24 Digital images were analysed using Sigma-Scan 2 0 software Th

24 Digital images were analysed using Sigma-Scan 2.0 software. The distance between the cemento–enamel junctions up to the height of alveolar bone of the first mandibular molar on the mesial side of the rat was recorded. Samples were homogenised in Trizol reagent (Invitrogen) for 1 min using a tissue homogenizer (Polytron-Agrgregate, Kinematica, Littau/Luzern, Switzerland) at maximum speed. Total RNA was isolated according to the manufacturer’s guidelines and quantified by a spectrophotometer. Cytoskeletal Signaling inhibitor The integrity of RNA was verified by agarose gel electrophoresis. Complementary DNA was prepared using 2 μg of total RNA and a reverse transcriptase. The primers used

in the experiments were the standard TaqMan (Applied Biosystems, Foster City, CA, USA) brand. The gene analysed were TNF-α

(primers: sense 5′ GGC ATG GAT CTC AAA GAC AAC C-3′ and antisense 5′-CAA ATC GGC TGA CGG TGT G-3′). Glyceraldehyde-3-phosphate dehydrogenase (GenBank NM_017008) was used as a housekeeping gene. Real-time polymerase chain reaction was carried out in the StepOne polymerase chain reaction cycler (Applied Biosystems, Foster City, CA, USA). The polymerase chain reaction conditions were 95 °C for 10 min, followed by 40 cycles at 95° for 10 s and 60 °C for 45 s. Real-time data were analysed using the Sequence Detector System 1.7 (Applied Biosystems, Foster City, CA, USA). Results are expressed as fold inductions compared with controls. Results www.selleckchem.com/products/Cyclopamine.html are presented as means ± SEM for the number of rats (n) indicated. The data were analysed by the unpaired Student’s t-test for two mean comparisons and one-way ANOVA (with Bonferroni post hoc test) for bone reabsorption and TNF-α expression. The level of significance was set at P < 0.05. Table 1 shows that the body weight and naso-anal length were 29% and 15% respectively, Dipeptidyl peptidase lower in MSG groups when compared with CTL (P < 0.05), however, the Lee Index was 8% higher in the MSG rats (P < 0.003). The retroperitoneal and perigonadal fat pads weight doubled in

MSG rats when compared with CTL rats (P < 0.0001, Fig. 1A and B). The neonatal MSG treatment did not influence the plasma concentration of glucose, NEFA and total CHOL (P > 0.05). However, in the MSG group plasma and TG concentrations were 3.0 and 4.0 times higher (P < 0.0001 and P < 0.0002), respectively than, CTL group ( Table 2). According to Fig. 2, alveolar bone resorption was 44% lower in obese-MSG group compared with CTL group (P < 0.01). In the presence of ligature, there was a significant increase in alveolar bone resorption in both groups CTL L and MSG L compared with CTL and MSG group respectively (P < 0.001). However, alveolar bone resorption in the MSG L animals was similar to that occurring in the CTL group (P > 0.05) ( Fig. 3A–D). The TNF-α gene expression in periodontal tissue was similar in MSG and CTL animals in the absence of ligature (P > 0.

Cases related to genetic mutations and metabolic abnormalities ha

Cases related to genetic mutations and metabolic abnormalities have also been described, although at least some of these cases also exhibited associated structural malformations. Even in some cases when no structural

lesion was evident on cranial imaging, postmortem examinations demonstrated evidence of a migration disorder or dysgenesis that was not previously appreciated on neuroimaging [3] and [16]. A variety of structural malformations have been associated with Ohtahara syndrome, including hemimegalencephaly [11] and [17], agenesis of the corpus callosum [3] and [8], porencephaly [8], agenesis of the mamillary bodies [18], and dentato-olivary dysplasia [17]. Hypoxic injury [3], cortical dysplasias, and cerebral migration disorders are also frequently described [16], [19] and [20]. Metabolic disorders that were reported to accompany E7080 Ohtahara syndrome include BAY 80-6946 in vivo nonketotic hyperglycinemia [3], cytochrome C oxidase deficiency [21], pyridoxine dependency, carnitine palmitoyltransferase deficiency [11], and a case of Leigh encephalopathy [22]. More recently, a patient with biotinidase deficiency [23] and two patients with mitochondrial respiratory chain complex I deficiency were described [24] and [25]. One of the patients with respiratory

chain complex I deficiency also manifested microcephaly, thinning of the corpus callosum, and cortical atrophy [24]. The other patient with a similar complex 1 deficiency demonstrated normal cranial imaging [25]. Deficiencies in cytochrome C oxidase or respiratory chain complex I may result in energy depletion during development, in turn leading to demyelination and abnormalities in neuronal migration [26]. Underlying genetic mutations have been increasingly reported with Ohtahara syndrome. Mutations in the syntaxin binding protein 1 (STXBP1) gene, for example, have been described in Ohtahara syndrome since 2008 [27]. A proportion of patients with known

Ohtahara syndrome is now thought to manifest underlying STXBP1 mutations, although the exact number of such patients has varied from study to study, ranging from 10-13% [28] and [29] to 38% in the original report [27]. Similarly, mutations of the Aristaless-related homeobox (ARX) gene Adenosine triphosphate have also been associated with Ohtahara syndrome [30], [31] and [32]. In keeping with the close relationship between the age-dependent epileptic encephalopathies, mutations in both ARX and STXBP1 have also been described in patients with West syndrome [28], [29] and [31]. Finally, two reports described patients with Ohtahara syndrome who had mutations in the solute carrier family 25 (SLC25A22) gene. Both patients were born to consanguinous parents [33]. As with the metabolic disturbances, the mechanisms by which these genetic abnormalities cause Ohtahara syndrome are thought to be related to brain dysgenesis or neuronal dysfunction.

No significant reduction in cervical cell viability was observed

No significant reduction in cervical cell viability was observed in the samples that were subjected to a delayed processing compared to those processed immediately ( Table 2). Because of the low yield of cells that can be recovered by cytobrush from the female genital tract (Nkwanyana et al., 2009), few studies have evaluated the feasibility and impact of cryopreservation on cell recovery and viability. We compared the number of CD3+

T cells isolated from the cervical cytobrushes of 13 HIV-infected women before and after storage in liquid nitrogen. In these samples, the median CD3+ T cell number obtained ex vivo was 75 280 (IQR 37 240–90 560), while VE-821 manufacturer a significantly lower median of 22 664 [(IQR 13 968–44 672); 48.7% recovery; p = 0.005] was recovered after thawing. Measurements of CD3+ event counts after ICS or CD3+ T cell numbers by Guava similarly showed that T cell numbers were relatively stable over the 24 h period at 37 °C, 4 °C and room temperature but

that there was a significantly lower T cell yield after cryopreservation. Annexin V and PI staining were used to evaluate the viability of CD3+ T cells before freezing and after thawing (Fig. 1). Fig. 1A shows a representative plot of Annexin V versus PI staining of CD3+ T cells from a cervical cytobrush sample. A median value of 99.5% (IQR 96.16–100.0%) of cervical cytobrush-derived CD3+ cells were viable ex vivo; of which, 18.3% co-expressed the late apoptotic markers Annexin V and PI (IQR 6.5–44.3%), 9.8% expressed Annexin V only and not PI indicating early apoptosis (IQR 3.3–15.7%; Annexin + PI−), while 61.4% were not apoptotic and lacked selleckchem expression of either marker ( Fig. 1B; IQR 39.3–82.60%). We found that only a small proportion of the cervical T cells were dead [1.0% Annexin V-PI+; IQR 0–3.2%; Fig. 1B]. After thawing cervical cytobrush cells taken from HIV-infected women, we found that 96.9% (IQR 89.3–99.4) Oxymatrine of CD3+ cells recovered were viable and a comparable proportion of thawed cells expressed early or late apoptotic markers Annexin V and PI as found on ex vivo T cells ( Fig. 1B).

If thawed cells were rested overnight (as is a common practise with thawed PBMCs prior to functional analysis), we found that the majority of CD3+ T cells were co-expressing late apoptotic markers Annexin V and PI (78.5% IQR 78.3–78.6) indicating that they were in the process of undergoing apoptosis. When we compared the impact of thawing and resting on cervical cytobrush cell viability from women who were not infected with HIV ( Fig. 1B; n = 2), we found that viability of thawed cells was comparable to HIV-infected women but that CD3+ T cells from uninfected women did not exhibit the massive increase in expression of apoptotic markers after resting as was noted in cytobrush samples from HIV-infected women. From this data, conducting analyses on HIV-infected samples is best performed immediately after thawing.

This appearance indicates the occurrence of protein denaturation,

This appearance indicates the occurrence of protein denaturation, which is compatible with the action of proteases. Furthermore, our study showed no evidence of significant vascular thrombosis or hemorrhage at any time, which reinforces the hypothesis that the venom induces tissue necrosis probably by the direct action of toxins/enzymes ( Barbaro et al., 2007). Envenomations caused by some species of snakes (Gutiérrez et al., 2005 and Moura-da-Silva et al., 2007), spiders (Ospedal et al., 2002 and Hogan et al., 2004) and fish (Lima et al., 2003 and Pareja-Santos

et al., 2009) are also characterized by severe local tissue damage. The venom of these animals has enzymes involved in the pathogenesis of local myonecrosis, skin

damage with intense inflammatory reaction. Barbaro et al. (2007) showed that P. falkneri tissue extract contains enzymes capable of degrading www.selleckchem.com/products/AZD2281(Olaparib).html distinct proteins such as casein, gelatin and fibrinogen. These data suggest that such proteases could contribute to degradation of proteins and extracellular matrix components, favouring the establishment of local injury. Additionally, the detection of hyaluronidase activity in Potamotrygon tissue extract seems to constitute Raf inhibitor strong evidence that in this genus there is an amplification of the local damage caused by toxins as well as of the injury caused by the stinger ( Haddad et al., 2004, Barbaro et al., 2007 and Magalhães et al., 2008). Other species of Potamotrygon genus (Potamotrygon cf. scobina and P. gr. orbignyi) can also cause necrosis as reported by Magalhães et al. (2006). The authors also observed that the mucus, which covers the animal, could augment this necrotic activity. Secondary infection is usually found in patients injured by marine (Clark et al., 2007 and Dehghani et al., 2009) or freshwater (Haddad et al., 2004) stingrays. In our experiments, two samples showed bacterial infection, one 24 h and the other 96 h after venom injection indicating that the site of injury becomes a breeding ground for bacterial contamination. Studies are being conducted to determine

which bacterial strains are more commonly associated with this type of envenoming. In conclusion, the toxins found in the tissue covering the stingers of P. falkneri were able to cause Terminal deoxynucleotidyl transferase severe local damage, characterized mainly by early necrosis. The association of the action of these toxins with the mechanical trauma caused by the stinger can explain the local necrosis and the severe sequelae observed in humans injured by freshwater stingrays. The authors declare that there are no conflicts of interest. This work was supported by FAPESP (07/55272-4). The authors thank Danieli M. Rangel, for technical assistance and Miss Ottilie Carolina Forster and Dr Maria José Alencar Vilela, who provided some of the conditions to develop this work.

Apheresis is also used for peripheral hematopoietic progenitor ce

Apheresis is also used for peripheral hematopoietic progenitor cell collection. The procedure can be safely performed in most children with modifications to account for smaller pediatric blood volumes. Index 1581 “
“Harold S. Pine Sharon D. Ramos, Shraddha Mukerji, and Harold S. Pine Adenotonsillectomy (AT) is one of the JQ1 solubility dmso most common pediatric surgical procedures performed in the United States; more than 530,000 are performed annually in children younger than 15 years of age. AT was traditionally performed for recurrent tonsillitis and its sequelae but in recent times,

sleep-disordered breathing/obstructive sleep apnea in children has emerged as the primary indication for surgical removal of adenoids and tonsils. The new guidelines used by clinicians to identify children who are appropriate candidates for AT address indications based primarily on obstructive and infectious causes. Elton Lambert

and Soham Roy The placement of myringotomy tubes remains an effective treatment of recurrent acute otitis media and chronic otitis media check details with effusion. Infants and young children are prone to these entities because of their immature anatomy and immunology. Several host, pathogenic, and environmental factors contribute to the development of these conditions. The identification and modification of some these factors can preclude the need for intervention. The procedure continues to be one of the most common outpatient pediatric procedures. Close vigilance and identification of potential complications is of utmost importance in the ongoing http://www.selleck.co.jp/products/Gemcitabine(Gemzar).html management of the child with middle ear disease. Nathan S. Alexander and James W. Schroeder Jr Pediatric obstructive sleep apnea syndrome (OSAS) is a common health problem diagnosed and managed by various medical specialists, including family practice physicians, pediatricians, pulmonologists, and general and pediatric otolaryngologists. If left untreated, the sequelae can be severe. Over the last decade, significant

advancements have been made in the evidence-based management of pediatric OSAS. This article focuses on the current understanding of this disease, its management, and related clinical practice guidelines. Joseph L. Russell, Harold S. Pine, and Dayton L. Young Cochlear implantation is a revolutionary yet time-sensitive treatment for deaf children that must be performed within a critical window of time, in early life, for a congenitally deafened child to receive maximum benefit. Potential candidates should therefore be referred for evaluation early. Primary reasons for delay of cochlear implantation include slow referrals for care, parental delays, and payer delays.

, 2006) The first PC from PCA applied to SPI fields explained a

, 2006). The first PC from PCA applied to SPI fields explained a high percentage of the total variance at all time scales analyzed and represented its average areal behavior. In PC1n (t) time series, n = 6, learn more 12 and 18 months, the T-PC1 from SSA was associated

with a positive nonlinear trend, whose low frequency behavior showed changes to wetter conditions from 1960 to 2000s, subsequent signs of stabilization and a trend reversal since the first decade of 21st century. The largest and more severe hydrological and agricultural droughts in the NEA occurred between 1901 and 1960 while a period of wet EPE of long duration and high intensity was recorded between years 1970 and 2005, causing the worst floods of the 20th century. Moreover, an extended period with very dry conditions was registered between 1921 and 1939 that might

extend the “Pampas Dust Bowl” to the bulk of the NEA. Almost the entire NEA—except the Northwestern corner—showed SPI18 (t) series whose low-frequency time response presented a nonlinear positive trend and oscillatory pairs with dominant periods T = 6.5 years and 8.7 years, determining the periodicity Sirtuin activator of EPE in the region. The Northwestern corner of the study region showed a possible oscillatory pair of very low frequency, an important cycle of 6 years and a quasioscillatory mode with T = 11.25 years/cycle. Our results showed that the linear combination of PC118 (t), PC218 (t) and PC318 (t) allowed an adequate reproduction of a high percentage of low frequency variance of EPE over an extensive area of NEA, especially in the West-Central zone, where the proportion of accounted variance was between 70 and 80%. The low frequency behavior of wetness area coverage time series showed

a remarkable nonlinear trend, particularly at longer time scales, with a trend reversal in the last years of the 2000s. This feature is similar to that found in the average areal behavior see more of SPI fields, suggesting that wet EPE of higher severity noted between 1970 and 2003 begin to decline. The most intense hydrological extremely wet events were recorded in the wet period of the late 20th century, with extraordinary peaks in October 1973 (consistent with strong El Niño event) and March 2003 (consistent with a moderate El Niño event). This last event caused the most catastrophic flood of the Salado Basin. On the other hand, no well-defined nonlinear negative trends were found in drought area coverage time series. Instead, this last series, presented an important oscillatory cycle with a dominant period of 6 years, showing a periodicity of extremely drought condition in the region, particularly differentiated in the first half of the 20th century.

There is increasing evidence that both trabecular and cortical bo

There is increasing evidence that both trabecular and cortical bone are important determinants of strength in patients with osteoporosis who experience fracture [3], [4], [5] and [6]. Assessing both trabecular and cortical bone is important as these compartments may lose or gain bone differently with aging and in response to therapies, impacting their specific relative contributions to bone strength [7], [8] and [9]. The amounts of

both trabecular and cortical bone decrease as osteoporosis progresses; however, as trabecular bone disappears with increasing bone loss, the extent to which the cortical compartment contributes to bone strength increases [8], [9] and [10]. Use of new image acquisition and analysis techniques can provide information on the effects of treatments on bone density and geometrical changes in the trabecular and cortical compartments. Quantitative computed tomography (QCT) complements DXA by GSK126 mw 3-dimensionally measuring Natural Product Library in vitro volumetric BMD (vBMD) and bone mineral content (BMC), commonly referred to as bone mass; these can be measured not only within the total bone

but also separately in the individual bone compartments [2] and [11]. Denosumab (Prolia®; Amgen Inc., Thousand Oaks, CA, USA) is a fully human monoclonal antibody that inhibits RANKL, a key modulator of osteoclast formation, function, and survival [12], [13], [14] and [15]. The mechanism of action of denosumab leads Protirelin to rapid and maximal reductions in bone resorption throughout the trabecular and cortical compartments [16]. Clinical trials, including

the FREEDOM (Fracture REduction Evaluation of Denosumab in Osteoporosis every 6 Months) study, have established that denosumab treatment results in a significant improvement in DXA aBMD at the hip in the majority of subjects [17], [18], [19], [20], [21], [22] and [23], and these gains significantly explained the observed fracture risk reductions [24]. Areal BMD gains are influenced by both trabecular and cortical changes, which cannot be precisely distinguished with DXA. In view of the strong association between gains in aBMD and the fracture risk reductions observed with denosumab treatment, and that both trabecular and cortical bone determine whole-bone strength, we have hypothesized and previously demonstrated using standard QCT analysis software that total hip BMD changes associated with denosumab would be apparent in both the trabecular and cortical compartments [25]. To further document and characterize the magnitude and distribution of the changes in BMD and BMC at the hip, and understand the relative contribution of each compartment, including the subcortical compartment, we applied Medical Image Analysis Framework (MIAF) software to hip QCT scans obtained in a subset of women who participated in the FREEDOM study. MIAF improves the 3D segmentation of the hip, and thus provides a more comprehensive method to evaluate integral and compartment changes [26] and [27].

3 and 6 However, how

3 and 6 However, how Alectinib molecular weight these events

are involved in the formation of cystic cavities and resorption of adjacent bone continues to be a matter of numerous researches. In this respect, altered expression of bone metabolism-related factors may favour an increase in osteolytic activity and the consequent cystic expansion into adjacent bone tissue. Odontogenic cysts are one of the most common osseous-destructive lesions affecting the jaws.7 and 8 They are classified traditionally into a developmental group, including dentigerous cysts, and an inflammatory group including radicular and residual cysts.4, 7 and 8 Developmental cysts are of unknown origin, but do not appear to result from an inflammatory process. On other hand, the inflammatory cysts, as their name implies, are associated with inflammation.8 Both radicular and dentigerous cysts can show a range from little to quite extensive primary/secondary inflammation4 and it is possible that the variation seen in the fibrous capsule of these cysts might reflect differences in the osteolytic activity. Moreover, the presence of hemorrhagic areas in the fibrous capsule of dentigerous cyst could also contribute to the

increase of osteolytic activity. Recent studies suggest an important role of receptor activator of nuclear factor-κB (RANK), RANK ligand (RANKL) and osteoprotegerin (OPG) in the pathogenesis of oral lesions characterised

by bone resorption.9, 10, 11, 12, 13, 14, 15, 16 and 17 Most of the bone diseases are ABT-263 datasheet caused by a disturbance in the number and activity of osteoclastic cells, resulting in improper bone resorption which exceeds the compensatory capacity of osteoblasts.18 and 19 Increased osteoclast activity is seen in many osteopenic disorders such as postmenopausal osteoporosis, Paget’s disease, bone metastases and rheumatoid arthritis.6, 17, 19 and 20 RANK, RANKL and OPG are key regulators in osteoclast biology and bone metabolism.21 and 22 RANKL interacts with its receptor RANK located on osteoclast precursors and dendritic cells, and activates c-Jun, O-methylated flavonoid NFkβ pathways that are related to the process of differentiation, proliferation and activation of osteoclasts.18 The effects of RANKL are blocked by soluble decoy receptors such as OPG that competes with RANK for binding to RANKL.18, 19 and 21 In vitro and in vivo studies have shown that RANK/RANKL/OPG are essential for the life of osteoclasts and, as mediators of bone diseases, are important molecular targets for diagnosis and therapeutic intervention.18 and 22 Thus, the aim of this study was to evaluate and compare the immunohistochemical expression of RANK, RANKL and OPG in radicular (RC) and dentigerous cyst (DC).

Two hundred nanograms of total RNA were reverse transcribed in a

Two hundred nanograms of total RNA were reverse transcribed in a 10 μl reaction volume. One microliter

of the RT reaction (equivalent to 20 ng of RNA) was subsequently used for the PCR, as described previously ( Cunningham et al., 2007). The housekeeping gene glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was measured in each sample using Applied Biosystems Rodent GAPDH Taqman Kit. All PCR data were normalised to the expression of GAPDH. More detailed description of these methods, and full primer sequences, are available in supplemental information. Core body temperature was measured using a thermocouple Compound C datasheet rectal probe (Thermalert TH5, Physitemp, Clifton, New Jersey). Temperature measurements were made on three separate occasions in the week prior to poly I:C injections to habituate mice to the procedure and thus minimise the effects of stress. Temperatures were recorded at baseline and then at 4, 9, 13 and 24 h

following i.p. challenge with poly I:C. Following systemic challenge with poly I:C, ME7 or NBH-inoculated mice were assessed for their co-ordination of motor function. The horizontal bar was designed to assess forelimb muscle strength and co-ordination, and consisted of a 26 cm long metal bar, 0.2 cm diameter, supported by a 19.5 cm high wooden column at each end. Each mouse was held by the tail, placed with its front paws at the central point of the bar, and rapidly released. Mice were scored based on whether they fell, held on for 60 s, or reached a platform on a supporting column, Selleck ISRIB with the latter two results scoring the maximum of 60 s. The inverted screen (Kondziela, 1964) assessed muscular strength for all four limbs. It consisted of a wooden frame, 43 cm square, covered with wire mesh (12 mm squares of 1 mm diameter wire). The mouse was placed on the screen and this was then slowly inverted.

The time it took for the PIK-5 mouse to fall was measured, up to a criterion of 60 s. Padding was provided to cushion mice falling from either apparatus. Behavioural data was analysed by repeated measures ANOVA with Bonferroni post hoc analysis after significant main effects. Peripheral ELISA data and CNS transcription data were analysed by two-way ANOVA with ME7/NBH and poly I:C/saline or time post-poly I:C as factors, with Bonferroni post hoc tests. One-way ANOVAs were also performed where the inclusion of multiple time points post-poly I:C did not allow a full factorial analysis. Cell counts were analysed by one-way ANOVA for IBA-1, IL-1β and TUNEL. Intra-peritoneal treatment of NBH and ME7 animals (18 weeks post-inoculation) with poly I:C resulted in the robust transcription of IFNβ in the hippocampus 6 h following administration of poly I:C (Fig. 1a). IFNβ was transcribed more robustly in ME7 animals than in NBH animals given the same poly I:C challenge. There was an effect of disease (F = 7.93, df 1, 14, p = 0.0137), an effect of poly I:C (F = 17.

The inhibition activity of quercetin is not significantly altered

The inhibition activity of quercetin is not significantly altered if the hydroxyl at position 3 is conjugated with glucose to generate isoquercitrin, but it loses half of its potency if this position is conjugated with rhamnose, as in quercitrin (da Silva et al., 2012a). Structural analysis from docking studies (Fig. 3) showed hydrogen bond (H-bond) interaction

between ARG-L and the substituent at the 3-positions present in isoquercitrin (quercetin-3-O-β-glucoside) and quercitrin (quercetin-3-O-rhamnoside) that inhibit ARG-L by a noncompetitive mechanism, where an inhibitor binds to both the enzyme-substrate Alectinib complex or to the free enzyme. The higher docking energies were observed just for these 2 compounds ( Table 2). In C-glucosides, such as orientin (luteolin-8-C-glucoside) and isoorientin (luteolin-6-C-glucoside), the glucoside group does not show any interaction with ARG-L residues, and both are uncompetitive inhibitors which bind exclusively to the enzyme–substrate complex, resulting in an inactivated enzyme–substrate–inhibitor complex. The aglycones fisetin and luteolin show common H-bonds with residues Asp245 and Ser150, and quercetin is a unique compound that shows H-bonding with His28 and Glu197. These three aglycones showed mixed see more inhibition

of ARG-L. In conclusion, the three mechanisms of inhibition shown here for these compounds were closely related to the absence or presence of a glucoside in the 3-O-glucoside position, where mixed and noncompetitive inhibition are observed, respectively, while the C-glucoside showed an uncompetitive inhibition. There are now multiple targets that have been described for the leishmanicidal action of flavonoids. Quercetin inhibits ARG-L and ribonucleotide reductase (da Silva et al., 2012a and Sen et al., 2008). Quercetin induces cell death by increasing second ROS (reactive oxygen species) and causing mitochondrial dysfunction in L. (L.) amazonensis ( Fonseca-Silva, Inacio, Canto-Cavalheiro, & Almeida-Amaral, 2011).

Luteolin and quercetin promote apoptosis mediated by topoisomerase II, resulting in kinetoplast DNA cleavage in L. (L.) donovani ( Mittra et al., 2000). The E  docking ( Table 2) results support the IC50 ( Table 1) data obtained from the aglycones and glycoside flavonoids. The only exception was that 7,8-dihydroxyflavone had an IC50 lower than those of kaempferol and galangin. Docking suggested interactions between the flavonoids and the amino acids Asp137, Asp141, Asp243, Asp245 and His139 (ARG-L numbering) that are involved in metal bridge MnA2+-MnB2+ coordination in the active site of arginase ( Kanyo et al., 1996). Another important interaction can be attributed to His154, which is a conserved amino acid involved in substrate binding ( Ash, 2004). His 139 and His 154 showed hydrophobic intermolecular interactions with several flavonoids ( Fig. 3).