RESUMO
Spontaneous dissection of the vessels of the neck is one of the main causes of ischemic stroke in young patients under 45 years of age. According to morphological studies, dissection of the vessels of the neck can be based on dysplastic changes in the arterial wall in arteriopathies, Marfan syndrome, Ehlers-Danlos syndrome, undifferentiated connective tissue dysplasia. The article presents a case of spontaneous dissection of the internal carotid artery in a 30-year-old patient with clinical manifestations of undifferentiated connective tissue dysplasia and carriage of homozygous variants of candidate genes: 4G/4G of the PAI-1 (-675, 4G/5G), T/T of the MTHFR C677T, 5A/5A of the MMP-3 (-1171 5A/6A) and A/A of the MMP-9 (8202A/G).
Assuntos
Dissecação da Artéria Carótida Interna/genética , Tecido Conjuntivo/patologia , Adulto , Homozigoto , Humanos , Metaloproteinase 3 da Matriz/genética , Metaloproteinase 9 da Matriz/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Acidente Vascular Cerebral/etiologiaRESUMO
AIM: To clarify the role of connective tissue dysplasia (CTD) in the development and course of intracranial arterial aneurysm (IAA) and arteriovenous malformation (AVM) in young patients. MATERIAL AND METHODS: The first stage of the study was a prospective 7-year follow-up of 549 patients with CDT signs, aged from 18 to 45 years, mean 23.51±8.67 years. The first stage included a comparative analysis of clinical characteristics of patients with DST with asymptomatic pathology of cerebral vessels and patients with DST without this pathology. At the second stage, there was a comparative study in 2 groups of patients with symptomatic pathology of cerebral vessels (AAA and/or AVM): with CTD (n=58) and without CTD (n=135). RESULTS: Symptomatic AAA and/or AVM were identified in 10.56% of young people with CTD including 37 patients with subarachnoid hemorrhages (SAH). The age of clinical manifestations was 25.55±8.13 years. Expressed manifestations of CTD were more frequent in the group of patients with cerebral vascular pathology compared to patients without CTD (p=0.008). The majority of patients had CTD manifestations of 3 or more systems, less than 2 systems were not involved, 12 patients had small abnormalities and/or malformations of the heart and other vessels. Hypertension, pathology of the vertebral arteries, skin, spine, veins, fully open Willis circle were independent risk factors for symptomatic pathology of cerebral vessels in patients with CTD. AVM and AAA in young patients with CTD compared with patients without CTD were characterized by the manifestation at an earlier age (25.55±8.13 years and 36.10±10.58 years, respectively; p=0.000), a more frequent combination with a fully open Willis circle (56.90 and 25.19%, respectively; df=1; p=0.000), more frequent multiple pathologies (15.52 and 4.44%, respectively, p=0.008), EAA in the posterior vascular bed (15.52 and 3.70%, respectively, p=0.004), SAH (63.79 and 35.56%, respectively, p=0.000) with lesser effects of general population risk factors. CONCLUSION: EAA and AVM in patients with CTD are likely to be considered in the context of vascular syndrome of connective tissue dysmorphogenesis, and CTD as a factor of adverse prognosis of IAA and AVM.
Assuntos
Tecido Conjuntivo , Aneurisma Intracraniano , Hemorragia Subaracnóidea , Adolescente , Adulto , Hemorragia Cerebral , Tecido Conjuntivo/patologia , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Hemorragia Subaracnóidea/etiologia , Adulto JovemRESUMO
A 14C study of chemobiokinetics of sarcolysin and its peptides of glutaminic acid, dosage and routes of administration was conducted in intact rats and those bearing Walker's carcinoma. Similar in shape for peptides, kinetic curves differed from those found for sarcolysin. The rates of absorption and excretion of sarcolysin peptides in intraperitoneal and, particularly, oral administration were lower than those of sarcolysin. Tumor appeared to play a role in a higher rate of peptide excretion. While sarcolysin and its peptides distribution in organs and tissues was generally identical, time of peak radioactive concentration build-up was different. Time needed for accumulation and excretion of peptides from tumor was much longer than from other organs or tissues. Sarcolysin went chiefly to urine while peptides--to faeces.
Assuntos
Antineoplásicos Alquilantes/farmacocinética , Carcinoma 256 de Walker/metabolismo , Glutamatos/farmacocinética , Melfalan/farmacocinética , Administração Oral , Animais , Antineoplásicos Alquilantes/administração & dosagem , Antineoplásicos Alquilantes/metabolismo , Área Sob a Curva , Radioisótopos de Carbono , Esquema de Medicação , Glutamatos/administração & dosagem , Glutamatos/metabolismo , Infusões Parenterais , Masculino , Melfalan/administração & dosagem , Melfalan/metabolismo , Peptídeos/farmacocinética , Ratos , Fatores de Tempo , Distribuição TecidualAssuntos
Encefalopatias/diagnóstico por imagem , Neoplasias Encefálicas/diagnóstico por imagem , Tomografia Computadorizada de Emissão , Adolescente , Adulto , Idoso , Radioisótopos de Carbono , Desoxiglucose , Diagnóstico Diferencial , Feminino , Radioisótopos de Flúor , Humanos , Masculino , Metionina , Pessoa de Meia-Idade , Radioisótopos de Oxigênio , Tomografia Computadorizada de Emissão/instrumentação , Tomografia Computadorizada de Emissão/métodos , ÁguaAssuntos
Antineoplásicos/uso terapêutico , Azirinas/uso terapêutico , Triazinas/uso terapêutico , Animais , Antineoplásicos/toxicidade , Azirinas/toxicidade , Carcinoma de Ehrlich/tratamento farmacológico , Feminino , Humanos , Neoplasias Renais/tratamento farmacológico , Leucemia Experimental/tratamento farmacológico , Masculino , Melanoma Experimental/tratamento farmacológico , Camundongos , Neoplasias Ovarianas/tratamento farmacológico , Ratos , Sarcoma Experimental/tratamento farmacológico , Triazinas/toxicidadeRESUMO
Exposure of solid thymine and uracil at room temperature to free methyl cations, produced due to beta-decay of tritiated methane, resulted in formation of their 1-, O2-, 3-, O4-, and 6-methyl derivatives. In addition, uracil formed a 5-methyl derivative (thymine); tritium-containing thymine and uracil were also detected. Both thymine and uracil formed predominantly unidentified products which resulted presumably from their oligomerization. Incubation at -195 degrees C did not markedly change the pattern of reaction products. Aqueous-ammonia solutions of these pyrimidines formed methylated derivatives and considerable amounts of methanol and tritiated water. The possible implication of these reactions in mutagenic and carcinogenic effects of tritium-substituted hydrocarbons is discussed.
Assuntos
Carcinógenos , Metano , Mutagênicos , Timina , Uracila , Alquilantes , Cátions , Fenômenos Químicos , Química , Cromatografia em Camada Fina/métodos , Metilação , Estrutura Molecular , TrítioAssuntos
Difosfonatos , Neoplasias Experimentais/diagnóstico , Neoplasias de Tecido Muscular/diagnóstico , Compostos Orgânicos de Estanho , Tecnécio , 9,10-Dimetil-1,2-benzantraceno , Animais , Meia-Vida , Matemática , Neoplasias Experimentais/induzido quimicamente , Neoplasias de Tecido Muscular/induzido quimicamente , Ratos , Fatores de TempoRESUMO
A newly-developed antitumor drug Dioxadet is capable of passing the blood-brain barrier. The specific activity of rat brain tissue ranged 8-55% of that of blood at different periods after intraperitoneal injection of 14C-labelled Dioxadet. Dioxadet treatment of mice and rats bearing intracranially-transplanted L1210 leukemia and glioma 35 was followed by a 38-48 and 29% increase in survival, respectively.
Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Triazinas/uso terapêutico , Animais , Barreira Hematoencefálica/efeitos dos fármacos , Neoplasias Encefálicas/secundário , Glioma/tratamento farmacológico , Leucemia L1210/tratamento farmacológico , Camundongos , Camundongos Endogâmicos DBA , Transplante de Neoplasias , RatosRESUMO
Three- and fourteen-month old female rats received a single intravenous injection of 50 mg/kg 14C-methylnitrosourea. Peculiarities of DNA purines alkylation and repair in different organs were studied. The difference in initial methylpurine levels between the two groups appeared insignificant and did not correlate with the rate of tumor frequency registered in chronic experiments using the same mode of treatment. In young animals, the rate of O6-methylguanine repair in all tissues tested equaled or exceeded that in older ones. It is inferred that the rate and site of tumor development are influenced by alkylation level and rates of repair and proliferation in target tissues during treatment.
Assuntos
Envelhecimento/efeitos dos fármacos , Reparo do DNA/efeitos dos fármacos , DNA/metabolismo , Metilnitrosoureia/toxicidade , Alquilação , Animais , Radioisótopos de Carbono , Feminino , Metilação , Purinas/metabolismo , Ratos , Fatores de Tempo , Distribuição TecidualAssuntos
Naftalenos/toxicidade , Neoplasias Experimentais/induzido quimicamente , Animais , Relação Dose-Resposta a Droga , Feminino , Linfoma não Hodgkin/induzido quimicamente , Neoplasias Mamárias Experimentais/induzido quimicamente , Camundongos , Camundongos Endogâmicos , Naftalenos/administração & dosagem , Neoplasias Experimentais/mortalidade , Ratos , Ratos Endogâmicos , Neoplasias Cutâneas/induzido quimicamente , Neoplasias Cutâneas/mortalidade , Fatores de TempoRESUMO
Formation and loss of methylated purines in DNA of various fetal and maternal tissues were measured up to 7 days following intravenous administration of N-[14C]methyl-N-nitrosourea to rats on the 21st day of gestation. Methylation products were detected in all tissues examined, the level in maternal liver being higher than in other tissues. The concentrations of 7-methylguanine and 3-methyladenine decreased faster in fetal than in corresponding maternal tissues, due to a higher rate of DNA synthesis in fetal tissues, as determined by incorporation of labelled thymidine. Removal of the promutagenic DNA lesion O6-methylguanine was most efficient in maternal and fetal liver; but it was very poorly repaired in kidney and brain. The persistence of O6-methylguanine relative to 7-methylguanine was highest in the DNA of fetal brain. The principal targets for the transplacental carcinogenic effect of N-methyl-N-nitrosourea under these experimental conditions were fetal neurogenic tissue and kidney; and malignant tumors developed at these sites in 31-34% and 15-16% of male and female descendants, respectively. These results support the concept that a complex interaction between DNA alkylation, repair and replication is the molecular basis of initiation of carcinogenesis by alkylating agents.
Assuntos
DNA/metabolismo , Feto/metabolismo , Metilnitrosoureia/administração & dosagem , Neoplasias Experimentais/induzido quimicamente , Compostos de Nitrosoureia/administração & dosagem , Placenta/efeitos dos fármacos , Purinas/metabolismo , Adenina/análogos & derivados , Adenina/metabolismo , Animais , Encéfalo/metabolismo , Feminino , Guanina/análogos & derivados , Guanina/metabolismo , Rim/metabolismo , Fígado/metabolismo , Metilação , Neoplasias Experimentais/metabolismo , Gravidez , Ratos , Fatores de TempoRESUMO
The investigation of 22 patients has established the concentration of fluothane in the blood to influence the catecholamine content and the cardio-vascular system. Its increased concentration in the blood results in certain decrease of the level of general catecholamines in the blood, decreased value of systolic arterial pressure and increased frequency of cardiac contractions.