RESUMO
Hermansky-Pudlak syndrome is a multisystem disorder with albinism, bleeding diathesis and visual impairment as the main features. We report a case of epidural analgesia in a pregnant patient, who was subsequently discovered to have this syndrome. We believe this to be the first such report.
Assuntos
Síndrome de Hermanski-Pudlak/diagnóstico , Complicações Hematológicas na Gravidez/diagnóstico , Adulto , Analgesia Epidural , Analgesia Obstétrica/métodos , Perda Sanguínea Cirúrgica , Parto Obstétrico/efeitos adversos , Feminino , Genitália Feminina/lesões , Humanos , GravidezAssuntos
Analgesia/métodos , Bupivacaína/uso terapêutico , Inibidores da Colinesterase/efeitos adversos , Náusea/induzido quimicamente , Neostigmina/efeitos adversos , Anestésicos Combinados/administração & dosagem , Anestésicos Combinados/efeitos adversos , Anestésicos Combinados/uso terapêutico , Anestésicos Locais/uso terapêutico , Inibidores da Colinesterase/administração & dosagem , Inibidores da Colinesterase/uso terapêutico , Sinergismo Farmacológico , Glucose/administração & dosagem , Humanos , Injeções Espinhais , Extremidade Inferior/cirurgia , Movimento/efeitos dos fármacos , Náusea/tratamento farmacológico , Neostigmina/administração & dosagem , Neostigmina/uso terapêutico , Sensação/efeitos dos fármacos , Fatores de Tempo , Resultado do TratamentoRESUMO
Phenothiazine derivatives chlorpromazine (cpz) and trifluoperazine (tfp) were found to induce apoptosis, abnormal cell cycle and expression of p53 in Chinese hamster lung fibroblast V79 cells. Both the drugs can induce apoptosis when cells are treated with drug at a concentration of 10 microg/ml within 4 h, as detected by propidium iodide staining and DNA fragmentation analysis. Flow cytometric analysis revealed that the apoptotic response is mediated by a loss of G(1) population of cells. In Western blot analysis, p21 is induced and p53 is accompanied by additional bands. Also indirect immunolabeling of single cells revealed that p21 is accumulated from cytoplasm into nucleus after the drug treatment and the intensities of p53 increased. Our findings demonstrate for the first time that phenothiazine derivatives, in addition to their cytotoxic effects, could induce apoptosis, an observation that has important clinical implications.
Assuntos
Apoptose/efeitos dos fármacos , Clorpromazina/farmacologia , Trifluoperazina/farmacologia , Animais , Cálcio/metabolismo , Ciclo Celular/efeitos dos fármacos , Células Cultivadas , Cricetinae , Cricetulus , Inibidor de Quinase Dependente de Ciclina p21 , Ciclinas/análise , Proteína Supressora de Tumor p53/análiseRESUMO
Binding modalities of chlorpromazine and trifluoperazine, two widely used antipsychotic phenothiazine drugs with hemoglobin and myoglobin have been studied to understand how the quaternary, tertiary and secondary structural organisations of the proteins regulate the binding process. NaCl-induced alteration in the quaternary structure of hemoglobin influences its binding modality with phenothiazines. Minor alterations in the tertiary structure of thermally denatured myoglobin (denaturation temperature ranging between 30-70 degrees C) do not affect its affinity and the modality of binding with the drugs, but alterations in the secondary structure of the protein denatured at temperatures between 70-80 degrees C influence its binding.
Assuntos
Antipsicóticos/metabolismo , Clorpromazina/metabolismo , Hemoglobinas/química , Hemoglobinas/metabolismo , Mioglobina/química , Mioglobina/metabolismo , Adulto , Antipsicóticos/química , Clorpromazina/química , Dicroísmo Circular , Humanos , Técnicas In Vitro , Substâncias Macromoleculares , Masculino , Ligação Proteica , Conformação Proteica , Desnaturação Proteica , Estrutura Secundária de Proteína , Estrutura Terciária de Proteína , Espectrometria de Fluorescência , Temperatura , Termodinâmica , Trifluoperazina/química , Trifluoperazina/metabolismoRESUMO
It is reported that ethanol enhances DNA synthesis in E. coli cells [Basu, T and Poddar, R. K. (1994), Folia. Microbiol. 39, 3-6]. This communication reports that during growth of E. coli in the presence of 5% v/v ethanol, the derepressed expression of the cytoplasmic enzymes beta-galactosidase and D-serine deaminase per cell increased approximately three fold, while that of the periplasmic enzyme alkaline phosphatase decreased approximately 40% compared to control cell levels. However, in cells transformed with the plasmid pSM 456, bearing phoA-lacZ fusion, the level of induced synthesis of the hybrid protein PhoA-LacZ, controlled by the phoA promoter, was elevated by 25% in the presence of 5% v/v ethanol. This result suggests that the induction of the alkaline phosphatase precursor has also been enhanced by the ethanol treatment, but the inhibition in the export of the precursor across the cytoplasmic membrane, by the influence of ethanol, may represent the reason for the deficient expression of active alkaline phosphatase. It is proposed that there is an ethanol-mediated increase in DNA synthesis, resulting in gene amplification, which may enhance the synthesis of inducible proteins in ethanol-treated cells.
Assuntos
Proteínas de Bactérias/biossíntese , Proteínas de Bactérias/efeitos dos fármacos , Proteínas de Escherichia coli , Escherichia coli/efeitos dos fármacos , Etanol/farmacologia , Proteínas de Transporte de Monossacarídeos , Simportadores , Fosfatase Alcalina/biossíntese , Fosfatase Alcalina/efeitos dos fármacos , Contagem de Células , Divisão Celular/efeitos dos fármacos , DNA Bacteriano/biossíntese , DNA Bacteriano/efeitos dos fármacos , Escherichia coli/crescimento & desenvolvimento , Escherichia coli/metabolismo , Etanol/metabolismo , Amplificação de Genes/efeitos dos fármacos , L-Serina Desidratase/biossíntese , L-Serina Desidratase/efeitos dos fármacos , Proteínas de Membrana Transportadoras/efeitos dos fármacos , Plasmídeos/efeitos dos fármacos , Plasmídeos/genética , Proteínas Recombinantes de Fusão/biossíntese , Proteínas Recombinantes de Fusão/efeitos dos fármacos , beta-Galactosidase/biossíntese , beta-Galactosidase/efeitos dos fármacosRESUMO
The extent of oxygen release from two heme proteins, haemoglobin and myoglobin have been studied in the presence of trifluoperazine and chlorpromazine (5-1000 microM). At a molar ratio (drug:protein) of 1.5, the release of oxygen from haemoglobin was 4 and 15% in the presence of chlorpromazine and trifluoperazine respectively, while from myoglobin the corresponding values were 20 and 40%. The findings were attributed to the greater extent of local conformational change around tryptophan moieties of each of the proteins induced by trifluoperazine.
Assuntos
Antipsicóticos/farmacologia , Clorpromazina/farmacologia , Hemoglobinas/metabolismo , Mioglobina/metabolismo , Consumo de Oxigênio/efeitos dos fármacos , Trifluoperazina/farmacologia , Adulto , Hemoglobinas/efeitos dos fármacos , Humanos , Técnicas In Vitro , Masculino , Mioglobina/efeitos dos fármacos , Oxiemoglobinas/efeitos dos fármacos , Oxiemoglobinas/metabolismoRESUMO
The mode and nature of the binding of chlorpromazine (CPZ), a psychotropic drug, with myoglobin, a monomeric muscle protein, were studied spectrofluorometrically and the results compared with those from the binding of CPZ to hemoglobin, a tetrameric allosteric protein from red blood cells (RBC). CPZ interacted with myoglobin in a non-cooperative mode, with a binding constant of 8.4 x 10(3) M-1 in 0.145 M NaCl, pH 6.8, whereas in the case of hemoglobin this interaction was found to be positively cooperative with a binding constant of 4.2 x 10(3) M-1. The interaction of CPZ with myoglobin was not influenced by the NaCl molarity of the solution, whereas CPZ interaction with hemoglobin significantly decreased with increasing NaCl molarity, indicating that CPZ-hemoglobin binding is mostly electrostatic in nature, whereas that of the CPZ-myoglobin complex is of a non-electrostatic type. Thermodynamic analysis revealed that binding of CPZ to hemoglobin was exothermic (delta H degrees = -2.65 kcal/mol), whereas binding to myoglobin was endothermic (delta H degrees = + 1.39 kcal/mol) with a high entropic contribution (delta S degrees = +23 cal/degree/mol), suggesting that CPZ binding to myoglobin is hydrophobic in nature. Such contrasting binding features of this drug have been discussed in the light of a typical subunit interaction property present and absent in hemoglobin and myoglobin, respectively.
Assuntos
Clorpromazina/química , Hemoglobinas/química , Mioglobina/química , Cloreto de Sódio , Espectrometria de Fluorescência , TermodinâmicaRESUMO
Human epidermoid carcinoma cells (Hep-2) were X-irradiated in the presence of 5-10 micrograms/ml of chlorpromazine (CPZ). Survival of the cells decreased with increasing CPZ concentration. Lymphocytes from three normal volunteers exposed to X-irradiation in the presence of CPZ showed an increased frequency of dicentric and ring formation.
Assuntos
Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Clorpromazina/toxicidade , Aberrações Cromossômicas , Tolerância a Radiação/efeitos dos fármacos , Adulto , Humanos , Cariotipagem , Linfócitos/efeitos dos fármacos , Linfócitos/efeitos da radiação , Células Tumorais Cultivadas , Raios XRESUMO
Increased ethanol concentration in the nutrient medium gradually slowed down the growth of Escherichia coli cells. However, during growth in the presence of 5% ethanol, DNA synthesis per cell increased about 2.5-fold compared to control cells. There was a 40-45% increase in plasmid copy number in the ethanol-treated cells.
Assuntos
Replicação do DNA/efeitos dos fármacos , DNA Bacteriano/biossíntese , Escherichia coli/efeitos dos fármacos , Etanol/farmacologia , Membrana Celular/efeitos dos fármacos , Escherichia coli/crescimento & desenvolvimento , Lipídeos de Membrana/metabolismo , Plasmídeos/efeitos dos fármacos , Estimulação QuímicaRESUMO
Normal human hemoglobin exceeding a certain minimum concentration (called critical aggregation concentration) undergoes aggregation in presence of the psychotherapeutic drug chlorpromazine (CPZ). The critical aggregation concentration decreases with the increase of CPZ concentration. Electron micrographs of CPZ-treated hemoglobin clearly indicate that the aggregates of hemoglobin are in filamentous form of average width 75 +/- 8 A. A possible mechanism for such aggregation has been discussed.
Assuntos
Clorpromazina/farmacologia , Eritrócitos/efeitos dos fármacos , Hemoglobinas/metabolismo , Eritrócitos/ultraestrutura , Hemoglobinas/efeitos dos fármacos , Hemoglobinas/ultraestrutura , Humanos , Cinética , Substâncias Macromoleculares , Microscopia Eletrônica , Modelos EstruturaisRESUMO
The interaction of chlorpromazine (CPZ), a widely used antipsychotic tranquillizer, with the allosteric protein haemoglobin, has been studied by different methods. From r versus Cf plot obtained by an equilibrium dialysis experiment, the maximum value of r was found to be 6.8 at 0.15 M NaCl. Binding parameters, namely the affinity constant K and the degree of cooperativity nH, were determined from the Hill plot. Circular dichroism studies indicate a conformation change of haemoglobin in the presence of CPZ. Oxygen has been found to be released from haemoglobin with the progressive addition of CPZ. The extent of the release of oxygen depends on the stoichiometric ratio of CPZ: haemoglobin (D/P). The possible nature of the binding site of the protein has been discussed on the basis of the information obtained from fluorescence measurements.
Assuntos
Clorpromazina/metabolismo , Hemoglobinas/metabolismo , Oxiemoglobinas/metabolismo , Sítios de Ligação , Dicroísmo Circular , Oxigênio/metabolismo , Conformação Proteica , Cloreto de Sódio/farmacologia , Espectrometria de FluorescênciaRESUMO
Binding of chlorpromazine (CPZ), a widely used antidepressant tranquilizer, with hemoglobin has been studied by equilibrium dialysis method. r/Cf versus r plot was typically concave downwards revealing the positive cooperative nature of binding. Binding parameters, namely the affinity constant (K) and the degree of cooperativity (nH) were determined from the Hill plot. Oxygen was found to be released gradually from hemoglobin with gradual addition of CPZ, the extent of oxygen release depending on the stoichiometric ratio of CPZ: hemoglobin (D/P).
Assuntos
Clorpromazina/metabolismo , Hemoglobinas/metabolismo , Sítios de Ligação , Clorpromazina/farmacologia , Hemoglobinas/efeitos dos fármacos , Humanos , Técnicas In Vitro , Cinética , Oxigênio/metabolismoRESUMO
Binding of chlorpromazine (CPZ) with human hemoglobin has been studied by equilibrium dialysis and fluorescence quenching. Results of equilibrium dialysis experiment when analysed by Hill plot revealed that the binding was positively cooperative with overall affinity constant K = 3.8 x 10(3) M-1. CPZ quenched the fluorescence of hemoglobin and the analysis of the quenching data by Stern-Volmer equation indicated two types of quenching process, namely, dynamic and static quenching. Dynamic quenching constant was measured from the decay of fluorescent life time of tryptophans of hemoglobin in presence of CPZ. Static quenching constant concerned with the ground state complex formation between CPZ and hemoglobin was found to be 5 x 10(3) M-1. Almost all the tryptophans of hemoglobin were found to be accessible for CPZ to interact with. Oxygen was found to be released when CPZ was added to hemoglobin. Extent of release of oxygen depends on the D/P ratio of CPZ(D): hemoglobin(P).
Assuntos
Clorpromazina/sangue , Hemoglobinas/metabolismo , Oxiemoglobinas/metabolismo , Diálise , Hemoglobinas/isolamento & purificação , Humanos , Cinética , Ligação Proteica , Espectrometria de Fluorescência , Espectrofotometria UltravioletaRESUMO
The binding of chlorpromazine (CPZ), an widely used tranquilizer, with hemoglobin (Hb) at pH 6.5 has been investigated by means of spectrophotometry, circular dichroism (CD), and equilibrium dialysis. In CD spectra Hb treated with CPZ exhibited a blue shift of 5 nm in the visible wavelength range. The positively cooperative nature of binding was revealed by equilibrium dialysis experiments. The basic parameters, namely, the cooperative binding constant (K), the degree of cooperativity (q), and the number of amino acids (n) occupied by one CPZ molecule were evaluated from spectrophotometric and dialysis experiments and found to be sensitive to NaCl concentration, suggesting the electrostatic nature of the binding process.
Assuntos
Clorpromazina/metabolismo , Hemoglobinas/metabolismo , Aminoácidos/metabolismo , Animais , Dicroísmo Circular , Cabras , Cloreto de Sódio/farmacologia , Análise EspectralAssuntos
Cardiomegalia/diagnóstico , Átrios do Coração , Adulto , Diagnóstico Diferencial , Feminino , HumanosRESUMO
Synthesis of tryptophanase, D-serine deaminase and alkaline phosphatase in Escherichia coli C was repressed as the result of infection with the single-stranded DNA bacteriophage phi X174. However, the degree of repression differed, the more catabolite-sensitive the operon was, the more severe was the repression. For the catabolite-sensitive enzymes it was found that cyclic adenosine 3'5' monophosphate (cyclic AMP or cAMP) was unable to release or reduce the phage-induced inhibition. Experiments with amber mutants of phi X174 revealed that A, product of cistron A, was responsible for the inhibition. The cistron A product probably acted at the level of transcription. The possible role of A in the observed modulation of gene expression is discussed.
Assuntos
Bacteriófago phi X 174/genética , Escherichia coli/genética , Regulação da Expressão Gênica , Proteínas Repressoras/genética , Fatores de Transcrição/genética , Fosfatase Alcalina/genética , AMP Cíclico/fisiologia , L-Serina Desidratase/genética , RNA Bacteriano/genética , RNA Mensageiro/genética , Transcrição Gênica , Triptofanase/genéticaRESUMO
Features of inactivation, repair and concomitant mutagenesis of hydroxylamine-treated phi X174 bacteriophages are reported here. (1) For reasons unknown, the nonsense phage mutants tested here were far more sensitive to hydroxylamine than the wild-type phage. In contrast, the sensitivities of these same phi X174 mutants to UV-irradiation are indistinguishable. (2) Hydroxylamine-treated amber phages mutated to ochre but not to wild-type particles, i.e., G leads to A transition events were recovered. (3) The repair of phi X174 phages from hydroxylamine-induced damage was error-prone, but unlike UV damage, did not require protein synthesis de novo. Possible mechanisms of these novel features are discussed.
Assuntos
Bacteriófago phi X 174/efeitos dos fármacos , Cloranfenicol/farmacologia , Hidroxilaminas/farmacologia , Mutação , Bacteriófago phi X 174/genética , Bacteriófago phi X 174/efeitos da radiação , Reparo do DNA/efeitos dos fármacos , Fatores de Tempo , Raios UltravioletaRESUMO
The cistron A proteins of bacteriophage phi X174 inhibit the synthesis of beta-galactosidase of host Escherichia coli. A drastic reduction in the rate of transcription of the lac gene is observed in infected cells. This loss in the efficiency of transcription is due to conformational changes in the host DNA. Probably the host DNA is nicked at a few sites along its length and some of its negative superhelical twists are released.