A further decrease in FA was seen with higher-order correction in

A further decrease in FA was seen with higher-order correction in the unipolar sequence, since there were more substantial higher-order eddy currents in the unipolar sequence relative to the bipolar sequence. The MD was found to be more robust against eddy-currents compared to the FA in this isotropic phantom, since higher-order

correction did not result in significant changes in the MD in either the unipolar or bipolar sequence. Differing MD values between bipolar and unipolar buy Ruxolitinib sequences could have been because they were estimated at different TEs and result in different SNRs. In a truly isotropic phantom where FA is zero, noise results in an upward bias in the FA and a negative bias in the MD (due to an apparently

insufficient decay in the diffusion signal). In addition to noise, the positive bias in the measured FA could also have been caused by systemic errors including the calibration of the diffusion gradients, the possibility that the phantom did not truly have an FA of zero, or by the presence of mechanical find more motion. Although the same b-values were used for comparison between the unipolar and bipolar sequence, different waveforms resulting in different diffusion times could also have led to a different q-values, and hence, signal intensity. The use of minimum TEs in this study reflects how the sequences would be used in clinical practice. Comparison of eddy-current corrected images with affine image registration shows that eddy-current correction with phases from the field camera performs Florfenicol better than image registration. In the presence of higher-order eddy-current distortions, it was expected that affine image registration would leave residual misalignment artifacts. The ability to correct distortions with image registration will depend

on the anatomy of interest and the nature of the eddy-current distortions. The drawback of affine image registration is that even if the distortions can be aligned, the intensities may not be fully recovered. Image registration has been shown to be suboptimal for diffusion images that have significant contrast changes due to directional anisotropy [36] and [37]. Another disadvantage of image registration is SNR dependency. It was found that image registration performed better on diffusion images obtained at lower b-values than those at higher b-values where the SNR was low [38]. Eddy-current correction with the field camera is expected to perform well regardless of the SNR in the image. However, the drawback of eddy-current correction with the field camera is that extra hardware is required. It was found that performing the first step of the full iterative procedure (as described in Wilm et al. [20]), i.e., conjugate phase reconstruction, was adequate for removing bulk object shifts arising from higher-order terms.

Exploring the toolkit’s usefulness and feasibility with a wider r

Exploring the toolkit’s usefulness and feasibility with a wider range of older adults, including those with varying levels of cognitive and functional ability, is also an important next step. Studies can examine resident and family feedback

on the interviews; stability of preferences and satisfaction over time; inter-rater reliability when different types of staff administer interviews; trends in NH performance; factors leading to success; and best practices to improve PCC care delivery. As of February 5, 2014, over 700 NH s have selected the AE PCC goal as a focus for quality improvement. They and other new adopters’ experiences will provide important insights about the toolkit’s applicability. Results from these pilot studies suggest that the learn more AE PCC toolkit can be used successfully to assess person-centered care. Staff at diverse NHs found the toolkit

easy this website to use and directly relevant to resident care and QI activities. The toolkit enables providers to move beyond anecdote and to systematically track whether residents’ important preferences for daily living are satisfied. Also, the toolkit’s online features provide opportunities to benchmark results and share best practices in order to enhance PCC for NH residents nationwide. Thank you to the nursing home staff and residents who contributed to the development of this tool by participating in the validation study and pilot evaluation, as well as to the members of the Advancing Excellence in America’s Nursing Homes Person-Centered Care Work Group. “
“In Australia the majority of taxonomists work in the seven state museums, which are funded by the relevant state government, there being no national museum for natural history. A similar Regorafenib pattern is found for the herbariums although in this case there is a national one in Canberra. Few taxonomists are associated with a University. A similar pattern occurs overseas and in my field of polychaetes most are associated with a natural history museum

although some of these also associated with a University and increasingly joint appointments are being considered. I wish to focus on the loss of marine taxonomic expertise and the consequences of this here in Australia where so much of the marine fauna is still undescribed, especially in northern Australia where massive infrastructure developments are occurring or planned for the export of coal, gas and minerals. A similar paucity of knowledge exists offshore in deeper water within Australia’s extensive EEZ. Here in Australia, as overseas, the role of natural history museums is being questioned and with government funding to them failing to keep up with costs, museums are having to assess where there limited funds should be spent.

Moreover, variations in the growing conditions such as climate ch

Moreover, variations in the growing conditions such as climate changes, sowing methods (Barampama & Simard, 1993), the high temperature during the grain filling, the shape of post-harvest processing (Sartori, 1996), time and storage conditions (Dalla Corte, Moda-Cirino, Scholz, & Destro, 2003) may influence the interaction between nutrients and enhance or hamper its bioavailability (Caldas & Blair, 2009). Tannins were found only in BAF 55 with 1.4 mg CAE/100 g sample, indicating that the high concentration of these compounds

determinate the highest values of total phenolics in this genotype. SCH727965 In the raw samples (R) the antioxidant activity was higher in the grains of the carioca commercial group (IAPAR-81), with 0.049 g of sample/mg of DPPH when compared to the black genotype

groups (BAF 55 and Uirapuru) (Table 1). The IAPAR genotype also showed a higher antioxidant potential (0.066 g of sample/mg of DPPH) when the samples were cooked without soaking (CWS), which demonstrates that genotypes with clear colored grains are related with a greater capacity to capture free radicals of the genotype. In the grain selleck chemicals llc samples cooked with and without soaking water samples (CWSW and COSW) no difference was observed between the genotypes with dark color, this may be due to a high lixiviation of compounds during the cooking and this might have been the reason of higher antioxidant activity for the cooking water making the samples similar. When compared to the four preparation methods in the same genotype, it was found that the samples cooked with and without soaking water (CWSW and COSW) obtained the best results with the lowest uptake values of the DPPH radical for the three

studied genotypes, resulting in 0.037, 0.035 and 0.040 g of sample/mg of DPPH to the CWSW preparation, and 0.039, 0.040 and 0.047 g of sample/mg of DPPH for the COSW preparation, in the IAPAR, Uirapuru and BAF 55 genotypes, respectively. It is probable that the water immersion leverages some reactive species to the capture free radicals. An experiment realized by Ranilla, Genovese, and Lajolo (2009) had identified a higher antioxidant activity (p < 0.05) in cooked bean samples without removing the soaking water when compared to cooked samples with drained soaking water, a difference that was Carnitine palmitoyltransferase II not detected in this study. In relation with the total phenolic levels (Table 1), differences were found only in raw grains (R) when comparing the genotypes among themselves, the IAPAR-81 (5.0 mg of GAE/g of sample) and Uirapuru (5.0 mg of GAE/g of sample) demonstrated the highest levels compared to BAF 55 (3.5 mg of GAE/g of sample). This variation may be attributed to the effect of the genotype, because both cultivars with the highest contents are commercial cultivars, and BAF 55 is a landrace genotype which did not pass through an improvement process (Coelho et al., 2007a and Pereira et al., 2009).

For our animals, aggressive behavior was observed during

For our animals, aggressive behavior was observed during

and after treatment and also during and after blood collection from the tails. These events may mimic provocative conditions that have often led to student unrests. Studies conducted earlier however showed that given acutely, over a few hours, no abnormal neurologic signs or behavior were notable in baboons [38]. This is in agreement with our findings where we noted no significant alteration in testosterone selleck inhibitor levels for the first week of supplementation. This means that it may requires chronic kerosene supplementation to see both increase in T levels in blood and the T mediated effects on behavior such as increased aggressive tendencies. The mechanism through which the kerosene results in the increase of T remains to be elucidated. Various studies have shown that ingestion or inhalation of kerosene could lead to various toxic effects [27], [39] and [40]. Reported clinical effects of accidental ingestion or suicide attempt are quite varied ranging from mild to fatal. The severities of the effects appear to be largely dependent on the quantity ingested, the age and interaction with drugs (such as metformin) that the victim might be using at the

time of ingestion [41] and [42]. The common effects include cough with difficulty in breathing, vomiting, fever, central nervous system involvement, severe lactic acidosis and acute renal failure, pyopneumothorax and deaths[41], [42] and [43]. It is important to note that effects reported on accidental ingestion or intended suicide crotamiton http://www.selleckchem.com/products/obeticholic-acid.html are acute effects occurring within a short period of time post ingestion and are usually due to ingestion of large quantities. We therefore postulated that chronic dietary kerosene supplementation albeit at lower doses than above (accidental or suicide attempt) may also be harmful to body tissues. We thus investigated the potential toxic effects of kerosene on the liver, kidney, blood and the brain, esophagus and

stomach lumen. It was notable from our findings that there was a uniform steady rate of increase in the body weights from all the three groups with no significant difference (P > 0.05) among the three groups. Regarding potential toxic effects to the liver, relative to the control group, kerosene supplementation showed little to no effects (Figs. A and B). The liver enzymes remained unchanged (ALT, P= 0.97 and P = 0.35, AST, P = 0.11 and P = 0.34 for low and high dose groups respectively. Similarly, kerosene supplementation did not have a significant effect on the serum total proteins. Although results depicted a decreasing trend, it did not reach statistical significance (low dose P = 0.064, high dose P = 0.068). Serum albumin levels showed a significant decrease of P = 0.

Fungos como do gênero aspergillus são encontrados nas placas, pro

Fungos como do gênero aspergillus são encontrados nas placas, provavelmente vindos do óleo mineral contaminado usado para sobreposição das gotas do meio de cultura. São fungos ambientais contaminantes do ar os gêneros aspergillus e penicillium. 14 Em medicina reprodutiva existe risco significativo de contaminação cruzada durante a criopreservação de gametas ou embriões. Em estudo de revisão, conclui‐se que há um risco negligenciado de contaminação cruzada em condições de FIV.15 Encontrou‐se relação

entre infertilidade e vírus da hepatite C em um grupo de casais inférteis, com prevalência de 3,2% para as mulheres e 3,6% para os homens,16 que pode ser transmitida de uma mulher para outra pela contaminação transvaginal por equipamentos ou dos pais para o concepto. Recomendou‐se que pacientes inférteis fossem rastreados antes de submetidos DAPT a técnicas de reprodução assistida. Kastrop et al. (2007)14 mTOR inhibitor descrevem incidência de 0,67% de contaminação nos LRH europeus. A amostra envolveu

mais de 13.000 casos.14 Um estudo de prevalência no Brasil encontrou 4,8% de contaminação nas placas por bactérias e fungos, considerando a contaminação como fator de contribuição do fracasso em reprodução assistida.17 Com a prevalência de contaminação conhecida e com os gêneros identificados, poder‐se analisar a interferência desta sobre o sucesso da reprodução assistida, pois o tipo de contaminação parece variar os resultados. Autores também divergem em seus resultados. most Candida albicans aumentou a fragmentação do DNA e apoptose, danos que podem ter causado fracasso após a fertilização. 19 Outros autores relatam que nascimentos após a transferência de embriões inseridos em meios contaminados com leveduras ocorrem dentro das taxas normais de freqüência para reprodução assistida,

concluindo que a contaminação pelo fungo não é razão para cancelar a transferência de embriões. 11 A primeira consequência observada, quando contaminados com patógenos, está na redução da formação de embriões viáveis para transferência. Os embriões podem não sobreviver nas primeiras clivagens, apresentar teratogenia, ou simplesmente não conseguirem implantar no útero. Também podem ocorrer síndromes que comprometam a saúde fetal, trazendo a possibilidade de aumento de natimortos, prematuridade, ou nascimento de conceptos pequenos para a idade gestacional, descritos em estudos com bovinos onde a fertilização assistida é amplamente utilizada.18 Em outra vertente, existe o risco de infectar o organismo materno, com consequências temporárias ou definitivas. Os procedimentos de controle de qualidade devem ser sempre atualizados para minimizar esses riscos, já que a contaminação pode ser vertical (dos progenitores para o embrião), ou lateral (de uma mulher para outra).

1 41 18 ± 3 25* pmol/mL) but, only for the higher concentration a

1 41.18 ± 3.25* pmol/mL) but, only for the higher concentration at 90 min (Cont. 10.81 ± 0.54; TsNP0.1 46.67 ± 1.60* pmol/mL) and 120 min (Cont. 9.84 ± 1.39; TsNP0.1 68.00 ± 7.60* pmol/mL). mRNA expression of the natriuretic peptide receptor-A, -B, -C, and of the guanylate cyclase-C genes was analyzed in the perfused kidneys because cGMP concentrations were elevated in the urine samples. NPR-A mRNA expression was down regulated in the kidneys treated with both concentrations of TsNP (0.03 and 0.1 μg/mL). In contrast,

the NPR-B, NPR-C and CG-C genes showed an up regulation following 0.1 μg/mL treatment (Fig. 5). As the expression of all of the genes was affected and because PD0325901 the NPR-C receptor does not act via cGMP as a second messenger, we decided to analyze other genes involved in NPR-C signal transduction. Therefore, we analyzed the mRNA levels of eNOS, MAPK-1 and TGFβ-1. A down regulation of eNOS mRNA was observed for both TsNP concentrations (Control 1.046 ± 0.082; TsNP0.03 0.156 ± 0.046*; TsNP0.1 0.276 ± 0.083* relative expression rate). However, an up regulation of TGFβ-1

mRNA was found for 0.1 μg/mL TsNP concentration (Control 1.124 ± 0.345; TsNP0.03 2.751 ± 0.969*; TsNP0.1 4.459 ± 1.020* relative expression rate). MAPK-1 gene expression was not affected by the TsNP treatment. Natriuretic peptides have been extensively investigated due to their potential for the treatment of cardiovascular diseases such as congestive heart failure. Despite all the advances that have been made in this field, only two NP-based drugs have been produced. Unfortunately, both of these http://www.selleckchem.com/products/Belinostat.html drugs possess poor pharmacokinetic properties and have adverse effects that limit their use (Vink et al., 2010). Since the discovery of venom-related natriuretic peptides, first in snakes, then in platypus, a number of chimeric peptides have been produced. These have resulted in peptides with greater stabilities and new pharmacological properties. These peptides have shown advantages over their mammalian counterparts for therapeutic use (Lisy et al., 2008 and Vink et al., 2010). In platypus and snake venoms,

Non-specific serine/threonine protein kinase natriuretic peptides are encoded in the same gene regions of bradykinin-potentiating peptides (BPP) or metalloprotease-inhibiting peptides and are posttranslationally liberated (Fry et al., 2009). This is the first report of the isolation of a natriuretic peptide from scorpion venom. Sequence alignment of TsNP shows a structural similarity to C-type natriuretic peptides. Recently, a family of peptides was isolated from T. serrulatus venom. These peptides shared a sequence signature with the bradykinin-potentiating peptides (BPP) found in snake venom ( Verano-Braga et al., 2008). Higuchi et al. (1999) showed that BPP and C-type natriuretic peptide are encoded by the same genes in species of the Crotalinae subfamily.

The difference in loss-of-QALE between operable and inoperable NS

The difference in loss-of-QALE between operable and inoperable NSCLC patients, or, the net difference after adjustment of potential lead-time bias for age Cell Cycle inhibitor between the two groups, was 9.00 ± 0.18 QALY. We conducted a sensitivity analysis for patients with performance status 0–4 (Table 2). As patients with performance status more than 2 were usually confined to bed and unavailable to answer the questionnaire, the resulted mean utility values of QoL were similar to those

of patients without including them. The difference in QALE between operable and inoperable NSCLC patients would be 10.26 QALY, which was not different from that using patients with performance status 0–1 alone. However, the difference in loss-of-QALE would be Selleck Venetoclax underestimated slightly (= 8.36 QALY), probably because of the older mean age of inoperable patients. Another sensitivity analysis was conducted by only including

the utility values of the first QoL measurements of 518 patients in the calculations, the difference in QALE would be 10.43 QALY and the difference in loss-of-QALE would be 9.20 QALY for patients with operable and inoperable NSCLC, and these results are not significantly different from those using repeated measurements. We also performed a stratified analysis among patients with stage IIIA NSCLC (Fig. 3). Compared with inoperable stage IIIA patients, operable stage IIIA patients had a longer QALE. Moreover, the loss-of-QALE for operable stage IIIA patients was greater than that of inoperable stage IIIA patients, probably because of the younger mean age at diagnosis. There were 262 patients with operable and 621 patients with inoperable NSCLC diagnosed during the first 4 years, between 2005 and 2008, of which the survival curves were extrapolated to 2011 and compared with the Kaplan–Meier estimates based on the 7-year follow-up. The relative biases

of the extrapolation ranged between −4.6% (p = 0.099) and −6.0% (p = 0.116) after 3 years of extrapolation ( Table 3). Although the QoL for NSCLC patients has 3-mercaptopyruvate sulfurtransferase been measured previously in several studies [20] and [21], integrating the survival with utility values of QoL to estimate the lifetime utility difference between patients with operable and inoperable NSCLC has never been comprehensively evaluated. In our study, the utility values of QoL for patients with operable and inoperable NSCLC were stratified into different age bands (Table 2), which show that compared with inoperable patients, operable patients had mean utility values closer to those for the general population (0.96, 0.93, 0.86 for men ≤54 years, 55–74 years, ≥75 years and 0.96, 0.91, 0.78 for women ≤54 years, 55–74 years, ≥75 years, respectively). In addition, we quantified the difference in loss-of-QALE (9.00 ± 0.

75% for LDA), sensitivity (82% vs 72%), and specificity (85% vs

75% for LDA), sensitivity (82% vs. 72%), and specificity (85% vs. 75%). When decreased liver weight was targeted, CBA scored better accuracy (86% vs. 73%) and sensitivity (22% vs. 6%), while LDA marked Crenolanib nmr better specificity (90% vs. 95%). We also compared between CBA and CBA-DR (CBA without Default Rule), our modified version of the original CBA (Table 2). CBA-DR does not predict if a sample does not match any rule except the default rule in a classifier, and, in turn, return a ‘hold’. When increased liver weight was targeted, CBA-DR marked lower accuracy (83% for CBA vs. 79% for CBA-DR) and specificity (85% vs. 29%) and higher sensitivity

(82% vs. 100%). When decreased liver weight was targeted, CBA-DR marked lower sensitivity (22% for CBA this website vs. 0% for CBA-DR) and higher accuracy (86% vs. 95%) and specificity (90% vs. 100%). We compared

the form of generated classifiers between CBA and LDA (Figure 1), when all the records were used as a training set for increased liver weight. CBA tells us a set of rules, arranged in order of confidence. Each rule consists of an antecedent, which is an itemset in the form of (non-class attribute, its discretized value), and a consequence in the form of (class attribute, its class label), shown after “- > ” here. On the other hand, LDA tells us a single discriminative function (fd), which is a polynomial of non-class attribute values with their coefficients. Coefficients in a discriminative function of LDA reflect discriminative power of each non-class attribute (gene, here), with higher positive values and lower negative values meaning larger contributions to each corresponding class label of a class attribute (liver weight, here). To look

into how biologically reasonable the CBA-generated classifier is, we conducted the canonical pathway analysis for the set of genes selected in the classifier when all the records were used as a training set for increased liver weight (Table 3) (for brevity, only top 10 pathways in order of -logp are shown). Because LDA itself, in contrast to CBA, does not explicitly select a set of genes in building a classifier, we did not compare CBA with LDA here. We could assume that the most Fossariinae significant pathways involved with the genes in our classifier were mainly drug metabolism-related ones, such as Xenobiotic Metabolism Signaling, LPS/IL-1 Mediated Inhibition of PXR Function, PXR/RXR Activation etc. Figure 2A is an excerpt around the NRF2 molecule from the illustration of the Xenobiotic Metabolism Signaling pathway, exported from IPA. NRF2 is a key modulator of oxidative stress responses. In response of oxidative stress, NRF2 is released into the nucleus and up-regulates downstream antioxidant enzymes, mainly drug metabolism enzymes.

From these

results it was conclude that to sustain highly

From these

results it was conclude that to sustain highly water soluble drug higher molecular weight intermediate ethoxyl content (48–49.5%) ethylcellulose polymer was more suitable. All authors have none to declare. Authors gratefully acknowledge the support of Department of Science and Technology, Nanomission (SR/NM/NS-101/2008), New Delhi for providing financial assistance. We also thankful to Aarti Drugs Pvt. Ltd. and Colorcorn Asia Pvt. Ltd. for providing Metformin hydrochloride and ethylcellulose respectively as gift samples. “
“Type 2 diabetes mellitus is a complex metabolic disorder that involves a huge number of pathophysiologic mechanism, including insulin resistance, decreased insulin secretion, and excess glucose production by liver among others.1 An oral hypoglycemic agent Repaglinide (REPA) is the first member of meglitinide class used in type 2 diabetes mellitus acts by binding to specific site on pancreatic β-cell click here and block ATP-dependent potassium channels to stimulate insulin release.2 Due to its short half-life (<1 h) required frequent dosing before meal and this may cause side effects

like headache, skeletal muscle pain and gastrointestinal effects.3 To enhance the bioavailability and decrease the side effects of REPA, a sustained release new drug delivery system is necessitate. Solvent evaporation, solvent diffusion, solvent extraction or any modification in the basic principle of emulsification technique produces the drug loaded controlled release nanoparticles of desired properties.4 Ethylcellulose this website (EC) is a non-biodegradable and biocompatible polymer which is extensively studied as encapsulating material for the controlled release of pharmaceuticals.5 and 6 A comparative study by Ubrich et al concludes that EC was efficiently sustained drug for maximum time than other polymers like PLGA and polycaprolactone.7 Therefore we selected EC as polymeric material for the preparation of repaglinide loaded ethylcellulose nanoparticles (REPA-EC

NPs). The aim of present study was to formulate REPA-EC NPs by solvent diffusion technique and characterize it. The characterization includes particle size and zeta potential determination, encapsulation efficiency, drug content, surface Montelukast Sodium morphology, drug–polymer interaction study by FTIR, comparative XRD, in vitro dissolution study and drug release kinetics determination by different models. Repaglinide (REPA) was kind gift from Wockhardt Research Centre (Aurangabad, India). Ethylcellulose (300 cps viscosity grade) procured from Sigma–Aldrich USA. Ethyl acetate was purchased from Merck (Mumbai, India). Polyvinyl alcohol (PVA, MW Approx. 1,25,000) from SD Fine Chem Ltd. (Mumbai, India). The experimental work was performed by using triple distilled water filtered with 0.22 μ membrane filter. REPA-EC NPs were prepared by emulsion solvent diffusion technique.

They may have ability to augments, restore,

They may have ability to augments, restore, PCI-32765 solubility dmso inhibit or help to produce the desired immune response.2 Immunomodulators include corticosteroids, cytotoxic agents, thymosin, and immunoglobulins. Some immunomodulators are naturally present in the body, and certain of these are available in pharmacologic preparations.3 Increasing number of people is adopting alternative systems of medicine owing to the irreversible effects of modern drugs and therapies.4 Hibiscus tiliaceus is a species of flowering tree in the mallow family, Malvaceae, that is native to the

old world tropics. H. tiliaceus leaf extracts are found to contain phenolic compounds, flavonoids, vitamin E and several derivatives of stigmasterol, which were identified in this extract. 5H. tiliaceus is used for treating dysentery ulcers and internal injury. Leaves are used to treat amoebic dysentery, infected wounds, flowers and leaves are used in inflammation, mutagenic diseases and hepatoprotective conditions. 6 As the plant is widely used in folk fore for the treatment of various conditions of immune system and so

far no pharmacological study has been carried out to prove the stimulatory actions of H. tiliaceus on immune system, therefore present study was undertaken using modern scientific techniques in experimental models of cellular and humoral immunity in animals. The collected plant material of H. tiliaceus was washed thoroughly in water, cut into small pieces and air dried for two weeks at 35–40 °C temperature. Extraction was done by using Soxhlet apparatus with selleck kinase inhibitor 70% methanol as solvent. The extract was concentrated under reduced pressure dried and stored in a dessicator for further studies. Pyrogallol was procured from Sigma–Aldrich Pvt. Ltd. India; Septilin syrup (Himalaya Ltd) procured from local market, and all other chemicals Buspirone HCl and reagents used were of analytical

grade, procured from SD fine chemicals Ltd., India. Male Wistar rats (150–200 g) were used. Animals were housed under standard conditions of temperature (23 ± 1 °C), 12 h light/dark cycle and fed with standard pellet diet (Mysore feeds, Bangalore, India.) and water ad libitum. The experimental protocol was approved by the Institutional Animal Ethical Committee of P. Rami Reddy Memorial College of Pharmacy prior to the commencement of research work. SRBC (sheep red blood cells) collected in Alsever’s solution, were washed three times in large volumes of pyrogen free 0.9% normal saline and adjusted to a concentration of 0.5 × 109 cells for immunization and challenge. Experimental rats were divided into five groups and each group consists of six animals (n = 6). Control group received a dose of pyrogallol 100 mg/kg i.p., once daily upto 7 days, while the normal group received only vehicle. Standard group received septilin syrup (1 ml/100 g), two groups received MLHT at a dose of 250 mg/kg and 500 mg/kg p.o.