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Effects of antithyroid drug on the rectal temperature and metabolic parameters of ducks (Cairina moschata).

Artoni, S. M.; Zuim, S. M.; Macari, Marcos
Fonte: Universidade Estadual Paulista Publicador: Universidade Estadual Paulista
Tipo: Artigo de Revista Científica Formato: 1381-1384
ENG
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The effect of propylthiouracil oral treatment (400 mg/day per bird for 20 days) on body and thyroid weight, rectal temperature and plasma metabolic parameters of ducks (Cairina moschata) was determined. Propylthiouracil treatment produced a reduction (P less than .01) in body weight and an increase (P less than .01) in thyroid weight. The antithyroid drug also produced a decrease in rectal temperature starting from the 15th day of treatment, but did not significantly change blood glucose. Plasma free fatty acids and cholesterol concentrations progressively increased from the 5th and 10th day, respectively, in treated animals.

Anti-genotoxic effect of aqueous extracts of sun mushroom (Agaricus blazei Murill lineage 99/26) in mammalian cells in vitro

Martins de Oliveira, J.; Jordão, B. Q.; Ribeiro, L. R.; Ferreira Da Eira, A.; Mantovani, M. S.
Fonte: Universidade Estadual Paulista Publicador: Universidade Estadual Paulista
Tipo: Artigo de Revista Científica Formato: 1775-1780
ENG
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The sun mushroom is the popular name for the Agaricus blazei Murill fungus, a mushroom native to south-eastern Brazil, which has been frequently used in popular medicine mainly in the form of tea to treat various ailments (stress, diabetes, etc.). In the present study, the genotoxic and/or anti-genotoxic effects ofA. blazei on mammalian cells in culture was assessed by checking the increase or reduction of micronucleus (MN) frequency and comets. The sun mushroom (lineage 99/26) was used as aqueous extracts prepared (2.5%) at three different temperatures (60, 25 and 4°C). The in vitro micronucleus (MN) test in binucleated cells and comet assay were used in V79 cells cultivated in HAM-F10+DMEM medium (1:1), supplemented with 10% of fetal bovine serum. The experiments were divided into four treatment types: 1. Negative control; 2. Positive control with MMS; 3. Treatments with the three forms of extracts (60, 25 and 4°C); and 4. Treatments with the extracts in different associations (simultaneous, pre-treatment, post-treatment and simultaneous after pre-incubation for 1 h) with MMS. None of the A. blazei extracts show genotoxic activity. In the comet assay no protecting effect was found. The results obtained in the MN test showed that the three forms of extracts used had protective activity...

Immune regulatory effect of pHSP65 DNA therapy in pulmonary tuberculosis: Activation of CD8+ cells, interferon-γ recovery and reduction of lung injury

Bonato, V. L D; Gonçalves, E. D C; Soares, E. G.; Santos, R. R.; Sartori, A.; Coelho-Castelo, A. A M; Silva, C. L.
Fonte: Universidade Estadual Paulista Publicador: Universidade Estadual Paulista
Tipo: Artigo de Revista Científica Formato: 130-138
ENG
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A DNA vaccine based on the heat-shock protein 65 Mycobacterium leprae gene (pHSP65) presented a prophylactic and therapeutic effect in an experimental model of tuberculosis. In this paper, we addressed the question of which protective mechanisms are activated in Mycobacterium tuberculosis-infected mice after immune therapy with pHSP65. We evaluated activation of the cellular immune response in the lungs of infected mice 30 days after infection (initiation of immune therapy) and in those of uninfected mice. After 70 days (end of immune therapy), the immune responses of infected untreated mice, infected pHSP65-treated mice and infected pCDNA3-treated mice were also evaluated. Our results show that the most significant effect of pHSP65 was the stimulation of CD8+ lung cell activation, interferon-γ recovery and reduction of lung injury. There was also partial restoration of the production of tumour necrosis factor-α. Treatment with pcDNA3 vector also induced an immune stimulatory effect. However, only infected pHSP65-treated mice were able to produce significant levels of interferon-γ and to restrict the growth of bacilli.

Lack of inhibitory effect of zinc on prolactin secretion induced by cimetidine

Castro, A. V. B.; Mendonça, B. B.; Bloise, W.; Shuhama, T.; Brandão-Neto, J.
Fonte: Universidade Estadual Paulista Publicador: Universidade Estadual Paulista
Tipo: Artigo de Revista Científica Formato: 133-138
ENG
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The dopaminergic, serotoninergic and GABA-ergic systems are closely involved in PRL secretion, as well as thyrotropin-releasing hormone. There is some evidence that zinc interacts with some of these neuroamines and neuropeptides. The histamine H2-receptor cimetidine stimulates PRL secretion rapidly following an intravenous injection in man. In this sense, we investigated probable inhibitory effect of zinc on prolactin secretion following cimetidine injection (300 mg). Therefore, we studied five healthy adult men, before and after oral zinc administration (25 mg elemental zinc) during three consecutive months. The results did not demonstrate any inhibitory effect of zinc on prolactin secretion. So, we originally concluded that zinc did not interact with dopamine, serotonine, gamma-aminobutyric acid and the thyrotropin-releasing hormone in humans. In addition, the intravenous administration of cimetidine did not change the serum zinc profile. © 2005 Dustri-Vertag Dr. K. Feistle.

Estudos sobre liberação controlada e vetorização de drogas através de lipossomas

Gomes de Oliveira, Anselmo; Cardillo, José Augusto; Scarpa, Maria Virgínia; Wanczinski, Bruna Juliana; Da Silva Jr., Arnóbio Antônio
Fonte: Universidade Estadual Paulista Publicador: Universidade Estadual Paulista
Tipo: Artigo de Revista Científica Formato: 238-244
POR
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The text highlights the state of research related with the application of liposomes in the control of drug delivery and drug target to infectious diseases. Liposomes have several pharmaceutical applications and this manuscript is primarily focused on the potential of this colloidal system as an antibiotic carrier system and of administration through several accesses via to organism. Numerous case studies in which liposomes have successfully been used to improve pharmacological drug effect are presented. Mechanisms involved in drug delivery, application possibilities, research and development and efforts to reach these objectives are discussed. © Copyright Moreira Jr. Editora. Todos os direitos reservados.

The effect of type of vaginal insert and dose of pLH on embryo production, following fixed-time AI in a progestin-based superstimulatory protocol in Nelore cattle

Nogueira, Marcelo F. Gouveia; Fragnito, Paulo S.; Trinca, Luzia A.; Barros, Ciro M.
Fonte: Universidade Estadual Paulista Publicador: Universidade Estadual Paulista
Tipo: Artigo de Revista Científica Formato: 655-660
ENG
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The objective was to analyze and report field data focusing on the effect of type of progesterone-releasing vaginal insert and dose of pLH on embryo production, following a superstimulatory protocol involving fixed-time artificial insemination (FTAI) in Nelore cattle (Bos taurus indicus). Donor heifers and cows (n = 68; 136 superstimulations over 2 years) received an intravaginal, progesterone-releasing insert (CIDR® or DIB®, with 1.9 or 1.0 g progesterone, respectively) and 3-4 mg of estradiol benzoate (EB) i.m. at random stages of the estrous cycle. Five days later (designated Day 0), cattle were superstimulated with a total of 120-200 mg of pFSH (Folltropin-V®), given twice daily in decreasing doses from Days 0 to 3. All cattle received two luteolytic doses of PGF2α at 08:00 and 20:00 h on Day 2 and progesterone inserts were removed at 20:00 h on Day 3 (36 h after the first PGF2α injection). Ovulation was induced with pLH (Lutropin-V®, 12.5 or 25 mg, i.m.) at 08:00 h on Day 4 with FTAI 12, 24 and in several cases, 36 h later. Embryos were recovered on Days 11 or 12, graded and transferred to synchronous recipients. Overall, the mean (±S.E.M.) number of total ova/embryos (13.3 ± 0.8) and viable embryos (9.4 ± 0.6) and pregnancy rate (43.5%; 528/1213) did not differ among groups...

Modulatory effect of Byrsonima basiloba extracts on the mutagenicity of certain direct and indirect-acting mutagens in Salmonella typhimurium assays

Lira, Walclecio de Moraes; Dos Santos, Fabio Vieira; Sannomiya, Miriam; Rodrigues, Clenilson Martins; Vilegas, Wagner; Varanda, Eliana Aparecida
Fonte: Universidade Estadual Paulista Publicador: Universidade Estadual Paulista
Tipo: Artigo de Revista Científica Formato: 111-119
ENG
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Byrsonima basiloba A. Juss. species is a native arboreal type from the Brazilian cerrado (tropical American savanna), and the local population uses it to treat diseases, such as diarrhea and gastric ulcer. It belongs to the Malpighiaceae family, and it is commonly known as murici. Considering the popular use of B. basiloba derivatives and the lack of pharmacological potential studies regarding this vegetal species, the mutagenic and antimutagenic effect of methanol (MeOH) and chloroform extracts were evaluated by the Ames test, using strains TA97a, TA98, TA100, and TA102 of Salmonella typhimurium. No mutagenic activity was observed in any of the extracts. To evaluate the antimutagenic potential, direct and indirect mutagenic agents were used: 4 nitro-o-phenylenediamine, sodium azide, mitomycin C, aflatoxin B1, benzo[a]pyrene, and hydrogen peroxide. Both the extracts evaluated showed antimutagenic activity, but the highest value of inhibition level (89%) was obtained with the MeOH extract and strain TA100 in the presence of aflatoxin B1. Phytochemical analysis of the extracts revealed the presence of n-alkanes, lupeol, ursolic and oleanolic acid, (+)-catechin, quercetin-3-O-α-L-arabinopyranoside, gallic acid, methyl gallate, amentoflavone...

The effect of carbamide peroxide bleaching agents on the microhardness of dental ceramics.

Passos, Sheila P; Vanderlei, Aleska D; Salazar-Marocho, Susana M; Azevedo, Sarina M B; Vasquez, Vanessa Z C; Kimpara, Estevão Tomomitsu
Fonte: Universidade Estadual Paulista Publicador: Universidade Estadual Paulista
Tipo: Artigo de Revista Científica Formato: 79-83
ENG
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This study examined the effect of 10% and 16% carbamide peroxide bleaching agents on the surface microhardness of micro-particulate feldspathic ceramics (VM7 and VM13, Vita Zahnfabrik). Forty specimens (8-mm diameter, 2-mm thickness) were divided into four groups (n=10): GI-VM7 + 10% Whiteness, G2-VM7 + 16% Whiteness, G3-VM13 + 10% and G4-VM13 + 16% Whiteness. The home-use bleaching agents were applied for 8 hours on 15 days, and the specimens were stored in distilled water at 37 degrees C. The Vickers hardness number (HV) was determined for each specimen. Data were analyzed by the Wilcoxon and Mann-Whitney tests (p < 0.05). The microhardness values before exposure were: g1-433 (57); g2-486 (22); g3-509 (28); g4-518 (24), and after exposure: G1-349 (32); G2-496 (95); G3-519 (38); G4-502 (81). G2 exhibited a higher and significant difference than GI in VM7 groups, and the effect of bleaching concentration was shown to be significant by the Mann-Whitney test. And for VM13, both the Wilcoxon and Mann-Whitney tests showed no significant differences. When using 10% carbamide peroxide, the microhardness of VM7 ceramic was affected, and there were no effect on the microhardness between VM7 and VM13 ceramics when 16% carbamide peroxide was used.

Mutagenic and genotoxic effect of hydroxyurea

Santos, Jean L.; Bosquesi, Priscila L.; Almeida, Adélia E.; Chin, Chung Man; Varanda, Eliana Aparecida
Fonte: Universidade Estadual Paulista Publicador: Universidade Estadual Paulista
Tipo: Artigo de Revista Científica
ENG
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The hydroxyurea, a cytotoxic drug, is the mainly available therapeutical strategy for the treatment of sickle cell disease. This study aimed to evaluate the mutagenic and genotoxic potential of the hydroxyurea through the Salmonella/Microsome assay and micronucleus test in peripheral blood of mice. The doses were evaluated at 29.25-468 μmol/plate in Salmonella/Microsome assay in presence and absence of metabolic activation the drug. In the micronucleus test the doses were evaluated at 12.5; 25; 50; 75 and 100 mg/kg. The results show that hydroxyurea present mutagenic activity in TA98 and TA100 in doses above 117 μmol/plate and 234 μmol/plate respectively. The drug induced a significant increase in the frequency of micronuclei in reticulocytes of mice at concentrations of 50, 75 and 100 mg/kg, compared to negative control (water). These results demonstrated the mutagenic and genotoxic potential of hydroxyurea. © 2011 Santos et al.

Phototoxic effect of curcumin on methicillin-resistant Staphylococcus aureus and L929 fibroblasts

Ribeiro, Ana Paula Dias; Pavarina, Ana Cláudia; Dovigo, Livia Nordi; Brunetti, Iguatemy Lourenço; Bagnato, Vanderlei Salvador; Vergani, Carlos Eduardo; De Souza Costa, Carlos Alberto
Fonte: Universidade Estadual Paulista Publicador: Universidade Estadual Paulista
Tipo: Artigo de Revista Científica Formato: 391-398
ENG
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Photodynamic therapy has been investigated as an alternative method of killing pathogens in response to the multiantibiotic resistance problem. This study evaluated the photodynamic effect of curcumin on methicillin-resistant Staphylococcus aureus (MRSA) compared to susceptible S. aureus (MSSA) and L929 fibroblasts. Suspensions of MSSA and MRSA were treated with different concentrations of curcumin and exposed to light-emitting diode (LED). Serial dilutions were obtained from each sample, and colony counts were quantified. For fibroblasts, the cell viability subsequent to the curcumin-mediated photodynamic therapy was evaluated using the MTT assay and morphological changes were assessed by SEM analysis. Curcumin concentrations ranging from 5.0 to 20.0 μM in combination with any tested LED fluences resulted in photokilling of MSSA. However, only the 20.0 μM concentration in combination with highest fluence resulted in photokilling of MRSA. This combination also promoted an 80% reduction in fibroblast cell metabolism and morphological changes were present, indicating that cell membrane was the main target of this phototherapy. The combination of curcumin with LED light caused photokilling of both S. aureus strains and may represent an alternative treatment for eradicating MRSA...

Evaluation of effect of cyclosporine A on the bone tissue with induced periodontal disease to ligature in rats

Nassar, P. O.; Felipetti, F. A.; Nassar, C. A.; Spolidorio, L. C.
Fonte: Universidade Estadual Paulista Publicador: Universidade Estadual Paulista
Tipo: Artigo de Revista Científica Formato: 778-782
ENG
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The administration of cyclosporine A (CsA) has been associated with significant bone loss and increased bone remodeling. The present investigation was designed to evaluate the effects of CsA on alveolar bone of rats subjected to experimental periodontitis, using histomorphometric and histological analysis. Twenty-four rats were divided into groups with 6 animals each: 1, control; 2, rats with ligature around the lower first molars; 3, rats with ligature around the lower first molars and that were treated with 10 mg CsA/kg of body weight/d; and 4, rats treated with 10 mg CsA/kg of body weight/d. At the end of 30 days, rats were humanely killed and subjected to a histological processing, with analysis of the distance cemento-enamel junction and alveolar bone crest, bone area, eroded bone area, and cemento surface. All of them were assessed at the mesial region of the alveolar bone. The CsA therapy combined with ligature placement decreased bone area and increased the eroded bone area around the tooth surface. The results at the histological analysis showed the same combination and changes. Therefore, in spite of the lack of a direct effect on the alveolar bone height, the CsA therapy intensified the imbalance of the alveolar bone homeostasia in a rat model of experimental periodontitis. © 2013 Elsevier Inc.

Mechanism and effect of esculetin in an experimental animal model of inflammatory bowel disease

Witaicenis, Aline; Luchini, A. C.; Hiruma-Lima, C. A.; Felisbino, S. L.; Justulin, L. A.; Garrido-Mesa, N.; Utrilla, P.; Gálvez, J.; Di Stasi, L. C.
Fonte: Universidade Estadual Paulista Publicador: Universidade Estadual Paulista
Tipo: Artigo de Revista Científica Formato: 433-446
ENG
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP); Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq); Processo FAPESP: 03/09324-1; Processo FAPESP: 06/55209-9; Processo FAPESP: 07/54516-7; Processo FAPESP: 11/50824-4; Processo FAPESP: 11/50512-2; Esculetin is a coumarin derivative with high antioxidant activity. In a rat experimental model of inflammatory bowel disease induced by trinitrobenzenesulfonic acid, esculetin at the dose of 5mg/Kg displayed intestinal anti-inflammatory activity; however, its mechanism of action needs to be elucidated. Our objective was to evaluate the effects of esculetin on the intestinal inflammatory process and to clarify the mechanism of action of this compound. We also compared its effects with prednisolone and sulphasalazine. Our results demonstrate that treatment with esculetin prevented an increase in malondialdehyde content, counteracted the depletion of glutathione content, reduced epithelial cell apoptosis, reduced the secretion of pro-inflammatory cytokines, such as IL-1β, IL-2 and IFN-γ, in vitro, and reduced the colonic levels of TNF-α and IL-1β in vivo. Additionally, esculetin treatment inhibited MPO and AP activities. These results demonstrated that esculetin produced a more effective intestinal anti-inflammatory effect than sulphasalazine because it was used at a 10-fold lower dose...

Peripheral kappa and delta opioid receptors are involved in the antinociceptive effect of crotalphine in a rat model of cancer pain

Brigatte, Patricia; Konno, Katsuhiro; Gutierrez, Vanessa Pacciari; Sampaio, Sandra Coccuzzo; Zambelli, Vanessa Olzon; Picolo, Gisele; Curi, Rui; Cury, Yara
Fonte: Universidade Estadual Paulista Publicador: Universidade Estadual Paulista
Tipo: Artigo de Revista Científica Formato: 1-7
ENG
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Cancer pain is an important clinical problem and may not respond satisfactorily to the current analgesic therapy. We have characterized a novel and potent analgesic peptide, crotalphine, from the venom of the South American rattlesnake Crotalus durissus terrificus. In the present work, the antinociceptive effect of crotalphine was evaluated in a rat model of cancer pain induced by intraplantar injection of Walker 256 carcinoma cells. Intraplantar injection of tumor cells caused the development of hyperalgesia and allodynia, detected on day 5 after tumor cell inoculation. Crotalphine (6 μg/kg), administered p.o., blocked both phenomena. The antinociceptive effect was detected 1 h after treatment and lasted for up to 48 h. Intraplantar injection of nor-binaltorphimine (50 g/paw), a selective antagonist of κ-opioid receptors, antagonized the antinociceptive effect of the peptide, whereas N,N-diallyl-Tyr-Aib-Phe-Leu (ICI 174,864, 10 μg/paw), a selective antagonist of δ-opioid receptors, partially reversed this effect. On the other hand, D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr amide (CTOP, 20 g/paw), an antagonist of μ-opioid receptors, did not modify crotalphine-induced antinociception. These data indicate that crotalphine induces a potent and long lasting opioid-mediated antinociception in cancer pain. © 2013 Elsevier Inc.

Effect of Propafenone on the Contractile Activity of Latissimus Dorsi Muscle Isolated in an Organ Chamber: Experimental Study in Rats

Simões,Ricardo; Machado,Eduardo Luis Guimarães; Freitas,Odilon Gariglio de Alvarenga; Moreira,Maria da Consolação Vieira; Gomes,Otoni Moreira
Fonte: Sociedade Brasileira de Cardiologia - SBC Publicador: Sociedade Brasileira de Cardiologia - SBC
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/03/2002 EN
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OBJECTIVE: To study the effect of propafenone on the contractile function of latissimus dorsi muscle isolated from rats in an organ chamber. METHODS: We studied 20 latissimus dorsi muscles of Wistar rats and divided them into 2 groups: group I (n=10), or control group - we studied the feasibility of muscle contractility; group II (n=10), in which the contralateral muscles were grouped - we analyzed the effect of propafenone on muscle contractility. After building a muscle ring, 8 periods of sequential 2-minute baths were performed, with intervals of preprogrammed electrical stimulation using a pacemaker of 50 stimuli/min. In group II, propafenone, at the concentration of 9.8 µg/mL, was added to the bath in period 2 and withdrawn in period 4. RESULTS: In group I, no significant depression in muscle contraction occurred up to period 5 (p>0.05). In group II, a significant depression occurred in all periods, except between the last 2 periods (p<0.05). Comparing groups I and II only in period 1, which was a standard period for both groups, we found no significant difference (p>0.05). CONCLUSION: Propafenone had a depressing effect on the contractile function of latissimus dorsi muscle isolated from rats and studied in an organ chamber.

Aspects of the Relationship Between Drug Dose and Drug Effect

Peper, Abraham
Fonte: International Hormesis Society Publicador: International Hormesis Society
Tipo: Artigo de Revista Científica
Publicado em 09/02/2009 EN
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It is generally assumed that there exists a well-defined relationship between drug dose and drug effect and that this can be expressed by a dose-response curve. This paper argues that there is no such clear relation and that the dose-response curve provides only limited information about the drug effect. It is demonstrated that tolerance development during the measurement of the dose-response curve may cause major distortion of the curve and it is argued that the curve may only be used to indicate the response to the first administration of a drug, before tolerance has developed. The precise effect of a drug on an individual depends on the dynamic relation between several variables, particularly the level of tolerance, the dose anticipated by the organism and the actual drug dose. Simulations with a previously published mathematical model of drug tolerance demonstrate that the effect of a dose smaller than the dose the organism has developed tolerance to is difficult to predict and may be opposite to the action of the usual dose.

Systematic analysis of BRAFV600E melanomas reveals a role for JNK/c-Jun pathway in adaptive resistance to drug-induced apoptosis

Fallahi-Sichani, Mohammad; Moerke, Nathan J; Niepel, Mario; Zhang, Tinghu; Gray, Nathanael S; Sorger, Peter K
Fonte: BlackWell Publishing Ltd Publicador: BlackWell Publishing Ltd
Tipo: Artigo de Revista Científica
EN_US
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Drugs that inhibit RAF/MEK signaling, such as vemurafenib, elicit profound but often temporary anti-tumor responses in patients with BRAFV600E melanoma. Adaptive responses to RAF/MEK inhibition occur on a timescale of hours to days, involve homeostatic responses that reactivate MAP kinase signaling and compensatory mitogenic pathways, and attenuate the anti-tumor effects of RAF/MEK inhibitors. We profile adaptive responses across a panel of melanoma cell lines using multiplex biochemical measurement, single-cell assays, and statistical modeling and show that adaptation involves at least six signaling cascades that act to reduce drug potency (IC50) and maximal effect (i.e., Emax ≪ 1). Among these cascades, we identify a role for JNK/c-Jun signaling in vemurafenib adaptation and show that RAF and JNK inhibitors synergize in cell killing. This arises because JNK inhibition prevents a subset of cells in a cycling population from becoming quiescent upon vemurafenib treatment, thereby reducing drug Emax. Our findings demonstrate the breadth and diversity of adaptive responses to RAF/MEK inhibition and a means to identify which steps in a signaling cascade are most predictive of phenotypic response.

Determinants of drug onset

Ludbrook, G.; Upton, R.
Fonte: Lippincott Williams & Wilkins Publicador: Lippincott Williams & Wilkins
Tipo: Artigo de Revista Científica
Publicado em //2002 EN
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462.4496%
PURPOSE OF REVIEW: The timing and magnitude of drug onset can be influenced by factors in the chain of drug delivery from the site of administration to the site of effect. This review examines recent evidence regarding the contribution and significance of these factors. RECENT FINDINGS: It is apparent that drug formulations and mixtures can play a significant role in drug onset. An extension of this is the effect of coadministration of drugs, which can influence drug effect both by altering the physiology underlying drug delivery and by an effect at the target organ. Of the physiological variables, cardiac output and its distribution are clearly important. Cardiac output is a significant source of variability in drug response, and indeed has been successfully incorporated into pharmacokinetic models. The pattern of cardiac output distribution is also relevant. In particular, the blood flow to target organs will influence both the timing and magnitude of the effect of some anaesthetic drugs. In addition, the role of the lung in affecting drug distribution may be important for some drugs. At the site or organ of effect itself, variability in drug distribution, drug-receptor interactions, and the influence of other drugs, can all impact on the profile of drug onset. SUMMARY: Factors in the chain of drug delivery have been demonstrated to affect the nature of drug onset...

Serum Concentration and Drug Effect After Intravenous and Rectal Administration of Diazepam

Lundgren, Stefan
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em //1987 EN
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449.14477%
In a randomized crossover study on sedation in outpatient oral surgery, the relation between the serum profile and the drug effect profile for intravenously (i.v.) and rectally administered diazepam was studied. Both sedation methods were found to be equally efficient at a mean dose of 0.25 mg/kg (range, 0.14—0.45) for i.v. administration, and 0.53 mg/kg (range, 0.50—0.58) for rectal administration. Both the serum concentration and the effect reached their mean peaks at the same time; however, this was 15 min later after rectal sedation than after i.v. sedation. Intravenous administration yielded a significantly higher serum concentration of diazepam at the clinical endpoint than did rectal administration, but the mean effect levels at the clinical endpoint were equal for both sedation methods. No linear correlation between log-serum concentration and the patient's estimation of effect was found.

RNAi-based discovery and validation of new drug targets in filarial nematodes

Behm, Carolyn; Bendig, Mary; McCarter, James; Sluder, Ann
Fonte: Elsevier Publicador: Elsevier
Tipo: Artigo de Revista Científica
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Human filarial nematodes cause river blindness and lymphatic filariasis, both of which are diseases that produce considerable morbidity. Control of these diseases relies on drug treatments that are ineffective against macrofilariae and are threatened by the development of resistance. New validated drug targets are required to allow development of new classes of antifilarial drugs. To identify and validate potential new drug targets, we propose a collaborative research strategy utilizing bioinformatic filters and assessment of gene function by RNA interference in Caenorhabditis elegans and Brugia malayi.

Drug dependence; La dépendance de drogues; Dependência de drogas

Garcia-Mijares, Miriam; Silva, Maria Teresa Araujo
Fonte: Universidade de São Paulo. Instituto de Psicologia Publicador: Universidade de São Paulo. Instituto de Psicologia
Tipo: info:eu-repo/semantics/article; info:eu-repo/semantics/publishedVersion; ; ; ; Formato: application/pdf
Publicado em 01/01/2006 POR
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O texto discute três teorias atuais de dependência de drogas: a Teoria Comportamental da dependência como escolha de Heyman, a Teoria da Sensibilização do incentivo de Robinson e Berridge, e a Teoria Neurobiológica da dependência como escolha, de Kalivas. Todas concordam em caracterizar a dependência como resultante de processos de aprendizagem em que droga e estímulos associados a seus efeitos adquirem controle potente sobre o comportamento. Diferenciam-se quanto aos processos de aprendizagem envolvidos. A Teoria Comportamental enfatiza componentes operantes e sustenta que o consumo repetido de drogas diminui o valor reforçador de atividades concorrentes. A Teoria da Sensibilização enfatiza componentes respondentes, propondo a dependência como resultado da sensibilização da potência eliciadora de estímulos condicionados aos efeitos da droga. A Teoria Neurobiológica integra as duas primeiras, descrevendo as mudanças no circuito do reforço que acontecem no processo de dependência.; This paper analyses three current theories about drug dependence: Heyman´s Behavioral Theory of dependence as choice, Robinson and Berridge´s incentive-Sensitization Theory, and Kalivas´ Neurobiological Theory of dependence as choice. All of them agree in defining dependence as a phenomenon resulting from learning processes in which drug and associated stimuli acquire powerful control over behavior. The three theories diverge as to the specific learning processes that could explain dependence. The Behavioral Theory emphasizes the operant component...