RESUMO
ENT manifestations are commonly observed in patients with small vessel vasculitis (SVV). The main aim of this study was to analyse and present the clinicopathological characteristics of individuals with SVV emphasising otorhinolaryngological symptoms. This study evaluated 64 patients, 41 with granulomatosis with polyangiitis (GPA) and 23 with microscopic polyangiitis (MPA). Herein, we compare the clinicopathologic features of GPA and MPA. The average age at diagnosis was 50.2 and 56.2 years, for GPA and MPA, respectively. 57 patients (89%) were antineutrophil cytoplasmic antibody (ANCA) positive, 34 (59.6%) for anti-proteinase 3 (PR3)-ANCA and 21 (36.8%) for myeloperoxidase (MPO)-ANCA. 7 patients (10.9%) were ANCA negative. The most commonly affected organs were lungs (76.56%), ear, nose, throat (ENT) (75%) and kidneys (73.44%). ENT disorders mainly appeared as chronic rhinosinusitis and epistaxis and preceded SVV diagnosis by an average 14.4 months. In the majority of patients, ENT disorders were the first symptoms of SVV and preceded its systemic transformation. Pulmonary, ENT and nervous manifestations were more common in GPA, whereas the prevalence of renal, gastrointestinal, cutaneous, cardiovascular and ocular disorders was higher in MPA. The results of our study emphasise the high prevalence of ENT symptoms in patients with SVV, especially in those with GPA. We highlight the significant role of the otorhinolaryngologist in early SVV diagnosis and management. Any patient with persistent ENT symptoms or ENT dysfunctions not responding to standard otorhinolaryngological treatment should be precisely and rapidly evaluated for the presence of systemic dysfunctions (especially renal and pulmonary). Realising the differences and similarities between GPA and MPA is crucial in undelayed SVV diagnosis and proper treatment.
Assuntos
Granulomatose com Poliangiite/diagnóstico , Poliangiite Microscópica/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Granulomatose com Poliangiite/complicações , Humanos , Masculino , Poliangiite Microscópica/complicações , Pessoa de Meia-Idade , Otorrinolaringopatias/etiologia , Adulto JovemRESUMO
Diabetes mellitus (DM), one of the most common life-threatening illnesses worldwide, is a group of metabolic diseases, characterized by sustained hyperglycemia. The global prevalence of diabetes mellitus among adults reached 387 millions in 2014 and is still rising. It is suggested there is a strong association between diabetes mellitus (especially type 2 diabetes mellitus) and carcinogenesis. The possible biological links between diabetes mellitus and cancer comprise hyperinsulinemia, hyperglycemia and fat-induced chronic inflammation. Although, the strongest association refers to pancreas and liver, there are many other organs involved in carcinogenesis in diabetic patients including breast, endometrium, bladder and kidney.Recent studies suggest that there is also association between cancer incidence and anti-diabetic medications. It was observed that some medications decrease the risk of carcinogenesis and some increase that risk. The majority of studies concern metformin, a drug of choice in type 2 diabetes mellitus, and its anti-neoplastic and tumor-suppressing activity. The positive effect of metformin was found in numerous researches investigating breast, pancreas, liver, colon, ovaries and prostate tumors.Because a variety of studies have suggested that diabetes mellitus and cancer are frequently coexisting diseases, recently published studies try to explain the influence of diabetes mellitus and anti-diabetic medications on carcinogenesis in different organs.We present the review of the latest studies investigating the association between both diabetes mellitus and anti-diabetic medications and cancer incidence and prognosis.Particularly we highlight the problem of concomitant head and neck cancers in diabetics, rarely analysed and often omitted in studies.
Assuntos
Comorbidade , Diabetes Mellitus/epidemiologia , Hipoglicemiantes/farmacologia , Neoplasias/epidemiologia , Diabetes Mellitus/tratamento farmacológico , HumanosRESUMO
The opinions of seven respondent groups about the relative importance of different practices pertaining to the welfare of Australian beef cattle, sheep and goats were surveyed. Respondent groups comprised farmers, livestock transportation representatives, veterinarians, meat processors, animal welfare advocates, animal welfare scientists and government officers. The survey consisted of a web-based adaptive conjoint analysis questionnaire, which was administered to a sample population that was selected randomly for large respondent groups and comprehensively for small groups. The hierarchy of opinion concerning the importance of the different beef cattle practices was: stockmanship > ground (road and rail) transport > spaying > food supply > dehorning > stunning > shelter > identification > pretransport food and water deprivation > castration > sea transport > mustering > confinement. For sheep/goat practices the hierarchy was: parasite control > mulesing > shelter > stockmanship > tail docking > ground transport > feeding > predation > stunning > castration > pretransport food and water deprivation > sea transport > mustering. The method of performing invasive procedures was perceived as less important than the provision of pain relief. Differences in opinion were evident between respondent groups, with animal welfare advocates tending to focus on painful procedures more than those with direct involvement in the industry.
RESUMO
In our search for new compounds acting on benzodiazepine receptors among the fused 2-thiohydantoin derivatives, a series of arylidene imidazo[2,1-b]thiazines was synthesized. The 1,2- and 2,3- cyclized derivatives of mono- and di-substituted Z-5-arylidene-2-thiohydantoins were examined (the X-ray crystal structure of Z-2-cinnamylidene-6,7-dihydro-5H-imidazo[2,1-b][1,3]thiazin-3(2H)-one was determined) and compared with the diphenyl derivatives. To investigate the influence of the type of annelated ring on the biological activity, imidazo[2,1-b]pyrimidinone and imidazo[2,1-b]diazepinone derivatives were obtained. The method used in annelation (1,2- and 2,3-cyclized isomers with the exception of fused arylidene imidazothiazines), the substitution pattern (arylidene towards diphenyl) as well as the character of the annelated ring had minor influence on the benzodiazepine receptor affinity of the investigated compounds. It appears that the greatest influence on the biological activity has the character and position of the substituents on the arylidene ring.
Assuntos
Diazepam/análogos & derivados , Diazepam/síntese química , Pirimidinonas/metabolismo , Receptores de GABA-A/metabolismo , Tiazinas/metabolismo , Animais , Ligação Competitiva , Córtex Cerebral/metabolismo , Diazepam/metabolismo , Diazepam/farmacologia , Desenho de Fármacos , Antagonistas de Receptores de GABA-A , Concentração Inibidora 50 , Modelos Moleculares , Pirimidinonas/síntese química , Pirimidinonas/química , Pirimidinonas/farmacologia , Ratos , Relação Estrutura-Atividade , Tiazinas/síntese química , Tiazinas/química , Tiazinas/farmacologia , Difração de Raios XRESUMO
A series of 6-substituted 2-aryl-N,N-dimethylimidazol[1,2-a] pyridine-3-acetamides, congeners of zolpidem and alpidem, was synthesized and tested in vitro for binding with the benzodiazepine receptor in the competition with 3H-zolpidem as an omega 1-selective radioligand. Molecular electrostatic potential (MEP) and the HOMO and LUMO energies were calculated for the compounds by semi-empirical quantum chemistry methods. The lipophilicity parameter of the compounds, expressed as the logarithm of the octanol-water partition coefficient (log P), was calculated; alternatively, standard values of the Hansch hydrophobic substituent constants pi were used. In agreement with earlier investigations on the benzodiazepine receptor ligands with a high preference for the omega 1-subtype, a quantitative correlation of the biological data with molecular parameters has revealed a significant dependence (r = 0.954) of the binding affinity (IC50) on the deepest MEP minimum, in this case associated with the amide carbonyl oxygen atom. The lipophilicity parameters were found to be of lower significance.
Assuntos
Agonistas GABAérgicos/metabolismo , Piridinas/metabolismo , Receptores de GABA-A/metabolismo , Animais , Diazepam/química , Agonistas GABAérgicos/química , Moduladores GABAérgicos/química , Piridinas/química , Ratos , Eletricidade Estática , Relação Estrutura-Atividade , ZolpidemRESUMO
Effective expression of the HIV-1 core protein Gag-p55 was obtained in Saccharomyces cerevisiae under control of the inducible UASgal/CYC1 promoter as a translational fusion with the prion-forming NM domain of the translation terminator Sup35p (eRF3) of S. cerevisiae. where only poor expression of the original-type Gag-p55 was observed. A deletion within the Sup35NM prion-forming domain altering Sup35-associated [PSI] inheritance did not compromise expression of the Sup35NM Gag-p55 fusion protein. Therefore, either the mechanism of this phenomenon is not directly related to the effect of Sup35p prion-formation or the modified protein maintains residual prion-forming abilities. The recombinant Sup35p-Gag-p55 protein was quite stable under boiling in an alkali/sodium dodecyl sulfate (SDS) solution and completely retained its antigenic properties. Moreover, 10-min boiling of the native yeast cells in this solution allowed immediate inhibition of lysosomal and other yeast proteases, responsible for autolysis of many natural and recombinant proteins. The use of this method of preliminary enrichment for the recombinant fusion protein Sup35p-Gag-p55 with the SDS-alkaline extraction could be useful for yeast heterologous expression and purification of other of insoluble and unstable proteins. A translational fusion with the NM domain of Sup35p was also used to produce another poorly soluble protein, the L-chain of botulinum exotoxin A, in S. cerevisiae. When the Sup35p fragment was removed from the recombinant construct encoding a fused Sup35/BoNT protein, a dramatic drop in both transformation efficiency and growth rate of transformants was shown.
Assuntos
Toxinas Botulínicas Tipo A/metabolismo , Proteínas Fúngicas/biossíntese , Produtos do Gene gag/biossíntese , Príons , Precursores de Proteínas/biossíntese , Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Biotecnologia/métodos , Toxinas Botulínicas Tipo A/genética , Proteínas Fúngicas/genética , Produtos do Gene gag/genética , Fatores de Terminação de Peptídeos , Plasmídeos , Precursores de Proteínas/genética , Proteínas Recombinantes de Fusão/biossíntese , Proteínas Recombinantes de Fusão/genética , Saccharomyces cerevisiae/crescimento & desenvolvimento , Transformação GenéticaRESUMO
Using the mouse cryptorchid model, degenerations of germ cells were observed as well as a reduced size of seminiferous tubules, while the area of the interstitial tissue increased. Aromatase, the enzyme responsible for the conversion of androgens into oestrogens, was immunolocalized in Leydig cells and in germ cells from both scrotal and abdominal testes, and in Sertoli cells only in a control testis. In the cryptorchid testis, aromatase was strongly expressed in a few tubules, including those spermatids that were still present. Other cells inside the tubules were negative for aromatase. In both testes, oestrogen receptors alpha were expressed only in Leydig cells. Strong aromatase expression in germ cells indicates an additional source of oestrogens in the testis besides the interstitial tissue.
Assuntos
Aromatase/biossíntese , Criptorquidismo/fisiopatologia , Receptores de Estrogênio/análise , Testículo/fisiologia , Animais , Aromatase/análise , Modelos Animais de Doenças , Estrogênios/biossíntese , Regulação da Expressão Gênica , Células Germinativas , Imuno-Histoquímica , Masculino , Camundongos , Testículo/enzimologiaRESUMO
Synthesis and antiparasitic activity vs T. cruzi and L. donovani of a series of 9-thioaryl acridines are reported. A convenient correlation between molecular structure and biological activity is proposed. Results not only agree with the classical interactions of acridines with DNA but also suggest possible role of charge transfer complexes.
Assuntos
Tripanossomicidas/síntese química , Trypanosoma/efeitos dos fármacos , Acridinas/síntese química , Acridinas/farmacologia , Animais , Cristalografia por Raios X , Espectroscopia de Ressonância Magnética , Relação Quantitativa Estrutura-Atividade , Tripanossomicidas/farmacologiaRESUMO
The basic model for glycine receptor site has been proposed based on the ligands incorporated spatially inflexible main skeleton. The search for compounds, which are selectively bound to the receptor, is now based on topological and/or stereochemical requirements and restrictions derived for the glycine binding site. IsoStar is the definitive database of experimental and theoretical information on non-bonded interactions. It has been designed to play a prominent role in the field of rational drug design. We applied IsoStar in our search for the model of glycine binding site of the NMDA receptor.
Assuntos
Cristalografia , Receptores de Glicina/efeitos dos fármacos , Desenho de Fármacos , Ligantes , Modelos Biológicos , Conformação MolecularRESUMO
The authors want to indicate, according to the case description, the danger of oral anticoagulants and nonsteroidal antiinflammatory drug's therapy in elderly patients.
Assuntos
Anemia/etiologia , Anti-Inflamatórios não Esteroides/efeitos adversos , Anticoagulantes/efeitos adversos , Hematoma , Hemotórax , Doenças Peritoneais , Espaço Retroperitoneal/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Hematoma/induzido quimicamente , Hematoma/complicações , Hematoma/diagnóstico por imagem , Hemotórax/induzido quimicamente , Hemotórax/complicações , Hemotórax/diagnóstico , Humanos , Masculino , Doenças Peritoneais/induzido quimicamente , Doenças Peritoneais/complicações , Doenças Peritoneais/diagnóstico por imagem , UltrassonografiaRESUMO
The synthesis of several acridinic thioethers is described. Compounds prepared were tested in vitro as potential drugs against the opportunistic infection known as cryptosporidiosis. With a view to predict activity, the quantitative structure-activity relationships were investigated. Correlations between experimental data and either log P or pKa are discussed.
Assuntos
Acridinas/síntese química , Coccidiostáticos/síntese química , Cryptosporidium parvum/efeitos dos fármacos , Acridinas/farmacologia , Acridinas/uso terapêutico , Animais , Animais Recém-Nascidos , Bovinos , Linhagem Celular , Coccidiostáticos/farmacologia , Coccidiostáticos/uso terapêutico , Criptosporidiose/tratamento farmacológico , Criptosporidiose/parasitologia , Cryptosporidium parvum/crescimento & desenvolvimento , Fezes/parasitologia , Ligação de Hidrogênio , Espectroscopia de Ressonância Magnética , Relação Estrutura-AtividadeRESUMO
Synthesis and activity, vs. leukaemia cells of new 9-thiadiazolo acridine derivatives are reported. In addition, electronic properties and molecular structure are correlated with biological activity of these molecules. Results are in agreement with the capability of drugs to intercalate into DNA.
Assuntos
Acridinas/farmacologia , Antineoplásicos/farmacologia , Tiadiazóis/farmacologia , Animais , Leucemia L1210/tratamento farmacológico , Leucemia L1210/patologia , Camundongos , Relação Quantitativa Estrutura-AtividadeRESUMO
New 1-arylpiperazine (series d-f) and 1,2,3,4-tetrahydroisoquinoline (series g) derivatives of 1,4-benzoxazin-3(4H)-one 1, 1,2-benzoxazolin-3-one 2, and 1,3-benzoxazolin-2,4-dione 3 with an n-butyl chain were synthesized in order to explore the effect of spacer elongation on their binding affinity and in vivo functional activity at 5-HT1A and 5-HT2A receptors in comparison with trimethylene analogues (a, bc). 5-HT1A receptor binding constants of derivatives 1d-g, 2d-f, and 3d-f were very high (Ki = 1.25-54 nM), and 5-HT2A affinities were maintained at a similar, high level (Ki = 27-85 nM) for series d and e, and moderate (Ki = 246-495 nM) for series f. In respect of a spacer, the obtained results showed either no effect or a slight increase in the 5-HT1A/5-HT2A affinity in case of derivatives of 1 and 2, respectively. A striking effect was observed for derivatives 3d and 3f, whose 5-HT1A affinity was reinforced by two orders of magnitude with a simultaneous decrease in 5-HT2A binding constants in comparison with trimethylene analogues. As shown by X-ray crystallography, this phenomenon may be attributed to the position of non-carbonyl oxygen atom in the amide moiety. In vivo studies demonstrated that compounds 1e-g, 2d-f, and 3f behaved like typical postsynaptic 5-HT1A receptor antagonists, whereas 3d and 3e might be qualified as their potential partial agonists. Moreover, 1e, 2e, and 3e demonstrated 5-HT2A receptor antagonistic properties. Of the tested compounds, two derivatives showed some very outstanding properties: 3e may be regarded as a potential anxiolytic and/or antidepressant agent, while 3f as a new potent 5-HT1A antagonist.
Assuntos
Benzoxazóis/química , Benzoxazóis/farmacologia , Piperazinas/química , Piperazinas/farmacologia , Receptores de Serotonina/efeitos dos fármacos , Antagonistas da Serotonina/química , Antagonistas da Serotonina/farmacologia , Animais , Comportamento Animal/efeitos dos fármacos , Benzoxazóis/síntese química , Masculino , Camundongos , Piperazinas/síntese química , Ratos , Ratos Wistar , Receptores de Serotonina/metabolismo , Antagonistas da Serotonina/síntese química , Relação Estrutura-AtividadeRESUMO
A case of drug-related hyperkaliemia linked to treatment with angiotensin converting enzyme inhibitors and spironolactone simultaneously. The paper presents the case of drug-related hiperkaliemia induced by captopril and spironolactone combined treatment in a patient with early stage of renal failure.
Assuntos
Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Diuréticos/efeitos adversos , Hiperpotassemia/induzido quimicamente , Espironolactona/efeitos adversos , Idoso , Humanos , Masculino , Insuficiência Renal/tratamento farmacológicoRESUMO
Synthesis and physicochemical properties of new N-pyridyl derivatives of 3-phenyl and 3,3-diphenylsuccinimides (1-12) have been described. The obtained compounds were evaluated in respect of their anticonvulsant activity. The N-pyridyl derivatives of 3-phenylsuccinimides (7-12) abolished the protection against MES- and scMET-induced seizures, whereas N-pyridyl derivatives of 3,3-diphenylsuccinimides (1-6) were inactive. After molecular modelling and quantum-chemistry calculations the theoretical activity test was applied (W. Kwiatkowski, J. Karolak-Wojciechowska, SAR and QSAR Envir. Res. 1 (1993) 233; Chem. Abstr. 120, 153001 (1994). J. Karolak-Wojciechowska, M. Blaszczyk, W. Kwiatkowski, J. Obniska, A. Zejc, J. Chem. Cryst. 27 (1997) 297; Chem. Abstr. 127, 277834k (1997)). The molecular electrostatic potential (MEP) of the active compounds differed significantly from that of the inactive ones.
Assuntos
Anticonvulsivantes/síntese química , Piridinas/síntese química , Succinimidas/síntese química , Animais , Anticonvulsivantes/farmacologia , Fenômenos Químicos , Físico-Química , Eletrochoque , Conformação Molecular , Pentilenotetrazol , Piridinas/farmacologia , Ratos , Convulsões/induzido quimicamente , Convulsões/prevenção & controle , Espectrofotometria Ultravioleta , Succinimidas/farmacologia , Difração de Raios XRESUMO
Genes cry26Aal and cry28Aal were cloned from Bacillus thuringiensis ssp. finitimus strain B-1166 VKPM. This strain forms insecticidal crystal bodies either outside or inside the exosporium. The deduced amino acid sequence of the cry26Aal gene product included seven residues determined to be an N-terminal part of a chymotrypsin-treated delta-endotoxin isolated from the same strain. Earlier this protein was detected in both free and spore-associated types of crystals [Revina et al., Biokhimia (1999) in press]. Neither BtI nor BtII promoter sequences were found upstream of the open reading frames in both genes. Southern hybridization has shown that the surroundings of both genes at least 3 kb upstream and downstream of the open reading frames are unique. We suggest that the protein Cry26Aal in both types of crystal bodies is synthesized under the control of one and the same genomic locus.
Assuntos
Bacillus thuringiensis/genética , Proteínas de Bactérias/genética , Toxinas Bacterianas , Endotoxinas/genética , Genes Bacterianos , Sequência de Aminoácidos , Bacillus thuringiensis/classificação , Toxinas de Bacillus thuringiensis , Clonagem Molecular , Proteínas Hemolisinas , Inseticidas , Dados de Sequência Molecular , Análise de Sequência de DNA , Homologia de Sequência de AminoácidosRESUMO
The authors present according to a case of acute intermittent porphyria, diagnostic and therapeutical problems, which are met by physicians in a regional hospital (case 1). Simultaneously the authors present a case of woman with opiate depends syndrome, who has simulated attacks of acute porphyria for the last few years in order to obtain narcotic drugs (case 2).
Assuntos
Transtornos Relacionados ao Uso de Opioides/complicações , Porfiria Aguda Intermitente/diagnóstico , Porfiria Aguda Intermitente/terapia , Adulto , Diagnóstico Diferencial , Feminino , Humanos , Pessoa de Meia-Idade , Porfirias/diagnóstico , Porfirias/etiologiaRESUMO
We present a 61-year old patient with diagnosis of progressive supranuclear palsy. 2 years after the beginning of her complaints the diagnosis was based on the results of neurological examination. The ENG examination (among others vertical gaze paralysis) and the MR examination (2 of 3 criteria were met). The course of the disease was complicated by epilepsy and the treatment with carbamazepine was commenced. A significant improvement of her neurological and mental status was observed. The authors suggest checking this observation on larger number of patients with PSP.
Assuntos
Anticonvulsivantes/uso terapêutico , Carbamazepina/uso terapêutico , Paralisia Supranuclear Progressiva/tratamento farmacológico , Eletroencefalografia , Feminino , Humanos , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Paralisia Supranuclear Progressiva/diagnóstico , Tomografia Computadorizada de Emissão de Fóton ÚnicoRESUMO
The series of glycine derivatives of diphenyl or (un)substituted arylidene imidazolones was designed and obtained as potential ligands of the glycine binding site of NMDA receptors. The compounds were evaluated in vitro for their affinity to the glycine binding site of NMDA receptors using as radioligand [3H]-L-689,560. Their anticonvulsant activity was estimated in vivo in maximal electroshock seizure (MES) and subcutaneous pentylenetetrazole (scMet) tests. To explain the structure, pharmacological activity results Multiple Linear Regression Analysis was used.
Assuntos
Anticonvulsivantes/síntese química , Glicina/análogos & derivados , Glicina/farmacologia , Imidazóis/síntese química , Receptores de Glicina/efeitos dos fármacos , Receptores de N-Metil-D-Aspartato/efeitos dos fármacos , Animais , Anticonvulsivantes/farmacologia , Convulsivantes/farmacologia , Eletrochoque , Imidazóis/farmacologia , Ligantes , Masculino , Camundongos , Pentilenotetrazol/antagonistas & inibidores , Ratos , Convulsões/induzido quimicamente , Convulsões/prevenção & controleRESUMO
A series of glycinamides, derivatives of diphenyl imidazolon-4-one was designed and obtained as potential ligands of the glycine binding site of NMDA receptors. The compounds were evaluated in vitro for their affinity for the glycine binding site of NMDA receptors using [3H]-L-689,560 as radioligand. Their anticonvulsant activity was estimated in vivo in a maximal electroshock seizure (MES) and subcutaneous pentylenetetrazole (scMet) tests. The volume and the surface of the molecules seem to be important in elucidating the relation between the structure and the pharmacological properties.