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1.
Pol J Vet Sci ; 26(3): 449-459, 2023 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-37727503

RESUMO

Otitis externa is a canine disease of multifactorial etiology in which bacteria plays a significant role. Due to the predominant bacterial etiology otitis is usually treated with antibiotics. However, non-prudent use of antibiotics promotes the emergence of antibiotic-resistant bacteria thus compromising the therapy effectiveness. Currently, the increase of antimicrobial resistance (AMR) is one of the biggest threats to global health. For this reason, the aim of the study was to investigate prevalence of the microbiological causes of canine otitis externa and the antibiotic susceptibility of the isolated bacterial strains. The research and sampling were conducted at Veterinary Clinics for small pets in Serbia. Samples were sent to laboratory for bacteriological and mycological testing. Additionally, the sensitivity of the isolated bacteria to antibiotics was evaluated using disc diffusion method. Sixty dogs with otitis externa clinical symptoms were included in the study. Out of a total of 53 positive samples for pathogen presence, bacteria were present in 40. The most prevalent bacteria was Staphylococcus pseudintermedius, followed by Pseudomonas aeruginosa and Proteus spp., while Malassezia pachydermatis was the only isolated yeast pathogen occurring in 36 samples. Generally, the lowest resistance against all bacteria showed enrofloxacin. On the contrary, high resistance to penicillin and amoxicillin was a common finding for G+ and G- bacteria. These results indicate the need for laboratory testing in terms of isolation, identification and antibiotic susceptibility testing, not only in the case of otitis externa in dogs, but in all diseases when it is possible, in order to enhance antimicrobial stewardship and consequently to contribute AMR reduction.


Assuntos
Otite Externa , Cães , Animais , Otite Externa/epidemiologia , Otite Externa/veterinária , Prevalência , Bactérias , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Amoxicilina , Saccharomyces cerevisiae
2.
J Small Anim Pract ; 64(10): 626-634, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37340896

RESUMO

OBJECTIVES: Amoxicillin/clavulanate is the most commonly used oral antimicrobial drug in companion animals. The objective of the study was to detect types and frequency of deficits in the quality of veterinary oral formulations of amoxicillin/clavulanate in various countries. MATERIALS AND METHODS: In a prospective study with purposive sampling, amoxicillin/clavulanate tablet formulations for canine use were collected in four countries (wholesalers or veterinary practice) and shipped to a central bioanalytical laboratory. Twenty-four samples were collected from the UK (nine), Malaysia (nine), Serbia (four) and Thailand (two), yielding 18 different formulations (10 veterinary). Packaging inspection, tablet disintegration and content assay were conducted (validated high-performance liquid chromatography with ultra-violet detection); content was acceptable when within the 90% to 120% pre-specified range (US Pharmacopeia). RESULTS: Secondary packaging was present for 13 of 24 samples and primary packaging integrity was verified for all but one sample. Amoxicillin trihydrate/potassium clavulanate label ratio was 4:1, except for three formulations (2:1). Tablet dose strength ranged from 250 to 625 mg. All formulations contained both analytes. For amoxicillin, two of 24 samples were out of specification with 72.8% (Malaysia) and 82.3% (Thailand) of labelled content. For clavulanate, four of 24 samples were out of specification with 46.9% (Serbia), 79.0% (UK), 84.3% (Serbia) and 86.5% (Thailand) of labelled content. One formulation (Thailand) failed for both analytes. CLINICAL SIGNIFICANCE: Antimicrobial formulations of substandard quality have negative consequences for efficacy in patients and potentially promote antimicrobial resistance. There was evidence of substandard formulations in all countries, not only for amoxicillin but especially for clavulanate; this could compromise equitable access to acceptable quality essential veterinary medicines worldwide.


Assuntos
Combinação Amoxicilina e Clavulanato de Potássio , Anti-Infecciosos , Animais , Cães , Combinação Amoxicilina e Clavulanato de Potássio/uso terapêutico , Malásia , Sérvia , Tailândia , Estudos Prospectivos , Amoxicilina , Ácido Clavulânico/uso terapêutico , Comprimidos , Reino Unido , Antibacterianos/uso terapêutico
3.
Pol J Vet Sci ; 24(3): 399-407, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34730304

RESUMO

Since drug companies are driven by the need to produce profit they are unwilling to make large investments in the development of new drugs if there is no market large enough to justify such investment. For this reason, veterinarians face a major obstacle - the veterinary drug market is not very profitable, which sometimes leads to not having a licensed drug available for treatment in veterinary practice. In this case, the cascade procedure allows veterinarians to, under certain circumstances, prescribe human approved drugs. The aim of our study was to analyze the pattern of human approved drugs prescription for 150 medical records of dogs participating in the survey. The results show that antimicrobial agents were the most commonly prescribed drugs for animals (50%) of all human approved drugs, and beta-lactams (38.6%) were the most widely used antibiotic classes. The most common general conditions for therapeutic use of antimicrobials in this study were digestive, skin and respiratory disorders. Our study shows that the frequency of bacterial culture, susceptibility testing and cytology was very low. Even though the off-label use of human approved drugs in animal practice is regulated by law, the results of this study indicate the need for more specific strategies and guidelines for such use. This may represent a potential for improvement by raising veterinarians' awareness toward more prudent use of human drugs.


Assuntos
Antibacterianos/uso terapêutico , Infecções Bacterianas/veterinária , Doenças do Cão/tratamento farmacológico , Hospitais Veterinários , Uso Off-Label , Animais , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/epidemiologia , Doenças do Cão/epidemiologia , Cães , Feminino , Humanos , Masculino , Sérvia/epidemiologia , Médicos Veterinários/estatística & dados numéricos
4.
Biochim Biophys Acta Mol Cell Res ; 1867(7): 118673, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32057919

RESUMO

Microtubules are polymers of α/ß-tubulin, with microtubule organization being regulated by microtubule-associated proteins (MAPs). Herein, we describe a novel role for the epithelial gene repressor, zinc finger E-box-binding homeobox 1 (ZEB1), that "switches" from a chromatin-associated protein during interphase, to a MAP that associates with α-, ß- and γ-tubulin during mitosis. Additionally, ZEB1 was also demonstrated to associate with γ-tubulin at the microtubule organizing center (MTOC). Using confocal microscopy, ZEB1 localization was predominantly nuclear during interphase, with α/ß-tubulin being primarily cytoplasmic and the association between these proteins being minimal. However, during the stages of mitosis, ZEB1 co-localization with α-, ß-, and γ-tubulin was significantly increased, with the association commonly peaking during metaphase in multiple tumor cell-types. ZEB1 was also observed to accumulate in the cleavage furrow during cytokinesis. The increased interaction between ZEB1 and α-tubulin during mitosis was also confirmed using the proximity ligation assay. In contrast to ZEB1, its paralog ZEB2, was mainly perinuclear and cytoplasmic during interphase, showing some co-localization with α-tubulin during mitosis. Considering the association between ZEB1 with α/ß/γ-tubulin during mitosis, studies investigated ZEB1's role in the cell cycle. Silencing ZEB1 resulted in a G2-M arrest, which could be mediated by the up-regulation of p21Waf1/Cip1 and p27Kip1 that are known downstream targets repressed by ZEB1. However, it cannot be excluded the G2/M arrest observed after ZEB1 silencing is not due to its roles as a MAP. Collectively, ZEB1 plays a role as a MAP during mitosis and could be functionally involved in this process.


Assuntos
Cromatina/genética , Proteínas Associadas aos Microtúbulos/genética , Mitose/genética , Homeobox 1 de Ligação a E-box em Dedo de Zinco/genética , Pontos de Checagem do Ciclo Celular/genética , Inibidor de Quinase Dependente de Ciclina p21/genética , Inibidor de Quinase Dependente de Ciclina p27/genética , Citocinese/genética , Humanos , Proteínas Associadas aos Microtúbulos/química , Ligação Proteica/genética , Fuso Acromático/genética , Tubulina (Proteína)/genética , Homeobox 2 de Ligação a E-box com Dedos de Zinco/genética , Homeobox 1 de Ligação a E-box em Dedo de Zinco/química
5.
Pol J Vet Sci ; 22(3): 609-615, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31560476

RESUMO

Early lactation period in dairy cows could be harmful to their health since it is challenging and demanding. Proinflammatory cytokine concentrations are increased in the early phase of the inflammatory response and during the early lactation period in cows. The aim of this study was to determine if ketoprofen treatment in the first days following parturition would decrease proinflammatory cytokine concentration and their correlation between lipid mobilization, ketogenesis and metabolic parameters in cows. The study was conducted on 30 cows divided into two groups of 15 cows each. The experimental group was treated with 3 mg × kg.bw.-1 ketoprofen for three consecutive days after parturition. The blood samples were collected on the first day of treatment and in the first and second week postpartum and they were analyzed for biochemical parameters such as non-esterified fatty acids (NEFA), beta-hydroxybutyrate (BHBA), glucose, cholesterol and total bilirubine and inflammatory parameters such as tumour necrosis factor-α (TNF-α), interleukin-1α (IL-1α) and interferon-γ (IFN-γ). The results suggested that ketoprofen- treated cows had a significantly lower concentration of TNF-α, IL-1α, IFN-γ, NEFA and BHBA in the first and second postpartum week compared to the control group. Ketoprofen administration increased glucose levels (the first week, p⟨0.05), increased cholesterol levels (the second week, p⟨0.01) and decreased serum total bilirubin levels (second week, p⟨0.01) compared to the control group of cows. A positive correlation was found between TNF-α and NEFA and total bilirubin, significantly more expressed in the control than in experimental group of cows (p⟨0.01) and it was also found between IL-1α and NEFA (p⟨0.01). A negative correlation was found between TNF-α and glucose and cholesterol, significantly more expressed in the control than in experimental group of cows (p⟨0.01). A positive correlation was also found between IL-1α and glucose (p⟨0.01). Ketoprofen given parenterally to Holstein cows immediately after calving could reduce inflammation and decrease the relation between inflammatory response and lipogenesis and ketogenesis in postpartum cows.


Assuntos
Bovinos , Citocinas/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Cetonas/metabolismo , Cetoprofeno/farmacologia , Lipogênese/efeitos dos fármacos , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/farmacologia , Citocinas/genética , Feminino , Cetoprofeno/administração & dosagem , Período Pós-Parto
6.
Pol J Vet Sci ; 21(2): 325-331, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30450872

RESUMO

Inflammation together with lipolysis and ketogenesis in early lactation can cause low productivity and may be harmful to the cow health. The objective of the study was to determine if ketoprofen treatment in the first days following parturition would positively affect the milk production and whether it was associated with the metabolic and inflammatory response. The study was conducted on 30 cows divided into two groups of 15 cows each. The experimental group was treated with 3 mg × kg. bw. -1 ketoprofen for three consecutive days after parturition. The blood samples were collected on the first day of treatment and in the first and second week postpartum and they were analyzed for non-esterified fatty acids (NEFA), beta-hydroxybutyrate (BHB), tumour necrosis factor-a(TNF-a) and haptoglobin. The results suggested that ketoprofen-treated cows with a higher milk production had a significantly lower concentration of NEFA, BHB, TNF-a and haptoglobin in the first and second week postpartum. No differences were found in the control group in metabolic status regardless of the achieved level of milk production. Ketoprofen administration in postpartum cows can enhance the milk yield. The higher milk yield in the experimental group might be associated with a lower degree of lipolysis, ketogenesis and reduced inflammatory response in the first two weeks postpartum.


Assuntos
Anti-Inflamatórios não Esteroides , Cetoprofeno , Lactação , Leite , Ácido 3-Hidroxibutírico , Animais , Anti-Inflamatórios não Esteroides/uso terapêutico , Bovinos , Metabolismo Energético , Ácidos Graxos não Esterificados , Feminino , Cetoprofeno/uso terapêutico , Período Pós-Parto , Gravidez
7.
Biochim Biophys Acta Gen Subj ; 1861(5 Pt A): 995-999, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28219722

RESUMO

We recently demonstrated that a novel storage and transport mechanism for nitric oxide (NO) mediated by glutathione-S-transferase P1 (GSTP1) and multidrug resistance protein 1 (MRP1/ABCC1), protects M1-macrophage (M1-MØ) models from large quantities of endogenous NO. This system stores and transports NO as dinitrosyl-dithiol-iron complexes (DNICs) composed of iron, NO and glutathione (GSH). Hence, this gas with contrasting anti- and pro-tumor effects, which has been assumed to be freely diffusible, is a tightly-regulated species in M1-MØs. These control systems prevent NO cytotoxicity and may be responsible for delivering cytotoxic NO as DNICs via MRP1 from M1-MØs, to tumor cell targets.


Assuntos
Glutationa S-Transferase pi/metabolismo , Células Matadoras Naturais/metabolismo , Macrófagos/metabolismo , Proteínas Associadas à Resistência a Múltiplos Medicamentos/metabolismo , Óxido Nítrico/metabolismo , Substâncias Protetoras/metabolismo , Glutationa/metabolismo , Humanos
8.
Free Radic Biol Med ; 75: 14-29, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25035074

RESUMO

Nitrogen monoxide (NO) is vital for many essential biological processes as a messenger and effector molecule. The physiological importance of NO is the result of its high affinity for iron in the active sites of proteins such as guanylate cyclase. Indeed, NO possesses a rich coordination chemistry with iron and the formation of dinitrosyl-dithiolato iron complexes (DNICs) is well documented. In mammals, NO generated by cytotoxic activated macrophages has been reported to play a role as a cytotoxic effector against tumor cells by binding and releasing intracellular iron. Studies from our laboratory have shown that two proteins traditionally involved in drug resistance, namely multidrug-resistance protein 1 and glutathione S-transferase, play critical roles in intracellular NO transport and storage through their interaction with DNICs (R.N. Watts et al., Proc. Natl. Acad. Sci. USA 103:7670-7675, 2006; H. Lok et al., J. Biol. Chem. 287:607-618, 2012). Notably, DNICs are present at high concentrations in cells and are biologically available. These complexes have a markedly longer half-life than free NO, making them an ideal "common currency" for this messenger molecule. Considering the many critical roles NO plays in health and disease, a better understanding of its intracellular trafficking mechanisms will be vital for the development of new therapeutics.


Assuntos
Glutationa Transferase/metabolismo , Compostos de Ferro/metabolismo , Macrófagos/metabolismo , Proteínas Associadas à Resistência a Múltiplos Medicamentos/metabolismo , Óxido Nítrico/metabolismo , Óxidos de Nitrogênio/metabolismo , Animais , Transporte Biológico , Resistencia a Medicamentos Antineoplásicos , Humanos , Ferro/metabolismo
9.
Br J Cancer ; 108(2): 409-19, 2013 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-23287991

RESUMO

BACKGROUND: Effective treatment of prostate cancer should be based on targeting interactions between tumour cell signalling pathways and key converging downstream effectors. Here, we determined how the tumourigenic phosphoinositide 3-kinase/protein kinase B (PI3K/AKT), tumour-suppressive phosphatase and tensin homologue deleted on chromosome 10 (PTEN) and transforming growth factor-ß (TGF-ß) pathways are integrated via the metastasis suppressor, N-myc downstream-regulated gene-1 (NDRG1). Moreover, we assessed how the novel anti-tumour agent, Dp44mT, may target these integrated pathways by increasing NDRG1 expression. METHODS: Protein expression in Dp44mT-treated normal human prostate epithelial cells and prostate cancer cells (PC-3, DU145) was assessed by western blotting. The role of NDRG1 was examined by transfection using an NDRG1 overexpression vector or shRNA. RESULTS: Dp44mT increased levels of tumour-suppressive PTEN, and decreased phosphorylation of ERK1/2 and SMAD2L, which are regulated by oncogenic Ras/MAPK signalling. Importantly, the effects of Dp44mT on NDRG1 and p-SMAD2L expression were more marked in prostate cancer cells than normal prostate epithelial cells. This may partly explain the anti-tumour selectivity of these agents. Silencing NDRG1 expression increased phosphorylation of tumourigenic AKT, ERK1/2 and SMAD2L and decreased PTEN levels, whereas NDRG1 overexpression induced the opposite effect. Furthermore, NDRG1 silencing significantly reduced the ability of Dp44mT to suppress p-SMAD2L and p-ERK1/2 levels. CONCLUSION: NDRG1 has an important role in mediating the tumour-suppressive effects of Dp44mT in prostate cancer via selective targeting of the PI3K/AKT, TGF-ß and ERK pathways.


Assuntos
Proteínas de Ciclo Celular/metabolismo , Células Epiteliais/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Próstata/metabolismo , Neoplasias da Próstata/metabolismo , Tiossemicarbazonas/farmacologia , Antineoplásicos/farmacologia , Proteínas de Ciclo Celular/genética , Linhagem Celular Tumoral , Proliferação de Células , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Masculino , PTEN Fosfo-Hidrolase/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação , Próstata/citologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Interferência de RNA , RNA Interferente Pequeno , Transdução de Sinais , Proteína Smad2/metabolismo , Fator de Crescimento Transformador beta/metabolismo
10.
Curr Med Chem ; 19(17): 2689-702, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22455580

RESUMO

The study of iron chelators as anti-tumor agents is still in its infancy. Iron is important for cellular proliferation and this is demonstrated by observations that iron-depletion results in cell cycle arrest and also apoptosis. In addition, many iron chelators are known to inhibit ribonucleotide reductase, the iron-containing enzyme that is the rate-limiting step for DNA synthesis. Desferrioxamine is a well known chelator used for the treatment of iron-overload disease, but it has also been shown to possess anti-cancer activity. Another class of chelators, namely the thiosemicarbazones, have been shown to possess anti-cancer activity since the 1950's, although their mechanism(s) of action have only recently been more comprehensively elucidated. In fact, the redox activity of thiosemicarbazone iron complexes is thought to be important in mediating their potent cytotoxicity. Moreover, unlike typical iron chelators which simply act to deplete tumors of iron, several thiosemicarbazones (i.e., Bp44mT and Dp44mT) do not induce this effect, their anti-cancer efficacy being due to other mechanisms e.g., redox activity. Other reports have also shown that some thiosemicarbazones inhibit topoisomerase IIα, demonstrating that this class of agents have multiple molecular targets and act by various mechanisms. The most well characterized thiosemicarbazone iron chelator in terms of its assessment in humans is 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP). Observations from these clinical trials highlight the less than optimal activity of this ligand and several side effects related to its use, including myelo-suppression, hypoxia and methemoglobinemia. The mechanisms responsible for these latter effects must be elucidated and the design of the ligand altered to minimize these problems and increase efficacy. This review discusses the development of chelators as unique agents for cancer treatment.


Assuntos
Antineoplásicos/uso terapêutico , Quelantes de Ferro/uso terapêutico , Neoplasias/tratamento farmacológico , Animais , Antineoplásicos/efeitos adversos , Antineoplásicos/química , Antineoplásicos/farmacologia , Ensaios Clínicos como Assunto , Humanos , Quelantes de Ferro/efeitos adversos , Quelantes de Ferro/química , Quelantes de Ferro/farmacologia , Neoplasias/patologia
11.
Curr Drug Deliv ; 7(3): 194-207, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20507267

RESUMO

Targeting essential nutrients (eg., those required for DNA synthesis) to inhibit cancer cell growth is a well established therapeutic strategy. A good example is the highly successful folate antagonist, methotrexate. However, up until recently, strategies to target iron which is also crucial for DNA synthesis have not been systematically explored to develop agents for the treatment of cancer. Over the last 15 years, our laboratory has embarked upon structure-activity studies designed to develop novel Fe chelators with anti-cancer efficacy. These studies have led to the development of the dipyridyl thiosemicarbazone chelators that show potent and selective anti-cancer activity and which overcome resistance to other cytotoxic agents. This class of compounds include the chelator, di-2-pyridylketone-4,4-dimethyl-3-thiosemicarbazone (Dp44mT), which at optimal doses markedly inhibits tumour growth and is well tolerated. Moreover, this ligand does not induce overt Fe-depletion in vivo, probably because very low doses (0.4 mg/kg) are effective at inhibiting tumour growth. Importantly, our compounds are far more active and less toxic than the chelator, Triapine®, that is being assessed in a wide variety of international clinical trials. A vital part of the mechanism of action of these compounds is their ability to form a redox-active Fe complex that generates radicals to inhibit tumour growth. Due to their relatively high lipophilicity and low molecular weight of this class of compounds, oral activity may be expected in addition to their well known efficacy via the intravenous route.


Assuntos
Antineoplásicos/uso terapêutico , Desenho de Fármacos , Quelantes de Ferro/uso terapêutico , Ferro/metabolismo , Neoplasias/tratamento farmacológico , Tiossemicarbazonas/uso terapêutico , Animais , Antineoplásicos/efeitos adversos , Antineoplásicos/química , Antineoplásicos/metabolismo , Transporte Biológico , Humanos , Quelantes de Ferro/efeitos adversos , Quelantes de Ferro/química , Quelantes de Ferro/metabolismo , Estrutura Molecular , Neoplasias/metabolismo , Neoplasias/patologia , Piridinas/uso terapêutico , Relação Estrutura-Atividade , Tiossemicarbazonas/efeitos adversos , Tiossemicarbazonas/química , Tiossemicarbazonas/metabolismo , Resultado do Tratamento
12.
Int J Clin Pract ; 62(3): 406-12, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18261076

RESUMO

AIM: The study involved 120 young males (aged 20.5 +/- 2.5 years) having undergone successful kidney biopsy because of asymptomatic haematuria with the aims to assess the prevalence of histological diagnosis and the natural history of the disease. METHODS: The patients were selected from the population of conscripts who were referred to our clinic as a result of asymptomatic microhaematuria. All patients had a negative history of kidney disease, normal creatinine clearance (Ccr), while extrarenal causes of microhaematuria were excluded. The patients were divided into a group of 62 patients with isolated microhaematuria (IMH; proteinuria < 0.3 g/day) and a group of 58 patients with asymptomatic microhaematuria and proteinuria (AMHP; proteinuria > 0.3 g/day). After kidney biopsy patients were monitored for 3-9 years. RESULTS: Normal biopsies and minor abnormalities were more frequent in IMH than in AMHP patients, who had IgA nephritis more frequently and significantly higher total pathohistological score. Based on the clinical and histological features, recommendations on patients' ability for military service were made. During the follow-up period, normal Ccr maintained in all patients. Macrohaematuria appeared in 42 patients and proteinuria worsened in eight patients (seven with AMHP). Urinary abnormalities disappeared in 20 patients with IMH and in eight with AMHP (p = 0.04). CONCLUSION: Minimal histological changes and disappearance of urinary abnormalities were more frequent in IMH than in AMHP patients. Kidney biopsy is useful only in patients with AMHP but it is not necessary in IMH patients.


Assuntos
Hematúria/etiologia , Nefropatias/diagnóstico , Rim/patologia , Proteinúria/etiologia , Adulto , Biópsia por Agulha/métodos , Humanos , Nefropatias/complicações , Nefropatias/patologia , Masculino , Valor Preditivo dos Testes , Estudos Prospectivos
13.
Glas Srp Akad Nauka Med ; (47): 149-61, 2002.
Artigo em Sérvio | MEDLINE | ID: mdl-16078449

RESUMO

AMP deaminase has a key position in regulation of the pool of adenine nucleotides and energetics in malignant cells. The aim of this investigation was to elucidate mechanism of regulation of activity of AMP deaminase in intact tumor cells. Using tiazofurin, which profoundly decreases the level of GTP, and guanosine which markedly increases its concentration in the Ehrlich ascites tumor cells under aerobic conditions, we have shown that this nucleotide is probably the major regulator of AMP deaminase activity in situ. This regulation, however, should be considered in relation to the time and the changes which occur during transition of the cells from aerobic to anaerobic phase, and reverse, when other factors, like concentrations of the substrate and ATP are involved.


Assuntos
AMP Desaminase/metabolismo , Antineoplásicos/farmacologia , Carcinoma de Ehrlich/enzimologia , Neoplasias Hepáticas Experimentais/enzimologia , Ribavirina/análogos & derivados , Animais , Guanosina/farmacologia , Guanosina Trifosfato/metabolismo , Guanosina Trifosfato/fisiologia , Camundongos , Ratos , Ratos Sprague-Dawley , Ribavirina/farmacologia , Células Tumorais Cultivadas
14.
Vojnosanit Pregl ; 58(3): 323-8, 2001.
Artigo em Sérvio | MEDLINE | ID: mdl-11548560

RESUMO

Microscopic polyangiitis is a very rare disease characterized by the lesions of arteriolae, venulae and capillaries--mainly of the kidneys and lungs, but also of other systems and organs. The elevated titer of anti-myeloperoxidase ANCA is very important immunological indicator. The main changes in our patient were related to the lung bleeding and rapidly progressive glomerulonephritis. The treatment has started according to the standard Fauci scheme adjusted to the level of disease severity and the age of patient (prednisone 60 mg/24 h, along with the gradual dosage decrease, cyclophosphamide 150 mg/24 h) and has lead to the clinical-laboratory remission. The patient had the leukocyte values irregularly controlled during the immunosuppressive therapy and agranulocytosis thus caused was not spotted in time, leading to the inadequate treatment of pneumonia that brought on the lethal outcome.


Assuntos
Nefropatias/diagnóstico , Pneumopatias/diagnóstico , Vasculite/diagnóstico , Anticorpos Anticitoplasma de Neutrófilos/análise , Humanos , Rim/irrigação sanguínea , Nefropatias/imunologia , Nefropatias/terapia , Pulmão/irrigação sanguínea , Pneumopatias/imunologia , Pneumopatias/terapia , Masculino , Microcirculação , Pessoa de Meia-Idade , Vasculite/imunologia , Vasculite/terapia
15.
J Am Acad Dermatol ; 45(3): 456-8, 2001 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11511847

RESUMO

The diagnosis of purpura pigmentosa progressiva in a female patient had to be changed to purpuric contact dermatitis after patch testing with textile dyes. A modified patch test performed in the area in which most of her skin lesions were located revealed a petechial reaction to the azo dye Disperse Blue 124/106. For evaluation of purpura pigmentosa progressiva we suggest a patch test with potential allergens, and, especially for textile dyes, a patch test at the lesion site may be helpful.


Assuntos
Alérgenos/efeitos adversos , Compostos Azo/efeitos adversos , Dermatite Alérgica de Contato/diagnóstico , Vasculite por IgA/diagnóstico , Dermatite Alérgica de Contato/etiologia , Dermatite Alérgica de Contato/patologia , Diagnóstico Diferencial , Feminino , Humanos , Vasculite por IgA/etiologia , Vasculite por IgA/patologia , Perna (Membro) , Pessoa de Meia-Idade , Testes do Emplastro
16.
Vojnosanit Pregl ; 58(2): 161-6, 2001.
Artigo em Sérvio | MEDLINE | ID: mdl-11475670

RESUMO

The aim of this study was to investigate the influence of the corticosteroid therapy on the development and prognosis of proststreptococcal glomerulonephritis (PSGN) in the period of five years. The investigation included a group of 54 patients who were in the acute phase of poststreptococcal glomerulonephritis (PSGN) when they were 18-22 years old. Corticosteroids were administered per os with the starting dose of 0.5 mg/kg bm, and the dose was subsequently decreased by 5 mg every 10 days to 20 mg/per day within 8 weeks of therapy. We have treated ten patients and all were with severe clinical manifestations of the disease (acute renal failure, oliguria, edemas, hypertension) and severe histopathologic (HP) finding of kidney tissue on the initial biopsy. On the basis of clinical parameters, HP changes on the repeated biopsy of the kidney and five years follow-up, we have concluded that the remission of the disease was achieved in patients who had received corticosteroid therapy. Clinical findings were confirmed by PH findings of repeated biopsies with less expressed residues of the disease. Corticosteroid therapy should be administered in adult patients who are in the acute phase of the disease, with clinical and HP severe form of PSGN, since the risk for the further progress of more serious sequelae of the disease is significantly decreased.


Assuntos
Glomerulonefrite/tratamento farmacológico , Glucocorticoides/uso terapêutico , Prednisona/uso terapêutico , Infecções Estreptocócicas/complicações , Doença Aguda , Injúria Renal Aguda/tratamento farmacológico , Injúria Renal Aguda/etiologia , Adolescente , Adulto , Glomerulonefrite/etiologia , Humanos
17.
Croat Med J ; 42(1): 88-91, 2001 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11172664

RESUMO

AIM: To compare the service quality in public and private pharmacies in the city of Kragujevac by measuring patient care and health facility indicators. METHODS: The patient care indicators and health facility indicators, established by the World Health Organization in 1995, were measured prospectively in 7 public and 7 private pharmacies in Kragujevac, Yugoslavia, during November and December 1999. A sample of 100 patient-visits was analyzed in each pharmacy. RESULTS: Our study showed that the average drug dispensing time ranged from 20.5 to 48.2 seconds, being significantly longer in private (21.1-48.2 s) than in public pharmacies (20.5-33.7 s) (F=13.12, p<0.001). The percentage of actually dispensed drugs ranged from 29% to 63%, and no significant difference was found between public and private pharmacies. Patients' knowledge of a correct dosage ranged from 30% to 74% and the availability of key drugs ranged from 67% to 93% with no significant difference between public and private pharmacies. There was serious negligence in labeling the dispensed drugs in both public and private pharmacies: not a single drug package was labeled according to the World Health Organization recommendations. Key drugs were highly available in both public and private pharmacies. CONCLUSION: The average drug dispensing time was too short for a proper interaction between a pharmacist and a patient in both public and private pharmacies. The results of our study suggest that there was no real difference in the service quality between the public and the private pharmacies.


Assuntos
Assistência Farmacêutica/normas , Farmácias/normas , Qualidade da Assistência à Saúde , Croácia , Rotulagem de Medicamentos/normas , Pesquisas sobre Atenção à Saúde , Humanos , Assistência Farmacêutica/economia , Farmácias/economia , Privatização/economia , População Urbana
18.
Vojnosanit Pregl ; 57(3): 303-7, 2000.
Artigo em Sérvio | MEDLINE | ID: mdl-11039311

RESUMO

The use of Cyclosporin A (CsA) in treatment nephrotic syndrome in the primary focal and segmental glomerulosclerosis (FSGS) is controversial. A prospective study was comprised of 10 adult patients with nephrotic syndrome caused by FSGS, treated with CsA and corticosteroids. Six patients were females, 4 males, aged 35 +/- 8 years. The daily urinary protein excretion ranged from 7 to 15 g/24 h (range 11.16 +/- 2.61 g/24 h). The follow-up interval lasted from 6-18 months. The serum CsA levels ranged from 80-120 ng/ml. Prednisone was administered orally 10-15 mg/day. Two months after the therapy onset, all patients experienced clinical improvement and reduction in the urinary daily protein excretion (range 9.74 +/- 2.14 g/24 h) with tendency to decrease, while a stable overall renal function was maintained. During 6 months, 6 patients were in remission (0.5 +/- 0.2 g/24 h), in two patients the proteinuria was retained 1.6-1.8 g/24 h and two patients had proteinuria 3.2-3.6 g/24 h. During the follow up period of this patients' group in the period of 18 months, the values of proteinuria were never above 3 g/24 h (1.15 +/- 0.9 g/24 h). These are encouraging results from initial treatment of FSGS with CsA and small doses prednisone.


Assuntos
Ciclosporina/uso terapêutico , Glomerulosclerose Segmentar e Focal/complicações , Imunossupressores/uso terapêutico , Síndrome Nefrótica/terapia , Adulto , Feminino , Humanos , Masculino , Síndrome Nefrótica/etiologia , Síndrome Nefrótica/urina , Estudos Prospectivos , Proteinúria
19.
Vojnosanit Pregl ; 57(2): 235-40, 2000.
Artigo em Sérvio | MEDLINE | ID: mdl-10934939

RESUMO

A patient suffering from viral hepatitis B and secondary membranoproliferative glomerulonephritis was presented. He was treated with recombinant alfa-2 interferon. The therapy led to clinical and biochemical remission of the liver and kidney lesions. The example of our patient justifies the use of recombinant alfa-2 interferon in the patients with chronic viral hepatitis B and secondary glomerulonephritis.


Assuntos
Glomerulonefrite Membranoproliferativa/complicações , Hepatite B Crônica/tratamento farmacológico , Interferon Tipo I/uso terapêutico , Adulto , Hepatite B Crônica/complicações , Humanos , Masculino , Proteínas Recombinantes
20.
Vojnosanit Pregl ; 57(5): 63-7, 2000.
Artigo em Sérvio | MEDLINE | ID: mdl-11213678

RESUMO

Cytomegalovirus (CMV) has a prominent position as the cause of severe cytomegalovirus infection (CMVI) in immunocompromised persons, such as: patients with primary or secondary immunodeficiency (risk group), blood/hemoproducts recipients, especially recipients of tissue and organ transplants, which have implications for difficult providing of CMV-seronegative (safe) blood. However, CMV-disease is manifested in the minority of immunocompetent persons. Sera of patients from the Center for Hemodialysis of the Clinic of Nephrology of the Military Medical Academy (MMA) were tested on the presence of CMVI markers. All patients belonged to the risk group considering the chronicity of the main disease, receiving of the large quantities of blood and as the possible potential recipients of kidney transplants. Testing was performed by commercial serologic-enzyme-immune tests (Abott--USA, Behring--Germany) for CMV antibodies of IgG and IgM classes by which was determined serologic state of patients. Test results: out of 106 tested sera samples, 100 (99.33%) were CMV-seropositive (CMV-IgG), 27 (25.47%) were positive on recent CMVI (CMV-IgM), 99 (93.39%) received the blood previously, the majority of patients were with the diagnosis of primary glomerulopathy--68 (64.15%) and tubulointerstitial nephropathy--32 (30.18). Such results indicate the potentional possibility of reactivation of latent CMV and development of CMVI, and in transplant recipients--its rejection. It can occur if appropriate measures of prevention from CMVI are not timely undertaken, which includes the providing of CMV-seronegative-safe blood/hemoproducts, as well as the appropriate application of combined medicamentous therapy by chemical agents and immunomodulators-specific hyperimmune anti-CMV immunoglobulins.


Assuntos
Infecções por Citomegalovirus/complicações , Nefropatias/virologia , Anticorpos Antivirais/sangue , Citomegalovirus/imunologia , Citomegalovirus/isolamento & purificação , Infecções por Citomegalovirus/diagnóstico , Humanos , Nefropatias/terapia , Diálise Renal , Fatores de Risco
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