RESUMO
Atmospheric acidity is increasingly determined by carbon dioxide and organic acids1-3. Among the latter, formic acid facilitates the nucleation of cloud droplets4 and contributes to the acidity of clouds and rainwater1,5. At present, chemistry-climate models greatly underestimate the atmospheric burden of formic acid, because key processes related to its sources and sinks remain poorly understood2,6-9. Here we present atmospheric chamber experiments that show that formaldehyde is efficiently converted to gaseous formic acid via a multiphase pathway that involves its hydrated form, methanediol. In warm cloud droplets, methanediol undergoes fast outgassing but slow dehydration. Using a chemistry-climate model, we estimate that the gas-phase oxidation of methanediol produces up to four times more formic acid than all other known chemical sources combined. Our findings reconcile model predictions and measurements of formic acid abundance. The additional formic acid burden increases atmospheric acidity by reducing the pH of clouds and rainwater by up to 0.3. The diol mechanism presented here probably applies to other aldehydes and may help to explain the high atmospheric levels of other organic acids that affect aerosol growth and cloud evolution.
RESUMO
This paper studies the effect of plant peptides of thionine Ns-W2 extracted from seeds of fennel flower (Nigella sativa) and ß-purothionine from wheat germs (Triticum kiharae), as well as a synthetic antimutagen (crown-compound), on the expression of several genes involved in the.control of cellular homeostasis, processes of carcinogenesis, and radiation response in human rhabdomyosarcoma cells (RD cells), T-lymphoblastoid cell line Jurkat, and blood cells. All of these agents acted as antimutagens-anticarcinogens, reducing the expression of genes involved in carcinogenesis (genes of families MMP, TIMP, and IAP and G-protein genes) in a tumor cell. A pronounced reduction in the mRNA level of these genes was caused by thionine Ns-W2, and the least effect was demonstrated by ß-purothionine. Antimutagens had very little effect on the mRNA levels of the several studied genes in normal blood cells.
Assuntos
Antimutagênicos/administração & dosagem , Peptídeos/administração & dosagem , Fenotiazinas/administração & dosagem , Extratos Vegetais/administração & dosagem , Rabdomiossarcoma/genética , Antimutagênicos/química , Carcinogênese/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Nigella sativa/química , Peptídeos/química , Fenotiazinas/química , Extratos Vegetais/química , Radiação Ionizante , Rabdomiossarcoma/tratamento farmacológico , Rabdomiossarcoma/patologia , Triticum/química , Proteína Supressora de Tumor p53/biossínteseRESUMO
The atmospheric oxidation of biogenic volatile organic compounds (BVOC) by OH radicals over tropical rainforests impacts local particle production and the lifetime of globally distributed chemically and radiatively active gases. For the pristine Amazon rainforest during the dry season, we empirically determined the diurnal OH radical variability at the forest-atmosphere interface region between 80 and 325 m from 07:00 to 15:00 LT using BVOC measurements. A dynamic time warping approach was applied showing that median averaged mixing times between 80 to 325 m decrease from 105 to 15 min over this time period. The inferred OH concentrations show evidence for an early morning OH peak (07:00-08:00 LT) and an OH maximum (14:00 LT) reaching 2.2 (0.2, 3.8) × 106 molecules cm-3 controlled by the coupling between BVOC emission fluxes, nocturnal NOx accumulation, convective turbulence, air chemistry and photolysis rates. The results were evaluated with a turbulence resolving transport (DALES), a regional scale (WRF-Chem) and a global (EMAC) atmospheric chemistry model.
Assuntos
Antimutagênicos/farmacologia , Benzodiazepinas/farmacologia , Regulação Neoplásica da Expressão Gênica , Linfócitos/metabolismo , Rabdomiossarcoma/metabolismo , Linhagem Celular Tumoral , Humanos , Proteínas Inibidoras de Apoptose/genética , Proteínas Inibidoras de Apoptose/metabolismo , Linfócitos/efeitos dos fármacos , Metaloproteinases da Matriz/genética , Metaloproteinases da Matriz/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , NF-kappa B/genética , NF-kappa B/metabolismo , Inibidor Tecidual de Metaloproteinase-1/genética , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Inibidor Tecidual de Metaloproteinase-2/genética , Inibidor Tecidual de Metaloproteinase-2/metabolismoAssuntos
Antimutagênicos/farmacologia , Transcrição Gênica/efeitos dos fármacos , Peptídeos Catiônicos Antimicrobianos/farmacologia , Estudos de Casos e Controles , Síndrome de Down/genética , Síndrome de Down/metabolismo , Glutationa Peroxidase/genética , Glutationa Peroxidase/metabolismo , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/metabolismo , Humanos , Linfócitos/efeitos dos fármacos , Linfócitos/metabolismo , Taxa de Mutação , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Nucleofosmina , Proteínas Oncogênicas/genética , Proteínas Oncogênicas/metabolismo , Proteínas de Plantas/farmacologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismoRESUMO
AIM: To optimize drug treatment in early (6 months) and late (up to 3 years) stages of postoperative period and to study its efficacy. MATERIAL AND METHODS: There were selected 72 patients with resistant epilepsy and epileptic encephalopathy symptoms from 467 patients operated for epilepsy. RESULTS: By the end of a 3-year follow-up observation, we found the reduction in seizure frequency and seizure control in 66.3% of patients; regression of EEG paroxysmal activity in 56.8% and reduction in mental disorder symptoms (anxiety and depression) in 12.7%. CONCLUSION: The data obtained substantiate the necessity to optimize antiepileptic and pathogenetic drug treatment of patients with resistant epilepsy and encephalopathy symptoms during the 3-year postoperative period.
Assuntos
Resistência a Medicamentos , Epilepsia/cirurgia , Anticonvulsivantes/uso terapêutico , Eletroencefalografia , Epilepsia/tratamento farmacológico , Feminino , Humanos , MasculinoRESUMO
The dynamics of growth-stimulating and cytotoxic activity of mouse peritoneal macrophages (PMo) in response to in vivo and in vitro bacillus Calmette-Guérin (BCG) or bestatin treatment was studied. It was shown that BCG and bestatin induce cytotoxicity in PMo, and that after the cytotoxic response strong growth-stimulating activity develops. PMo, rendered cytotoxic in vivo and afterwards cultivated in vitro, displayed the same switch from a cytotoxic to a growth-stimulating phase. These results suggest that the growth-stimulating phase is the obligatory PMo response to biological response modifiers (BRM) at least to BCG and bestatin. The growth rate of tumours, transplanted into mice during the cytotoxic phase of the response to BCG, was suppressed, whereas tumours transplanted during the growth-stimulating phase were stimulated. It appears that the development of a growth-stimulating phase after the cytotoxic phase of response to activation by BRM could be one of the reasons for the limited effectiveness of immunotherapy based on the application of macrophage activators.
Assuntos
Antibióticos Antineoplásicos/uso terapêutico , Vacina BCG/uso terapêutico , Fatores Imunológicos/uso terapêutico , Leucina/análogos & derivados , Ativação de Macrófagos/fisiologia , Neoplasias Experimentais/terapia , Animais , Divisão Celular/efeitos dos fármacos , Citotoxicidade Imunológica/efeitos dos fármacos , Feminino , Fibroblastos/efeitos dos fármacos , Técnicas In Vitro , Leucina/uso terapêutico , Ativação de Macrófagos/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Transplante de Neoplasias , Neoplasias Experimentais/imunologia , Neoplasias Experimentais/patologiaRESUMO
We have analyzed the serum from patients with refractory epilepsy for the presence of autoreactive antibodies to AMPA glutamate receptor subunits. The presence and the level of autoantibodies were assessed using immunoblot and ELISA with synthetic peptides specific for subregions of AMPA glutamate receptor subunits. Patients with refractory epilepsy exhibited strong immunoreactivity to GluR1 subunit compared to healthy donors and patients with Parkinson's disease and Alzheimer's disease. Weak immunoreactivity to other AMPA glutamate receptor subunits was also detected and the signal was diminished in the raw GluR4>GluR3>GluR2. The occurrence of autoantibodies to specific neurotransmitter subunits in the sera of patients with refractory epilepsy suggest that autoimmune process may underlie this disorder.
Assuntos
Autoanticorpos/sangue , Epilepsia/imunologia , Receptores de AMPA/imunologia , Ensaio de Imunoadsorção Enzimática , Epitopos/química , Epitopos/imunologia , Humanos , Receptores de AMPA/químicaRESUMO
The novel amphiphilic benzodithia-18-crown-6 butadienyl dye (1) forms relatively stable insoluble monolayers on distilled water (collapse pressure of 41 mN/m) and on aqueous subphases containing alkali metal or heavy metal salts (collapse pressures in the range of 27-38 mN/m, respectively). The dye 1 monolayer organization depends on chromophore association and interactions (especially complex formation) with heavy and alkali metal ions as deduced from surface pressure-area and surface potential-area isotherms as well as reflection spectra and Brewster angle microscopy observations. Dye 1 undergoes specific interactions with Hg(2+) and Ag(+), respectively (formation of different complexes). Nonspecific interactions have been observed with other salts, such as KClO(4) or Pb(ClO(4))(2). Further, dye 1 monolayers on 1 mM Hg(ClO(4))(2) solution undergo reversible photoisomerization, in contrast to monolayers on water and other aqueous salt subphases.
RESUMO
Peritoneal macrophages activated by BCG and cyclophosphamide were unable to complete elimination of small numbers of tumour cells in spite of high level of cytotoxicity and cytostatic activity of these cells. It is appeared useful to evaluate the influence of new immunomodulators and combinations of immunomodulators with chemotherapeutic drugs not only on the cytotoxic and cytostatic, but also on the "feeder" activity of macrophages.
Assuntos
Vacina BCG/farmacologia , Ciclofosfamida/farmacologia , Macrófagos/efeitos dos fármacos , Mieloma Múltiplo/imunologia , Animais , Citotoxicidade Imunológica/efeitos dos fármacos , Hibridomas/efeitos dos fármacos , Hibridomas/imunologia , Ativação de Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C3H , Cavidade Peritoneal/citologia , Fatores de TempoRESUMO
New amphiphilic photochromic benzo-15(18)-crown-5(6) ethers (APC) differing in the position of the octadecyl substituent and the size of the crown cavity were synthesized. The compounds form stable monolayers in the air/water and air/alkaline metal salt solution interfaces. The results of the pressure isotherm measurements, atomic force microscopy (AFM), and electronic spectroscopy show that the structure of the monolayers formed depends on the structure of the parent APC and the nature of the cation in salt solutions. The area per molecule of APC in the monolayer (specific area) is the smallest on the water surface and increases by 20-40% on the aqueous subphase surface with an increasing concentration of salts therein to indicate the formation of APC complexes with the metal cations. When the hydrophobic aliphatic substituent is displaced from position 3 to position 5 of the benzothiazole ring, the specific area on the surface of water and subphases decreases twofold, which indicates the compactization of the monolayer on this modification. A reversible E-Z-photoisomerization of APC was found in the monolayers formed in the salt solution/air interface. The features of the reaction are defined by the specific organization of the amphiphilic molecules in the monolayer and by the nature of the cation.
Assuntos
Corantes/síntese química , Éteres Cíclicos/síntese química , Luz , Tensoativos/síntese química , Ar , Álcalis , Corantes/química , Corantes/efeitos da radiação , Éteres Cíclicos/química , Éteres Cíclicos/efeitos da radiação , Espectroscopia de Ressonância Magnética , Microscopia de Força Atômica , Microscopia Eletrônica , Soluções , Estereoisomerismo , Propriedades de Superfície , Tensoativos/química , Tensoativos/efeitos da radiação , ÁguaRESUMO
According to the data available in Soviet and foreign literature and the author's personal experience, the issues of combined pharmacological treatment of different types of epileptic seizures are discussed. General knowledge of the pharmacokinetics of antiepileptic drugs in the patient's body is taken into account as well as EEG data. Possible interchangeability of the drugs is reviewed.
Assuntos
Epilepsia/tratamento farmacológico , Anticonvulsivantes/administração & dosagem , Anticonvulsivantes/farmacocinética , Combinação de Medicamentos , Quimioterapia Combinada , Epilepsias Mioclônicas/tratamento farmacológico , Epilepsias Mioclônicas/metabolismo , Epilepsia/metabolismo , Epilepsia/psicologia , Epilepsia Tipo Ausência/tratamento farmacológico , Epilepsia Tipo Ausência/metabolismo , Humanos , Psicopatologia , Fatores de TempoRESUMO
The work is devoted to the rehabilitation of epileptic patients under outpatient conditions. On the basis of the data of epidemiologic studies the author considers the specific nature of rehabilitation measures provided to patients on an outpatient basis, describes the drawbacks of drug therapy, and proposes new forms of the organization of specialized cost-effective medical care to patients (a regional epilepsy centre).
Assuntos
Epilepsia/reabilitação , Centros de Reabilitação/organização & administração , Assistência Ambulatorial/economia , Assistência Ambulatorial/organização & administração , Epilepsia/economia , Humanos , Centros de Reabilitação/economia , Reabilitação Vocacional , Ajustamento Social , U.R.S.S.RESUMO
Using the clinical data on 270 epileptic patients, the author offers the biological validation of occupational treatment, determines the role of the psychological effects in the system of patients' rehabilitation and validates the significance of the EEG as a method for objective assessment of the degree of the regression of the clinical and subclinical manifestations of epilepsy in the process of biological therapy. It has been established that: 1) psychosocial effects, in particular, the patients' occupational activity help to decrease the frequency of attacks and inhibit the paroxysmal activity on the EEG during an experiment simulating a working process; 2) a long-term (up to 8 years) absence of seizures according to the EEG readings is not always attended with the regression of the subclinical manifestations of epilepsy; 3) the realization of rehabilitation programmes should be evaluated, appart from the duration of the attack-free period, by the EEG readings as well.
Assuntos
Epilepsia/reabilitação , Adolescente , Adulto , Idoso , Encéfalo/fisiopatologia , Eletroencefalografia , Epilepsia/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reabilitação Vocacional , Ajustamento SocialRESUMO
The authors consider the results of the psychological analysis of individual characteristics of intellectual and mnemonic activity, of emotional response, behaviour and the system of relations determined with the help of 10 experimental psychological techniques in 239 epileptic patients with a variable clinical picture of the disease in the process of their rehabilitation. The data obtained by the psychologist are correlated with the assessment of mental disorders by both the patient himself and the doctor. A conclusion is made that the psychological diagnosis is more accurate and its results may be used as an important criterion in the process of rehabilitation of epileptic patients.
Assuntos
Epilepsia/psicologia , Adolescente , Adulto , Eletroencefalografia , Epilepsia/reabilitação , Feminino , Humanos , Testes de Inteligência , Masculino , Personalidade , Testes de Personalidade , Testes PsicológicosRESUMO
In 74 patients with different attack rates and patterns mean levels of hexamidine in the blood plasma and cerebrospinal fluid were 15.9 micrograms/ml and 7.86 micrograms/ml, respectively, the former almost twice as high as the latter. Both were found to correlate with the drug daily doses and other anticonvulsants administration.
Assuntos
Epilepsia/metabolismo , Primidona/análise , Adolescente , Adulto , Benzamidinas/sangue , Benzamidinas/líquido cefalorraquidiano , Benzamidinas/uso terapêutico , Relação Dose-Resposta a Droga , Epilepsia/tratamento farmacológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Primidona/farmacocinética , Primidona/uso terapêutico , Radioimunoensaio , Fatores de TempoRESUMO
A study involving 36 epileptic patients and 8 control subjects was devoted to the optimization of antiepileptic drug therapy with the help of determining the blood levels of anticonvulsants (benzonal, phenobarbital). The daily dose of an anticonvulsant directly correlated with its blood levels. Blood levels of benzonal increased upon the additional administration to patients of hexamidine or hexamidine and diphenylhydantoin mixtures. A reduction in the daily dose of benzonal by 2/3 was attended by a 50% decline in its blood levels.
Assuntos
Anticonvulsivantes/administração & dosagem , Barbitúricos/sangue , Epilepsia/tratamento farmacológico , Adolescente , Adulto , Barbitúricos/administração & dosagem , Benzamidinas/administração & dosagem , Epilepsia/sangue , Feminino , Humanos , Masculino , Fenobarbital/administração & dosagem , Fenobarbital/análogos & derivados , Fenitoína/administração & dosagemRESUMO
A total of 50 patients with epilepsy underwent an electroencephalographic investigation at the rehabilitation stage during remission. EEG tests established that the discontinuation of epileptic seizures was followed by a stepwise compensatory EEG rearrangement. In patients that had had rare seizures, the EEG normalization was characteristic of the 2 to 3 years-long remissions. With frequent polymorphic seizures, the background activity was normalized in the steady remission of many (5 and more) years duration. The cessation of antiepileptic therapy should be effected under a mandatory EEG control. The absence of negative EEG changes on anticonvulsants discontinuation is a sign of correct treatment paradigm.
Assuntos
Córtex Cerebral/fisiopatologia , Epilepsia/reabilitação , Anticonvulsivantes/uso terapêutico , Eletroencefalografia , Epilepsia/tratamento farmacológico , Epilepsia/fisiopatologia , Humanos , Indução de Remissão , Fatores de TempoRESUMO
The authors suggest a program of improving health services for patients suffering from epilepsy (the setting up of the Regional Epileptological Centre). The clinical material provided by 1350 patients with epilepsy is analyzed for cost and therapeutic efficacy of the conducted organizational measures. Improvement of the treatment and diagnostic work, upgrading of the patients' examination quality have been demonstrated. The economic efficiency has been computed.
Assuntos
Centros Comunitários de Saúde/organização & administração , Serviços de Saúde Comunitária/organização & administração , Epilepsia/terapia , Centros Comunitários de Saúde/economia , Centros Comunitários de Saúde/normas , Serviços de Saúde Comunitária/economia , Serviços de Saúde Comunitária/normas , Análise Custo-Benefício , Epilepsia/economia , Epilepsia/reabilitação , Humanos , Federação Russa , População UrbanaRESUMO
The treatment with primidone alone of 53 epileptic patients with generalized tonic-clonic seizures, partial attacks with elementary symptomatology, and partial fits with complex symptomatology removed them completely in 75, 64.2, and 36.9% of the patients, respectively. The number of attacks was decreased as a result by 50% and over in 90, 78.6, and 73.7% of the patients, respectively. The attainment of such high efficacy of the monotherapy (called by the author intensive in contrast to routine or inadequate therapy carried out, as a rule, in standard doses) appeared possible only under the conditions of individualization of the drug doses which ranged within 250-2500 mg/day. The concentration of phenobarbital, the main end metabolite of primidone, in the blood serum of patients, in whom the attacks were completely arrested and who developed no clinical side effects with no toxic action on the internal organs, ranged from 14 to 59.1 mg/l. In partial fits with complex symptomatology, primidone appeared least effective for those types of fits in the treatment of which it was viewed as most adequate.