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Population pharmacokinetic modelling of repaglinide in healthy volunteers by using Non-Parametric Adaptive Grid Algorithm

Ruzilawati AB, Mohd Suhaimi AW, Gan SH

J Clin Pharm Ther, 2010 Feb;35(1):105-12.
PMID: 20175819 DOI: 10.1111/j.1365-2710.2009.01042.x

To estimate population pharmacokinetic parameters of repaglinide in 121 healthy Malaysian volunteers.

Matched MeSH terms: Models, Biological
Using response surface methodology to optimize process parameters and cross-linking agents for production of combined-cross-linked bovine serum albumin gels

Gan CY, Alkarkhi AF, Easa AM

J Biosci Bioeng, 2009 Apr;107(4):366-72.
PMID: 19332294 DOI: 10.1016/j.jbiosc.2008.12.007

D-optimal design was employed to optimize the mixture of cross-linking agents formulation: microbial transglutaminase (MTGase) and ribose, and the processing parameters (i.e. incubation and heating time) in the mixture in order to obtain combined-cross-linked bovine serum albumin gels that have high gel strength, pH close to neutral and yet medium in browning. Analysis of variance (ANOVA) showed that the contribution of quadratic term to the model over the linear was significant for pH and L* value, whereas linear model was significant for gel strength. Optimization study using response surface methodology (RSM) was performed to the mixture components and process variables and the optimum conditions obtained were: MTGase of 1.34-1.43 g/100 mL, ribose of 1.07-1.16 g/100 mL, incubation time of 5 h at 40 degrees C and heating time of 3 h at 90 degrees C.

Matched MeSH terms: Models, Biological
The anomalous origin and branches of the obturator artery with its clinical implications

Jusoh AR, Abd Rahman N, Abd Latiff A, Othman F, Das S, Abd Ghafar N, et al.

Rom J Morphol Embryol, 2010;51(1):163-6.
PMID: 20191138

The obturator artery (OA) originates from the internal iliac artery. Variation in the origin of the OA may be asymptomatic in individuals and occasionally be detected during routine cadaveric dissections or autopsies. In the present study, we observed the origin and the branching pattern of the OA on 34 lower limbs (17 right sides and 17 left sides) irrespective of sex. The bifurcation of the common iliac artery into internal and external iliac from the sacral ala varied between 4.3-5.3 cm. The distance of the origin of the anterior division of internal iliac artery from the bifurcation of common iliac artery varied between 1-6 cm. The distance of the origin of the posterior division of the internal iliac artery from the point of bifurcation of the common iliac artery varied between 0-6 cm. Out of 34 lower limbs studied, two specimens (5.8%) showed anomalous origin of the OA originating from the posterior division of the internal iliac artery. Of these two, one limb belonged to the right side while the other was from the left side. The anomalous OA gave off an inferior vesical branch to the prostate in both the specimens. No other associated anomalies regarding the origin or branching pattern of the OA were observed. Prior knowledge of the anatomical variations may be beneficial for vascular surgeons ligating the internal iliac artery or its branches and the radiologists interpreting angiograms of the pelvic region.

Matched MeSH terms: Models, Biological
Coordination of Ce(III) and Nd(III) with pentaethylene glycol in the presence of picrate anion: spectroscopic and X-ray structural studies

Kusrini E, Saleh MI, Lecomte C

Spectrochim Acta A Mol Biomol Spectrosc, 2009 Sep 15;74(1):120-6.
PMID: 19560960 DOI: 10.1016/j.saa.2009.05.024

(1)H NMR evidence for direct coordination between the Ln(III) ion and the oxygen atoms of the pentaethylene glycol (EO5) ligand and the picrate anion (Pic) in [Ln(Pic)(2)(EO5)][Pic] {Ln=Ce and Nd} complexes are confirmed by single X-ray diffraction. No dissociation of Ln-O bonds in dimethyl sulfoxide-d solution was observed in NMR studies conducted at different temperatures ranging 25-100 degrees C. The Ln(III) ion was chelated to nine oxygen atoms from the EO5 ligand in a hexadentate manner and the two Pic anions in each bidentate and monodentate modes. Both compounds are isostructural and crystallized in monoclinic with space group P2(1)/c. Coordination environment around the Ce1 and Nd1 atoms can be described as tricapped trigonal prismatic and monocapped square antiprismatic geometries, respectively. The crystal packing of the complexes have stabilized by one dimensional (1D) chains along the [001] direction to form intermolecular O-Hcdots, three dots, centeredO and C-Hcdots, three dots, centeredO hydrogen bonding. The molar conductance of the complexes in DMSO solution indicated that both compounds are ionic. The complexes had a good thermal stability. Under the UV-excitation, these complexes exhibited the red-shift emission.

Matched MeSH terms: Models, Biological
The effect of vitamin E on basic fibroblast growth factor level in human fibroblast cell culture

Rashid SA, Halim AS, Muhammad NA

Med J Malaysia, 2008 Jul;63 Suppl A:69-70.
PMID: 19024988

Basic fibroblast growth factor (bFGF) is angiogenic and effective in down-regulating excess collagen production. The aim of this study is to evaluate the effectiveness of vitamin E (Tocotrienol Rich Fraction) in altering the level of bFGF, a cytokine involved in the scar formation process. In this model, normal human fibroblasts were treated with various concentrations of vitamin E at different time frames. The levels of bFGF were determined by Enzyme-Linked Immunosorbant Assay (ELISA). This study demonstrated that Tocotrienol Rich Fraction (TRF) stimulated bFGF production by fibroblast and postulate that vitamin E may decrease aberrant scar formation.

Matched MeSH terms: Models, Biological
Interface pressure profile analysis for patellar tendon-bearing socket and hydrostatic socket

Moo EK, Osman NA, Pingguan-Murphy B, Abas WA, Spence WD, Solomonidis SE

Acta Bioeng Biomech, 2009;11(4):37-43.
PMID: 20405814

Conventionally, patellar tendon-bearing (PTB) sockets, which need high dexterity of prosthetist, are widely used. Lack of chartered and experienced prosthetist has often led to painful experience of wearing prosthesis and this will in turn deter the patients to wear the prosthesis, which will further aggravate stump shrinkage. Thus, the hydrostatic socket which demands relatively lower level of fabricating skill is proposed to replace the PTB socket in order to produce the equivalent, if not better, quality of support to the amputee patients. Both sockets' pressure profiles are studied and compared using finite element analysis (FEA) software. Three-dimensional models of both sockets were developed using MIMICS software. The analysis results showed that hydrostatic socket did exhibit more uniform pressure profiles than that of PTB socket. PTB socket showed pressure concentration near the proximal brim of the socket and also at the distal fibula. It was also found that the pressure magnitude in hydrostatic socket is relatively lower than that of PTB socket.

Matched MeSH terms: Models, Biological
Rare anatomical variant: arterial circle in palm and at the base of the thumb

Vollala VR, Nagabhooshana S, Bhat SM, Rodrigues V, Rao M, Pamidi N, et al.

Rom J Morphol Embryol, 2008;49(4):585-7.
PMID: 19050813

In this article, we describe anomalous formation, distribution of superficial palmar arch and an arterial circle at the base of the thumb found during routine dissection classes in the right hand of a 45-year-old male cadaver. These variations are unique and provide significant information to surgeons dissecting the hand region.

Matched MeSH terms: Models, Biological
Corneal elevation indices in normal and keratoconic eyes

Fam HB, Lim KL

J Cataract Refract Surg, 2006 Aug;32(8):1281-7.
PMID: 16863962 DOI: 10.1016/j.jcrs.2006.02.060

PURPOSE: To determine an index that distinguishes keratoconus and keratoconus-suspect eyes from normal eyes with Orbscan (Bausch & Lomb) corneal elevation maps.
SETTING: Department of Ophthalmology, Tan Tock Seng Hospital, Singapore, and iLaser Centre, Island Hospital, Penang, Malaysia.
METHODS: In this initial phase of this multicenter nonrandomized retrospective study, 1 eye of 166 normal subjects, 15 keratoconus patients, and 11 keratoconus suspects was examined at 1 clinic. The anterior best-fit sphere (BFS), posterior BFS, anterior elevation, posterior elevation, and maximum and minimum keratometries were analyzed. Two indices with the highest sensitivity and specificity classifying these conditions were identified using receiver operating characteristic curves. These 2 indices were evaluated in a subsequent validation study using 1 eye of 221 normal subjects, 43 keratoconus patients, and 23 keratoconus suspects from another clinic.
RESULTS: The anterior elevation and anterior elevation ratio (anterior elevation ratio = anterior elevation/anterior BFS) best classified the different groups. An anterior elevation ratio of 0.5122 mm or less had 99% sensitivity and 95.2% specificity while a ratio 16.5 mum or less had 80.1% sensitivity and 80.8% specificity in discriminating normal eyes from keratoconus and keratoconus suspects. The results were similar in the validation study. In addition, these anterior elevation and anterior elevation ratio cutoff values had high sensitivity and specificity in identifying keratoconus suspects from normal eyes in the validation study.
CONCLUSION: Anterior corneal elevation parameters are clinically relevant measures for detecting keratoconus and suspected keratoconus eyes.

Matched MeSH terms: Models, Biological
Antioxidant synergism between ethanolic Centella asiatica extracts and α-tocopherol in model systems

Thoo YY, Abas F, Lai OM, Ho CW, Yin J, Hedegaard RV, et al.

Food Chem, 2013 Jun 1;138(2-3):1215-9.
PMID: 23411234 DOI: 10.1016/j.foodchem.2012.11.013

The synergistic antioxidant effects of ethanolic extracts of Centella asiatica (CE), and α-tocopherol have been studied. The types of interactions exhibited by CE and α-tocopherol combined at different ratios were measured using three assays: 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) diammonium salt (ABTS) radical-scavenging capacity, the β-carotene bleaching system and liposome peroxidation assays. Fixed-fraction isobolographic analysis was used to detect any inducement of the antioxidant activity compared with the individual activities of CE and α-tocopherol. Of all synergistic combinations of CE and α-tocopherol, only fraction 2/3 showed the synergistic combination that fits well in three different assays and can be explained by the regeneration of α-tocopherol by CE despite the interaction effect of β-carotene present in the analytical assay. This phenomenon involved complex interactions between CE and α-tocopherol to exhibit different degrees of interactions that eventually increased antioxidant activity.

Matched MeSH terms: Models, Biological
Modeling growth rate and assessing aflatoxins production by Aspergillus flavus as a function of water activity and temperature on polished and brown rice

Mousa W, Ghazali FM, Jinap S, Ghazali HM, Radu S

J Food Sci, 2013 Jan;78(1):M56-63.
PMID: 23301606 DOI: 10.1111/j.1750-3841.2012.02986.x

The aim of this study was to model the radial growth rate and to assess aflatoxin production by Aspergillus flavus as a function of water activity (a(w) 0.82 to 0.92) and temperature (12 to 42 °C) on polished and brown rice. The growth of the fungi, expressed as colony diameter (mm) was measured daily, and the aflatoxins were analyzed using HPLC with a fluorescence detector. The growth rates were estimated using the primary model of Baranyi, which describes the change in colony radius as a function of time. Total of 2 secondary models were used to describe the combined effects of a(w) and temperature on the growth rates. The models were validated using independent experimental data. Linear Arrhenius-Davey model proved to be the best predictor of A. flavus growth rates on polished and brown rice followed by polynomial model. The estimated optimal growth temperature was around 30 °C. A. flavus growth and aflatoxins were not detected at 0.82 a(w) on polished rice while growth and aflatoxins were detected at this a(w) between 25 and 35 °C on brown rice. The highest amounts of toxins were formed at the highest a(w) values (0.90 to 0.92) at a temperature of 20 °C after 21 d of incubation on both types of rice. Nevertheless, the consistencies of toxin production within a wider range of a(w) values occurred between 25 to 30 °C. Brown rice seems to support A. flavus growth and aflatoxin production more than the polished rice.

Matched MeSH terms: Models, Biological
Optimization of medium composition for the production of a probiotic microorganism, Lactobacillus rhamnosus, using response surface methodology

Liew SL, Ariff AB, Raha AR, Ho YW

Int J Food Microbiol, 2005 Jul 15;102(2):137-42.
PMID: 15992613

This study was undertaken to optimize yeast extract, glucose, and vitamin concentrations; and also culture pH for maximizing the growth of a probiotic bacterium, Lactobacillus rhamnosus, and to assess the effects of these factors by using response surface methodology. A central composite design was used as an experimental design for the allocation of treatment combinations. A polynomial regression model with cubic and quartic terms was used for analysis of the experimental data. It was found that the effects involving yeast extract, glucose, vitamins and pH on the growth of L. rhamnosus were significant, and the strongest effect was given by the yeast extract concentration. Estimated optimum conditions of the factors for the growth of L. rhamnosus are as follows: pH=6.9; vitamin solution=1.28% (v/v); glucose=5.01% (w/v) and yeast extract=6.0% (w/v).

Matched MeSH terms: Models, Biological
Iron-Binding Capacity of Defatted Rice Bran Hydrolysate and Bioavailability of Iron in Caco-2 Cells

Foong LC, Imam MU, Ismail M

J Agric Food Chem, 2015 Oct 21;63(41):9029-36.
PMID: 26435326 DOI: 10.1021/acs.jafc.5b03420

The present study was aimed at utilizing defatted rice bran (DRB) protein as an iron-binding peptide to enhance iron uptake in humans. DRB samples were treated with Alcalase and Flavourzyme, and the total extractable peptides were determined. Furthermore, the iron-binding capacities of the DRB protein hydrolysates were determined, whereas iron bioavailability studies were conducted using an in vitro digestion and absorption model (Caco-2 cells). The results showed that the DRB protein hydrolysates produced by combined Alcalase and Flavourzyme hydrolysis had the best iron-binding capacity (83%) after 90 min of hydrolysis. The optimal hydrolysis time to produce the best iron-uptake in Caco-2 cells was found to be 180 min. The results suggested that DRB protein hydrolysates have potent iron-binding capacities and may enhance the bioavailability of iron, hence their suitability for use as iron-fortified supplements.

Matched MeSH terms: Models, Biological
Fulltext Validation of ethnopharmacological uses of Murraya paniculata in disorders of diarrhea, asthma and hypertension

Saqib F, Ahmed MG, Janbaz KH, Dewanjee S, Jaafar HZ, Zia-Ul-Haq M

BMC Complement Altern Med, 2015;15:319.
PMID: 26354022 DOI: 10.1186/s12906-015-0837-7

Murraya paniculata is traditionally used for management of gut, air way and cardiovascular disorders. The study was conducted for provision of pharmacological rationalization for folkloric uses of Murraya paniculata in gut, air way and cardiovascular problems.

Matched MeSH terms: Models, Biological
Optimization of Salmonella Typhi biofilm assay on polypropylene microtiter plates using response surface methodology

Ganjali Dashti M, Abdeshahian P, Sudesh K, Phua KK

Biofouling, 2016;32(4):477-87.
PMID: 26963754 DOI: 10.1080/08927014.2015.1135328

The objective of this study was to develop an optimized assay for Salmonella Typhi biofilm that mimics the environment of the gallbladder as an experimental model for chronic typhoid fever. Multi-factorial assays are difficult to optimize using traditional one-factor-at-a-time optimization methods. Response surface methodology (RSM) was used to optimize six key variables involved in S. Typhi biofilm formation on cholesterol-coated polypropylene 96-well microtiter plates. The results showed that bile (1.22%), glucose (2%), cholesterol (0.05%) and potassium chloride (0.25%) were critical factors affecting the amount of biofilm produced, but agitation (275 rpm) and sodium chloride (0.5%) had antagonistic effects on each other. Under these optimum conditions the maximum OD reading for biofilm formation was 3.4 (λ600 nm), and the coefficients of variation for intra-plate and inter-plate assays were 3% (n = 20) and 5% (n = 8), respectively. These results showed that RSM is an effective approach for biofilm assay optimization.

Matched MeSH terms: Models, Biological
Fulltext Projections of the current and future disease burden of hepatitis C virus infection in Malaysia

McDonald SA, Dahlui M, Mohamed R, Naning H, Shabaruddin FH, Kamarulzaman A

PLoS One, 2015;10(6):e0128091.
PMID: 26042425 DOI: 10.1371/journal.pone.0128091

BACKGROUND: The prevalence of hepatitis C virus (HCV) infection in Malaysia has been estimated at 2.5% of the adult population. Our objective, satisfying one of the directives of the WHO Framework for Global Action on Viral Hepatitis, was to forecast the HCV disease burden in Malaysia using modelling methods.
METHODS: An age-structured multi-state Markov model was developed to simulate the natural history of HCV infection. We tested three historical incidence scenarios that would give rise to the estimated prevalence in 2009, and calculated the incidence of cirrhosis, end-stage liver disease, and death, and disability-adjusted life-years (DALYs) under each scenario, to the year 2039. In the baseline scenario, current antiviral treatment levels were extended from 2014 to the end of the simulation period. To estimate the disease burden averted under current sustained virological response rates and treatment levels, the baseline scenario was compared to a counterfactual scenario in which no past or future treatment is assumed.
RESULTS: In the baseline scenario, the projected disease burden for the year 2039 is 94,900 DALYs/year (95% credible interval (CrI): 77,100 to 124,500), with 2,002 (95% CrI: 1340 to 3040) and 540 (95% CrI: 251 to 1,030) individuals predicted to develop decompensated cirrhosis and hepatocellular carcinoma, respectively, in that year. Although current treatment practice is estimated to avert a cumulative total of 2,200 deaths from DC or HCC, a cumulative total of 63,900 HCV-related deaths is projected by 2039.
CONCLUSIONS: The HCV-related disease burden is already high and is forecast to rise steeply over the coming decades under current levels of antiviral treatment. Increased governmental resources to improve HCV screening and treatment rates and to reduce transmission are essential to address the high projected HCV disease burden in Malaysia.

Matched MeSH terms: Models, Biological
Cerebroprotective effects of RAS inhibitors: Beyond their cardio-renal actions

Kalra J, Prakash A, Kumar P, Majeed AB

J Renin Angiotensin Aldosterone Syst, 2015 Sep;16(3):459-68.
PMID: 25944853 DOI: 10.1177/1470320315583582

Work on the brain renin-angiotensin system has been explored by various researchers and has led to elucidation of its basic physiologies and behavior, including its role in reabsorption and uptake of body fluid, blood pressure maintenance with angiotensin II being its prominent effector. Currently, this system has been implicated for its newly established effects, which are far beyond its cardio-renal effects accounting for maintenance of cerebral blood flow and cerebroprotection, seizure, in the etiology of Alzheimer's disease, Parkinson's disease, multiple sclerosis, and bipolar disorder. In this review, we have discussed the distribution of angiotensin receptor subtypes in the central nervous system (CNS) together with enzymatic pathways leading to active angiotensin ligands and its interaction with angiotensin receptor 2 (AT2) and Mas receptors. Secondly, the use of angiotensin analogues (angiotensin converting enzyme inhibitors and AT1 and/or AT2 receptor blockers) in the treatment and management of the CNS disorders mentioned above has been discussed.

Matched MeSH terms: Models, Biological
A simplified approach for exit dose in vivo measurements in radiotherapy and its clinical application

Banjade DP, Shrestha SL, Shukri A, Tajuddin AA, Bhat M

Australas Phys Eng Sci Med, 2002 Sep;25(3):110-8.
PMID: 12416587

This is a study using LiF:Mg;Ti thermoluminescent dosimeter (TLD) rods in phantoms to investigate the effect of lack of backscatter on exit dose. Comparing the measured dose with anticipated dose calculated using tissue maximum ratio (TMR) or percentage depth dose (PDD) gives rise to a correction factor. This correction factor may be applied to in-vivo dosimetry results to derive true dose to a point within the patient. Measurements in a specially designed humanoid breast phantom as well as patients undergoing radiotherapy treatment were also been done. TLDs with reproducibility of within +/- 3% (1 SD) are irradiated in a series of measurements for 6 and 10 MV photon beams from a medical linear accelerator. The measured exit doses for the different phantom thickness for 6 MV beams are found to be lowered by 10.9 to 14.0% compared to the dose derived from theoretical estimation (normalized dose at dmax). The same measurements for 10 MV beams are lowered by 9.0 to 13.5%. The variations of measured exit dose for different field sizes are found to be within 2.5%. The exit doses with added backscatter material from 2 mm up to 15 cm, shows gradual increase and the saturated values agreed within 1.5% with the expected results for both beams. The measured exit doses in humanoid breast phantom as well as in the clinical trial on patients undergoing radiotherapy also agreed with the predicted results based on phantom measurements. The authors' viewpoint is that this technique provides sufficient information to design exit surface bolus to restore build down effect in cases where part of the exit surface is being considered as a target volume. It indicates that the technique could be translated for in vivo dose measurements, which may be a conspicuous step of quality assurance in clinical practice.

Matched MeSH terms: Models, Biological
The kinetics of bioaccumulation of zinc, copper, lead and cadmium by oysters (Crassostrea iredalei and C. belcheri) under tropical field conditions

Lim PE, Lee CK, Din Z

Sci Total Environ, 1998 May 14;216(1-2):147-57.
PMID: 9618930

A study on the kinetics of accumulation and depuration of Zn, Cu, Pb and Cd by the oysters (Crassostrea iredalei and Crassostrea belcheri) cultured at two locations in the Merbok Estuary, Malaysia was conducted. A first-order kinetic model was employed to fit the experimental data in order to estimate the rate constants for uptake and elimination processes and to predict the bioconcentration factors (BCF). Among the four metals studied, only the Zn accumulation process could not be modelled using first-order kinetics. The elimination rate constants estimated from depuration data for C. iredalei are found to be much greater than those from accumulation data. The results suggest that the values of kinetic parameters and BCFs derived under conditions of both aqueous and dietary exposure are probably more site- than species-specific.

Matched MeSH terms: Models, Biological
Contribution of kinin system to the antihypertensive action of angiotensin converting enzyme inhibitors

Sharma JN

Adv Exp Med Biol, 1989;247A:197-205.
PMID: 2690588
Matched MeSH terms: Models, Biological
Involvement of the kinin-forming system in the physiopathology of rheumatoid inflammation

Sharma JN

Agents Actions Suppl., 1992;38 ( Pt 3):343-61.
PMID: 1334358

Kinins are potent mediators of rheumatoid inflammation. The components of the kinin-forming system are hyperactive in RA. Excessive release of kinins in the synovial fluid can produce oedema, pain and loss of functions due to activation of B1 and B2 receptors. These receptors could be stimulated via injury, trauma, coagulation pathways (Hageman factor and thrombin) and immune complexes. The activated B1 and B2 receptors might cause release of other powerful non-cytokines and cytokines mediators of inflammation, for example, PGE2, PGI2, LTs, histamine, PAF, IL-1 and TNF derived mainly from polymorphonuclear leukocytes, macrophages, endothelial cells and synovial tissue. These mediators are capable of inducing bone and cartilage damage, hypertrophic synovitis, vessels proliferation, inflammatory cells migration, and possibly angiogenesis in pannus formation. These pathological changes, however, are not yet defined in human model of chronic inflammation (RA). Hence, the role of kinin and its interacting inflammatory mediators would soon start to clarify the detailed questions they revealed in clinical and experimental models of chronic inflammatory joint diseases. Several B1 and B2 receptor antagonists are being synthesized in an attempt to study the molecular functions of kinins in inflammatory processes (RA, periodontitis and osteomyelitis), and they represent and important area for continued research in rheumatology. Future development of specific, potent and stable B1 and B2 receptor antagonists or combined B1 and B2 antagonists with y-IFN might serve as pharmacological basis of more effective rationally-based therapies for RA. This may lead to significant advances in our knowledge of the mechanisms and therapeutics of rheumatic diseases.

Matched MeSH terms: Models, Biological

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