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Randomized two-way cross-over bioequivalence study of two amoxicillin formulations and inter-ethnicity pharmacokinetic variation in healthy Malay volunteers

Liew KB, Loh GO, Tan YT, Peh KK

Biomed Chromatogr, 2014 Sep;28(9):1246-53.
PMID: 24585432 DOI: 10.1002/bmc.3153

The objectives of this study were to develop a new deproteinization method to extract amoxicillin from human plasma and evaluate the inter-ethnic variation of amoxicillin pharmacokinetics in healthy Malay volunteers. A single-dose, randomized, fasting, two-period, two-treatment, two-sequence crossover, open-label bioequivalence study was conducted in 18 healthy Malay adult male volunteers, with one week washout period. The drug concentration in the sample was analyzed using high-performance liquid chromatography (UV-vis HPLC). The mean (standard deviation) pharmacokinetic parameter results of Moxilen® were: peak concentration (Cmax ), 6.72 (1.56) µg/mL; area under the concentration-time graph (AUC0-8 ), 17.79 (4.29) µg/mL h; AUC0-∞ , 18.84 (4.62) µg/mL h. Those of YSP Amoxicillin® capsule were: Cmax , 6.69 (1.44) µg/mL; AUC0-8 , 18.69 (3.78) µg/mL h; AUC00-∞ , 19.95 (3.81) µg/mL h. The 90% confidence intervals for the logarithmic transformed Cmax , AUC0-8 and AUC0-∞ of Moxilen® vs YSP Amoxicillin® capsule was between 0.80 and 1.25. Both Cmax and AUC met the predetermined criteria for assuming bioequivalence. Both formulations were well tolerated. The results showed significant inter-ethnicity variation in pharmacokinetics of amoxicillin. The Cmax and AUC of amoxicillin in Malay population were slightly lower compared with other populations.

Matched MeSH terms: Area Under Curve
Fulltext Investigating meta-approaches for reconstructing gene networks in a mammalian cellular context

Nazri A, Lio P

PLoS One, 2012;7(1):e28713.
PMID: 22253694 DOI: 10.1371/journal.pone.0028713

The output of state-of-the-art reverse-engineering methods for biological networks is often based on the fitting of a mathematical model to the data. Typically, different datasets do not give single consistent network predictions but rather an ensemble of inconsistent networks inferred under the same reverse-engineering method that are only consistent with the specific experimentally measured data. Here, we focus on an alternative approach for combining the information contained within such an ensemble of inconsistent gene networks called meta-analysis, to make more accurate predictions and to estimate the reliability of these predictions. We review two existing meta-analysis approaches; the Fisher transformation combined coefficient test (FTCCT) and Fisher's inverse combined probability test (FICPT); and compare their performance with five well-known methods, ARACNe, Context Likelihood or Relatedness network (CLR), Maximum Relevance Minimum Redundancy (MRNET), Relevance Network (RN) and Bayesian Network (BN). We conducted in-depth numerical ensemble simulations and demonstrated for biological expression data that the meta-analysis approaches consistently outperformed the best gene regulatory network inference (GRNI) methods in the literature. Furthermore, the meta-analysis approaches have a low computational complexity. We conclude that the meta-analysis approaches are a powerful tool for integrating different datasets to give more accurate and reliable predictions for biological networks.

Matched MeSH terms: Area Under Curve
Fulltext Analytical and diagnostic performance of an automated anti-CCP assay

Pavai S, Sargunan S, Zain AA, Chow SK

Malays J Pathol, 2011 Dec;33(2):101-6.
PMID: 22299210 MyJurnal

Aim: Autoantibodies against cyclic citrullinated peptide (anti-CCP) are considered to be a sensitive and specific marker for rheumatoid arthritis (RA). This study evaluated the diagnostic and analytical performances of the automated anti-CCP assay.
Materials and Method: Sera from 80 patients with established RA, 65 from other rheumatic diseases (non-RA) and 55 from healthy controls were studied using second generation anti-CCP. Rheumatoid factor (RF) was also assayed in each sample, and the results were compared to the anti-CCP fi ndings. Serum pools were used to determine the precision and linearity.
Results: At a cut-off of 7.4 U/ml for anti-CCP, the sensitivity and specificity for RA were 65% and 98% respectively. RF had a sensitivity of 58% and a lower specifi city of 93 % than anti-CCP. Conclusion: The high specificity of the assay suggests that anti-CCP is useful in the diagnosis of rheumatoid arthritis and in our cohort of study population anti-CCP exhibits a better diagnostic value than RF. A considerable proportion (28%) of RF-negative RA patients were anti-CCP positive. Based on analytical performance of the assay, we conclude that full automation and high throughput features of AxSYM makes it an ideal platform for routine testing of anti-CCP.
Study site: Rheumatology clinic, University Malaya Medical Centre (UMMC), Kuala Lumpur, Malaysia

Matched MeSH terms: Area Under Curve
Glycaemic index of four commercially available breads in Malaysia

Yusof BN, Abd Talib R, Karim NA, Kamarudin NA, Arshad F

Int J Food Sci Nutr, 2009 Sep;60(6):487-96.
PMID: 18785052 DOI: 10.1080/09637480701804268

This study was carried out to determine the blood glucose response and glycaemic index (GI) values of four types of commercially available breads in Malaysia. Twelve healthy volunteers (six men, six women; body mass index, 21.9±1.6 kg/m(2); age, 22.9±1.7 years) participated in this study. The breads tested were multi-grains bread (M-Grains), wholemeal bread (WM), wholemeal bread with oatmeal (WM-Oat) and white bread (WB). The subjects were studied on seven different occasions (four tests for the tested breads and three repeated tests of the reference food) after an overnight fast. Capillary blood samples were taken immediately before (0 min) and 15, 30, 45, 60, 90 and 120 min after consumption of the test foods. The blood glucose response was obtained by calculating the incremental area under the curve. The GI values were determined according to the standardized methodology. Our results showed that the M-Grains and WM-Oat could be categorized as intermediate GI while the WM and WB breads were high GI foods, respectively. The GI of M-Grains (56±6.2) and WM-Oat (67±6.9) were significantly lower than the reference food (glucose; GI = 100) (P < 0.05). No significant difference in GI value was seen between the reference food and the GI of WM (85±5.9) and WB (82±6.5) (P > 0.05). Among the tested breads, the GI values of M-Grains and WM-Oat were significantly lower (P < 0.05) than those of WM and WB. There was no relationship between the dietary fibre content of the bread with the incremental area under the curve (r = 0.15, P = 0.15) or their GI values (r = 0.17, P = 0.12), indicating that the GI value of the test breads were unaffected by the fibre content of the breads. The result of this study will provide useful nutritional information for dieticians and the public alike who may prefer low-GI over high-GI foods.

Matched MeSH terms: Area Under Curve
Fulltext Glycemic index of common Malaysian fruits

Robert SD, Ismail AA, Winn T, Wolever TM

Asia Pac J Clin Nutr, 2008;17(1):35-9.
PMID: 18364324

The objective of the present study was to measure the glycemic index of durian, papaya, pineapple and water-melon grown in Malaysia. Ten (10) healthy volunteers (5 females, 5 males; body mass index 21.18+/-1.7 kg/m2) consumed 50 g of available carbohydrate portions of glucose (reference food) and four test foods (durian, papaya, pineapple and watermelon) in random order after an overnight fast. Glucose was tested on three separate occasions, and the test foods were each tested once. Postprandial plasma glucose was measured at intervals for two hours after intake of the test foods. Incremental areas under the curve were calculated, and the glycemic index was determined by expressing the area under the curve after the test foods as a percentage of the mean area under the curve after glucose. The results showed that the area under the curve after pineapple, 232+/-24 mmolxmin/L, was significantly greater than those after papaya, 147+/-14, watermelon, 139+/-8, and durian, 124+/-13 mmolxmin/L (p<0.05). Similarly, the glycemic index of pineapple, 82+/-4, was significantly greater than those of papaya, 58+/-6, watermelon, 55+/-3, and durian, 49+/-5 (p<0.05). The differences in area under the curve and glycemic index among papaya, watermelon and durian were not statistically significant. We conclude that pineapple has a high glycemic index, whereas papaya is intermediate and watermelon and durian are low glycemic index foods. The validity of these results depends on the accuracy of the data in the food tables upon which the portion sizes tested were based.

Matched MeSH terms: Area Under Curve
Fulltext Categorization of low cardiorespiratory fitness using obesity indices in non-smoking Singaporean women

Pua YH, Lim CK, Ang A

Obesity (Silver Spring), 2006 Nov;14(11):1992-9.
PMID: 17135616 DOI: 10.1038/oby.2006.233

OBJECTIVE: To revisit cut-off values of BMI, waist circumference (WC), and waist-to-stature ratio (WSR) based on their association with cardiorespiratory fitness (CRF). The derived cut-off points were compared with current values (BMI, 25.0 kg/m(2); WC, 80 cm) as recommended by the World Health Organization.
RESEARCH METHODS AND PROCEDURES: Anthropometric indices were measured in a cross sectional study of 358 Singaporean female employees of a large tertiary hospital (63% Singaporean Chinese, 28% Malays, and 9% Indians). CRF was determined by the 1-mile walk test. Receiver operating characteristic curves were constructed to determine cut-off points.
RESULTS: The cut-off points for BMI, WC, and WSR were 23.6 kg/m(2), 75.3 cm, and 0.48, respectively. The areas under the curve of BMI, WC, and WSR were 0.68, 0.74, and 0.74, respectively. For a given BMI, women with low CRF had higher WSR compared with women with high CRF.
DISCUSSION: These findings provide convergent evidence that the cut-off points for Singaporean women were lower than the World Health Organization's criteria but were in good agreement with those reported for Asians.

Matched MeSH terms: Area Under Curve
Clinicians' diagnostic practice of dengue infections

Ng CF, Lum LC, Ismail NA, Tan LH, Tan CP

J Clin Virol, 2007 Nov;40(3):202-6.
PMID: 17928264 DOI: 10.1016/j.jcv.2007.08.017

BACKGROUND: Difficulties in the classification of dengue infection have been documented. Such difficulties could be due to the low awareness of the World Health Organization diagnostic guidelines among clinicians.
OBJECTIVE: To study the diagnostic practices of clinicians in classifying patients as dengue fever (DF) or dengue haemorrhagic fever (DHF)/dengue shock syndrome (DSS) at the time of discharge during an outbreak.
METHODS: A prospective descriptive study of clinical features and disease classification in adult and pediatric dengue patients in the University of Malaya Medical Centre.
RESULTS: Five hundred and twenty adult and 191 pediatric patients were enrolled. Thrombocytopenia and evidence of plasma leakage were present in 8% of adult and 19% of pediatric patients. Of these, 93% and 49%, respectively, were given the discharge diagnoses of DF instead of DHF/DSS. Hemoconcentration, serous effusion and thrombocytopenia were not recognized in clinicians' discharge diagnosis of DHF/DSS for adult patients. The receiver operating characteristic (ROC) curve suggested a lack of consistency in the use of WHO guidelines in establishing DHF/DSS in adult patients, while implying otherwise for pediatric patients.
CONCLUSION: DHF/DSS is an under-recognized condition by clinicians managing these patients. This can affect the case fatality rate of DHF/DSS and the economic burden of the disease. The lack of awareness in disease manifestations especially plasma leakage, can lead to delayed recognition of DHF/DSS.
Study site: Outpatient department and inpatients, adult medical and pediatric wards, University Malaya Medical Center (UMMC), Kuala Lumpur, Malaysia

Matched MeSH terms: Area Under Curve
Computational Analysis and In silico Predictive Modeling for Inhibitors of PhoP Regulon in S. typhi on High-Throughput Screening Bioassay Dataset

Kaur H, Ahmad M, Scaria V

Interdiscip Sci, 2016 Mar;8(1):95-101.
PMID: 26298582 DOI: 10.1007/s12539-015-0273-x

There is emergence of multidrug-resistant Salmonella enterica serotype typhi in pandemic proportions throughout the world, and therefore, there is a necessity to speed up the discovery of novel molecules having different modes of action and also less influenced by the resistance formation that would be used as drug for the treatment of salmonellosis particularly typhoid fever. The PhoP regulon is well studied and has now been shown to be a critical regulator of number of gene expressions which are required for intracellular survival of S. enterica and pathophysiology of disease like typhoid. The evident roles of two-component PhoP-/PhoQ-regulated products in salmonella virulence have motivated attempts to target them therapeutically. Although the discovery process of biologically active compounds for the treatment of typhoid relies on hit-finding procedure, using high-throughput screening technology alone is very expensive, as well as time consuming when performed on large scales. With the recent advancement in combinatorial chemistry and contemporary technique for compounds synthesis, there are more and more compounds available which give ample growth of diverse compound library, but the time and endeavor required to screen these unfocused massive and diverse library have been slightly reduced in the past years. Hence, there is demand to improve the high-quality hits and success rate for high-throughput screening that required focused and biased compound library toward the particular target. Therefore, we still need an advantageous and expedient method to prioritize the molecules that will be utilized for biological screens, which saves time and is also inexpensive. In this concept, in silico methods like machine learning are widely applicable technique used to build computational model for high-throughput virtual screens to prioritize molecules for advance study. Furthermore, in computational analysis, we extended our study to identify the common enriched structural entities among the biologically active compound toward finding out the privileged scaffold.

Matched MeSH terms: Area Under Curve
Nanoemulsion-based Parenteral Drug Delivery System of Carbamazepine: Preparation, Characterization, Stability Evaluation and Blood-Brain Pharmacokinetics

Tan SL, Stanslas J, Basri M, Abedi Karjiban RA, Kirby BP, Sani D, et al.

Curr Drug Deliv, 2015;12(6):795-804.
PMID: 26324229

Carbamzepine (CBZ) was encapsulated in a parenteral oil-in-water nanoemulsion, in an attempt to improve its bioavailability. The particle size, polydispersity index and zeta potential were measured using dynamic light scattering. Other parameters such as pH, osmolality, viscosity, drug loading efficiency and entrapment efficiency were also recorded. Transmission electron microscopy revealed that emulsion droplets were almost spherical in shape and in the nano-range. The in vitro release profile was best characterized by Higuchi's equation. The parenteral nanoemulsion of CBZ showed significantly higher AUC0→5, AUC0→∞, AUMC0→5, AUMC0→∞, Cmax and lower clearance than that of CBZ solution in plasma. Additionally, parenteral nanoemulsion of CBZ showed significantly higher AUC0→∞, AUMC0→∞ and Cmaxthan that of CBZ solution in brain. The parenteral nanoemulsion of CBZ could therefore use as a carrier, worth exploring further for brain targeting.

Matched MeSH terms: Area Under Curve
Geriatric Nutrition Risk Index is comparable to the mini nutritional assessment for assessing nutritional status in elderly hospitalized patients

Abd Aziz NAS, Mohd Fahmi Teng NI, Kamarul Zaman M

Clin Nutr ESPEN, 2019 02;29:77-85.
PMID: 30661705 DOI: 10.1016/j.clnesp.2018.12.002

BACKGROUND & AIMS: Malnutrition is common among hospitalized elderly patients, and the prevalence is increasing not only in Malaysia but also in the rest of the world. The Geriatric Nutrition Risk Index (GNRI) and the Mini Nutritional Assessment (MNA) were developed to identify malnourished individuals among this group. The MNA was validated as a nutritional assessment tool for the elderly. The GNRI is simpler and more efficient than the MNA, but studies on the use of the GNRI and its validity among the Malaysian population are absent. This study aimed to determine the prevalence of malnourished hospitalized elderly patients and assess the criterion validity of the GNRI and MNA among the geriatric Malaysian population against the reference standard for malnutrition, the Subjective Global Assessment (SGA), and determine whether the optimal cutoff value of the GNRI is suitable for the Malaysian population and determine the optimal tool for use in this population.
METHODS: A cross-sectional study was conducted among 134 geriatric patients with a mean age of 68.9 ± 8.4 who stayed at acute care wards in Hospital Tuanku Ampuan Rahimah, Klang from July 2017 to August 2017. The SGA, MNA, and GNRI were administered through face-to-face interviews with all the participants who gave their consent. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the GNRI and MNA were analyzed against the SGA. Receiver-operating characteristic (ROC) curve analysis was used to obtain the area under the curve (AUC) and suitable optimal cutoff values for both the GNRI and MNA.
RESULTS: According to the SGA, MNA, and GNRI, 26.9%, 42.5%, and 44.0% of the participants were malnourished, respectively. The sensitivity, specificity, PPV, and NPV for the GNRI were 0.622, 0.977, 0.982, and 0.558, respectively, while those for the MNA were 0.611, 0.909, 0.932, and 0.533, respectively. The AUC of the GNRI was comparable to that of the MNA (0.831 and 0.898, respectively). Moreover, the optimal malnutrition cutoff value for the GNRI was 94.95.
CONCLUSIONS: The prevalence of malnutrition remains high among hospitalized elderly patients. Validity of the GNRI is comparable to that of the MNA, and use of the GNRI to assess the nutritional status of this group is proposed with the new suggested cutoff value (GNRI ≤ 94.95), as it is simpler and more efficient. Underdiagnosis of malnutrition can be prevented, possibly reducing the prevalence of malnourished hospitalized elderly patients and improving the quality of the nutritional care process practiced in Malaysia.

Matched MeSH terms: Area Under Curve
Fulltext Treatment of Autosomal Dominant Hypocalcemia Type 1 With the Calcilytic NPSP795 (SHP635)

Roberts MS, Gafni RI, Brillante B, Guthrie LC, Streit J, Gash D, et al.

J. Bone Miner. Res., 2019 09;34(9):1609-1618.
PMID: 31063613 DOI: 10.1002/jbmr.3747

Autosomal dominant hypocalcemia type 1 (ADH1) is a rare form of hypoparathyroidism caused by heterozygous, gain-of-function mutations of the calcium-sensing receptor gene (CAR). Individuals are hypocalcemic with inappropriately low parathyroid hormone (PTH) secretion and relative hypercalciuria. Calcilytics are negative allosteric modulators of the extracellular calcium receptor (CaR) and therefore may have therapeutic benefits in ADH1. Five adults with ADH1 due to four distinct CAR mutations received escalating doses of the calcilytic compound NPSP795 (SHP635) on 3 consecutive days. Pharmacokinetics, pharmacodynamics, efficacy, and safety were assessed. Parallel in vitro testing with subject CaR mutations assessed the effects of NPSP795 on cytoplasmic calcium concentrations (Ca2+i ), and ERK and p38MAPK phosphorylation. These effects were correlated with clinical responses to administration of NPSP795. NPSP795 increased plasma PTH levels in a concentration-dependent manner up to 129% above baseline (p = 0.013) at the highest exposure levels. Fractional excretion of calcium (FECa) trended down but not significantly so. Blood ionized calcium levels remained stable during NPSP795 infusion despite fasting, no calcitriol supplementation, and little calcium supplementation. NPSP795 was generally safe and well-tolerated. There was significant variability in response clinically across genotypes. In vitro, all mutant CaRs were half-maximally activated (EC50 ) at lower concentrations of extracellular calcium (Ca2+o ) compared to wild-type (WT) CaR; NPSP795 exposure increased the EC50 for all CaR activity readouts. However, the in vitro responses to NPSP795 did not correlate with any clinical parameters. NPSP795 increased plasma PTH levels in subjects with ADH1 in a dose-dependent manner, and thus, serves as proof-of-concept that calcilytics could be an effective treatment for ADH1. Albeit all mutations appear to be activating at the CaR, in vitro observations were not predictive of the in vivo phenotype or the response to calcilytics, suggesting that other parameters impact the response to the drug. © 2019 American Society for Bone and Mineral Research.

Matched MeSH terms: Area Under Curve
Pharmacokinetics of the Sri Lankan hump-nosed pit viper (Hypnale hypnale) venom following intravenous and intramuscular injections of the venom into rabbits

Tan CH, Sim SM, Gnanathasan CA, Fung SY, Tan NH

Toxicon, 2014 Mar;79:37-44.
PMID: 24412778 DOI: 10.1016/j.toxicon.2013.12.011

The knowledge of venom pharmacokinetics is essential to improve the understanding of envenomation pathophysiology. Using a double-sandwich ELISA, this study investigated the pharmacokinetics of the venom of hump-nosed pit viper (Hypnale hypnale) following intravenous and intramuscular injections into rabbits. The pharmacokinetics of the venom injected intravenously fitted a three-compartment model. There is a rapid (t1/2π = 0.4 h) and a slow (t1/2α = 0.8 h) distribution phase, followed by a long elimination phase (t1/2β = 19.3 h) with a systemic clearance of 6.8 mL h(-1) kg(-1), consistent with the prolonged abnormal hemostasis reported in H. hypnale envenomation. On intramuscular route, multiple peak concentrations observed in the beginning implied a more complex venom absorption and/or distribution pattern. The terminal half-life, volume of distribution by area and systemic clearance of the venom injected intramuscularly were nevertheless not significantly different (p > 0.05) from that of the venom injected intravenously. The intramuscular bioavailability was exceptionally low (Fi.m. = 4%), accountable for the highly varied median lethal doses between intravenous and intramuscular envenomations in animals. The findings indicate that the intramuscular route of administration does not significantly alter the pharmacokinetics of H. hypnale venom although it significantly reduces the systemic bioavailability of the venom.

Matched MeSH terms: Area Under Curve
Quantification of (+)-calanolide A, a novel and naturally occurring anti-HIV agent, by high-performance liquid chromatography in plasma from rat, dog and human

Xu ZQ, Norris KJ, Weinberg DS, Kardatzke J, Wertz P, Frank P, et al.

J Chromatogr B Biomed Sci Appl, 2000 Jun 09;742(2):267-75.
PMID: 10901131

A HPLC method was validated for quantification of (+)-calanolide A (1), a novel anti-HIV agent, in rat, dog and human plasma. The synthetic intermediate (+/-)-12-oxocalanolide A (2) was found to be a suitable internal standard. Compounds were extracted from plasma using a solid-phase C(18) cartridge and quantified over the assay range of 12.5 to 800 ng/ml. The method was utilized to determine (+)-calanolide A pharmacokinetics in rats, dogs and humans. This is the first report of a validated HPLC assay for determination of (+)-calanolide A concentrations in rat and dog plasma as well as human plasma obtained from clinical trials. There was no evidence of in vivo epimerization of (+)-calanolide A to its inactive epimer (+)-calanolide B (3).

Matched MeSH terms: Area Under Curve
Significance of lipid matrix aging on in vitro release and in vivo bioavailability

Choy YW, Khan N, Yuen KH

Int J Pharm, 2005 Aug 11;299(1-2):55-64.
PMID: 15955645

A polyglycolised glyceride carrier, Gelucire 50/13, was incorporated with paracetamol as a model drug, filled into hard gelatin capsules and stored at three different temperatures for various lengths of time. The resultant solidified matrix within the capsule was subjected to thermal analysis using differential scanning calorimetry (DSC) to ascertain its supramolecular structure. Polymorphic transformations towards more stable gelucire forms were observed upon aging the matrices, with samples stored at a temperature near the melting range of the lower temperature gelucire melting fraction showing the most profound changes. The increase in the rate of drug release from aged samples could be correlated to the alterations to the supramolecular structure of the gelucire. Accelerated drug release from aged samples could also be seen from in vivo studies using healthy human volunteers, although the extent of absorption was not affected. Therefore, even though the sustainability of release may be compromised by aging the gelucire matrices, the bioavailability of the incorporated drug is unlikely to be affected.

Matched MeSH terms: Area Under Curve
Gamma-scintigraphic study of the gastrointestinal transit and in vivo dissolution of a controlled release diclofenac sodium formulation in xanthan gum matrices

Billa N, Yuen KH, Khader MA, Omar A

Int J Pharm, 2000 May 15;201(1):109-20.
PMID: 10867269

A xanthan gum matrix controlled release tablet formulation containing diclofenac sodium was evaluated in vitro and was found to release the drug at a uniform rate. The gastrointestinal transit behaviour of the formulation as determined by gamma scintigraphy, using healthy male volunteers under fasted and fed conditions, indicated that gastric emptying was delayed with food intake. In contrast, the small intestinal transit remained practically unchanged under both food statuses. Therefore, the delay in caecal arrival observed in the fed state can be attributed to the delay in gastric emptying. Rate of diclofenac sodium absorption was generally higher in the fed state compared to the fasted state, however the total amount absorbed under both food statuses remained practically the same. The rate of in vivo dissolution of the drug in the fed state was faster compared to that in the fasted state. Thus, at the time of caecal arrival, in vivo dissolution was complete in the fed state, unlike in the fasted state, where almost 60% of the drug was delivered to the colon.

Matched MeSH terms: Area Under Curve
Fulltext MicroRNAs regulating cluster of differentiation 46 (CD46) in cardioembolic and non-cardioembolic stroke

Tan JR, Tan KS, Yong FL, Armugam A, Wang CW, Jeyaseelan K, et al.

PLoS One, 2017;12(2):e0172131.
PMID: 28199366 DOI: 10.1371/journal.pone.0172131

Ischemic stroke is a major cause of mortality and morbidity globally. Among the ischemic stroke subtypes, cardioembolic stroke is with poor functional outcome (Modified Rankin score ≥ 2). Early diagnosis of cardioembolic stroke will prove beneficial. This study examined the microRNAs targeting cluster of differentiation 46 (CD46), a potential biomarker for cardioembolic stroke. CD46 mRNA level was shown to be differentially expressed (p < 0.001) between cardioembolic stroke (median = 1.32) and non-cardioembolic stroke subtypes (large artery stroke median = 5.05; small vessel stroke median = 6.45). Bioinformatic search showed that miR-19a, -20a, -185 and -374b were found to target CD46 mRNA and further verified by luciferase reporter assay. The levels of miRNAs targeting CD46 were significantly reduced (p < 0.05) in non-cardioembolic stroke patients (large artery stroke median: miR-19a = 0.63, miR-20a = 0.42, miR-185 = 0.32, miR-374b = 0.27; small artery stroke median: miR-19a = 0.07, miR-20a = 0.06, miR-185 = 0.07, miR-374b = 0.05) as compared to cardioembolic stroke patients (median: miR-19a = 2.69, miR-20a = 1.36, miR-185 = 1.05, miR-374b = 1.23). ROC curve showed that the miRNAs could distinguish cardioembolic stroke from non-cardioembolic stroke with better AUC value as compared to CD46. Endogenous expression of CD46 in Human Umbilical Vein Endothelial Cells (HUVECs) were found to be regulated by miR-19a and miR-20a. Thus implicating that miR-19a and -20a may play a role in pathogenesis of cardioembolic stroke, possibly via the endothelial cells.

Matched MeSH terms: Area Under Curve
Validation of an informant-based cognitive screening tool for Parkinson disease

Chee KY, Ong KY, Mak CY, Yacob S, Yeo SC, Thrichelam N, et al.

Asia Pac Psychiatry, 2017 Dec;9(4).
PMID: 28326670 DOI: 10.1111/appy.12278

INTRODUCTION: The objective of this study was to establish the psychometric properties of the AD8 Dementia Screening Interview in patients with Parkinson disease (PD) with or without cognitive impairment using the Montreal Cognitive Assessment Tool (MoCA) for comparison.
METHODS: The AD8 was translated into Malay for Malay-speaking participants. A correlation analysis and a receiver operator characteristic curve were generated to establish the psychometric properties of the AD8 in relation to the MoCA.
RESULTS: One hundred fifty patients and their caretakers completed the AD8 and MoCA. Using a cutoff score of 1/8, the AD8 had 81% sensitivity and 59% specificity for the detection of cognitive impairment in PD. With a cutoff score of 2/8, the AD8 had 83% specificity and 64% sensitivity. The area under the receiver operator characteristic curve was 80%, indicating good-to-excellent discriminative ability.
DISCUSSION: These findings suggest that the AD8 can reliably differentiate between cognitively impaired and cognitively normal patients with PD and is a useful caregiver screening tool for PD.

Matched MeSH terms: Area Under Curve
Diagnostic values of different cytokines in identifying tuberculous pleural effusion

Nguyen MH, Dao QM, Bui TTH, Le VHT

Trop Biomed, 2020 Jun 01;37(2):372-378.
PMID: 33612806

Interleukin (IL)-1 beta (IL-1β), IL-2, Interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α) in the pleural fluid are valuable biomarkers in early diagnosis of Tuberculous Pleural Effusion (TPE). This study aimed to analyze the diagnostic values of some cytokines (IFN-γ, TNF-α, IL-1β, and IL-2) in pleural fluid for identifying TPE in Vietnam. We performed a cross-sectional study on tuberculosis (TB) patients with pleural effusion. Pleural IFN-γ, TNF-α, IL-1β, IL-2 were measured by ELISA® Kit (Abcam, USA) on Biotek system. Receiver operating characteristic curves (ROC), an area under the curve (AUC), sensitivity (Se), specificity (Sp), positive predictive value (PPV), negative predictive value (NPV) and accuracy (ACC) of IFN-γ, TNF-α, IL-1β, IL-2 in identifying TBE were assessed. Among 386 patients, 234 (60,6%) had TPE, and 152 (39,4%) did not have TPE. The median of IL-2, TNF-α, and IFN-γ levels were significantly higher in TPE compared to the non-TPE group (p<0.05). AUC for IL-1β, IL-2, TNF-α, and IFN-γ were 0.54, 0.57, 0.62. 0.84 (p<0.05), respectively. The sensitivity of IL-1β, IL-2, TNF-α, and IFN-γ in the diagnosis of TPE were 82.1, 53.4, 77.8, and 80.3, while the specificity was 28,4, 69.7, 47.4, and 80.9, respectively. IFN-γ and TNF-α are potential biomarkers in diagnosing TPE.

Matched MeSH terms: Area Under Curve
Enhanced oral bioavailability and intestinal lymphatic transport of a hydrophilic drug using liposomes

Ling SS, Magosso E, Khan NA, Yuen KH, Barker SA

Drug Dev Ind Pharm, 2006 Mar;32(3):335-45.
PMID: 16556538

A liposome system was evaluated for oral delivery of a poorly bioavailable hydrophilic drug. The system was prepared from proliposome, which consisted of negatively charged phosphatidylcholine, whereas cefotaxime was chosen as the model drug. An in vivo study was carried out on nine rats according to a three-way crossover design to compare the oral bioavailability of cefotaxime from the liposomal formulation with that of an aqueous drug solution and a physical mixture of cefotaxime with blank liposomes. The results indicated that the extent of bioavailability of cefotaxime was increased approximately 2.7 and 2.3 times compared with that of the aqueous solution and the physical mixture, respectively. In a separate study, simultaneous determination of cefotaxime in intestinal lymph (collected from the mesenteric lymph duct) and in plasma (collected from the tail vein) revealed that its concentration was consistently higher in the lymph than in the plasma when administered via the liposomal formulation, whereas the reverse was observed with the aqueous solution. Thus, the results indicated that the liposomes system has the potential of increasing the oral bioavailability of poorly bioavailable hydrophilic drugs and also promote their lymphatic transport in the intestinal lymph.

Matched MeSH terms: Area Under Curve
Comparative bioavailability study of two controlled-release pentoxifylline tablet preparations

Yuen KH, Wong JW, Peh KK, Julianto T, Choy WP

Drug Dev Ind Pharm, 2000 Jul;26(7):803-7.
PMID: 10872103

The bioavailability of a generic preparation of pentoxifylline sustained-release (SR) tablet was evaluated in comparison with a proprietary product (Trental 400). For the study, 12 healthy male volunteers participated; the study was conducted according to a randomized, two-way crossover design. The bioavailability was compared using the parameters total area under the plasma level-time curve AUC0-infinity, peak plasma concentration Cmax, and time to reach peak plasma concentration Tmax. No statistically significant difference was observed between the values of the two products in all three parameters. The 90% confidence interval for the ratio of the logarithmic transformed AUC0-infinity values of the generic pentoxifylline over those of Trental 400 was found to lie between 0.83 and 1.00, while that of the parameter Cmax was between 0.91 and 1.29. In addition, elimination half-life t1/2 and apparent volume of distribution Vd were calculated. There was no statistically significant difference between the t1/2 Vd values obtained from the data of the two preparations.

Matched MeSH terms: Area Under Curve

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