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.

Stabilities and partitioning of arenonium ions in aqueous media.

The phenathrenonium ion is formed as a reactive intermediate in the solvolysis of 9-dichloroacetoxy-9,10-dihydrophenanthrene in aqueous acetonitrile and undergoes competing reactions with water acting as a base and nucleophile. Measurements of product ratios in the presence of azide ion as a trap and 'clock' yield rate constants kp = 3.7 x 10(10) and kH2O = 1.5 x 10(8) s(-1), respectively. Combining these with rate constants for the reverse reactions (protonation of phenanthrene and acid-catalyzed aromatization of its water adduct) gives equilibrium constants pKa = -20.9 and pK(R) = -11.6. For a series of arenonium and benzylic cations, correlation of log kp with pKa, taking account of the limit to kp set by the relaxation of water (10(11) s(-1)), leads to extrapolation of kp = 9.0 x 10(10) s(-1) and pKa = -24.5 for the benzenonium ion and kp = 6.5 x 10(10) s(-1) and pKa = -22.5 for the 1-naphthalenonium ion. Combining these pKa's with estimates of equilibrium constants pKH2O for the hydration of benzene and naphthalene, and the relationship pKR = pKa + pKH2O based on Hess's law, gives pKR = -2.3 and -8.0 respectively, and highlights the inherent stability of the benzenonium ion. A correlation exists between the partitioning ratio, kp/kH2O, for carbocations reacting in water and KH2O the equilibrium constant between the respective reaction products, i.e., log(kp/kH2O) = 0.46pKH2O - 3.7. It implies that kp exceeds kH2O only when KH2O > 10(8). This is consistent with the proton transfer (a) possessing a lower intrinsic reactivity than reaction of the carbocation with water as a nucleophile and (b) being rate-determining in the hydration of alkenes (and dehydration of alcohols) except when the double bond of the alkene is unusually stabilized, as in the case of aromatic molecules.

Central dopaminergic system plays a role in the analgesic action of paracetamol: Preclinical evidence.

OBJECTIVE: Even after 100 years of discovery, the exact mechanisms for the analgesic action of paracetamol are under scanner. It was recently proposed that paracetamol may act through different mechanisms, especially altering the serotoninergic system. The main objective of this preclinical study was to verify the role of drugs modulating dopaminergic system (l-dopa, bromocriptine, olanzapine) on the analgesic effect of paracetamol. MATERIALS AND METHODS: Thirty adult male albino mice were divided into five groups: distilled water (0.5 ml/25 g), paracetamol (200 mg/kg), levodopa (10 mg/kg) + paracetamol, bromocriptine (5 mg/kg) + paracetamol (200 mg/kg), and olanzapine (2 mg/kg) + paracetamol (200 mg/kg). All drugs were administered orally for 14 days. Eddy's hot plate and tail immersion tests were used to determine analgesic activity. Tests were conducted 1 h after the drug administration on the 14th day. After that, animals were sacrificed and brains were dissected out, to measure the levels of dopamine. Statistical comparisons among the groups were performed by one-way analysis of variance followed by Tukey-Kramer test. RESULTS: Coadministration of l-dopa and bromocriptine with paracetamol increased the antinociceptive activity of paracetamol significantly, whereas coadministration of olanzapine with paracetamol decreased the analgesic activity of paracetamol in the Eddy's hot plate and tail immersion tests considerably. There was a significant increase (P < 0.001) in the levels of dopamine in the brains of mice, which received levodopa, bromocriptine, and paracetamol. However, it was opposite in the brains of animals which received olanzapine. CONCLUSION: The results suggest that analgesic action of paracetamol is influenced by dopaminergic system.

Tiagabine in the treatment of acute affective episodes in bipolar disorder: efficacy and acceptability.

BACKGROUND: Bipolar disorder is a common recurrent illness with high levels of chronicity. Treatment resistance persists despite the use of established medications, such as lithium and valproate. New medications are required for the treatment of refractory cases. Some open-label reports have suggested that the anticonvulsant tiagabine may be efficacious in bipolar disorder. There is a need to clarify the evidence available, in the form of randomised controlled trials, for its use in the treatment of acute affective episodes in bipolar disorder OBJECTIVES: To review the evidence for the efficacy and acceptability of tiagabine in the treatment of acute mood episodes in bipolar disorder. SEARCH STRATEGY: The following databases were searched on 13-10-2005. The Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Registers (CCDANCTR-Studies and CCDANCTR-References),The Cochrane Controlled Clinical Trials Register (CCCTR),EMBASE,MEDLINE,LILACS,PsycLIT andPsyndex. Reference lists of relevant papers and major textbooks of mood disorder were searched. Handsearches were done (specialist journals and conference proceedings). Authors, other experts in the field and pharmaceutical companies were contacted for knowledge of suitable published or unpublished trials. SELECTION CRITERIA: Randomised controlled trials, which compared tiagabine with placebo or with active agents in the treatment of any acute mood episodes in bipolar disorder, were selected. Studies of participants with bipolar disorder were to be included. Subjects could be of either sex and of all ages. DATA COLLECTION AND ANALYSIS: Data extraction and methodological quality assessment were performed independently by two reviewers. For analysis, relative risk was used for binary efficacy outcomes and the weighted mean difference or standardised mean differerence was used for continuously distributed outcomes MAIN RESULTS: We did not find any studies which fulfilled the Cochrane criteria of randomised controlled trials. However, one uncontrolled open label study and one case series were found. There were also three case reports/series of acute treatment which were continued into maintenance therapy, and one open non-randomised study with this design. The results of these studies are inconsistent. AUTHORS' CONCLUSIONS: We found no randomised controlled trials of tiagabine in bipolar disorder. In the reported cases, a significant proportion of patients suffered episodes of syncope or seizure. There is a need for randomised controlled trials examining the efficacy and acceptability of tiagabine in the acute treatment of bipolar disorder, after the nature of these episodes has been clarified.

Tiagabine in the maintenance treatment of bipolar disorders.

BACKGROUND: Tiagabine, an anticonvulsant, has been reported to have efficacy in prophylactic treatment of bipolar disorder in case reports and in case series. OBJECTIVES: To review the efficacy and acceptability of tiagabine, relative to placebo, and other agents in the prevention and/or attenuation of episodes of bipolar affective disorder. The efficacy and acceptability of tiagabine were considered in terms of mood symptoms, mortality, general health, social functioning, adverse effects and overall acceptability to patients. SEARCH STRATEGY: The following databases were searched on 13-10-2005. The Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Registers (CCDANCTR-Studies and CCDANCTR-References),The Cochrane Controlled Clinical Trials Register (CCCTR),EMBASE,MEDLINE,LILACS,PsycLIT andPsyndex. Reference lists of relevant papers and major textbooks of affective disorder were examined.Authors, other experts in the field and pharmaceutical companies were contacted for knowledge of suitable published or unpublished trials. Specialist journals and conference proceedings were handsearched. SELECTION CRITERIA: Randomised controlled trials which compare tiagabine with placebo, alternative mood stabilisers or antipsychotics, where the stated intent of intervention was the maintenance treatment of bipolar affective disorder, were sought. Bipolar patients, male and female, of all ages were to be included. DATA COLLECTION AND ANALYSIS: Data were to be extracted from the original reports if they met our inclusion criteria. The main outcomes to be assessed were:(1) The efficacy of tiagabine treatment in preventing or attenuating further episodes of bipolar affective disorder, including its efficacy in rapid cycling disorder.(2) The acceptability of tiagabine treatment to patients.(3) The prevalence of side effects.(4) Mortality, if any, on tiagabine treatment.Outcomes concerning relapse or recurrence were to be analysed excluding data from studies using discontinuation protocols, which were to be analysed separately. Sub-group analyses were to be performed to examine the effects of tiagabine treatment in rapid cycling bipolar disorder and previous mood stabiliser non-responders. Data were to be analysed using Review Manager version 4.2.8. MAIN RESULTS: No randomised controlled trials of tiagabine in the maintenance treatment of bipolar disorder were found. AUTHORS' CONCLUSIONS: There is an insufficient methodologically rigorous evidence base to provide guidance on the use of tiagabine in the maintenance treatment of bipolar disorder. There is a need for randomised controlled trials examining the therapeutic potential of this agent in bipolar disorder, after the nature of reported episodes of syncope or seizure in tiagabine-treated bipolar patients has been established.

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.

Guillain-Barré syndrome-like presentation in borderline leprosy with type-2 reaction.

A 46-year-old man with borderline lepromatous leprosy with type-2 reaction being treated with multi-bacilliary-multiple drug therapy and steroids presented with an acute onset of flaccid quadriparesis. A nerve conduction study and CSF analysis were similar to that seen in Guillain Barre syndrome. Muscle weakness improved considerably with an increased dose of corticosteroid; after 6 months the patient recovered completely.

Influence of fatty acid and time of focusing on the isoelectric focusing of human plasma albumin.

In the isoelectric focusing of human plasma albumin, two major peaks of pI 4.8 and 5.6 are observed. As fatty acids are removed from the albumin either by defatting before the focusing experiment or gradually during the focusing experiment, the pI 4.8 peak diminishes and the pI 5.6 peak increases. The interpretation of this effect is confirmed by fatty acid analysis before and after focusing. Alkylation of the free sulfhydryl group changes the focusing position of the defatted peak to pI 5.7. Otherwise the isoelectric focusing pattern of human albumin is unaffected by the status of the free sulfhydryl group or by the ampholine concentration.

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.

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.

Heterosupramolecular chemistry: programmed pseudorotaxane assembly at the surface of a nanocrystal.

Gold nanocrystals, stabilized by thiols covalently bound to a dibenzo[24]crown-8 moiety, have been programmed to recognize and selectively bind dibenzylammonium cations in solution. This results in a self-organization process at the surface of a nanocrystal with the assembly of a pseudorotaxane (see picture).

Lipoprotein levels and tissue lipids in fatty-fibrous atherosclerosis induced in rabbits by two years' cholesterol feeding at a low level.

A group of 12 young NZW rabbits of the same breeding strain were fed a diet enriched with 0.1% cholesterol by weight. The resulting modest hypercholesterolaemia resolved after 4-5 months. Two animals that died during this period showed no gross or microscopic atherosclerosis. After 6 months, the dietary cholesterol was increased to 0.2%. In some animals this resulted in moderate hypercholesterolaemia. One animal that died at this time showed no atherosclerosis with a mean serum cholesterol level of 224 mg/dl. Just after one year, dietary cholesterol was increased to 0.3%. This resulted in definite hypercholesterolaemia in some animals, but a few resisted the treatment with mean serum cholesterol levels around 40-60 mg/dl. In general, animals with established hypercholesterolaemia showed severe atherosclerosis, but often of a more fibrous and less cellular nature than is usual in the rabbit. Aortic wall cholesterol content (on a weight basis) correlated positively with serum cholesterol concentration (r = + 0.69, P approximately 0.05) and negatively with the ratio of HDL cholesterol to (LDL plus VLDL) cholesterol (double log plot: r = -0.79, P less than 0.025).

A longitudinal study of the biological variability of plasma lipoproteins in healthy young adults.

The fasting serum concentrations of total cholesterol, low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), total triglyceride and apoprotein A1 were measured at intervals of 12-18 weeks for 60 weeks in 17 male and 11 female healthy young adults in order to assess the variability of these risk factors for coronary disease. No statistically significant seasonal changes were detected in any variable in either sex, although a progressive rise in apoprotein A1 concentration was observed. The coefficients of variation for random fluctuations with time were in the rank order: total cholesterol less than HDL-C less than apoprotein A1 less than LDL-C less than triglyceride. These differences were attributable to biological, rather than to methodological, factors. Within subjects, HDL cholesterol concentration varied inversely with triglyceride concentration and directly with apoprotein A1 concentration. The marked differences which exist in the biological variability of lipid risk factors for atherosclerosis need to be taken into account when making comparisons in epidemiological studies of the predictive powers of single on-entry measurements for future disease. Fluctuations of HDL-C with time appear to be related in part to variations in triglyceride-rich lipoprotein metabolism.

All atom molecular mechanics simulations on covalent complexes of anthramycin and neothramycin with deoxydecanucleotides.

We present molecular mechanics simulations on covalent complexes between d[(GC)5]2, d(G10).d(C10), d(GCGCGAGCGC).d(GCGCTCGCGC), d(GCGCGTGCGC).d(GCGCACGCGC), d(G5AG4).d(C4TC5), and d(G5TG4).d(C4AC5) on one hand and potent antitumor antibiotics anthramycin and neothramycin A on the other, using the all atom force field in the framework of the program AMBER(UCSF). The energy-refined models of both the sets of complexes show minimal distortions for the nucleotides, consistent with the results of 2D NMR studies on these complexes. The drugs have 3'-orientation in the minor groove, consistent with the previously reported investigations employing the united atom force field and with the experimental observations. Both anthramycin and neothramycin are calculated to bind preferentially to the puGpu sequences over pyGpy. This is in qualitative agreement with experimental studies for anthramycin, while for neothramycin A, this result is in apparent disagreement with experimental observations which have reported preferential binding of neothramycin A to poly(dG-dC).poly(dG-dC) over poly(dG).poly(dC). While the present study brings out the usefulness of the simple molecular mechanics approach (using an all atom force field) in rationalizing substantial experimental observations, it also emphasizes the need for further investigations on solvent and dynamics effects in understanding the sequence specificity of drug-DNA binding.

Molecular mechanics simulations on covalent complexes between anthramycin and B DNA.

We present molecular mechanics simulation of the covalent interactions of the potent antitumor antibiotic belonging to the pyrrolo[1,4]benzodiazepine class, anthramycin, with six deoxydecanucleotides, d(GCGCGCGCGC)2, d(G10) X d(C10), d(GCGCGTGCGC) X d(GCGCACGCGC), d(GCGCGAGCGC) X d(GCGCTCGCGC), d(GGGGGAGGGG) X d(CCCCTCCCCC), and d(GGGGGTGGGG) X d(CCCCACCCCC), in their minor grooves. The complexes are characterized by both a network of hydrogen bonds between the drug and the polynucleotide and good packing interactions. The DNA double helix in these complexes shows very minimal distortion, and interactions of the drug with the decanucleotides seem to be not very sensitive to the sequence variation around the site of complex formation. The conformational features in the complexes obtained are generally consistent with the experimentally derived conclusions by recent NMR and 2-D NOE studies.

Molecular mechanics simulations on covalent complexes of mitomycin C and its analogues with left-handed DNA duplexes.

We present molecular mechanics simulations on covalent complexes between d(GCGCGCGCGC).d(GCGCGCGCGC) in the left-handed double helical forms (B and Z) and potent antitumor antibiotics mitomycin C and three of its analogues using the all atom force field in the framework of the program AMBER(UCSF). The energy-refined models of the complexes show interesting networks of hydrogen-bonding interactions between the drugs and DNA groups in the minor groove of the left-handed helices. The energy-refined models suggest that mitomycins could bind strongly to left-handed helices. This result might be relevant to the interpretation of earlier experiments which suggested that DNA bound by mitomycin C underwent a transition to a non-Z left-handed structure.

Conformations of complexes between mitomycin and decanucleotides. 2. Application of the model to mitomycin C derivatives. Extension to covalent binding with adenine.

Molecular mechanics simulation of the interactions of important mitomycin C analogues monocovalently bound to DNA models are presented. These analogues included substituents such as p-hydroxyphenyl, 2-mercaptoethyl, and dimethylamidinium on N7 of mitomycin C and the DNA models consisted of d(GCGCGCGCGC)2 and d(GCGCATGCGC)2. The excellent fits and strong binding affinities of these highly potent analogues support the usefulness of the model. The binding of a mitomycin-related N-phenylpyrrole with a carbamoyloxy substituent to 06 of guanine was studied. Finally, a reactive mitomycin intermediate proposed by Moore was shown to interact with DNA in a way consistent with the formation of a covalent adduct.

Conformations of complexes between mitomycins and decanucleotides. 3. Sequence specificity, binding at C-10, and mitomycin analogues.

Molecular mechanics simulation of the interactions of mitomycin C and certain analogues with DNA models are presented. The sequence specificity of mitomycin C binding was investigated by using a d(GCGCGCGCGC)2 decanucleotide duplex, abbreviated herein as GC10, in which the base pair was varied on either side of the covalent binding site. A CGT fragment was favored, although its correlation with the diverse findings in the literature is questionable. A model was derived for the monocovalent binding at C10 of 2,7-diaminomitosene with GC10 and for the noncovalently bound hydroquinone intermediate. Revised models were established for three highly active mitomycin C analogues: M-83, BMY-25282, and RR-150. They involved covalent binding at the 2-amino group of a guanine residue, and they accounted for enhanced noncovalent binding afforded by specific interactions of the C7 substituents with residues in GC10.

N-substituted dibenzoxazepines as analgesic PGE2 antagonists.

8-Chlorodibenz[b,f][1,4]oxazepine-10(11H)-carboxylic acid, 2-acetylhydrazide (1, SC-19220) has been previously reported by us and others to be a PGE2 antagonist selective for the EP1 receptor subtype with antinociceptive activities. Analogs of SC-19220, in which the acetyl moiety has been replaced with pyridylpropionyl groups and their homologs, have been synthesized as illustrated by compounds 13 and 29. These and other members of this series have been shown to be efficacious analgesics and PGE2 antagonists of the EP1 subtype. This report discusses the structure activity relationships within this series.

Potent in vitro and in vivo inhibitors of platelet aggregation based upon the Arg-Gly-Asp-Phe sequence of fibrinogen. A proposal on the nature of the binding interaction between the Arg-guanidine of RGDX mimetics and the platelet GP IIb-IIIa receptor.

Peptide mimetics of the RGDF sequence in which Arg-Gly has been replaced with 5-(4-amidinophenyl)pentanoyl mimetic has led to a 1000-fold increase in inhibitory potency over the natural RGDF ligand. The guanidine residue of the arginine may be involved in a reinforced ionic interaction with a carboxylate of the receptor which could explain the dramatic increase in potency upon replacement with benzamidine. This hypothesis is supported by the observation of low inhibitory potency of the corresponding benzylamine (18) and no activity with the corresponding imidazoline derivative (19); plus, ab initio calculations on the respective complexes suggest that the benzamidine-carboxylate is more favorable than the guanidine-carboxylate interaction. The ED50 for the inhibition of ex vivo collagen induced platelet aggregation in the dog for SC-52012 (1) was 0.32 microgram/kg/min by iv infusion with a pharmacodynamic half-life for recovery of approximately 40 min.