Two phase-matching regimes in high-order harmonic generation.

High-order harmonic generation (HHG) provides scalable sources of coherent extreme ultraviolet radiation with pulse duration down to the attosecond time scale. Efficient HHG requires the constructive interplay between microscopic and macroscopic effects in the generation volume, which can be achieved over a large range of experimental parameters from the driving field properties to those of the generating medium. Here, we present a systematic study of the harmonic yield as a function of gas pressure and medium length. Two regimes for optimum yield are identified, supporting the predictions of a recently proposed analytical model. Our observations are independent on the focusing geometry and, to a large extent, on the pulse duration and laser intensity, providing a versatile approach to HHG optimization.

Incidence and antibiotic susceptibility of genital mycoplasmas in sexually active individuals in Hungary.

The aim of this study was to examine the incidence and antibiotic sensitivity of Ureaplasma urealyticum and Mycoplasma hominis strains cultured from the genital discharges of sexually active individuals who attended our STD outpatient service. Samples were taken with universal swab (Biolab®, Budapest, Hungary) into the Urea-Myco DUO kit (Bio-Rad®, Budapest, Hungary) and incubated in ambient air for 48 h at 37 °C. The determination of antibiotic sensitivity was performed in U9 and arginin broth using the SIR Mycoplasma kit (Bio-Rad®, Budapest, Hungary) under the same conditions. Between 01.05.2008 and 31.12.2011, 373/4,466 (8.35 %) genito-urethral samples with U. urealyticum and 41/4,466 (0.91 %) genito-urethral samples with M. hominis infection were diagnosed in sexually active individuals in the National STD Center, Semmelweis University. U. urealyticum was isolated in 12.54 % in the cervix and 4.1 % in the male urethra, while M. hominis was isolated in 1.33 % in the cervix and 0.51 % in the male urethra. The affected age group was between 21 and 60 years old. U. urealyticum strains were sensitive to tetracycline (95.9 %), doxycycline (97.32 %), and azithromycin (85.79 %), and resistant to erythromycin (81.23 %), clindamycin (75.06 %), and ofloxacin (25.2 %). Cross-resistance occurred in 38.71 % of patients to erythromycin and clindamycin. M. hominis strains were sensitive to clindamycin, ofloxacin, and doxycycline in more than 95 %, to tetracycline in 82.92 %, and no cross-resistance was detected among the antibiotics. Our study confirms that the continuously changing antibiotic resistance of ureaplasmas and mycoplasmas should be followed at least in a few centers in every country, so as to determine the best local therapy options for sexually transmitted infection (STI) patients.

Bimoclomol: a nontoxic, hydroxylamine derivative with stress protein-inducing activity and cytoprotective effects.

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.

Economic weights of production and functional traits for Holstein-Friesian cattle in Hungary.

A bio-economic model was used to estimate economic values of 15 milk production, functional, growth and carcass traits for Hungarian Holstein-Friesian cattle. The calculations were carried out for the situation in Hungary from 2000 to 2007, assuming no production quotas. The marginal economic values were defined as partial derivatives of the profit function with respect to each trait in a production system with dairy cow herds and with sales of surplus male calves. The economic weights for maternal and direct components of traits were calculated multiplying the marginal economic values by the number of discounted expression summed over a 25-year investment period for 2-year-old bulls (candidates for selection). The standardized economic weight (economic weight x genetic standard deviation) of the trait or trait component expressed as percentage of the sum of the standardized economic weights for all traits and trait components represented the relative economic importance of this trait or trait component. The highest relative economic importance was obtained for milk yield (25%), followed by productive lifetime of cows (23%), protein yield and the direct component of a cow's total conception rate (9% each), the maternal effect of the total conception rate of cows and the somatic cell score (approximately 7% each), fat yield (5%) and mature weight of cows and daily gain in rearing of calves (approximately 4% each). Other functional traits (clinical mastitis incidence, calving difficulty score, total conception rate of heifers and calf mortality) reached a relative economic importance between 0.5% and 2%. Birth weight and dressing percentage were least important (<0.5%). Based on these results, the inclusion of productive lifetime and cow fertility in the breeding programme for Holstein-Friesian cattle in Hungary is advisable.

[Gastric cystic duplication--case report]. / Duplicatia chistica gastrica--prezentare de caz.

Gastrointestinal duplication is a rare surgical pathology, with unspecified symptoms, which explains why these malformations are difficult to diagnose correctly before surgery. The authors present a case of a gastric cystic duplication, that was diagnosed before surgery, as a pancreatic pseudocyst. The accurate diagnosis was established by surgery and based on histopathological examination.

Inactivation of bacterial pathogens in human milk by high-pressure processing.

Low-temperature, long-time (LTLT) pasteurization assures the safety of banked human milk; however, heat can destroy important nutritional biomolecules. High-pressure processing (HPP) shows promise as an alternative for pasteurization of breast milk. The purpose of this study was to investigate the efficacy of HPP for inactivation of selected bacterial pathogens in human milk. Human milk was inoculated with one of five pathogens (10(8) to 10(9) CFU/ml), while 0.1% peptone solution solutions with the same levels of each organism were used as controls. The samples were subjected to 400 MPa at 21 to 31 degrees C for 0 to 50 min or to 62.5 degrees C for 0 to 30 min (capillary tube method) to simulate LTLT pasteurization. Tryptic soy agar and selective media were used for enumeration. Traditional thermal pasteurization resulted in inactivation (> 7 log) of all pathogens within 10 min. In human milk and in peptone solution, a 6-log reduction was achieved after 30 min of HPP for Staphylococcus aureus ATCC 6538. After 30 min, S. aureus ATCC 25923 was reduced by 8 log and 6 log in human milk and peptone solution, respectively. Treatments of 4 and 7 min resulted in an 8-log inactivation of Streptococcus agalactiae ATCC 12927 in human milk and peptone solution, respectively, while Listeria monocytogenes ATCC 19115 required 2 min for an 8-log inactivation in human milk. Escherichia coli ATCC 25922 was inactivated by 8 log after 10 min in peptone solution and by 6 log after 30 min in human milk. These data suggest that HPP may be a promising alternative for pasteurization of human milk. Further research should evaluate the efficacy of HPP in the inactivation of relevant viral pathogens.

Supercomplex wave-vortex multiscale phenomena induced in laser-matter interactions.

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.

First occurrence of periosteal chondroma (juxtacortical chondroma) in Uromastyxmaliensis (Reptilia: Sauria: Agamidae).

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.

Does glutamate influence myocardial and peripheral tissue metabolism after aortic valve replacement for aortic stenosis?

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.

Detailed stability investigation of amorphous solid dispersions prepared by single-needle and high speed electrospinning.

In this research the long-term stability (one year) of amorphous solid dispersions (ASDs) prepared by high speed electrospinning was investigated at 25 °C/60% relative humidity (RH) (closed conditions) and 40 °C/75% RH (open conditions). Single needle electrospinning and film casting were applied as reference technologies. Itraconazole (ITR) was used as the model API in 40% concentration and the ASDs consisted of either one of the following polymers as a comparison: polyvinylpyrrolidone-vinyl acetate 6:4 copolymer (no hydrogen bonds between API and polymer) and hydroxypropyl methylcellulose (possible hydrogen bonds between oxo or tertiary nitrogen function of API and hydroxyl moiety of polymer). DSC, XRPD and dissolution characteristics of samples at 0, 3 and 12 months were investigated. In addition, Raman maps of certain electrospun ASDs were assessed to investigate crystallinity. A new chemometric method, based on Multivariate Curve Resolution-Alternating Least Squares algorithm, was developed to calculate the spectrum of amorphous ITR in the matrices and to determine the crystalline/amorphous ratio of aged samples. As it was expected ITR in single needle electrospun SDs was totally amorphous at the beginning, in addition hydroxypropyl methylcellulose could keep ITR in this form at 40 °C/75% RH up to one year due to the hydrogen bonds and high glass transition temperature of the SD. In polyvinylpyrrolidone-vinyl acetate matrix ITR remained amorphous at 25 °C/60% RH throughout one year. Materials prepared by scaled-up, high throughput version of electrospinning, which is compatible with pharmaceutical industry, also gained the same quality. Therefore these ASDs are industrially applicable and with an appropriate downstream process it would be possible to bring them to the market.

Enhancement of synaptic strength in the somatosensory cortex following nerve injury does not parallel behavioural alterations.

Following infraorbital nerve transection, underlying mechanisms of the altered synaptic strength were studied in rat barrel cortex slice experiments. In addition to the in vitro electrophysiological studies, open-field tests were run to detect possible behavioural changes associated with cortical oversensitization. Enhanced NMDA receptor-mediated component of the evoked field response appeared in the barrel cortex after nerve injury. The alteration was transient, very distinct on the first day following injury, and almost returned to normal level by the end of the second week. Behavioural changes had not followed this time-course since long-lasting alterations were detected in the open-field test. These observations are in agreement with findings that showed biphasic regenerative processes following nerve injuries in other cortical areas.

BGP-15, a nicotinic amidoxime derivate protecting heart from ischemia reperfusion injury through modulation of poly(ADP-ribose) polymerase.

The protective effect of O-(3-piperidino-2-hydroxy-1-propyl)nicotinic amidoxime (BGP-15) against ischemia-reperfusion-induced injury was studied in the Langendorff heart perfusion system. To understand the molecular mechanism of the cardioprotection, the effect of BGP-15 on ischemic-reperfusion-induced reactive oxygen species (ROS) formation, lipid peroxidation single-strand DNA break formation, NAD(+) catabolism, and endogenous ADP-ribosylation reactions were investigated. These studies showed that BGP-15 significantly decreased leakage of lactate dehydrogenase, creatine kinase, and aspartate aminotransferase in reperfused hearts, and reduced the rate of NAD(+) catabolism. In addition, BGP-15 dramatically decreased the ischemia-reperfusion-induced self-ADP-ribosylation of nuclear poly(ADP-ribose) polymerase(PARP) and the mono-ADP-ribosylation of an endoplasmic reticulum chaperone GRP78. These data raise the possibility that BGP-15 may have a direct inhibitory effect on PARP. This hypothesis was tested on isolated enzyme, and kinetic analysis showed a mixed-type (noncompetitive) inhibition with a K(i) = 57 +/- 6 microM. Furthermore, BGP-15 decreased levels of ROS, lipid peroxidation, and single-strand DNA breaks in reperfused hearts. These data suggest that PARP may be an important molecular target of BGP-15 and that BGP-15 decreases ROS levels and cell injury during ischemia-reperfusion in the heart by inhibiting PARP activity.

The interleukin-8 receptor: a potential target for antipsoriatic therapy?

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.

Impairment of neurogenic inflammatory and anti-inflammatory responses in diabetic rats.

The effect was studied of a primary (preconditioning) neurogenic inflammatory challenge induced by electrical stimulation of the peripheral stump of the sciatic nerve (20 V, 0.5 ms, 5 Hz, for 5 min) on neurogenic oedema (5 min later) induced by stimulation of the contralateral sciatic nerve. Plasma extravasation due to the second stimulation was decreased by 52.7+/-3.1% (P<0.01) in normal animals and by 29.7+/-2.2 and 18.1+/-1.5% with 50 mg/kg streptozotocin pretreatment i.v. 4 and 8 weeks previously, respectively. Subsequently, bilateral sciatic nerve stimulation increased baseline plasma somatostatin levels from 6.4+/-0.3, 11. 7+/-1.4, and 16.8+/-3.8 to 28.3+/-2.9 (P<0.01), 17.9+/-3.7, and 25. 1+/-1.7 pmol/l in normal, and 4- and 8-week diabetic animals, respectively. We conclude that experimental diabetes impairs the capability of a preconditioning neurogenic inflammatory episode to elicit a systemic anti-inflammatory effect. This is accompanied by a deficiency in elevation of the plasma somatostatin level in response to nerve stimulation, although the baseline plasma somatostatin level increases proportionally to the duration of experimental diabetes.

Reliability of the sensory responder classification to learned flavor cues: a test-retest study.

Previous work from this laboratory has examined the extent to which learned associations between the flavor of food and the caloric consequences of food ingestion influence daily energy intake in humans. We have consistently identified a subset of subjects, called sensory responders, whose intakes were strongly guided by flavor cues. Sensory responders were identified on the basis of post hoc examination of energy intake patterns. The purpose of this study was to confirm the reliability of this classification scheme using a test-retest paradigm. Eighteen normal-weight, free-living adults participated in the study. Subjects were first fed a high-calorie lunch with distinctive flavors for 5 consecutive days then a low-calorie lunch with different distinctive flavors for an additional 5 days. Following this training, the flavors in the lunches were covertly switched. Subjects whose intakes were influenced by the change in the flavor cues were classified as sensory responders and those whose intakes were not influenced by the switch in the flavor cues were classified as sensory nonresponders. Subjects then repeated the protocol. All subjects who were classified as sensory responders at the end of the first trial were similarly classified at the end of the second trial, indicating that their initial responses were reliable.

Immunomodulatory treatment with low-dose interferon-alpha and oral retinoic acid in lymphangioma-like Kaposi's sarcoma.

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.

Cancer protection in xeroderma pigmentosum variant (XP-V).

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.

Repeated treatment with dithranol induces a tolerance reaction in keratinocytes in vitro.

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.

Lactate dehydrogenase release as an indicator of dithranol-induced membrane injury in cultured human keratinocytes. A time profile study.

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.

Use of mutant strain for evaluating processing strategies to inactivate Vibrio vulnificus in oysters.

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.