Protocol for Clozapine Rechallenge in a Case of Clozapine-Induced Myocarditis.

OBJECTIVE: Protocol for clozapine rechallenge in patients with a history of clozapine-induced myocarditis. METHOD: Clozapine-related cardiovascular adverse effects including myocarditis and cardiomyopathy have limited its widespread use in treatment-resistant schizophrenia. Here, we present a case of clozapine-induced myocarditis and successful cautious rechallenge. Ms. AA, a young female patient with severe psychosis developed myocarditis during her initial clozapine titration phase, which was thus discontinued. Subsequent response to other medications was poor, and she remained significantly disabled. We reviewed blood-based biomarkers identified during the emergence of her index episode of myocarditis and developed a successful clozapine rechallenge protocol, based on careful monitoring of changes in these indices and a very slow clozapine re-titration. RESULTS AND CONCLUSIONS: This protocol may have utility in the management of patients with a history of clozapine-induced myocarditis.

Headspace collection of grapevine volatiles in a Hungarian vineyard.

L. botrana is a major pest of the grapevine, the larvae is feeding on the flower buds and the berries. Because of the damage of the larvae, secondary fungal infection can be evolved by the grey mold (Botrytis cinerea). A special blend of plant volatiles are emitted by the host plant. Mated L. botrana females use olfactory cues to find their host plant and oviposition sites. Grapevine volatiles were collected in 2012 and the blend was analyzed with GC, numerous compounds were present in the collected blend. More grapevine volatiles will be collected in 2013, in several phenological stadia of different grapevine varieties.

Toxicity of chlorothalonil containing formulation and Cu-sulphate to chicken.

The agrochemicals are being used increasing amounts in plant protection. The plant protection must pay close attention to the decrease or complete elimination of the damage to the environment which affects wildlife, because the cultivated plants provided not only feedstuffs for wild birds but a living and hatching territory as well. The pesticides sprayed during the plant protection activities might have an influence not only on mature birds but also on the embryos in the eggs. The eggs may be exposed to pesticides, the toxic effect of which may appear as embryo lethality and development anomalies. The aim of this study was to determine the individual and combined toxic effects of a chlorothalonil containing fungicide formulation (BRAVO 500) and copper sulphate on the development of chicken embryos. The test materials were injected directly into the air-chamber in a volume of 0.1 ml/egg on the first day of incubation. Applied concentration of copper sulphate was 0.01% and the concentrations of fungicide BRAVO 500 were 1% and 10%. The chicken embryos were examined for the followings: rate of embryo mortality, body weight, type of developmental anomalies, light microscopic examination. Our teratogenicity study revealed that, the combined administration of injected copper sulphate and chlorothalonil containing fungicide formulation (BRAVO 500) caused a significant reduction in the body weight of embryos, markedly increased the rate of embryonic mortality and the incidence of developmental anomalies. The joint toxic effect of copper sulphate and chlorothalonil containing fungicide formulation (BRAVO 500) is an additive effect compared to the individual toxicity of the test materials.

First Report of Tomato chlorosis virus in Tomato from Hungary.

A disease of tomato (Lycopersicon esculentum Mill.) was observed in three greenhouses in Tömörkény in southern Hungary in the autumn of 2007. Thirty percent of the plants were chlorotic and stunted and had mottled leaves with interveinal yellowing and necrosis. Similar symptoms induced by Tomato chlorosis virus (ToCV) on tomato have been reported in other countries (1,2). ToCV is a Crinivirus in the Closteroviridae family, which can cause a decline in plant vigor and reduced fruit yield. ToCV is transmitted by whiteflies (Trialeurodes vaporariorum West., T. abutilonea Hald., and Bemisia tabaci Genn.) and grafting, but cannot be transmitted mechanically. Only T. vaporariorum is known to be present and widespread in Hungary. Virus presence was confirmed by reverse transcription-PCR as described by Louro et al. (2). cDNA synthesis with ToCV specific primers (ToCV-UP 5'-TCATTAAAACTCAATGGGACCGAG-3' (3) and ToCV-DW 5'-GCGACGTAAATTGAAACCC-3') was successful and electron microscopy revealed ToCV-like particles. The PCR product has been sequenced (GenBank Accession No. HQ444266) and showed 97 to 99% identity to ToCV isolates in GenBank. According to the symptoms, amplified region, sequence data, and electron microscopy, the tomato samples from Tömörkény were confirmed to be infected with ToCV. The economic losses associated with ToCV were minor. To our knowledge, this is the first report on the occurrence of ToCV in Hungary. References: (1) G. P. Accotto et al. Plant Dis. 85:1208, 2001. (2) D. Louro et al. Eur. J. Plant Pathol. 106:589, 2000 (3) J. Th. J. Verhoven et al. Plant Dis. 87:872, 2003.

Magnetoelectric coupling at metal surfaces.

Magnetoelectric coupling allows the magnetic state of a material to be changed by an applied electric field. To date, this phenomenon has mainly been observed in insulating materials such as complex multiferroic oxides. Bulk metallic systems do not exhibit magnetoelectric coupling, because applied electric fields are screened by conduction electrons. We demonstrate strong magnetoelectric coupling at the surface of thin iron films using the electric field from a scanning tunnelling microscope, and are able to write, store and read information to areas with sides of a few nanometres. Our work demonstrates that high-density, non-volatile information storage is possible in metals.

Magnetic anisotropy and magnetization dynamics of individual atoms and clusters of Fe and Co on Pt(111).

The recently discovered giant magnetic anisotropy of single magnetic Co atoms raises the hope of magnetic storage in small clusters. We present a joint experimental and theoretical study of the magnetic anisotropy and the spin dynamics of Fe and Co atoms, dimers, and trimers on Pt(111). Giant anisotropies of individual atoms and clusters as well as lifetimes of the excited states were determined with inelastic scanning tunneling spectroscopy. The short lifetimes due to hybridization-induced electron-electron scattering oppose the magnetic stability provided by the magnetic anisotropies.

First Report of Impatiens necrotic spot virus in Ornamental Plants in Hungary.

Economically important viruses such as Tomato spotted wilt virus, genus Tospovirus, are transmissible mechanically and mainly by two thrips species (Thrips tabaci and Frankliniella occidentalis) in Hungary (1). Samples (31) of eight ornamental plant species (Catharanthus roseus, Cyclamen persicum, Dendranthema × grandiflorum, Eustoma grandiflorum, Gerbera sp., Impatiens walleriana, Ocimum basilicum, and Verbena hybrida) were studied. Symptoms including color breaking on flowers and necrotic symptoms on leaves were observed on four samples (C. persicum, I. walleriana, O. basilicum, and E. grandiflorum). Infection by Impatiens necrotic spot virus (INSV) was determined by double-antibody sandwich-ELISA and triple-antibody sandwich-ELISA using antisera obtained from Loewe (Sauerlach, Germany) and the DSMZ. Back inoculation with the F. occidentalis vector was also carried out to Lycopersicon esculentum as indicator plants. Back inoculation was also positive for INSV by symptoms and ELISA. The high amount of ornamental plant production together with the use of virus-infected propagation material and the increasing thrips vector populations may result in significantly increased establishment and distribution of INSV in Hungary. References: (1) M. L. Daughtrey et al. Plant Dis. 81:1220, 1997.

Magnon excitation with spin-polarized scanning tunneling microscopy.

Using spin-polarized scanning tunneling microscopy, the local excitation of magnons in Fe and Co has been studied. A large cross section for magnon excitation was found for bulk Fe samples while for thin Co films on Cu(111) the cross section linearly scales with film thickness. Recording inelastic tunneling spectra with Fe coated W tips in a magnetic field, the magnonic nature of the excitation was proven. Magnon excitation could be detected without the use of a separating insulating layer opening up the possibility to directly study magnons in magnetic nanostructures via spin-polarized currents.

Electronic structure study by means of x-ray spectroscopy and theoretical calculations of the "ferric star" single molecule magnet.

The electronic structure of the single molecule magnet system {M[Fe(L(1))(2)](3)}4CHCl(3) [M=Fe,Cr;L(1)=CH(3)N(CH(2)CH(2)O)(2) (2-)] has been studied using x-ray photoelectron spectroscopy, x-ray-absorption spectroscopy, soft-x-ray emission spectroscopy, as well as theoretical density-functional-based methods. There is a good agreement between theoretical calculations and experimental data. The valence band mainly consists of three bands between 2 and 30 eV. Both theory and experiments show that the top of the valence band is dominated by the hybridization between Fe 3d and O 2p bands. From the shape of the Fe 2p spectra it is argued that Fe in the molecule is most likely in the 2+ charge state. Its neighboring atoms (O,N) exhibit a magnetic polarization yielding effective spin S=52 per iron atom, giving a high-spin state molecule with a total S=5 effective spin for the case of M=Fe.

Crop-weed competition between sunflower (Helianthus annuus L.) and Convolvulus arvensis L. in substitutive experiments.

The main characteristics of a substitutive experiment is that the proportions of two species in the mixtures are varied while the overall density of the two species is maintained constant - a replacement series. In our experiments early competition between sunflower and field bindweed (Convolvulus arvensis) was studied in a replacement studies under glasshouse conditions. Pot experiments were set up with the following treatments: 1, sunflower 100% (6 plants pot(-1)); 2, sunflower 66.6% (4 plants pot(-1)) + C. arvensis 33.3% (2 plants pot(-1)); 3, sunflower 33.3% (2 plants pot(-1)) + C. arvensis 66.6% (4 plants pot(-1)); 4, C. arvensis 100% (6 plants pot(-1)). Sixty eight days after sowing dry weight of shoots and roots were measured and nitrogen (N), phosphorus (P) and potassium (K) content was also determined. Dry biomass production of sunflower was almost twice higher as compared to that of C. arvensis without interspecific competition. Dry weight of sunflower and C. arvensis shoots and roots for a plant continuously decreased by reducing their proportion in the mixtures. Higher biomass production of sunflower suggests, that its development is faster at the beginning of vegetation penod, therefore sunflower has better competitive ability in sunflower--C. arvensis mixtures in the early competition as compared to C. arvensis. Shoot:root ratio of plants did not change considerably in mixtures, but generally was ten times higher in sunflower plants, as compared to that of C. arvensis. Shoots generally contained macro elements at higher concentration as compared to those of roots. Total NPK content of sunflower was reduced by 53 and 82% for a pot, as its proportion decreased in the mixtures. More severe reduction in NPK content was observed in case of C. arvensis, which also proves stronger competitive ability of sunflower in the early vegetation.

Susceptibility of some Lycopersicon species and varieties to cucumber mosaic virus (CMV) and tobacco mosaic virus (TMV).

Susceptibility of 33 Lycopersicon species and varieties to Tobacco mosaic virus (TMV) and Cucumber mosaic virus (CMV) were studied. Plants were mechanically inoculated with the C/U1 strain of TMV and U/246 strain of CMV. Virus infection was checked by symptomatology, DAS ELISA and back inoculation (biotest). All the studied Lycopersicon species and varieties were susceptible to TMV-C/U1. L. esculentum Mill. convar. infiniens Lehm. var. flammatum Lehm., L. esculentum Mill. convar. fruticosum Lehm. var. speciosum Lehm. and L. esculentum Mill. convar. infiniens Lehm. var. validum Bail. showed extreme resistance to CMV-U/246. The other 30 species and varieties were susceptible to CMV-U/246. New compatible and incompatible host-virus relations have been reported. The extreme resistant Lycopersicon varieties could be used as resistance sources in tomato breeding.

Susceptibility of some weed species to Pepino mosaic virus (PepMV).

The aim of our investigations was to study the susceptibility of 22 weed species to Pepino mosaic virus (PepMV). Seven plants of each species were mechanically inoculated at 4-6 leaf stage with PepMV in a vector free virological glasshouse. Inoculated plants were tested on the basis of symptoms, by DAS ELISA serological method and back inoculation. Among the 22 weed species, only some Solanum ones (S. aethiopicum, S. dulcamara, S. luteum, S. nigrum) were susceptible to PepMV infection. All of them--except S. aethiopicum--belong to Hungarian weed flora, therefore these weeds--occurring mainly in tomato ecosystems--may play important role in the epidemiology of PepMV. Other 18 weed species seemed to be resistant to PepMV, and on the basis of back inoculation not even latent infection has been observed.

Experimental and natural weed host-virus relations.

Weeds, as alternative hosts of plant viruses and nutrient plants of virus vectors play important role in virus ecology and epidemiology. The aim of our study was to discover new weed-virus relations. Therefore some weed species were mechanically inoculated with 28 viruses (strains or isolates) maintained in our glasshouse. Different weed species with and without visible symptoms were collected from agro-, water ecosystems and wastelands of Hungary between 1997 and 2003. Virus infections were evaluated by biotests, DAS ELISA serological methods, electronmicroscopy and immunosorbent electronmicroscopy (ISEM). Under glasshouse conditions Ambrosia artemisifolia was considered as a virophob species, showing resistance to all viruses listed above. A series of new artificial (Chenopodium album--SoMV (LH+SH)*, AMV (LH+SH); C. berlandieri--PVY(NTN) (LH), AMV (LH+SH), CMV (LH), SoMV (LH+SH), ObPV (LH+SH), ZYMV-10 (LH): C. ugandae--ObPV (LH), SoMV (L); C. glaucum--ObPV (LH), SoMV (L); Echinocystis lobata--PVX (L), ZYMV (LH+SH); Solanum nigrum--MYFV (LH+SH), PVY(N) (L), PVY(NTN) (LH+SH), SoMV (LH), TMV (SH), CMV (SH); S. dulcamara--CMV-U/246 (SH), PVY(NTN) (LH), SoMV-H (L), TMV-O (L); S. luteum--PVY(N) (SH), PVY(NTN) (LH+L), TMV(SH).) and natural (Asclepias syriaca--TMV, AMV, TSWV; Alisma plantago-aquatica--PVY, SoMV; Ambrosia artemisiifolia--CMV; Chenopodium album--CMV, PVS, PLRV; C. hybridum--CMV; Cirsium canum--CMV, PVM; Carex vulpina--CMV; Comium maculatum--PVY; Datura stramonium--PVA, PVX, PVS, PVM, CMV, TMV; Lysimachia vulgaris--ArMV, BNYVV, CMV, TMV; Lythrum salicaria--ArMV; Malva neglecta--CMV; Mercurialis annua--SoMV; Solanum nigrum--CMV, PVY, PVY(N); Solidago gigantea--CMV, RpRSV, BNYVV; Stenactis annua--PVM, PVA) weed--virus relations were detected. The epidemiological role of perennial hosts (A. syriaca, A. planlago aquatica, C. canurm, L. vulgaris, L. salicaria, S. gigantea) is especially high, because they can serve as infection sources as well as overwintering hosts of different plant viruses.

Effective control method of larvae of Diabrotica virgifera virgifera Leconte.

Larvae of WCR are feeding on the roots of corn while plants fall down. The egg hatching is continuous and soil insecticides are not effective to kill larvae. Unfortunately the recent control methods while we incorporate disinfectors Into the soil under seeding are not able to give enough effect on larvae of WCR under the whole period of larval development. We use to saw corn in the middle of April but eggs hatching start in the middle of May. The effectiveness of insecticides takes about one month so they are not able to protect plants from larvae are feeding on roots (Luckman et al., 1974 and Luckmann et al., 1975). They cause yield losses or in case of plant fall we can not harvest the corn. We have tested a material in greenhouse screening and field trips that is able to absorb insecticides and bind them into its body. This material is able to emit the agents continuously under the vegetation and we can protect our plants against the damages of WCR larvae. Our results shows that the material is able to elongate the effectiveness of the pesticides over 60 days and able to push the number of larvae under the economical threshold.

The ecological study of cotton bollworm (Helicoverpa rmigera Hubner 1808) in Hungary.

The cotton bollworm (Helicoverpa armigera Hbn.) is a poliphagous pest. Caterpillars feed on flowers, crops and seeds. In 2001 the meaningful catching-period was in August (Szeoke, 2001). In 2003 we detected the swarming already in June. We observed many caterpillars on its nutritive crops. It caused significant economic damage in this year. 1ST EXAMINATION: We collected larvae and reared pupae out of it in a pot. We took it into the soil. The swarming of the moths from the pots was in June. The mortality was high, more than 90%. 2ND EXAMINATION: We made cold tests with pupae. We examined 5 x 10 pupae in three treatments. In the first treatment we reduced the temperature to -2 degrees C for 4 weeks. 92% of the pupae survived this cold. In the second treatment we reduced the temperature to -2 degrees C for 3 weeks and to -7 degrees C for 1 week. 86% of the pupae survived this procedure. In the third treatment we reduced the temperature to -2 degreesbC for 3 weeks and -15 degrees C for 1 week. 100% of the pupae were perished. 3RD EXAMINATION: In the first treatment we raised caterpillars on 13 hours lighting and 24 degrees C. The swarming was from 20th April to 4th May 2004. In the second treatment we reared the worms on 20 hours lighting and 18 degrees C. The main swarming was on 3rd January 2004. So we could say that the cotton bollworm has diapause. The more effective factor of the diapause is the length of the lighting.

Susceptibility of Capsicum breeding lines to NTN strain of Potato virus Y (PVY(NTN)) and Obuda pepper virus (ObPV).

The objective of this study was to examine the reaction of 12 Capsicum breeding lines to NTN strain of Potato virus Y (PVY(NTN)) and 16 lines to Obuda pepper virus (ObPV). Inoculated plants were symptomatologically and serologically checked for virus infection. Back inoculation was also carried out to Nicotiana tabacum 'Xanthi-nc' and N. tabacum 'Samsun' as indicator plants. Out of the 12 lines tested four (32.Bogyiszlói, 4/99 F2, 17/99 F2 and VI-61 in.) proved to be resistant (immune) to PVY(NTN). Seven Capsicum lines (9/99 F2, 17/99 F2, V-21 = 28/98 F3, V-28 = 36/98 F3, V-3 = 7/98 F2, V-6 = 13/98 F2, and V-10 = 17/98 F2) showed hypersensitive reaction to ObPV. Other breeding lines were susceptible to ObPV infection. One line (17/99 F2) showed immunity to PVY(NTN) and hypersensitivity to ObPV at the same time, therefore this one is considerably valuable for breeding pepper varieties for multivirus resistance.

Reaction of Lycopersicon species and varieties to Potato virus Y (PVY(NTN)) and Tomato mosaic virus (ToMV).

Virus susceptibility of 33 Lycopersicon species and varieties to NTN strain of Potato virus Y (PVY(NTN)) and Tomato mosaic virus (ToMV) were studied. Inoculated plants were tested for infection symptomatologically, serologically and by back inoculation as well. New incompatible and compatible host-virus relations have been determined. All tested plants were susceptible to ToMV. However, Lycopersicon esculentum Mill. convar. parviboccatum Lehm. var. cerasiforme (Dun.) Alef. s.l., L. peruvianum (L.) Mill. and L. hirsutum Humb. et Bonpl. were extreme resistant (immune) to PVY(NTN). Other species were susceptible. Resistant lycopersicon genotypes could be used as sources for virus resistance.

New host-virus relations between different Solanum species and viruses.

We have studied the susceptibility or resistance of Solanum capsicastrum Link. et Schauer, S. comatum Sendt., S. dulcamara L., S. luteum Mill., S. malacoxylon Sendt. and S. nigrum L. to three aphid transmissible viruses [alfalfa mosaic alfamovirus (AMV), potato M. carlavirus (PVM) and potato S carlavirus (PVS)]. Out of the species, S. capsicastrum, S. comatum, S. dulcamara, S. malacoxylon and S. nigrum to AMV, S. capsicastrum and S. malacoxylon to PVM and S. capsicastrum, S. luteum and S. nigrum to PVS showed the highest resistance (immunity). Symptoms could not be seen on inoculated plants and the virus could be detected by them neither by serological nor biological tests. Solanum luteum plants were susceptible to AMV. Solanum comatum, S. dulcamara, S. luteum and S. nigrum showed susceptibility to PVM. Solanum comatum and S. dulcamara were susceptible to PVS. Symptoms (necrotic lesions, mosaic and chlorosis) could be seen after inoculation and the absorbance values (DAS-ELISA) exceeded twice that of the healthy control samples during the serological tests.

In vitro metabolism of mifepristone (RU-486) in rat, monkey and human hepatic S9 fractions: identification of three new mifepristone metabolites.

1. In vitro metabolism of the antiprogestin drug mifepristone (RU-486) was studied after incubation with rat, monkey and human hepatic S9 fractions in the presence of an NADPH-generating system. 2. Unchanged mifepristone (approximately 45% of the sample(s) in rat; approximately 70% in monkey; approximately 65% in human) plus six metabolites, three known and three new, were profiled, quantified and tentatively identified on the basis of MS and MS/MS data. 3. The proposed metabolic pathways for mifepristone are proposed, and the two metabolic steps are (A) N-demethylation and (B) methyl oxidation. 4. Step A formed N-desmethyl mifepristone (M1) in major amounts (approximately 35% s in rat, 16% in monkey and human) and N,N-didesmethyl mifepristone (M2) in minor amounts (< 5% s in all species). Step B, or in conjunction with step A, produced four minor/trace metabolites, namely hydroxymethyl mifepristone (M3), hydroxymethyl M1 (M4), hydroxymethyl M2 (M5) and formyl mifepristone (M6).

Biotransformation of the antipsychotic agent, mazapertine, in dog--mass spectral characterization and identification of metabolites.

1. Biotransformation of the antipsychotic agent, mazapertine, was studied after a single oral administration of 14C-mazapertine succinate (10 mg/kg, free base) to six beagle dogs (three male, three female). 2. Following oral administration of 14C-mazapertine, plasma (0-48 h), urine (0-7 days), and faeces (0-7 days) were collected. Recoveries of total radioactivity in urine and faeces were 26.9 and 62.0% of the dose, respectively. 3. Unchanged mazapertine plus 14 metabolites were isolated and identified, which accounted for > 60% of the sample radioactivity in the plasma, 17% of the dose in urine and 28% of the dose in faecal extract. 4. Unchanged mazapertine accounted for < 4% of the radioactive dose in excreta samples and < 21% of the sample radioactivity present in plasma samples. 5. Seven metabolic pathways for the formation of metabolites were identified including: (1) phenyl hydroxylation, (2) piperidyl oxidation, (3) O-dealkylation, (4) N-dephenylation, (5) oxidative N-debenzylation, (6) depiperidylation and (7) conjugation. 6. Pathways 1, 2, 5 and 6 produced 4-OH-piperidyl, OH-phenyl-OH-piperidyl, carboxybenzoyl piperidine and depiperidyl analogues of mazapertine as major metabolites.