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Background: Theileria spp. were targeted for detection and differentiation from clinical samples using PCR in the current investigation and the diagnostic sensitivity of this method was evaluated in comparison to microscopic observations. The clinical characteristics of bovine tropical theileriosis as clinical markers were also analysed based on the PCR data. Methods: On the basis of clinical evaluation and microscopic inspection of blood smears, 200 blood samples from cattle suspected of having theileriosis were examined. To confirm the disease, the PCR method was employed by using 18S rRNA and Cyto b1 gene to confirm Theileria spp. and Theileria annulata respectively in clinical samples. Result: The results showed that microscopic examination detected 65/200 (32.50%), whereas, the PCR assay identified 120/200 (60.00%) for Theileria spp. Of the total 200 samples studied, 77 (38.50.3%) were positive for T. annulata specific PCR. Based on PCR confirmation of T. annulata infection in cattle, the predominant clinical signs were pyrexia, ticks’ infestations, anorexia, enlargement of lymph node, pale mucous membrane, lacrimation, coughing, drop in milk production and emaciation. The other clinical signs were observed as icterus, nasal discharge, salivation, melena and exophthalmia.

AIMS Endophytes are a rich source for structurally complex chemical scaffolds with interesting biological activities. Endophytes associated with Brugmansia aurea L. (family: Solanaceae), a medicinal plant, have not yet explored for the bioactive metabolites. METHOD AND RESULTS Hence, Macrophomina phaseolina, a fungal endophyte, was isolated from the roots of the plant. Its methanolic extract was found active against human cancer cell lines with IC50

Background As per the recent statistical reports of World Health Organisation (WHO), 13% of total global population is obese. Orlistat remains to be the only drug approved for the long term treatment of obesity. Recent findings highlighted severe adverse effects of orlistat that included hepatotoxicity, gall stones, kidney stones and acute pancreatitis. Therefore, search for new drug is required. The investigations based on endophytic natural products would prove pivotal in the global fight against this health issue. Methods Obesity is associated with lipid metabolism involving pancreatic lipase enzyme. The inhibition of pancreatic lipase is demonstrated by using the extracts of endophytes isolated from Viola odorata Linn. In addition, endophytes were identified using ITS based rDNA sequencing. Results Present study involves the isolation and identification of 27 endophytes from V. odorata. All the endophytes were evaluated for lipase inhibitory activities. The extracts of seven endophytes exhibited lipase inhibitory activity with IC50

A safe school environment is central to learners' academic performance and holistic development. This article reports on part of a study that sought to identify the forms of learner aggression, the contributory factors to aggression, the consequences and psychological effects of learner aggression and the identification of strategies that can help to manage learner aggression in rural secondary schools in the Empangeni district of KwaZulu-Natal. A qualitative research design was deemed to be most appropriate for the purpose of this study and interviews were conducted with principals, teachers and students in the selected schools. The findings identify a number of psychological responses of victims to learner aggression and the consequences of learner aggression in schools, which have had a negative impact on the quality of teaching and learning in these schools. This research concluded that the consequences of learner aggression are devastating, have a serious effect on the victims mental health and leads to high levels of stress, anxiety, depression and even suicide.

The genotoxic potential of anti-inflammatory/anti-arthritic and anticancer plant based drug molecule Boswelic acids (BA) was studied by in vivo system. Systematic literature survey revealed that studies on the genotoxicity of BA are not available. Although reports on genotoxicity of Boswellia serrata dry extract and modified 3-O-acetyl-11-keto-β-boswelic acid are available and these studies were conducted in in vitro systems. The earlier general toxicity study of BA has been conducted by us, revealed it to be non toxic. The genotoxicity was carried out in Wistar rats using different cytogenetic assay system-abnormalities viz. chromosomal aberrations; sperm morphology, micronuclei and comet assays. Six groups of animals, each comprised of five rats, were taken for each study. Group1-4 received BA at 125, 250, 500 and 1000 mg/kg p.o., respectively prepared as 2% gum acacia suspension, fifth group received a positive control cyclophosphamide (CP) 40 mg/kg p.o. or metronedazole (MTZ) 130 mg/kg p.o. or mercuric chloride (HgCl2) 0.864 mg/kg p.o. (as per the experiment requirement) whereas the sixth group kept as vehicle control. The results on the bases of the data obtained revealed that BA is quite safe as it did not show any genotoxicity at any dose level up to 1000 mg/kg. The positive controls used in different experiments showed highly significant abnormal cytogenetic changes in comparison to the control group.

The Euphorbia hirta ethanolic extract (EH A001) was found to possess a prominent anti-anaphylactic activity. A preventive effect of EH-A001 given by oral route at dose from 100 to 1000 mg/kg was observed against compound 48/80-induced systemic anaphylaxis. At the same range of dose, EH-A001 inhibited passive cutaneous anaphylaxis (PCA) in rat and active paw anaphylaxis in mice. A suppressive effect of EH-A001 was observed on the release of TNF-alpha and IL-6 from anti-DNP-HSA activated rat peritoneal mast cells.

Taking lead from a naturally occurring quinazolin vasicine, a number of compounds were developed and evaluated for bronchodilator and anti-allergic activities. One of these compounds was 2,4-diethoxy-6,7,8,9,10,12-hexahydroazepino[2,1-b]quinazolin-12-one, hereinafter named 95-4, exhibited marked bronchodilator activity evaluated on contracted trachea or constricted tracheo-bronchial tree. On intestinal smooth muscle too it showed relaxant effect. Tracheal relaxant effect was not found to be mediated through β-adrenoceptors. Cumulative dose–response study with acetylcholine and histamine indicated for its non-specific direct effect on smooth muscles. 95-4 was found to be more potent than theophylline and less to that of salbutamol on dose basis. Tested by a number of experimental models, it was found devoid of anti-allergic activity. It was also found to be free from any adverse effect. 95-4 due to its marked bronchial muscle relaxant effect can find use in conditions associated with spasm of bronchial muscles.

To analyze changes in mandibular form associated with an inverted-L osteotomy and autogenous bone graft, preoperative, early postoperative (EPO), and late postoperative (LPO) lateral cephalographs of 14 children (mean age approximately 9 years) with unilateral craniofacial microsomia (CFM) were scanned and nine mandibular landmarks digitized. Average mandibular geometries, scaled to an equivalent size, were generated using Procrustes superimposition. Cephalometry, Euclidean distance matrix analysis (EDMA), and thin-plate spline (TPS) analyses were carried out on mean mandibular configurations. Cephalometric results showed increases in oblique mandibular length (approximately 9% on average, P < 0.05) and increased ramus height (P < 0.05). Similarly, using EDMA there were also significant differences (P < 0.05) between the mean preoperative, EPO, and LPO configurations. The most demonstrable EPO change in the mandibular configuration using EDMA was increased oblique length (approximately 11%). This improvement depended on ramus oblique lengths increasing by approximately 26%, ramus height increasing by approximately 25%, and mandibular body length increasing by approximately 5%. For TPS analysis, affine and nonaffine changes contributed to the total spline. In all three comparisons the affine transformation showed an antero-inferior rotation of the mandibular configuration. For nonaffine changes the EPO configuration indicated a supero-inferior stretch of the mandibular configuration. The nonaffine LPO changes maintained the supero-inferior stretch of the mandibular configuration. It is concluded that improvements in the lateral facial profile of CFM patients can be achieved using an inverted-L osteotomy, with little relapse approximately 2 years postoperatively.

Thirty mandibular landmarks were digitized from cephalographs of 46 children (prepubertal, approximately 10 years old) and 53 adolescents (pubertal, approximately 13 years old) to determine mandibular morphological changes in patients with Class II Division 1 malocclusions treated with Twin-block appliances. Procrustes superimposition computed average geometries and an analysis of variance were performed on the cephalographs. Prepubertal pretreatment and approximately 13-month-posttreatment profiles and pubertal pretreatment and approximately 22-month-posttreatment profiles were statistically different (P

This paper presents a method for minimizing the sum of the square of voltage deviations by a least-square minimization technique, and thus improving the voltage profile in a given system by adjusting control variables, such as tap position of transformers, reactive power injection of VAR sources and generator excitations. The control variables and dependent variables are related by a matrix J whose elements are computed as the sensitivity matrix. Linear programming is used to calculate voltage increments that minimize transmission losses. The active and reactive power optimization sub-problems are solved separately taking advantage of the loose coupling between the two problems. The proposed algorithm is applied to IEEE 14-and 30-bus systems and numerical results are presented. The method is computationally fast and promises to be suitable for implementation in real-time dispatch centres.

The synthesis and hydration of glycosaminoglycans (GAG) has been implicated in the generation of a palatal shelf-elevating force in mammals. This study quantifies the GAG composition in the palatal shelves of Wistar rat fetuses at various stages of palatogenesis. Hyaluronan, heparan sulphate and chondroitin-4-sulphate were detected but not dermatan sulphate or chondroitin-6-sulphate. The distribution of the GAG differed in the anterior and posterior regions (i.e. the presumptive hard and soft palates) and with the stage of development. At the time of palatal-shelf reorientation, there were no significant differences for either the total amount of GAG or for the percentages of specific GAG types between anterior and posterior regions. Indeed, the most marked differences were detected at the stages of histogenesis after shelf elevation. Nevertheless, the results support the view that hyaluronan is involved in palatal-shelf reorientation, its percentage being initially high and decreasing after shelf elevation. No changes were detected for the other (sulphated) GAG during the time of elevation. The findings point to the need to correlate the events during histogenesis with changes in the ground substance of palatal-shelf mesenchyme and indicate that there are different developmental mechanisms within the presumptive hard and soft palates.

The parents of an Indonesian patient were concerned with the facial appearance of their child. A medical, family and social history was taken for the patient with the detection of no specific, systemic abnormalities or unusual conditions, although it was noted that the family lived in an area associated with pollutants. On examination, the facial appearance was asymmetric with inferior displacement of the right eye. The zygomatic-maxillary region appeared to be enlarged and deformed. There was unilateral macrostomia with the upper lip appearing elongated. Intra-oral examination revealed that there was duplication of the maxilla and associated structures. The maxilla had a normal complement of deciduous teeth but gross caries was noted. A supernumerary maxilla appeared to be responsible for the extra-oral, zygomatic-maxillary deformation, and its deciduous dentition was incomplete intra-orally. For the mandibular structures, the tongue was abnormally small, giving the appearance of microglossia. The mandibular dentition appeared to be incomplete with gross caries. Further posteriorly, there appeared to be clefting of the individual soft palates. Photographs and radiological examinations were undertaken but CAT scans were not possible. For patient management, a comprehensive surgical strategy is indicated with full family support, education and cooperation.

Etoposide, a semi-synthetic derivative of podophyllotoxin, is widely used anticancer agent. Etoposide presents low bioavailability with wide inter-, and intra-patient variability after oral dosing. In an earlier study a piperine analogue, namely, 4-ethyl 5-(3, 4-methylenedioxyphenyl)-2E,4E-pentadienoic acid piperidide (PA-1), was shown to cause 2.32-fold enhancement of the absolute bioavailability of co-dosed etoposide in mice. In the present investigation a mechanistic evaluation was undertaken using various in vitro and animal-derived models. In everted rat gut sac studies PA-1 enhanced mucosal uptake of the drug while it inhibited efflux of Rh-123, a P-glycoprotein substrate from serosal-to-mucosal direction. In a single pass in situ perfusion experiment PA-1 significantly reduced the intestinal exsorption rate, exsorption clearance and the total plasma clearance of etoposide. On the other hand PA-1 did not alter the passive diffusion pattern of the drug in PAMPA assay. PA-1 was inhibitory to NADPH-assisted deethylation and demethylation reactions catalyzed by erythromycin N-demethylase, 7-methoxycoumarin-O-demethylase (MOCD) and ethoxyresorufin-O-deethylase (EROD). PA-1 was not cytotoxic to mucosal membrane and showed no adverse effect in acute toxicity determination. The results suggested that PA-1-mediated enhancement in the oral bioavailability of etoposide could possibly be due to its ability to modify P-gp/CYP 3A4 mediated drug disposition mechanisms.

An immunopharmacological profile of 2, 7-dimethyl-3-nitro-4H pyrido [1,2-a] pyrimidine-4-one (P-I) has been investigated using in vitro and in vivo models representing various features of Type I allergy. P-I prevented compound 48/80-mediated histamine release from rat peritoneal mast cells. A promising anti-inflammatory activity of P-I was evident in active paw anaphylaxis (mice) and carragenan-induced paw edema (rat). P-I inhibited eosonophil accumulation and eosinophil peroxidase activity in bronchoalveolar lavage fluid from ovalbumin challenged balb/c mice: in these animals blood levels of IL-5, and CD4+ T cells also remained attenuated. A promising bronchorelaxant effect of P-I was observed in histamine-contracted guinea pig tracheal chain via its antagonism to H1 receptor. These findings were compared with some known compounds (ketotifen, cetirizine and promethazine). The anti-histaminic, anti-inflammatory and bronchorelaxant activities of P-I has been discussed in context with its potential profile as an anti-allergic and anti-asthmatic agent.

Three-dimensional imaging techniques, such as computed tomograms (CT), structured light, and stereophotogrammetry, can be used to capture three-dimensional coordinate data, but comprehensive analysis is required to transform these techniques into powerful diagnostic tools. The object of this review is to highlight analytical functionality using software developed to study three-dimensional digital imaging and communications in medicine (DICOM) based digital data for diagnosis, planning of treatment, and evaluation of craniofacial changes. My specific aim was to apply three-dimensional software routines using geometric morphometrics or conventional measurements. These routines rely on robust algorithms to construct mean objects by manipulating the three-dimensional x , y , and z coordinates of all the objects’ vertices. Conventional measurements and statistical tests can then be applied to the changes in the vertices, say, before and after treatment. Using graphical and geometric morphometric techniques such as finite-element analysis and principal components analysis, clinical craniofacial modelling can be used for the localisation and quantification of soft and hard tissue changes; diagnostic modelling can be undertaken for planning of treatment, and data-driven predictive modelling can be undertaken for the planning of many procedures based on the surgeon's own experience, patients, and resources. Three-dimensional modelling of digital data may therefore have added value for clinical diagnosis, and planning and assessment of treatment, including audit.

Betulinic acid (BA) is a pentacyclic triterpenoid natural product reported to inhibit cell growth in a variety of cancers. However, the further clinical development of BA got hampered because of poor solubility and pharmacological properties. Interestingly, this molecule offer several hotspots for structural modifications in order to address its associated issues. In our endeavor, we selected C-3 position for the desirable chemical modification in order to improve its cytotoxic and pharmacological potential and prepared a library of different triazoline derivatives of BA. Among them, we previously reported the identification of a potential molecule, that is, 3{1N(5-hydroxy-naphth-1yl)-1H-1,2,3-triazol-4yl}methyloxy betulinic acid (HBA) with significant inhibition of cancer cell growth and their properties. In the present study, we have shown for the first time that HBA decreased the expression of phosphotidylinositol-3 kinase (PI3K) p110α and p85α and caused significant downregulation of pAKT and of NFκB using human leukemia and breast cancer cells as in vitro models. Further it was revealed that PI3K inhibition by HBA induced cell cycle arrest via effects on different cell cycle regulatory proteins that include CDKis cyclins and pGSK3β. Also, this target-specific inhibition was associated with mitochondrial apoptosis as was reflected by the increased expression of mitochondrial bax, downregulated bcl2 and decreased mitochondrial levels of cytochrome c, together with reactive oxygen species generation and decline in mitochondrial membrane potential. The apoptotic effectors such as caspase 8, caspase 9 and caspase 3 were found to be upregulated besides DNA repair-associated enzyme, that is, PARP cleavage caused cancer cell death. Pharmacodynamic evaluation revealed that both HBA and BA were safe upto the dose of 2000 mg/kg body weight and with acceptable pharmacodynamic parameters. The in vitro data corroborated with in vivo anticancer activity wherein Ehrlich solid tumor showed that HBA as a more potent agent than BA without any body weight loss and mortality.

Objective This study tested the hypothesis that altered craniofacial morphology does not affect the expression of extracellular matrix (ECM) molecules such as fibronectin (FN), laminin (LN), type IV collagen, and tenascin-C (TN) but is associated with failure of palatal shelf elevation and fusion concomitant with cleft palate formation. Design To test this hypothesis, a comparative immunohistological analysis of FN, LN, type IV collagen, and TN was undertaken on brachyrrhine (Br/Br) mice and normal (+/+) fetuses during secondary palate formation. Normal and Br/Br fetuses were collected at gestational days E13 and E14 (representing prefusion stages) and E15 and E18 (representing postfusion stages). Cryostat palatal sections (8 μm) were postfixed in methanol, washed, and stained with primary antibody. All sections were washed and coated with secondary antibody (swine-anti-rabbit IgG) and mounted with citifluor. Results Immunohistological analysis showed that LN and type IV collagen were located near the presumptive medial epithelial seam (MES) or edge (MEE) in +/+ or Br/Br fetuses, respectively. Fibronectin showed a homogeneous distribution at all stages in both groups of mice. In contrast, TN became localized below the presumptive MES or MEE in both groups of mice at E14. In +/+ animals at E15, TN dissipated and became confined to the oral basement membrane by E18. At E15 and E18 in cleft Br/Br mutants, TN stained beneath the MEE. Conclusion Although the distributions of ECM molecules are similar during normal and cleft palatogenesis, differences in TN expression are associated with cleft palate formation.

Blade-root fastening of the fir-tree shape, used in securing turbomachinery blades to the rotor has been analysed by considering it as an assembly of the step-segments, the stiffness characteristics of which are already obtained in Part-I. The general equation of equilibrium as well as the compatability of deformation between the steps of the blade and the disc give the necessary ‘ n ’ linear algebraic equations for the evaluation of the step loads in the n- step root. The method can accommodate the centrifugal body forces of the root itself, the friction between the blade and disc-steps and the difference in the material of the blade and the disc.

Fir tree root fastenings are widely used for securing steam turbine blades onto the disc. The existing experimental and theoretical approaches for the stress analysis, treat the root as a whole, thus giving the stress distribution for that particular root only. The root is made up of several steps and in each step various geometrical parameters are involved. For proper understanding the designer must know the effect of variation of different parameters on the loads carried by each step. The new design approach suggested is to treat the root as an assembly of steps. The study of the stiffness of a generalised step is presented here, while the assembly of the steps is the subject matter of Part II.