Grey wolf assisted dragonfly-based weighted rule generation for predicting heart disease and breast cancer.

Disease prediction plays a significant role in the life of people, as predicting the threat of diseases is necessary for citizens to live life in a healthy manner. The current development of data mining schemes has offered several systems that concern on disease prediction. Even though the disease prediction system includes more advantages, there are still many challenges that might limit its realistic use, such as the efficiency of prediction and information protection. This paper intends to develop an improved disease prediction model, which includes three phases: Weighted Coalesce rule generation, Optimized feature extraction, and Classification. At first, Coalesce rule generation is carried out after data transformation that involves normalization and sequential labeling. Here, rule generation is done based on the weights (priority level) assigned for each attribute by the expert. The support of each rule is multiplied with the proposed weighted function, and the resultant weighted support is compared with the minimum support for selecting the rules. Further, the obtained rule is subject to the optimal feature selection process. The hybrid classifiers that merge Support Vector Machine (SVM), and Deep Belief Network (DBN) takes the role of classification, which characterizes whether the patient is affected with the disease or not. In fact, the optimized feature selection process depends on a new hybrid optimization algorithm by linking the Grey Wolf Optimization (GWO) with Dragonfly Algorithm (DA) and hence, the presented model is termed as Grey Wolf Levy Updated-DA (GWU-DA). Here, the heart disease and breast cancer data are taken, where the efficiency of the proposed model is validated by comparing over the state-of-the-art models. From the analysis, the proposed GWU-DA model for accuracy is 65.98 %, 53.61 %, 42.27 %, 35.05 %, 34.02 %, 11.34 %, 13.4 %, 10.31 %, 9.28 % and 9.89 % better than CBA + CPAR, MKL + ANFIS, RF + EA, WCBA, IQR + KNN + PSO, NL-DA + SVM + DBN, AWFS-RA, HCS-RFRS, ADS-SM-DNN and OSSVM-HGSA models at 60th learning percentage.

Preclinical screening of phyllanthus amarus ethanolic extract for its analgesic and antimicrobial activity.

BACKGROUND: To discover a new agent which possesses dual property of analgesic and antimicrobial activity, thereby reducing the burden of polypharmacy. Phyllanthus amarus was screened for its analgesic and antimicrobial activities. OBJECTIVES: The objective was to evaluate the analgesic and antimicrobial activity, of P. amarus ethanolic extract (PAEE). MATERIALS AND METHODS: The ethanolic extract of P. amarus was prepared using Soxhlet apparatus. An in vivo study using Swiss albino mice was done to screen the central and peripheral analgesic activity of P. amarus extract. The extract was administered at a dose of 100 mg/kg body weight orally. The peripheral analgesic activity was assessed using acetic acid induced writhing test. The central analgesic activity was assessed using Eddy's hot plate apparatus. An in vitro study was carried out to study the antimicrobial activity of the above extract using selected species of Streptococcus mutans, and S. salivarius. The antimicrobial activities were determined using the agar well method. RESULTS: The ethanolic extract of P. amarus showed significant (P < 0.05) peripheral and central analgesic activity. In vitro antimicrobial screening indicated that the ethanolic extract had shown a zone of inhibition against S. mutans and S. salivarius in the agar wells. CONCLUSION: This study showed that PAEE exhibited significant analgesic and antimicrobial activities.

Is povidone-iodine a hemostyptic? A clinical study.

Povidone-iodine (PVP-I) is an antiseptic agent commonly used on intact skin in preparation for surgery and on open wounds. In oral surgery it is used for irrigating alveolar sockets following extraction. The present authors found by chance that irrigation of extraction sockets with povidone-iodine led to cessation of bleeding in patients without recurrence. Fifty patients were selected and divided equally into treatment and control groups. Povidone-iodine (1%, w/v) was used for irrigation of extraction sockets in the treatment group and saline was used in the control group. In the treatment group, 19 patients showed cessation of bleeding compared to only 5 in the control group. Povidone-iodine significantly (P<0.01) controlled bleeding as compared to saline. Iodine is corrosive due to its oxidizing potential while povidone is a thickening and granulating agent; together they may have a chemocauterizing effect that could be the reason for the cessation of bleeding. These results suggest that povidone-iodine may act as a hemostyptic as well as an antiseptic.

Co-existence of lepromatous leprosy and myasthenia gravis.

Various circulating autoantibodies are known to occur commonly in patients with lepromatous leprosy. However, the association with autoimmune diseases has rarely been reported. One such association of lepromatous leprosy with myasthenia gravis is being reported.

Prediction of organophosphorus acetylcholinesterase inhibition using three-dimensional quantitative structure-activity relationship (3D-QSAR) methods.

Neurotoxic organophosphorous compounds are known to modulate their biological effects through the inhibition of a number of esterases including acetylcholinesterase (AChE), the enzyme responsible for the degradation of the neurotransmitter acetylcholine. In this light, molecular modeling studies were performed on a collection of organophosphorous acetylcholinesterase inhibitors by the combined use of conformational analysis and 3D-QSAR methods to rationalize their inhibitory potencies against the enzyme. The Catalyst program was used to identify the structural features in the group of 8 inhibitors whose IC(50) values ranged from 0.34 nM to 1.2 microM. The 3-D pharmacophore models are characterized by at least one hydrogen bond acceptor site and 2-3 hydrophobic sites and demonstrate very good correlation between the predicted and experimental IC(50) values. Our models can be useful in screening databases of organophosphorous compounds for their neurotoxicity potential via the inhibition of acetylcholinesterase. Also, the pharmacophores offer an additional means of designing AChE inhibitors as potential therapeutic agents for central nervous system diseases.

Effect of age on the refractive outcome of myopic photorefractive keratectomy.

PURPOSE: To evaluate the effect of age on the outcome of myopic photorefractive keratectomy (PRK). SETTING: University-based refractive surgery practice. METHODS: A retrospective analysis of 197 eyes that had PRK for myopia was performed. Four groups of patients were compared: Group 1, patients < 30 years (n=35); Group 2, patients 31 to 40 years (n=56); Group 3, patients 41 to 50 year s (n=47); Group 4, patients > 50 years (n=59). The percentage of eyes with an uncorrected visual acuity of 20/20 or better and 20/40 or better and the percentage of eyes with spherical correction within +/-0.5 and +/-1.0 diopter (D) of the attempted correction were derived for each age group. The percentage of patients overcorrected and undercorrected by 1.0 D or more in each age group was also calculated. The difference between the percentage of patients who achieved a visual acuity of 20/20 or better in Group 4 and in the younger groups was statistically significant at 3 months (P =.02) but not at 6 months (P =.70) and 12 months (P =.55). The difference between the percentage of patients who achieved an acuity of 20/40 or better was not significant at any time. The difference between the percentage of patients who were within +/-0.5 D of intended correction in Group 4 and in the younger groups was statistically significant at 3 months (P =.001), 6 months (P =.006), and 12 months (P =.008); the difference between the percentage of patients who were within +/-1.0 D of intended correction was not significant at any time. The difference between the percentage of patients overcorrected and undercorrected by 1.0 D or more in Group 4 and in the younger groups was not significant at any time. In the 3 younger groups, age did not significantly affect visual outcome or predictability. However, there was a significant difference between Group 4 and the 3 younger groups in predictability of the refractive outcome at 3, 6, and 12 months. Age may play a role in the outcome of refractive surgery.

Local anaesthetic for minor oral surgical procedures. Review.

Pain following any surgical procedure is difficult to combat by man. Analgesics can be given for some amount of symptomatic relief. The need for a long lasting local anaesthetic is with the intention to reduce the most severe nature of pain, and decrease the analgesic consumption. This study was conducted to compare the efficacy of, Bupivacaine over Lidocaine for minor oral surgical procedures. The popularly used lidocaine works for 3 to 3.9 hours. This is not sufficient since the most severe nature of pain is felt six to eight hours post surgery, where as Bupivacaine has duration of action of seven to eight hours. Hence the post operative pain experienced following administration of bupivacaine was found to be considerably lesser in degree than compared to the lidocaine group. To avoid severe pain and discomfort to the patient following any minor oral surgical, the use of bupivacaine is recommended.

A new nomenclature for oral and maxillofacial surgery that is facial and oral surgery.

To assess whether majority of the public and medical professionals do understand the field Oral & Maxillo-Facial Surgery. To find this, a questionnaire was devised based on P. Ammerally et al. 200 members of the public with educated background and 100 general medical practitioners participated in this study. The results revealed that majority of the public needed more information on the field where as the General medical practitioners were aware, but lacked information about the majority of activity in the field.

Effect of dietary fish on antioxidant parameters of normal and cholesterol stressed rats.

Feeding fish (Sardinella longiceps) to normal rats increased lipid peroxidation and total and Se-dependent glutathione peroxidase (GSH-px) activity in erythrocytes and manganese dependent superoxide dismutase (Mn-SOD) activity in liver. Feeding fish to cholesterol stressed rats showed a significant increase in the activity of GSH-px and cholesterol feeding alone, resulted in a significant increase in the lipid peroxidation and liver Mn-SOD activity. The results suggest that the high polyunsaturated fatty acid content of S. longiceps, the fish abundantly available in the west coast of India, does not have any deleterious effect by way of free radical generation. The observed lipid peroxidation is not critical as is evident from the results of glutathione level and other scavenging enzymes.

Functional homodimeric glycoprotein hormones: implications for hormone action and evolution.

BACKGROUND: Human chorionic gonadotropin (hCG), lutropin, follitropin, and thyrotropin act as alpha beta heterodimers to control reproduction and thyroid function. The alpha and beta subunits of these proteins are divided into three loops (alpha 1,alpha 2,alpha 3; beta 1,beta 2,beta 3) by cysteine knots and the heterodimer is stabilized by 20 beta-subunit residues wrapped around alpha 2 like a seatbelt. Understanding how these hormones interact with their receptors, a matter of considerable dispute, would facilitate design of pro- and anti-fertility agents. RESULTS: By swapping alpha 2 for beta 2 and vice versa and, in some cases, adding an amino-terminal coiled-coil dimerization domain, we prepared homodimeric analogs that have the conformation found in each 'half' of hCG. Homodimers containing loops beta 1,alpha 2,beta 3 and none, part, or all of the seatbelt stimulated signal transduction to the same extent as hCG, albeit with lower potency. Those containing alpha 1,beta 2,alpha 3 were inactive. CONCLUSIONS: The activities of homodimers containing the beta 1,alpha 2,beta 3 groove exceed those of other minimized analogs more than 100-1000-fold, suggesting this portion of the hormone forms the major receptor contact. The discovery that glycoprotein hormone heterodimers can be converted to functional homodimers supports the proposal that this protein family evolved from an active homodimeric ancestor by gene duplication and acquisition of mutations to loop 2 that prevent homodimerization. This approach to protein minimization should be applicable to other proteins composed of architecturally related subunits, including those that might have arisen by gene duplication.

Molecular mechanics studies on dipeptide models of diphenylalanine and its derivatives.

As a part of our studies on the structure and conformations of peptidomimetics, we present conformational energy calculations on model peptides with (a) diphenyl alanine and its tricyclic derivatives and (b) triphenyl alanine residues using molecular mechanics and conformational analysis methods. The energies are calculated as a function of the backbone torsions (phi and psi), and the results are presented in terms of isoenergy contours in the phi-psi space. The low-energy models adopt conformations characteristic of a variety of regular structures such as the alpha-helix, gamma-turn and polyproline-II-type three- and four-fold helices. The conformational preferences in the model peptides with diphenyl alanine and its tricyclic derivatives are sensitive to the side-chain torsion, with some similarities to the corresponding preferences of L-Ala dipeptide. The energy profile of the model peptide with triphenyl alanine is similar to that of the model peptide with Tle (tert-leucine) residue. The results of our studies have implications in the design of conformationally constrained peptidomimetics with structures in the beta- and alpha-helical regions.

Model of human chorionic gonadotropin and lutropin receptor interaction that explains signal transduction of the glycoprotein hormones.

The goal of these studies was to devise a model that explains how human chorionic gonadotropin (hCG) interacts with lutropin (LH) receptors to elicit a hormone signal. Here we show that alpha-subunit residues near the N terminus, the exposed surface of the cysteine knot, and portions of the first and third loops most distant from the beta-subunit interface were recognized by antibodies that bound to hCG-receptor complexes. These observations were combined with similar data obtained for the beta-subunit (Cosowsky, L., Rao, S.N.V., Macdonald, G.J., Papkoff, H., Campbell, R.K., and Moyle, W.R. (1995) J. Biol. Chem. 270, 20011-20019), information on residues of hCG that can be changed without disrupting hormone function, the crystal structure of deglycosylated hCG, and the crystal structure of a leucine-repeat protein to devise a model of hCG-receptor interaction. This model suggest that the extracellular domain of the LH receptor is "U-" or "J"-shaped and makes several contacts with the transmembrane domain. High affinity hormone binding results from interactions between residues in the curved portion of the extracellular domain of the receptor and the groove in the hormone formed by the apposition of the second alpha-subunit loop and the first and third beta-subunit loops. Most of the remainder of the hormone is found in the large space between the arms of the extracellular domain and makes few, if any, additional specific contacts with the receptor needed for high affinity binding. Signal transduction is caused by steric or other influences of the hormone on the distance between the arms of the extracellular domain, an effect augmented by the oligosaccharides. Because the extracellular domain is coupled at multiple sites to the transmembrane domain, the change in conformation of the extracellular domain is relayed to the transmembrane domain and subsequently to the cytoplasmic surface of the plasma membrane. While the model does not require the hormone to contact the transmembrane domain to initiate signal transduction, small portions of both subunits may be near the transmembrane domain and assist in initiating the hormonal signal. This is the first model that is consistent with all known information on the activity of the gonadotropins including the amounts of the hormone that are exposed in the hormone-receptor complex, the apparent lack of specific contacts between much of the hormone and the receptor, and the roles of the oligosaccharides in signal transduction.(ABSTRACT TRUNCATED AT 400 WORDS)

Thymomatous myasthenia gravis.

Ten cases of thymoma associated myasthenia were seen in the last 7 years. They constitute 17.2% of all cases of Myasthenia gravis seen during the same period. Five of these patients presented in the third decade, all of them presenting with acute generalised Myasthenia (Osserman stage-III). Two patients presented with tumour related symptoms of chest pain, cough and dyspnea both of them having large, invasive and partially resectable tumours. Five patients underwent complete thymectomy and 3 patients underwent partial resection of tumour. Two patients underwent radiotherapy subsequently. Histologically, mixed lymphoepithelial tumours were common (70%). Tumour recurrence was seen in one patient. Two patients died, one in the post operative period. The surviving 8 patients followed up over 1-8 years remained in partial remission, on maintenance dose of steroids. The special problems related to thymomatous MG and practical approach to management are highlighted.

Conformational studies on model peptides with 1-aminocyclobutane 1-carboxylic acid residues.

Conformationally constrained peptidomimetics are being increasingly used in the development of 3-D pharmacophores of peptide-based drug candidates and to alter their metabolic stability towards achievements of oral bioavailability. Here we present conformational energy calculations on model compounds containing 1-aminocyclobutane carboxylic acid (ACBC) and its derivatives using molecular mechanics methods. The low-energy models adopt conformations characteristic of a variety of regular structures such as the alpha-helix, 3(10)-helix, gamma-turn and polyproline-II-type three- and fourfold helices. The energetically most favored models adopt the gamma-turn (2.2(7) helix) conformation or alpha-/3(10)-helical conformation, both of either handedness, depending on the substituents on the cyclobutane. These results are qualitatively consistent with the crystal structures of peptide analogs containing ACBC and have implications for the design of peptidomimetics.

Circulating immune complexes in intracranial neoplasms.

The levels of circulating immune complexes (CIC) were assayed in the sera of 109 patients with intracranial space occupying lesions. The CIC levels were significantly increased in all the brain tumours. After treatment, the CIC levels were still significantly increased when compared to the controls but showed no change when compared to their respective pre-operative values. Further, no change was observed in the CIC levels between the malignant and benign tumour case. Moreover, in brain tumours, 90% of the CIC precipitate consisted of IgG. However, the CIC levels fail to prognosticate the process of the disease in these patients.

Conformational studies on model peptides with 1-aminocyclopropane 1-carboxylic acid residues.

The design of metabolically stable, conformationally constrained peptidomimetics is an increasingly used approach in developing orally active drug candidates in pharmaceutical research. In this paper we present conformational energy calculations on model compounds containing 1-aminocyclopropane carboxylic acid (ACC) and its derivatives using molecular mechanics methods. The low energy models adopt conformations characteristic of a variety of regular structures such as the alpha-helix, gamma-turn and three- and fourfold helices. The energetically most favored models adopt either the left- or right-handed 2.2(7) helical conformation or the gamma-turn. These results are qualitatively consistent with the crystal structures of peptide analogs containing ACC and have potential implications for the design of peptidomimetics where the conformational features characteristic of a specific type of gamma-turn are desired.

Serum adenosine deaminase activity in brain tumours.

Adenosine deaminase (ADA) activity in serum was estimated in 86 patients with intracranial tumours and 40 healthy volunteers. Although high ADA concentrations in biological fluids and tumour tissues were observed in several neoplastic conditions, there was no significant difference in the ADA in sera of brain tumour patients when compared to the control values. Therefore, cell-mediated immunity probably does not play a significant role in brain tumours.

Conformational studies on beta-amino acid-containing peptides. I.

Modified amino acids (such as beta-amino acids) are becoming increasingly popular research tools in the development of orally active and metabolically stable peptidomimetics. We present conformational energy calculations using molecular mechanics (MM2) on two model compounds containing beta-amino acids. The low-energy models are characterized by a lack of intramolecular hydrogen-bonding interactions, qualitatively consistent with the results of the IR studies. The structures obtained from the limited amount of x-ray crystal data on compounds with beta-amino acid incorporated lie within 3 kcal/mol of the global minimum obtained from the present calculations. Preliminary stereochemical guidelines for the incorporation of beta-amino acid residues have been proposed.

Elevation of serum ceruloplasmin levels in brain tumours.

Serum ceruloplasmin levels have been estimated in 80 patients with various intracranial space occupying lesions and in 30 controls. The ceruloplasmin levels were significantly increased in all brain tumours except in meningiomas. After therapy, the ceruloplasmin levels were still significantly increased when compared to controls and their respective preoperative values. However, the rise in levels of ceruloplasmin in malignant tumours compared to benign was statistically not significant. It is concluded that ceruloplasmin may have a role to play as an acute phase reactant protein in brain tumours.