RESUMO
Primary effusion lymphoma (PEL) is an incurable malignancy that develops in immunodeficient patients as a consequence of latent infection of B-cells with Kaposi's sarcoma-associated herpes virus (KSHV). Malignant growth of KSHV-infected B cells requires the activity of the transcription factor nuclear factor (NF)-κB, which controls maintenance of viral latency and suppression of the viral lytic program. Here we show that the KSHV proteins K13 and K15 promote NF-κB activation via the protease mucosa-associated lymphoid tissue lymphoma translocation protein-1 (MALT1), a key driver of NF-κB activation in lymphocytes. Inhibition of the MALT1 protease activity induced a switch from the latent to the lytic stage of viral infection, and led to reduced growth and survival of PEL cell lines in vitro and in a xenograft model. These results demonstrate a key role for the proteolytic activity of MALT1 in PEL, and provide a rationale for the pharmacological targeting of MALT1 in PEL therapy.
Assuntos
Caspases/metabolismo , Infecções por Herpesviridae/complicações , Infecções por Herpesviridae/virologia , Herpesvirus Humano 8/fisiologia , Linfoma de Efusão Primária/etiologia , Linfoma de Efusão Primária/patologia , Proteínas de Neoplasias/metabolismo , Latência Viral , Animais , Biomarcadores , Caspases/genética , Linhagem Celular , Sobrevivência Celular/genética , Modelos Animais de Doenças , Ativação Enzimática , Citometria de Fluxo , Inativação Gênica , Interações Hospedeiro-Patógeno , Humanos , Proteína de Translocação 1 do Linfoma de Tecido Linfoide Associado à Mucosa , NF-kappa B/metabolismo , Proteínas de Neoplasias/genética , Ligação Proteica , Proteínas Virais/metabolismo , Ativação Viral , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
In this study we used a rat model of graded perinatal asphyxia to study the long-term consequences of this manipulation on rat maternal behavior at adulthood. Rats were delivered by cesarean (C) section and the pups, still in the uterus horns, were placed into a water bath at 37 degrees C for periods of 0 (controls) or 20 min (asphyxia). Subsequently, female pups were given to surrogate mothers, weaned at 21 days postnatally and then left undisturbed until adulthood, when they were mated. Once they gave birth, on postnatal days (Pnds) 1, 3, 5, 7, 9, 11 and 13 they were observed in the home cage five times per day to assess their maternal behavior in an undisturbed condition. In addition, maternal behavior was observed for 30 min in a novel cage on Pnds 4 and 8. Perinatal asphyxia affected maternal behavior in the home cage, hypoxic females being more often found outside the nest area and performing more often behaviors such as self-grooming. Principal component analysis confirmed a more 'active' behavioral profile for hypoxic females. Hypoxic mothers were characterized by a longer latency to perform on-nest behavior and by a reduced frequency of pup retrieval and licking in the novel cage. No significant differences in corticosterone secretion in response to an acute stressor were found in dams belonging to the different treatments or in the body weights of the offspring. These results are suggestive of an arousal deficit due to perinatal hypoxia and point to the dopaminergic system as a potential neurochemical target for an early hypoxic insult.
Assuntos
Asfixia/psicologia , Comportamento Materno/fisiologia , Tempo , Fatores Etários , Análise de Variância , Animais , Comportamento Animal , Peso Corporal/fisiologia , Estudos de Casos e Controles , Cesárea/métodos , Comportamento Exploratório , Feminino , Hipóxia , Masculino , Gravidez , Ratos , Ratos Wistar , Tempo de ReaçãoRESUMO
Several arylideneisothiosemicarbazones and arylidenehydrazothiazoles have been synthesised to obtain new antimicrobial agents. Their activity against both bacteria and fungi has been tested and some interesting informations about their biological activity have been obtained.
Assuntos
Antibacterianos/farmacologia , Antifúngicos/farmacologia , Tiossemicarbazonas/farmacologia , Antibacterianos/química , Antifúngicos/química , Desenho de Fármacos , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Relação Estrutura-Atividade , Tiossemicarbazonas/química , Leveduras/efeitos dos fármacosRESUMO
It is known that some derivatives of both thiourea and thiosemicarbazide exhibit potent anti-microbial activity. In order to investigate the effects on the biological properties of structural modifications of such structures, we have synthesised and studied some arylidenisothiosemicarbazones. In this paper we report on the synthesis and structure-activity relationships of some isothiosemicarbazones, where the arylidene group has been replaced with a cycloalkyl group and the sulfur atom has been either differently substituted or enclosed in a thiazole ring.
Assuntos
Anti-Infecciosos/farmacologia , Tiossemicarbazonas/química , Tiossemicarbazonas/farmacologia , Animais , Antibacterianos , Anti-Infecciosos/síntese química , Chlorocebus aethiops , Fungos/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Interações Hidrofóbicas e Hidrofílicas , Testes de Sensibilidade Microbiana , Espectrometria de Massas por Ionização por Electrospray , Relação Estrutura-Atividade , Células Vero/efeitos dos fármacosRESUMO
OBJECTIVE: To determine whether the surgical diagnosis of endometriosis can be predicted using symptoms, signs, and ultrasound findings. DESIGN: Prospective study (study sample); retrospective record review (test sample). SETTING: Hospital of Desio (study sample) and Mangiagalli Hospital (test sample), Italy. PATIENT(S): Ninety women scheduled to undergo laparoscopy or laparotomy (study sample); 120 women who underwent laparoscopy (test sample). INTERVENTION: The study sample group was interviewed before surgery about infertility and dysmenorrhea, dyspareunia, and noncyclic pelvic pain and each member had a pelvic examination and a transvaginal ultrasound. At surgery, endometriosis was noted. For the test sample, the same information was abstracted from medical records after laparoscopy. MAIN OUTCOME MEASURE(S): The ability of symptoms, signs, and ultrasound to predict endometriosis at surgery. A classification tree was developed with the study sample and evaluated with the test sample. RESULT(S): Ovarian endometriosis, but not nonovarian endometriosis, could be reliably predicted with noninvasive tools. Ultrasound and examination best predicted ovarian endometriosis, correctly classifying 100% of cases with no false positive diagnoses in the study sample. Similar results were found in the test sample. CONCLUSION(S): Noninvasive tools may be used to identify women with ovarian, but not nonovarian endometriosis, with excellent agreement with surgical diagnosis.
Assuntos
Endometriose/diagnóstico , Adulto , Endometriose/fisiopatologia , Feminino , Humanos , Pessoa de Meia-Idade , Doenças Ovarianas/diagnóstico , Exame Físico , Estudos Prospectivos , Estudos Retrospectivos , UltrassonografiaRESUMO
The present work was carried out to study the effect of some plant methanol extracts and essential oils on lipid peroxidation in simple in vitro systems. The tested extracts were obtained from four plants, commonly known in the Mediterranean area, indigenous to Sardinia: Artemisia arborescens L., Calycotome villosa L., Daphne gnidium L. or naturalized in the island, Eucalyptus globulus Labill. The activity of the extracts was investigated during both autoxidation and iron or EDTA-mediated oxidation of linoleic acid at 37 degrees C in the absence of solvent, and compared with that of BHT, alpha-tocopherol and EDTA. During linoleic acid autoxidation all the extracts were active, showing an antioxidant activity in the order: BHT >alpha- tocopherol >Daphne gnidium (methanol extract) >Eucalyptus globulus (essential oil) >Calycotome villosa (essential oil) >Artemisia arborescens (essential oil and methanol extract) >Calycotome villosa (methanol extract). None showed any prooxidant activity. During the iron-catalysed oxidation of linoleic acid the oils were not active, while all the methanol extracts showed some efficiency in preventing the oxidation process. All the extracts were also tested on cell cultures to investigate their cytotoxic activity or their ability to inhibit the growth of some pathogenic microorganisms.
Assuntos
Antioxidantes/farmacologia , Magnoliopsida , Extratos Vegetais/farmacologia , Animais , Anti-Infecciosos/farmacologia , Antioxidantes/uso terapêutico , Chlorocebus aethiops , Medicina Herbária , Itália , Ácidos Linoleicos/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Peróxidos Lipídicos/metabolismo , Medicina Tradicional , Óleos Voláteis/análise , Fitoterapia , Extratos Vegetais/uso terapêutico , Plantas Medicinais , Células VeroRESUMO
The chemical composition of the essential oil and methanol extract of Calycotome villosa (Poiret) Link leaves collected in Sardinia (Italy) has been studied by analytical and spectroscopic methods. Falcarinol and some alcohols, terpenes, furan derivatives, and paraffins have been isolated from the essential oil. Thirteen alkaloids and falcarinol have been identified in the chloroform fraction of the basic methanol extract. Six flavonoids and four anthraquinones have been isolated in the chloroform fraction after acidification of the basic methanol extract. The cytotoxic and antimicrobial activities have also been evaluated. The essential oil, the methanol extract in toto, and the fraction of the basic extract showed strong cytotoxicity, whereas the fraction of the acid extract showed lower cytotoxicity. Furthermore, this fraction showed good antibacterial activity against Staphylococcus aureus, Bacillus lentus, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Providencia rettgeri, and Morganella morganii. It can therefore be stated that this plant's cytotoxicity is prevalently due to falcarinol.
Assuntos
Anti-Infecciosos/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Plantas Medicinais/química , Anti-Infecciosos/isolamento & purificação , Antineoplásicos Fitogênicos/isolamento & purificação , Cromatografia Gasosa , Ensaios de Seleção de Medicamentos Antitumorais , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Itália , Óleos Voláteis/química , Extratos Vegetais/química , Folhas de Planta/química , Espectroscopia de Infravermelho com Transformada de Fourier , Células Tumorais CultivadasRESUMO
Following studies on the properties of spontaneous plants in Sardinia we have evaluated the tissue regenerating action of a mixture of oily extracts of Hypericum perforatum and Calendula arvensis on surgical wounds from childbirth with caesarean section.
Assuntos
Calendula/química , Cesárea , Hypericum/química , Óleos Voláteis/uso terapêutico , Cicatrização/efeitos dos fármacos , Administração Tópica , Adulto , Epitélio/efeitos dos fármacos , Feminino , Humanos , Itália , Óleos Voláteis/administração & dosagem , Período Pós-Operatório , Regeneração/efeitos dos fármacosRESUMO
The antimicrobial activity of stems methanol extract from Daphne gnidium L. collected from Sardinia (Italy) was evaluated against 6 strains of standard and clinical isolated gram (+/-) bacteria. The antimicrobial effect on two strains of fungi was also tested. The extract in toto exhibited antibacterial activity against Bacillus lentus and Escherichia coli, but was inactive against fungi. Four coumarins (daphnetin, daphnin, acetylumbelliferone, daphnoretin) and seven flavonoids (luteolin, orientin, isoorientin, apigenin-7-O-glucoside, genkwanin, 5-O-beta-D-primeverosyl genkwanine, 2,5,7,4'-tetrahydroxyisoflavanol) present in the plant extract were also investigated against the same strains of bacteria and fungi assayed for the crude extract. The most active compounds were daphnetin, genkwanin, and 2,5,7,4'-tetrahydroxyisoflavanol.
Assuntos
Anti-Infecciosos/farmacologia , Bactérias/efeitos dos fármacos , Fitoterapia , Extratos Vegetais/farmacologia , Thymelaeaceae , Antibacterianos , Anti-Infecciosos/uso terapêutico , Bacillus/efeitos dos fármacos , Cumarínicos/química , Cumarínicos/farmacologia , Escherichia coli/efeitos dos fármacos , Flavonoides/química , Flavonoides/farmacologia , Fungos/efeitos dos fármacos , Humanos , Testes de Sensibilidade Microbiana , Extratos Vegetais/uso terapêutico , Caules de PlantaRESUMO
The effect of liposomal inclusion on the stability and in vitro antiherpetic activity of Santolina insularis essential oil was investigated. In order to study the influence of vesicle structure on the liposome properties, multilamellar and unilamellar vesicles were prepared by the film method and sonication, respectively. Vesicles were obtained from hydrogenated soya phosphatydilcholine and cholesterol. Formulations were examined for their stability for over one year monitoring the drug leakage from vesicles and the average size distribution. The stability of the incorporated oil was verified by studying its quali-quantitative composition. The antiviral activity was studied against Herpes simplex virus type 1 (HSV-1) by plaque reduction and yield reduction assays. Results showed that Santolina insularis essential oil can be incorporated in high amounts in the prepared liposomes, which successfully prevented its degradation. Moreover, stability studies pointed out that vesicle dispersions were stable for at least one year and neither oil leakage nor vesicle size alteration occurred during this period. Antiviral activity assays demonstrated that Santolina insularis essential oil is effective in inactivating HSV-1 and that the activity is principally due to direct virucidal effects. Free essential oil proved to be more effective than liposomal oil and a different activity was discovered which related to the vesicular structure. The ED(50) values, significantly lower when cells were pre-incubated with the essential oil before the virus adsorption, indicate an intracellular mechanism in the antiviral activity of Santolina insularis. Moreover, liposomal Santolina essential oil is non toxic in the range of the concentration tested.
RESUMO
The essential oil obtained in toto from Santolina insularis was investigated for its antiviral activity on herpes simplex type 1 (HSV-1) and type 2 (HSV-2) in vitro. The IC(50) values, determined by plaque reduction assays, were 0.88 and 0.7 microg/ml for HSV-1 and HSV-2, respectively, while the CC(50) determined by the MTT test on Vero cells was 112 microg/ml, indicating a CC(50)/IC(50) ratio of 127 for HSV-1 and 160 for HSV-2. Results obtained by plaque reduction assays also indicated that the antiviral activity of S. insularis was principally due to direct virucidal effects. Antiviral activity against HSV-1 and HSV-2 was not observed in a post-attachment assay, and attachment assays indicated that virus adsorption was not inhibited. Up to 80% inhibition of HSV-1 was achieved at the concentration of 40 microg/ml by yield reduction assay. Furthermore, reduction of plaque formation assays also showed that S. insularis essential oil inhibits cell-to-cell transmission of both HSV-1 and HSV-2.
Assuntos
Asteraceae , Herpesvirus Humano 1/efeitos dos fármacos , Herpesvirus Humano 2/efeitos dos fármacos , Óleos Voláteis/farmacologia , Óleos de Plantas/farmacologia , Adsorção , Animais , Chlorocebus aethiops , Herpes Genital/virologia , Herpes Simples/virologia , Herpesvirus Humano 1/patogenicidade , Herpesvirus Humano 1/fisiologia , Herpesvirus Humano 2/patogenicidade , Herpesvirus Humano 2/fisiologia , Humanos , Células Vero , Ensaio de Placa ViralRESUMO
Some coumarin 7-substituted cephalosporins and related sulfones were prepared and an antimicrobial assay was performed. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) carried out on cephalosporins showed a potential activity of some of the synthesized compounds against Gram-positive microorganisms. The tests performed on the corresponding sulfones showed no significant activity, neither as antimicrobial agents nor as inhibitors of beta-lactamase. An association of sulfone 6a with ampicillin was observed to inhibit Gram-positive microorganisms with a lower MIC than for ampicillin alone.
Assuntos
Cefalosporinas/síntese química , Sulfonas/síntese química , Cefalosporinas/farmacologia , Bactérias Gram-Positivas/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Sulfonas/farmacologiaRESUMO
The extracts of the aerial parts and tubers of Asphodelus microcarpus (Liliacee) were studied. The fatty acids, the sugars and some anthraquinone glycosides were determined by means of GC/FTIR, GC/MS and HPLC. The antimicrobial activity of essential oil of aerial parts against blastomycetes, Gram-positive and Gram-negative bacteria was evaluated.
Assuntos
Antibacterianos/farmacologia , Plantas Medicinais/química , Testes de Sensibilidade Microbiana , Extratos Vegetais/farmacologiaRESUMO
This report sums up the research work since 1993 on the synthesis of coumarin derivatives using carbon suboxide as reagent.
Assuntos
Compostos Inorgânicos de Carbono , Cumarínicos/síntese química , Diuréticos/síntese química , Óxidos , Cumarínicos/farmacologia , Diuréticos/farmacologia , Testes de Sensibilidade Microbiana , Relação Estrutura-AtividadeRESUMO
A comparative study of the essential oils of Santolina insularis and Santolina corsica has been carried out. The two specimens are found in Sardinia and were indiscriminately used in traditional medicine on the island. The essential oil was extracted by steam distillation of fresh aerial parts and analysed by GC, GC-MS and GC-FTIR. The analysis of the essential oils shows substantial qualitative and quantitative differences. Some of the components identified were present in both investigated species, others were characteristic of one species only.
Assuntos
Óleos de Plantas/isolamento & purificação , Plantas Medicinais/química , Cromatografia Gasosa-Espectrometria de Massas , Itália , Espectroscopia de Ressonância Magnética , Medicina Tradicional , Especificidade da Espécie , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
The synthesis of (N-substituted)amino-spiroalkan-dione derivatives 3 is described starting from enamines 1 and carbon suboxide 2, and their inhibitory effects on blood coagulation in vivo and on platelet aggregation in vitro are determined. Some of synthesized compounds showed a strong anticoagulant activity. A comparative pharmacological study of the anticoagulant effects of the new compounds versus Warfarin suggests that their behaviour is analogous, though the action mechanism is different.
Assuntos
Ciclobutanos/síntese química , Ciclobutanos/farmacologia , Inibidores da Agregação Plaquetária/síntese química , Inibidores da Agregação Plaquetária/farmacologia , Compostos de Espiro/síntese química , Compostos de Espiro/farmacologia , Difosfato de Adenosina/farmacologia , Animais , Colágeno/farmacologia , Ciclobutanos/química , Estrutura Molecular , Fator de Ativação de Plaquetas/farmacologia , Inibidores da Agregação Plaquetária/química , Ratos , Ratos Wistar , Padrões de Referência , Análise Espectral , Compostos de Espiro/químicaRESUMO
Microalbuminuria is considered as a sign of high risk of renal disease in type 1 diabetes mellitus, and of cardiovascular disease in types 1 and 2 diabetes. In recent years numerous studies have suggested that microalbuminuria may be associated with atherosclerotic vascular disease, independently from diabetes mellitus. The presence of microalbuminuria was investigated in 30 patients suffering from atherosclerotic vascular disease: ischemic heart disease, cerebrovascular disease or arterial disease of the lower extremities. They were divided into two groups similar in age: 13 with type 2 diabetes mellitus, and 17 without diabetes. The aim of the research was to reveal eventually different prevalence of microalbuminuria in patients with vascular disease associated with diabetes or without diabetes. Microalbuminuria was present in 52.9% of the non diabetic patients and in 76.9% of the diabetics, but the difference did not reach statistical significance (in Mann-Whitney test p = 0.18; Chi-square test = 0.83; p = 0.3). No significant correlation was found between microalbuminuria and fibrinogen, total cholesterol, HDL-cholesterol and triglycerides. The hypertensive patients presented higher mean values of microalbuminuria than the normotensive ones (3.2 +/- 3.8 and 2.8 +/- 4.4 mg %, respectively), but the difference was again not significant (t = 0.25; p = 0.8). In the light of this research microalbuminuria seems to be a condition associated with atherosclerotic vascular disease, independently from the presence of diabetes mellitus and arterial hypertension.
RESUMO
The synthesis of N-substituted-2-oxo-(2H)1-Benzopyran-3-Carboxamide derivatives starting from semicarbazones or thiosemicarbazones and Carbon Suboxide (ratio 1:2) is described. Some compounds showed an interesting analgesic and/or diuretic activity in mice.
Assuntos
Analgésicos não Narcóticos/síntese química , Diuréticos/síntese química , Analgésicos não Narcóticos/farmacologia , Animais , Diuréticos/farmacologia , Masculino , Camundongos , Ratos , Relação Estrutura-AtividadeRESUMO
The synthesis of 2,4-dione derivatives of 1,5-benzodithiepine, 1,5-benzodiazepine and 1,5-benzothiazepine and the anti-microbial activity in vitro of these derivatives and of analogous of 1,5-benzodioxepine, 1,5-benzoxathiepine and 1,5-benzoxazepine, previously prepared, are reported. Some of these compounds showed a good activity against some Gram positive microorganisms and blastomycetes.
Assuntos
Anti-Infecciosos/síntese química , Benzodiazepinas/síntese química , Benzotiepinas/síntese química , Compostos Heterocíclicos/síntese química , Oxepinas/síntese química , Tiazepinas/síntese química , Antibacterianos , Bactérias/efeitos dos fármacos , Benzodiazepinas/química , Benzodiazepinas/farmacologia , Benzotiepinas/química , Benzotiepinas/farmacologia , Blastomyces/efeitos dos fármacos , Fenômenos Químicos , Físico-Química , Compostos Heterocíclicos/química , Compostos Heterocíclicos/farmacologia , Espectroscopia de Ressonância Magnética , Testes de Sensibilidade Microbiana , Oxepinas/química , Oxepinas/farmacologia , Espectrofotometria Infravermelho , Tiazepinas/química , Tiazepinas/farmacologiaRESUMO
A unique case in which a tentative diagnosis of congenital heart disease was made by fetal ECG is presented. A new averaging technique allowed an accurate analysis of the QRS complexes obtained from the maternal surface. This is the first case of fetal arrhythmias in which an early prenatal diagnosis of an anatomical lesion of the heart was suspected by reason of an abnormal fetal ECG and confirmed clinically at birth.