Use of a simple pain model to evaluate analgesic activity of ibuprofen versus paracetamol

Objective: To evaluate the analgesic activity of ibuprofen against paracetamol using a simple pain model.Design: A double-blind study.Setting: Twenty general practitioners in Harare, Zimbabwe.Patients: Adults with acute sore throat of a maximum of two days’ duration.Interventions: One hundred and thirteen patients with acute pain associated with tonsillopharyngitis randomly received either 400mg ibuprofen or 1000mg paracetamol. The study design included repeated administration up to 48 hours to assess tolerability.Main outcome measures: At hourly intervals for six hours after the first dose of treatment, the patients evaluated pain intensity on swallowing, difficulty in swallowing and global pain relief according to visual analogue scales.Results: Ibuprofen 400mg was significantly more effective than paracetamol 1000mg in all three ratings, at all time-points for pain intensity and difficulty in swallowing, and from two hours onwards for pain relief. There were no serious adverse effects and no statisticallysignificant difference in the incidence of adverse effects in the two treatment groups.Conclusions: Sore throat pain provided a sensitive model to assess the analgesic efficacy of class I analgesics and discriminated between the analgesic efficacy of ibuprofen and paracetamol

Intramolecular remote functionalisation of steroids by benzophenone- increased specificity by solvent-induced hydrophobic interactions

Proximity of reactant sites is one of the major factors that contributes to specificity and high reaction rates observed in enzyme catalysis. Enzymes achieve this proximity between the reactant sites by having high affinity for the substrate. Structural studies on enzyme-substrate complexes provide sufficient evidence in this context and indicate that weak bonding interaction are involved in formation of such complexes. We have exploited the hydrophobic interaction between cholesterol and benzophenone to carry out photoinduced remote functionalisation of cholesterol at specific sites. Thus, using polar solvents intramolecular hydrophobic interaction between cholesterol and benzophenone permitted exclusive functionalisation of ring D in cholesterol. The current study indicates that weak interactions between the reactants can be used to bring them in proximity and photochemical reactions can provide the method for functionalising even inert sites like C-H bonds

Advanced information processing system: The Army fault tolerant architecture conceptual study. Volume 1: Army fault tolerant architecture overview

Digital computing systems needed for Army programs such as the Computer-Aided Low Altitude Helicopter Flight Program and the Armored Systems Modernization (ASM) vehicles may be characterized by high computational throughput and input/output bandwidth, hard real-time response, high reliability and availability, and maintainability, testability, and producibility requirements. In addition, such a system should be affordable to produce, procure, maintain, and upgrade. To address these needs, the Army Fault Tolerant Architecture (AFTA) is being designed and constructed under a three-year program comprised of a conceptual study, detailed design and fabrication, and demonstration and validation phases. Described here are the results of the conceptual study phase of the AFTA development. Given here is an introduction to the AFTA program, its objectives, and key elements of its technical approach. A format is designed for representing mission requirements in a manner suitable for first order AFTA sizing and analysis, followed by a discussion of the current state of mission requirements acquisition for the targeted Army missions. An overview is given of AFTA's architectural theory of operation

Advanced information processing system: The Army fault tolerant architecture conceptual study. Volume 2: Army fault tolerant architecture design and analysis

Described here is the Army Fault Tolerant Architecture (AFTA) hardware architecture and components and the operating system. The architectural and operational theory of the AFTA Fault Tolerant Data Bus is discussed. The test and maintenance strategy developed for use in fielded AFTA installations is presented. An approach to be used in reducing the probability of AFTA failure due to common mode faults is described. Analytical models for AFTA performance, reliability, availability, life cycle cost, weight, power, and volume are developed. An approach is presented for using VHSIC Hardware Description Language (VHDL) to describe and design AFTA's developmental hardware. A plan is described for verifying and validating key AFTA concepts during the Dem/Val phase. Analytical models and partial mission requirements are used to generate AFTA configurations for the TF/TA/NOE and Ground Vehicle missions

Optimization of Vertical Well Placement for Oil Field Development Based on Basic Reservoir Rock Properties Using a Genetic Algorithm

Comparing the quality of basic reservoir rock properties is a common practice to locate new infill or development wells for optimizing oil field development using reservoir simulation. The conventional technique employs a manual trial-and-error process to find new well locations, which proves to be time-consuming, especially for large fields. Concerning this practical matter, an alternative in the form of a robust technique is introduced in order to reduce time and effort in finding new well locations capable of producing the highest oil recovery. The objective of this research was to apply a genetic algorithm (GA) for determining well locations using reservoir simulation, in order to avoid the conventional manual trial-and-error method. This GA involved the basic rock properties, i.e. porosity, permeability, and oil saturation, of each grid block obtained from a reservoir simulation model, to which a newly generated fitness function was applied, formulated by translating common engineering practice in reservoir simulation into a mathematical equation and then into a computer program. The maximum fitness value indicates the best grid location for a new well. In order to validate the proposed GA method and evaluate the performance of the program, two fields with different production profile characteristics were used, fields X and Y. The proposed method proved to be a robust and accurate method to find the best new well locations for oil field development. The key to the success of the proposed GA method lies in the formulation of the objective functions

GROWTH PERFORMANCE, NUTRIENT DIGESTIBILITY AND BLOOD INDICES OF FINISHING BROILER CHICKENS FED VARYING LEVELS OF PRE-GELATINIZED CASSAVA GRITS AS A REPLACEMENT FOR MAIZE

Pre gelatinized cassava grit (PGCG) is a new cassava product produced mechanically and commercially for poultry feeding. Five dietary treatments were formulated with PGCG replacing maize at 0, 25, 50, 75 and 100 % in broiler starter (0-4 weeks) and finisher (4-8 weeks) diets. Two hundred (200) day-old broiler chickens were allotted to the five dietary treatments in a completely random design.  Each treatment was replicated four times with 10 birds per replicate and 40 birds per treatment. At the end of week 4 and 8 of the experiment, data were collected on growth performance, nutrient digestibility, haematological and serum biochemical indices. Final weight and weight gain were significantly (P < 0.05) highest in broilers fed 25 % PGCG diet, followed by those fed control diet. While, (P < 0.05) similar and lower values were obtained from broilers fed other PGCG diets. Feed intake decreased (P < 0.05) with PGCG in the diets at the starting and finishing phases. Dry matter and crude protein digestibility was (P < 0.05) highest in starting broilers fed 25 % PGCG diet, while digestibility (P < 0.05) declined with higher levels of PGCG. At the finishing phase, digestibility of all nutrients was similar (P < 0.05). Apparent metabolizable energy was (P < 0.05) higher in birds fed PGCG diets in the starting and finishing phases. Haematological and serum biochemical indices showed no significant (P>0.05) difference in the broiler chickens fed varying levels of PGCG in the diets. Broiler chickens fed PGCG above 25% in the diet had significantly (P < 0.05) higher proventriculus values when compared with those fed the control diet and 25% PGCG diet. The study revealed that substituting maize with 25 % PGCG in broiler diets improved growth and nutrient digestibility. Reduction in weight gain and non significant increased thiocyanate at higher PGCG inclusion should be improved for effective utilization of pre gelatinized cassava grit in broiler diets. &nbsp

Phase transition and scaling behavior of topological charged black holes in Horava-Lifshitz gravity

Gravity can be thought as an emergent phenomenon and it has a nice "thermodynamic" structure. In this context, it is then possible to study the thermodynamics without knowing the details of the underlying microscopic degrees of freedom. Here, based on the ordinary thermodynamics, we investigate the phase transition of the static, spherically symmetric charged black hole solution with arbitrary scalar curvature $2k$ in Ho\v{r}ava-Lifshitz gravity at the Lifshitz point $z=3$. The analysis is done using the canonical ensemble frame work; i.e. the charge is kept fixed. We find (a) for both $k=0$ and $k=1$, there is no phase transition, (b) while $k=-1$ case exhibits the second order phase transition within the {\it physical region} of the black hole. The critical point of second order phase transition is obtained by the divergence of the heat capacity at constant charge. Near the critical point, we find the various critical exponents. It is also observed that they satisfy the usual thermodynamic scaling laws.Comment: Minor corrections, refs. added, to appear in Class. Quant. Grav. arXiv admin note: text overlap with arXiv:1111.0973 by other author

The pathogen recognition sensor, NOD2, is variably expressed in patients with pulmonary tuberculosis

Background: NOD2, an intracellular pathogen recognition sensor, modulates innate defences to muropeptides derived from various bacterial species, including Mycobacterium tuberculosis (MTB). Experimentally, NOD2 attenuates two key putative mycobactericidal mechanisms. TNF-alpha synthesis is markedly reduced in MTB-antigen stimulated-mononuclear cells expressing mutant NOD2 proteins. NOD2 agonists also induce resistance to apoptosis, and may thus facilitate the survival of MTB in infected macrophages. To further define a role for NOD2 in disease pathogenesis, we analysed NOD2 transcriptional responses in pulmonary leucocytes and mononuclear cells harvested from patients with pulmonary tuberculosis (PTB).Methods: We analysed NOD2 mRNA expression by real-time polymerase chain-reaction in alveolar lavage cells obtained from 15 patients with pulmonary tuberculosis and their matched controls. We compared NOD2 transcriptional responses, in peripheral leucocytes, before and after anti-tuberculous treatment in 10 patients. In vitro, we measured NOD2 mRNA levels in MTB-antigen stimulated-mononuclear cells.Results: No significant differences in NOD2 transcriptional responses were detected in patients and controls. In some patients, however, NOD2 expression was markedly increased and correlated with toll-like-receptor 2 and 4 expression. In whole blood, NOD2 mRNA levels increased significantly after completion of anti-tuberculosis treatment. NOD2 expression levels did not change significantly in mononuclear cells stimulated with mycobacterial antigens in vitro.Conclusion: There are no characteristic NOD2 transcriptional responses in PTB. Nonetheless, the increased levels of NOD2 expression in some patients with severe tuberculosis, and the increases in expression levels within peripheral leucocytes following treatment merit further studies in selected patient and control populations

COX-2-mediated stimulation of the lymphangiogenic factor VEGF-C in human breast cancer

Increased expression of COX-2 or VEGF-C has been correlated with progressive disease in certain cancers. Present study utilized several human breast cancer cell lines (MCF-7, T-47D, Hs578T and MDA-MB-231, varying in COX-2 expression) as well as 10 human breast cancer specimens to examine the roles of COX-2 and prostaglandin E (EP) receptors in VEGF-C expression or secretion, and the relationship of COX-2 or VEGF-C expression to lymphangiogenesis. We found a strong correlation between COX-2 mRNA expression and VEGF-C expression or secretion levels in breast cancer cell lines and VEGF-C expression in breast cancer tissues. Expression of LYVE-1, a selective marker for lymphatic endothelium, was also positively correlated with COX-2 or VEGF-C expression in breast cancer tissues. Inhibition of VEGF-C expression and secretion in the presence of COX-1/2 or COX-2 inhibitors or following downregulation of COX-2 with COX-2 siRNA established a stimulatory role COX-2 in VEGF-C synthesis by breast cancer cells. EP1 as well as EP4 receptor antagonists inhibited VEGF-C production indicating the roles of EP1 and EP4 in VEGF-C upregulation by endogenous PGE2. Finally, VEGF-C secretion by MDA-MB-231 cells was inhibited in the presence of kinase inhibitors for Her-2/neu, Src and p38 MAPK, indicating a requirement of these kinases for VEGF-C synthesis. These results, for the first time, demonstrate a regulatory role of COX-2 in VEGF-C synthesis (and thereby lymphangiogenesis) in human breast cancer, which is mediated at least in part by EP1/EP4 receptors