RESUMO
BACKGROUND: Deoxyxylulose 5-phosphate synthase (DXS) and deoxyxylulose 5-phosphate reductoisomerase (DXR) are the enzymes that catalyze the first two enzyme steps of the methylerythritol 4-phosphate (MEP) pathway to supply the isoprene building-blocks of carotenoids. Plant DXR and DXS enzymes have been reported to function differently depending on the plant species. In this study, the differential roles of rice DXS and DXR genes in carotenoid metabolism were investigated. RESULTS: The accumulation of carotenoids in rice seeds co-expressing OsDXS2 and stPAC was largely enhanced by 3.4-fold relative to the stPAC seeds and 315.3-fold relative to non-transgenic (NT) seeds, while the overexpression of each OsDXS2 or OsDXR caused no positive effect on the accumulation of either carotenoids or chlorophylls in leaves and seeds, suggesting that OsDXS2 functions as a rate-limiting enzyme supplying IPP/DMAPPs to seed carotenoid metabolism, but OsDXR doesn't in either leaves or seeds. The expressions of OsDXS1, OsPSY1, OsPSY2, and OsBCH2 genes were upregulated regardless of the reductions of chlorophylls and carotenoids in leaves; however, there was no significant change in the expression of most carotenogenic genes, even though there was a 315.3-fold increase in the amount of carotenoid in rice seeds. These non-proportional expression patterns in leaves and seeds suggest that those metabolic changes of carotenoids were associated with overexpression of the OsDXS2, OsDXR and stPAC transgenes, and the capacities of the intermediate biosynthetic enzymes might be much more important for those metabolic alterations than the transcript levels of intermediate biosynthetic genes are. Taken together, we propose a 'Three Faucets and Cisterns Model' about the relationship among the rate-limiting enzymes OsDXSs, OsPSYs, and OsBCHs as a "Faucet", the biosynthetic capacity of intermediate metabolites as a "Cistern", and the carotenoid accumulations as the content of "Cistern". CONCLUSION: Our study suggests that OsDXS2 plays an important role as a rate-limiting enzyme supplying IPP/DMAPPs to the seed-carotenoid accumulation, and rice seed carotenoid metabolism could be largely enhanced without any significant transcriptional alteration of carotenogenic genes. Finally, the "Three Faucets and Cisterns model" presents the extenuating circumstance to elucidate rice seed carotenoid metabolism.
Assuntos
Aldose-Cetose Isomerases/fisiologia , Carotenoides/metabolismo , Eritritol/análogos & derivados , Oryza/enzimologia , Fosfatos Açúcares/fisiologia , Aldose-Cetose Isomerases/genética , Butadienos/síntese química , Butadienos/metabolismo , Eritritol/genética , Eritritol/fisiologia , Hemiterpenos/síntese química , Hemiterpenos/metabolismo , Folhas de Planta/enzimologia , Sementes/enzimologia , Fosfatos Açúcares/genética , Transferases/genética , Transferases/fisiologiaRESUMO
Janus kinase (JAK) is one of the main upstream activators of signal transducers and activators of transcription (STAT) that are constitutively activated in various malignancies and are associated with cell growth, survival, and carcinogenesis. Here, we investigated the role of JAKs in colorectal cancer in order to develop effective therapeutic targets for INCB018424, which is the first JAK1/2 inhibitor to be approved by FDA. After examining the basal expression levels of phospho-JAK1 and phospho-JAK2, we measured the effects of INCB018424 on the phosphorylation of JAK1/2 using western blot analysis. Cell viability was determined using the trypan blue exclusion assay. The cell death mechanism was identified by the activation of caspase 3 using western blot and annexin V staining. The basal levels of phospho-JAK1 and phospho-JAK2 were cancer cell type dependent. Colorectal cancer cell lines that phosphorylate both JAK1 and JAK2 include DLD-1 and RKO. INCB018424 inactivates both JAK1 and JAK2 in DLD-1 cells but inactivates only JAK1 in RKO cells. Cell death was proportional to the inactivation of JAK1 but not JAK2. INCB018424 causes caspase-dependent cell death, which is prevented by treatment with z-VAD. The inhibition of JAK1 phosphorylation seemed sufficient to allow INCB018424-mediated apoptosis. JAK1 is a key molecule that is involved in colon cancer cell survival and the inhibition of JAK1 by INCB01424 results in caspase-dependent apoptosis in colorectal cancer cells. The use of selective JAK1 inhibitors could be an attractive therapy against colorectal cancer, but further clinical investigations are needed to test this possibility.
Assuntos
Apoptose/efeitos dos fármacos , Neoplasias do Colo/tratamento farmacológico , Janus Quinase 1/antagonistas & inibidores , Pirazóis/farmacologia , Linhagem Celular Tumoral , Neoplasias do Colo/patologia , Humanos , Janus Quinase 1/metabolismo , Nitrilas , Fosforilação , Pirimidinas , Fatores de Transcrição STAT/fisiologia , Transdução de SinaisRESUMO
BACKGROUND AND PURPOSE: A cardiogenic embolus could reach the posterior circulation through the right vertebral artery because of a relatively larger diameter in cases of left vertebral artery hypoplasia. Hence, we investigated whether left vertebral artery hypoplasia is associated with cardiac embolisms with atrial fibrillation in the posterior circulation and its functional outcomes. MATERIALS AND METHODS: In this monocentric retrospective study, patients with acute cardioembolic stroke with atrial fibrillation were enrolled and underwent CT or neck MRA, which visualized the aortic arch and subclavian arteries. The laterality and size of vertebral artery hypoplasia were recorded. Posterior circulation stroke, basilar artery occlusion, and the functional outcomes after 3 months were investigated. RESULTS: This study included 407 patients; the patients with left vertebral artery hypoplasia experienced a higher rate of posterior circulation stroke (19 versus 73; 42.2% versus 20.2%; P = .001) and basilar artery occlusion (5 versus 10; 11.1% versus 2.8%; P = .005) than the patients without left vertebral artery hypoplasia. Multivariate analysis revealed that left vertebral artery hypoplasia showed an association with lower odds of achieving a good functional outcome 3 months after the stroke (OR = 0.4; 95% CI, 0.2-0.9; P = .027). CONCLUSIONS: Patients with cardioembolic stroke and left vertebral artery hypoplasia had posterior circulation stroke, basilar artery occlusion, and poor functional outcomes after 3 months.
Assuntos
Arteriopatias Oclusivas , Fibrilação Atrial , AVC Embólico , Acidente Vascular Cerebral , Insuficiência Vertebrobasilar , Humanos , Artéria Vertebral/diagnóstico por imagem , AVC Embólico/complicações , Fibrilação Atrial/complicações , Fibrilação Atrial/diagnóstico por imagem , Aorta Torácica , Estudos Retrospectivos , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico por imagem , Arteriopatias Oclusivas/complicações , Insuficiência Vertebrobasilar/complicações , Insuficiência Vertebrobasilar/diagnóstico por imagemRESUMO
Tomentosin, a sesquiterpene lactone, is known to possess various biological activities. However, its anticarcinogenic activity against human hepatocellular carcinoma (HCC) cells has not been investigated in detail. Thus, this study aimed to elucidate the cytotoxic mechanism of tomentosin in human HCC cell lines HepG2 and Huh7. WST-1, cell counting, and colony formation assay results showed that treatment with tomentosin decreased the viability and suppressed the proliferation rate of HepG2 and Huh7 cells in a dose- and time-dependent manner. Cell cycle analysis revealed increased population of cells at the SubG1 and G2/M stage, and decreased population of cells at the G0/1 stage in HepG2 and Huh7 cells treated with tomentosin. Annexin V/propidium iodide double staining and TUNEL assay results showed increased apoptotic cell population and DNA fragmentation in HepG2 and Huh7 cells treated with tomentosin. Western blotting analysis results showed that tomentosin treatment significantly increased the expression level of Bax, Bim (short form), cleaved PARP1, FOXO3, p53, pSer15p53, pSer20p53, pSer46p53, p21, and p27, but decreased the expression of Bcl2, caspase3, caspase7, caspase9, cyclin-dependent kinase 2 (CDK2), CDK4, CDK6, cyclinB1, cyclinD1, cyclinD2, cyclinD3, and cyclinE in a dose-dependent manner. Taken together, this study revealed that tomentosin, which acted through cell cycle arrest and apoptosis, may be a useful therapeutic option against HCC.
Assuntos
Antineoplásicos/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Lactonas/farmacologia , Neoplasias Hepáticas/tratamento farmacológico , Sesquiterpenos/farmacologia , Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular/metabolismo , Caspases/metabolismo , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Quinases Ciclina-Dependentes/metabolismo , Ciclinas/metabolismo , Proteína Forkhead Box O3/metabolismo , Humanos , Neoplasias Hepáticas/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteína Supressora de Tumor p53/metabolismoRESUMO
This study investigated the effect of intrathecal fentanyl on the dose of propofol during sedation guided by Cerebral State Index monitoring. Seventy patients were randomly assigned to receive either fentanyl 25 microg (n = 35) or normal saline (n = 35) with hyperbaric bupivacaine 12.5 mg for spinal anaesthesia. Propofol was infused to maintain a Cerebral State Index value of 65-75 for 30 min. The propofol infusion time and dose required to reach a Cerebral State Index value of 75 were recorded together with the time required to reach a Cerebral State Index value higher than 90 after cessation of sedation. The onset time for sedation was faster and the recovery time was slower in the fentanyl group compared to those in the saline group (p = 0.018 and 0.027, respectively). The propofol doses required for onset and maintenance of sedation were significantly lower in the fentanyl group compared to those in the control group (p = 0.018 and < 0.001, respectively). In conclusion, adding intrathecal fentanyl 25 microg during spinal anaesthesia significantly reduced the dose of propofol required for sedation and prolonged the subsequent recovery time.
Assuntos
Adjuvantes Anestésicos/farmacologia , Raquianestesia/métodos , Fentanila/farmacologia , Hipnóticos e Sedativos/administração & dosagem , Propofol/administração & dosagem , Adulto , Período de Recuperação da Anestesia , Anestésicos Locais/administração & dosagem , Bupivacaína/administração & dosagem , Sedação Consciente/métodos , Estado de Consciência/efeitos dos fármacos , Interações Medicamentosas , Monitoramento de Medicamentos/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Monitorização Intraoperatória/métodosRESUMO
BACKGROUND: In 2006, the European Union (EU) has decided to forbid use of antibiotics as growth promoters. Although many researches had been conducted about fiber source as alternatives of antibiotics, there are still lack of reports in the literature about the optimum level of sugar beet pulp supplementation, affecting growth performance and nutrient digestibility in weaning pigs. Therefore, different level of sugar beet pulp was added to diets to determine the effects of sugar beet pulp supplementation on growth performance, nutrient digestibility, fecal microflora, blood profile and incidence of diarrhea in weaning pigs. METHODS: A total of 200 weaning pigs [(Yorkshire × Landrace) × Duroc], averaging 9.01 ± 1.389 kg of initial body weight were, allotted to 5 treatments in a randomized complete block (RCB) design. Each treatment was composed of 4 replicates with 10 pigs per pen. The treatments were control treatment: Corn-SBM basal diet + ZnO (phase 1: 0.05%; phase 2; 0.03%) and four different levels of sugar beet pulp were supplemented in Corn-SBM basal diet (3, 6, 9 or 12%). Two phase feeding programs (phase 1: 1-2 weeks; phase 2: 3-5 weeks) were used for 5 week of growth trial. RESULTS: In feeding trial, there were no significant differences in growth performance and incidence of diarrhea among treatments. The E.coli counts were not significantly different among dietary treatments but linear response was observed in Lactobacillus counts as sugar beet pulp supplementation increased (P < 0.05). In addition, IGF-1, IgA and IgG were not affected by dietary treatments. However, the BUN concentration was decreased when pigs were fed the treatments of diets with SBP compared to that of control treatment (P < 0.05). In nutrient digestibility, crude fiber and NDF digestibilities were improved as the sugar beet pulp increased (P < 0.05). However, digestibilities of crude ash, crude fat, crude fiber and nitrogen retention were not affected by dietary sugar beet pulp levels. CONCLUSION: This experiment demonstrated that sugar beet pulp can be supplemented in weaning pigs' diet instead of ZnO to prevent postweaning diarrhea without any detrimental effect on growth performance.
RESUMO
BACKGROUND: To reduce use of main feed ingredient like corn, soy bean meal (SBM) and wheat, alternative ingredients has been studied like copra meal (CM). Production amount of CM which has been high makes CM to be an alternative feed stuff. However, low digestibility on AA and low energy content by high fiber content can be an obstacle for using CM. This experiment was conducted to evaluate the effects of CM supplementation with ß-mannanase on growth performance, blood profile, nutrient digestibility, pork quality and economic analysis in growing-finishing pigs. METHODS: A total of 100 growing pigs ([Yorkshire × Landrace] × Duroc) averaging 31.22 ± 2.04 kg body weight were allotted to 5 different treatments by weight and sex in a randomized complete block (RCB) design in 5 replicate with 4 pigs per pen. Treatments were 1) Control (corn-SBM based diet + 0.1% of ß-mannanase (800 IU)), 2) CM10 (10% copra meal + 0.1% ß-mannanase (800 IU)), 3) CM15 (15% copra meal + 0.1% ß-mannanase (800 IU)), 4) CM20 (20% copra meal + 0.1% ß-mannanase (800 IU)) and 5) CM25 (25% copra meal + 0.1% ß-mannanase (800 IU)). Four phase feeding program was used: growing I (week 1-3), growing II (week 4-6), finishing I (week 7-9) and finishing II (week 10-12). RESULTS: In growth performance, there was no significant difference among treatments during whole experimental period. In growingI phase, G:F ratio tended to increase when CM was increased (P = 0.05), but ADG and ADFI tended to decrease in finishingII phase (linear, P = 0.08). Also, increasing CM reduced ADG (linear, P = 0.02) and feed efficiency (linear, P = 0.08) during the whole finishing period. In blood profiles, BUN was linearly increased as CM increased (linear, P = 0.02) at growingII period. In digestibility trial, there was no significant difference in dry matter, crude fat, crude ash and nitrogen digestibility. However, crude protein digestibility was decreased linearly (linear, P = 0.02). In economic analysis, feed cost per weight gain and total feed cost per pig were reduced in overall period when CM was provided by 25% (linear, P = 0.02). CONCLUSION: CM with 0.1% of ß-mannanase (800 IU) could be supplemented instead of corn and SBM up to 25% without detrimental effects on growth performance and pork quality of growing-finishing pigs.
RESUMO
Negative cooperativity is a phenomenon in which the binding of one or more molecules of a ligand to a multimeric receptor makes it more difficult for subsequent ligand molecules to bind. Negative cooperativity can make a multimeric receptor's response more graded than it would otherwise be. However, through theory and experimental results, we show that if the ligand binds the receptor with high affinity and can be appreciably depleted by receptor binding, then negative cooperativity produces a qualitatively different type of response: a highly ultrasensitive response with a pronounced threshold. Because ultrasensitivity and thresholds are important for generating various complex systems-level behaviors, including bistability and oscillations, negative cooperativity may be an important ingredient in many types of biological responses.
Assuntos
Complexos Multiproteicos/química , Ligação Proteica , Receptores de Superfície Celular/química , Transdução de Sinais , DNA/química , Ligantes , Modelos Moleculares , Multimerização ProteicaRESUMO
Spontaneous flexor tendon rupture is a rare condition and the aetiology is not clear. We report 12 elderly Korean farmers with spontaneous flexor tendon ruptures. We found the rupture in the dominant hand in ten patients. A rupture in the little finger was found in all 12 patients (seven with both flexor tendons ruptured and five with only the profundus ruptured), in the ring finger in four patients (the profundus ruptured in all and both flexor tendons in two patients), and in the middle finger a partial rupture of the profundus in one patient. The tendons were ruptured close to the hook of the hamate. Repetitive friction between the flexor tendons and the hamate hook may cause the ruptures. The hamate hook was excised and the ruptured profundus tendons were reconstructed with tendon transfers with quite favourable functional recovery at follow-up of 1 to 2 years. The ruptured superficialis tendons were not reconstructed. Level of Evidence IV.
Assuntos
Traumatismos da Mão/cirurgia , Procedimentos Ortopédicos/métodos , Procedimentos de Cirurgia Plástica/métodos , Traumatismos dos Tendões/cirurgia , Adolescente , Adulto , Humanos , Articulação Metacarpofalângica/fisiopatologia , Amplitude de Movimento Articular , Recuperação de Função Fisiológica , República da Coreia , Estudos Retrospectivos , Ruptura , Adulto JovemRESUMO
Three genes encoding 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR, EC1.1.1.34), which converts HMG-CoA into mevalonate in the early key step of the plant isoprenoid pathway, were isolated by RT-PCR and rice cDNA and genomic library screening. A genomic Southern blot analysis confirmed that HMGR genes are present in three copies in rice. Of the three, the HMGR 2 gene (Hmg2) obtained as a cDNA clone and its genomic clone had 4 exons and 3 introns, and encoded a 576 amino acid peptide containing an open reading frame of 1,728 bp with a calculated Mw. of 61,150. The structure of rice Hmg2 had common features, based on its nucleotide and deduced amino acid sequence homologies, with other plant HMGR genes published to date. Rice Hmg2 transcripts were constitutively detected in all parts of the rice plant, except in lamina and their levels were high particularly in the leaf part of the dark-grown seedlings and mature flowers. Our result showed that mRNA levels of rice Hmg2 were strongly induced in seedlings and influorescence in the early development stage. Rice Hmg2 possibly has a housekeeping role involved in the sterol biosynthesis, among the possible roles of plant HMGR genes that have been suggested in other plants [Weissenborn et al. (1995)].
Assuntos
Hidroximetilglutaril-CoA Redutases/genética , Oryza/genética , Sequência de Aminoácidos , Sequência de Bases , Southern Blotting , DNA de Plantas/análise , Regulação da Expressão Gênica no Desenvolvimento , Regulação Enzimológica da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Biblioteca Gênica , Dados de Sequência Molecular , Mapeamento por Restrição , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
Epithelial cells within the mammary gland undergo apoptosis during weaning. To determine the expression of Bok mRNA (a member of the pro-apoptotic Bcl-2 family) in the mammary gland and its regulation, we examined the expression of the Bok transcript in the mouse mammary gland and HC11 mammary epithelial cells in culture through RT-PCR. The Bok mRNA expression was found in the mammary gland. The expression of the Bok mRNA level was induced through serum starvation and overexpression of Bok induced apoptosis in HC11 cells in culture. These results indicate that the expression of Bok mRNA in the mammary gland is regulated through serum starvation. It also may be related to the mammary involution.
Assuntos
Proteínas de Transporte/biossíntese , Glândulas Mamárias Animais/metabolismo , Proteínas de Membrana/biossíntese , Animais , Apoptose , Proteínas de Transporte/genética , Células Cultivadas , Meios de Cultura Livres de Soro , Células Epiteliais/metabolismo , Feminino , Regulação da Expressão Gênica , Proteínas de Membrana/genética , Camundongos , Ovário/metabolismo , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
Phosphine emission fluxes from paddy fields, phosphine ambient levels in air, and the vertical profile of matrix-bound phosphine in soil have been measured throughout the growing season of rice in Beijing, China. It was found that both the seasonal and diurnal emission fluxes and ambient levels fluctuate significantly. During the drainage period, phosphine released from the soil with the highest diurnal average flux on the first period of drainage (approx. 17.7 ng m(-2) h(-1)), whereas its highest ambient level (approx. 250 ng m(-3)) occurred at 06.00 h. During the flooded period, phosphine emission was low, and the peaks of phosphine emissions occurred at midnight. The average flux of PH3 emission for the whole season was found to be approximately 1.78 ng m(-2) h(-1). The mass fraction of matrix-bound phosphine is approximately 0.18 approximately 1.42 x 10(-7) (m/m) part of organic phosphorus or 3.4 approximately 9.2 x 10(-9) (m/m) part of total phosphorus in paddy soil. The amount of phosphine emitted to the atmosphere was only a small fraction of the phosphine that remained in the soil in the matrix-bound form. Soil serves both as the source and the sink of PH3.
Assuntos
Poluentes Atmosféricos/análise , Fosfinas/farmacocinética , Poluentes Químicos da Água/farmacocinética , Oryza , Fosfinas/análise , Poluentes do Solo/análise , Poluentes do Solo/farmacocinética , Poluentes Químicos da Água/análiseRESUMO
Epidemiological studies have demonstrated that nonsteroidal anti-inflammatory drugs (NSAIDs) decrease the incidence of colon cancer. In addition, NSAIDs reduce the number and size of polyps in patients with familial adenomatous polyposis. The mechanisms of the anti-neoplastic effect of NSAIDs are still far from complete understanding, but one possible mechanism is the induction of apoptosis. Several lines of evidence suggest that NSAIDs-induced apoptosis in colon cancer cells are mediated through the cyclooxygenase (COX)-independent pathway. In this study we explored the mechanism of NSAIDs-induced apoptosis in the colon cancer cell line, HT-29. We confirmed that NSAIDs induce apoptosis in HT-29 cells irrespective of their COX-selectivity. Indomethacin enhanced the expression of p21waf-1 in HT-29 cells. However the expression of apoptosis-related genes such as Fas, bcl-2 and bax was not affected by indomethacin. Intra- and extra-cellular calcium chelators, protein tyrosine kinase (PTK) inhibitor, protein kinase A (PKA) inhibitor and protein kinase C (PKC) inhibitors did not influence indomethacin-induced apoptosis in HT-29 cells. We concluded that NSAIDs-induced apoptosis in colon cancer cells may be independent from signals transducted through [Ca++]i, PTK, PKA, PKC or the expression of apoptosis-related genes. In contrast, our results demonstrating the induction of p21waf-1 transcription by NSAIDs suggest the possible association of NSAIDs-induced apoptosis and cell-cycle control in colon cancer cells.
Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias do Colo/prevenção & controle , Cálcio/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Neoplasias do Colo/patologia , Inibidor de Quinase Dependente de Ciclina p21 , Ciclinas/biossíntese , Ciclinas/genética , Células HT29 , Humanos , Proteínas Quinases/fisiologia , Proteínas Proto-Oncogênicas c-bcl-2/análise , RNA Mensageiro/análise , Proteína Supressora de Tumor p53/fisiologiaRESUMO
The toxicity of combined use of blood schizontocide pyronaridine (PND) and primaquine (PQ) in mice and rats was significantly lower than that of chloroquine (CQ) plus primaquine (PQ). PND 1/2 LD50 (ca 600 mg/kg) in combination with PQ reduced the toxic action of PQ in mice, while CQ 1/2 LD50 (ca 300 mg/kg) plus PQ produced synergistic toxic effect. In animal models such as Plasmodium yoelii sporozoite infection in mice and P. cynomolgi sporozoite infection in rhesus monkeys, the tissue schizontocidal action of PQ was not affected by PND. Therefore, clinical evaluation of PND/PQ in comparison with CQ/PQ in treating vivax malaria is suggested.
Assuntos
Antimaláricos/toxicidade , Cloroquina/toxicidade , Naftiridinas/toxicidade , Plasmodium yoelii , Primaquina/toxicidade , Animais , Quimioterapia Combinada , Macaca mulatta , Malária/tratamento farmacológico , Camundongos , PlasmodiumRESUMO
The triple combination of pyronaridine, sulfadoxine and pyrimethamine which has been proven to be efficient in delaying emergence of drug resistance of rodent malarial parasites was further studied for potential application to malaria control. The antimalarial effect of the triple combination on Plasmodium berghei ANKA-infected mice and the toxic effects in mice and rats were additive. A single dose of pyronaridine 500 mg in combination with sulfadoxine, 1000 or 1500 mg, and pyrimethamine, 50 or 75 mg, given to 72 acute falciparum malaria patients resulted in a 100% cure rate with nil or mild side effects, and no recrudescence of asexual parasite over 4-week follow-up. Preliminary experiments on the drug effect on sporogony showed that the drug combination at the dose used could not completely interrupt the sporozoite formation although many retarded oocysts were found.
Assuntos
Antimaláricos/uso terapêutico , Malária/tratamento farmacológico , Naftiridinas/administração & dosagem , Pirimetamina/administração & dosagem , Sulfadoxina/administração & dosagem , Sulfanilamidas/administração & dosagem , Animais , Antimaláricos/toxicidade , Quimioterapia Combinada , Seguimentos , Humanos , Camundongos , Naftiridinas/toxicidade , Plasmodium falciparum/efeitos dos fármacos , Pirimetamina/toxicidade , Ratos , Sulfadoxina/toxicidadeRESUMO
OBJECTIVE: To investigate the in vitro and in vivo schizontocidal activity of daphnetin. METHODS: Schizontocidal activity of daphnetin was tested using an in vitro assay based on the routine in vitro cultivation of P. falciparum FCC1 strain. The in vivo antimalarial effects of daphnetin at various dosages were assessed in mice infected with P. b. erghei ANKA according to "4-day suppress assay". RESULTS: In vitro, daphnetin exhibited potent schizontocidal activity comparable to chloroquine(CQ) at the dose range of 1-10 mumol/L. In vivo, 50 or 100 mg/kg.d-1 x 4 d daphnetin i.g. and 10, 50 or 100 mg/kg.d-1 x 4 d dephnetin i.p. showed antimalarial efficacy comparable to CQ 10 mg/kg.d-1 x 4 d i.g. in mice infected with P. berghei ANKA, evaluated by both the reduction rate of parasitemia on D4 and the average surviving days in 30 days. CONCLUSION: Daphnetin displays certain schizontocidal activity both in vitro and in vivo.