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1.
Lupus ; 19(11): 1261-71, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20530521

RESUMO

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the generation of autoantibodies against a diverse array of self-antigens. The B cells producing immunoglobulin G (IgG) antibodies to double-stranded DNA appear to play a main role in the disease progression. Their specific elimination is a reasonable mechanism for effective therapy of SLE. The presently used approaches for silencing autoreactive disease-associated B cells are nonspecific and more precise therapies are needed. We have previously constructed a chimeric protein molecule consisting of several DNA-mimotope peptides coupled to a rat monoclonal anti-mouse CD32 (FcγRIIb) antibody. The mineral oil pristane induces a lupus-like syndrome in non-autoimmune mice leading to the development of glomerulonephritis and lupus-associated autoantibodies. In the present paper, using a pristane-induced autoimmune model in SCID mice, we analyzed the ability of the chimeric antibody to suppress selectively the autoreactive B lymphocytes by cross-linking B-cell surface immunoglobulin receptors with the inhibitory IgG FcγRIIb receptors. Treatment with DNA-like chimeric molecules inhibited B- and T-cell proliferation, restricted the number of anti-DNA antibody-producing cells and suppressed the generation of IgG anti-DNA antibodies. In contrast, phosphate buffered saline (PBS)-injected control mice experienced an increase of disease-associated antibody levels and developed glomerulonephritis similar to pristane-treated donor Balb/c mice.


Assuntos
Autoimunidade/imunologia , Linfócitos B/fisiologia , Imunossupressores/farmacologia , Lúpus Eritematoso Sistêmico/induzido quimicamente , Camundongos SCID , Terpenos/farmacologia , Animais , Linfócitos B/imunologia , Linhagem Celular , Citocinas/sangue , Citocinas/imunologia , DNA/imunologia , Feminino , Humanos , Lúpus Eritematoso Sistêmico/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Ratos , Receptores de Antígenos de Linfócitos B/imunologia , Receptores de IgG/imunologia , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/imunologia
2.
Drug Res (Stuttg) ; 65(6): 317-22, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24992498

RESUMO

In this work we present 3 new complexes of Ruthenium (III) with a general formula HL[Ru(L)2Cl4], where L=benzothiazole, 2-methylbenzothiazole and 2-mercaptobenzothiazole. The syntheses were carried out in polar medium under argon. The compounds obtained were characterised by IR-, (1)H-NMR- (13)C-NMR-, UV-VIS-spectroscopy and conductivity measurements. The ligands behaved as monodentate, bounding Ru(III) through the nitrogen atoms from the heterocycle. The cytotoxicity of the new complexes was tested against 2 human leukemic cell lines (K-562 and KE-37), using the MTT-dye reduction assay. The Ru(III) coordination compound with 2-methylbenzothiazole displayed superior activity compared to the other novel complexes. Its IC50 values were comparable to that of the reference cytotoxic drug cisplatin. In general, the ligands displayed only marginal inhibitory effects on the human leukemic cell lines. Moreover, the ability of the complexes to trigger apoptosis was evaluated using a commercially available DNA-fragmentation ELISA kit and the obtained data indicated that their proapoptotic effects well correlate to the MTT-bioassay data.


Assuntos
Benzotiazóis/química , Benzotiazóis/farmacologia , Rutênio/química , Rutênio/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Cisplatino/farmacologia , Humanos , Leucemia/tratamento farmacológico , Espectroscopia de Ressonância Magnética/métodos
3.
Methods Find Exp Clin Pharmacol ; 16(8): 609-13, 1994 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-7760586

RESUMO

The effect of flunarizine in the treatment of post-phlebitic syndrome (PPS) and venous leg ulcers was studied in 42 patients in a double-blind, placebo-controlled trial over a period of 3 months. During the first month the dose of flunarizine or the matching placebo was 1 capsule of 5 mg twice-daily, and during the following 2 months 1 capsule of 5 mg once-daily. Most of the subjective symptoms such as heaviness in the legs, pain, paraesthesia, cramps at night, and swelling of the ankles considerably improved during treatment with flunarizine and were slightly improved in the placebo group. The ulcer surface area decreased after 3 months' treatment with flunarizine by 68.3% (p < 0.001), and after treatment with placebo by 20.5% (p > 0.05). In 15 patients treated with flunarizine and 1 with placebo the ulcers vanished completely. An improvement in the photoplethysmographic record of the lower legs in the flunarizine group was observed, as shown by increase in the index recovery time, while there were no significant changes in the placebo group. The results show that the favorable effect of flunarizine in the treatment of PPS and venous leg ulcers might be due largely to an improvement in subcutaneous circulation of the lower legs. Flunarizine may be an important adjunct to the conservative management of the complications caused by chronic venous insufficiency.


Assuntos
Flunarizina/uso terapêutico , Úlcera da Perna/tratamento farmacológico , Flebite/complicações , Flebite/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Método Duplo-Cego , Edema/tratamento farmacológico , Edema/etiologia , Feminino , Humanos , Úlcera da Perna/patologia , Masculino , Pessoa de Meia-Idade , Dor/tratamento farmacológico , Dor/etiologia , Flebite/patologia , Fotopletismografia
4.
Methods Find Exp Clin Pharmacol ; 17(8): 545-9, 1995 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-8749228

RESUMO

The effect of nifedipine in the treatment of hypertensive venous leg ulcers was studied on 30 outpatients in a double-blind placebo-controlled trail over a period of 2 months. The dose of nifedipine or the matching placebo was 10 mg 3 times daily. Most of the subjective symptoms such as pain, paraesthesia and cramps at night considerably improved during the treatment with nifedipine and were slightly affected in the placebo group. The ulcer surface area decreased after 2 months treatment with nifedipine by 26.9% (p < 0.05), and after treatment with placebo by 8.6% (p > 0.05). An improvement of the photopletysmographic record of the lower legs in the nifedipine group was observed, demonstrated by an increase of the index recovery time (by 36.1%, p < 0.05), while there were no significant changes in the placebo group. The results show favorable effect of nifedipine in the treatment of hypertensive venous leg ulcers which might be due to a great extent to improvement of the subcutaneous circulation of the lower legs. Nifedipine may be an important adjunct to the conservative management of the complications caused by chronic venous insufficiency and hypertension.


Assuntos
Hipertensão/tratamento farmacológico , Úlcera da Perna/tratamento farmacológico , Nifedipino/uso terapêutico , Adulto , Idoso , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Método Duplo-Cego , Feminino , Humanos , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Fatores de Tempo
5.
Methods Find Exp Clin Pharmacol ; 9(2): 85-9, 1987 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-3586772

RESUMO

The antimycotic effect of 5-fluoroorotic acid (FOA) was studied in experimental and clinical conditions. The experiments in vitro were performed on 21 strains of fungi isolated mainly from clinical material. The effect of FOA was compared with those of the structurally related drug 5-fluorocytosine. The clinical study was performed on 40 patients aged 18 to 75 years with mycological diseases. FOA in different dosage forms was applied topically 2 to 3 times daily for 30 days. Microscopic and cultured mycological studies were performed before and after treatment. The results showed that FOA possesses a well-expressed anticandidal effect close to that of 5-fluorocytosine, as well as moderate antidermatophytal effects. Clinical studies of 1% FOA cream showed good therapeutic effects similar to that of Ung. Whitfield, but 55% of the patients developed relapse of the lesions after discontinuation of the treatment. Higher concentrations of FOA included in milk suspension and powder induced severe side effects of local irritability.


Assuntos
Antifúngicos , Arthrodermataceae/efeitos dos fármacos , Candida/efeitos dos fármacos , Dermatomicoses/tratamento farmacológico , Ácido Orótico/análogos & derivados , Adolescente , Adulto , Idoso , Animais , Feminino , Flucitosina/farmacologia , Humanos , Linimentos , Masculino , Camundongos , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Pomadas , Ácido Orótico/farmacologia , Pós
6.
Int J Legal Med ; 120(1): 53-5, 2006 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-16088410

RESUMO

Allele frequencies of 15 STR loci (D8S1179, D21S11, D7S820, CSF1PO, D3S1358, TH01, D13S317, D16S539, D2S1338, D19S433, vWA, TPOX, D18S51, D5S818, and FGA) were determined in a sample of 163 unrelated individuals from the Republic of Macedonia. AmpFISTR Identifiler Kit (Applied Biosystems) was used for PCR amplification. For all 15 loci, the combined matching chance is 6.6 x 10(18) and the power of exclusion is 99.999954%.


Assuntos
Frequência do Gene , Genética Populacional , Sequências de Repetição em Tandem , Impressões Digitais de DNA , Humanos , Reação em Cadeia da Polimerase , República da Macedônia do Norte
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