homeostasis is the rapid expression of genes whose products are specifically dedicated to protect cellular functions against stress. One of the best known mechanisms protecting cells from various stresses is the heat-shock response which results in the induction of the synthesis of heat-shock proteins (HSPs or stress proteins). A large body of information supports that stress proteins--many of them molecular chaperones--are crucial for the maintenance of cell integrity during normal growth as well as during pathophysiological conditions, and thus can be considered "homeostatic proteins." Recently emphasis is being placed on the potential use of these proteins in preventing and/or treating diseases. Therefore, it would be of great therapeutic benefit to discover compounds that are clinically safe yet able to induce the accumulation of HSPs in patients with chronic disorders such as diabetes mellitus, heart disease or kidney failure. Here we show that a novel cytoprotective hydroxylamine derivative, [2-hydroxy-3-(1-piperidinyl) propoxy]-3-pyridinecarboximidoil-chloride maleate, Bimoclomol, facilitates the formation of chaperone molecules in eukaryotic cells by inducing or amplifying expression of heat-shock genes. The cytoprotective effects observed under several experimental conditions, including a murine model of ischemia and wound healing in the diabetic rat, are likely mediated by the coordinate expression of all major HSPs. This nontoxic drug, which is under Phase II clinical trials, has enormous potential therapeutic applications.

Interleukin-8 is assumed to play a central role in the pathogenesis of psoriasis. Since an increased expression of the interleukin-8 receptor has been observed both in polymorphonuclear leukocytes and in affected psoriatic epidermis, we were interested in whether the interleukin-8 receptor could be a molecular target of antipsoriatic compounds. Cyclosporine, calcitriol, calcipotriol or dithranol caused a dose-dependent decrease in interleukin-8 binding to cultured human keratinocytes, while interleukin-8 binding to granulocytes was not affected. In addition, the interleukin-8-induced human leukocyte antigen-DR (HLA-DR) expression of keratinocytes was nearly completely blocked by treatment of the cells with these substances. The inhibition of the keratinocyte interleukin-8 receptor and its function by antipsoriatic drugs may contribute to their therapeutic action.

The functional regeneration of sensory nerves was investigated in 5 patients with skin defects (caused by leg ulcers, a burn or fasciitis necrotisans) after transplantation with a keratinocyte suspension. In this area, first the pain sense and soon after wards the cold and heat sense returned, followed finally by the flare reaction caused by the mustard oil test. No sweat production could be observed during the study, because sweat glands were not found after the keratinocyte transplantation. The reinnervation course is roughly the same for skin defects covered with split skin graft or with a keratinocyte suspension.

A case of cholangitis due to the migration of a metal clip used for surgical cholecystectomy 4 years earlier, is reported. The diagnostic approach and therapeutic options, either endoscopic or surgical are discussed. The use of resorbable clips during the performance of laparoscopic cholecystectomy should avoid this type of complication.

The hyperproliferative human keratinocyte line (HaCaT) was tested for dithranol tolerance (tachyphylaxis) at the cellular level. At day 4 after seeding, keratinocytes were treated with 0.3 or 1.0 microM dithranol. Data were compared with those from experiments including additional pretreatments with 0.3 microM at day 3, or at days 1 and 3. Protein content, DNA synthesis and protein synthesis (incorporation of 3H-thymidine and 14C-amino acids per protein) were determined at 24, 48 and 72 h after the last drug exposure. Protein content of attached cells decreased in relation to dose and frequency of treatments. Inhibition of DNA and protein synthesis (38.2% and 32.3%, respectively) also occurred 24 h after a single treatment with 0.3 microM dithranol, but was only 18.4% and 9.1% after pretreatment twice with 0.3 microM dithranol. This tolerance reaction in vitro, after repeated dithranol exposure of human keratinocytes, may be explained by a selective loss of drug-sensitive cells.

HaCaT cells, a rapidly multiplying human keratinocyte line, were tested for their sensitivity to antipsoriatic dithranol with regard to classical proliferation parameters and for the drug's action on the plasma membrane integrity by the dose- and time-dependent release of cytosolic lactate dehydrogenase (LDH). In the case of 3H thymidine as well as 14C amino acid incorporation the 50% inhibition concentration (IC50) was 0.2 microM dithranol 24 h after initial exposure to the drug. For protein content of attached cells the IC50 proved to be greater than 3.0 microM. Using 0.3, 1.0 and 3.0 microM dithranol, significant (p less than 0.05) dose dependent LDH release of 0.866 +/- 0.387, 1.842 +/- 1.127 and 2.938 +/- 1.635 mU per hour and cm2 confluent culture area was measured between the 5th and the 24th hour, compared to an acetone control of 0.504 +/- 0.299 mU/h x cm2. Between the 2nd and the 4th hour as well as from the 25th to the 48th hour and the 49th to the 72nd hour the LDH release after dithranol treatment did not exceed the control value. In accordance with these findings dose-dependent morphological signs of cell injury were detected by phase contrast microscopy beyond the 4th hour. The data reveal that: HaCaT cells are a very sensitive target for the antiproliferative action of dithranol; the drug causes considerable plasma membrane damage even at concentrations as low as 0.3 microM; and this membrane damage becomes evident after a latency of at least 4 h and for a limited period of up to 24 h.

With the advent of extended wear contact lenses, new potential benefits, risk and responsibilities have come into existence for contact lens patients and practitioners alike. Without a careful, thorough and systematic clinical approach, the practitioner will find himself experiencing only the pitfalls without enjoying the possible benefits. This paper will attempt to present such a clinical approach, emphasizing a deductive and holistic approach to extended wear lens fitting. Previous clinical and laboratory work will be reviewed as it pertains to this presentation. Through the use of a thorough case history and diagnostic evaluation, patients can be effectively screened and counseled as to their acceptability and selection into an extended wear lens program. Mutual patient and a doctor goals must be established and be compatible. Subsequent contact lens selection and patient management will be discussed as they relate to the fulfillment of these goals. Commonly found complications with extended wear of contact lenses will be reviewed as they pertain to both the lenses and the ocular structures. Methods of management of these complications will be discussed.