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LC-MS/MS quantitation of antimalarial drug piperaquine and metabolites in human plasma

Aziz MY, Hoffmann KJ, Ashton M

J Chromatogr B Analyt Technol Biomed Life Sci, 2017 Sep 15;1063:253-258.
PMID: 28863865 DOI: 10.1016/j.jchromb.2017.06.035

PURPOSE: This study aimed to develop a sensitive, quantitative assay for the antimalarial piperaquine (PQ) and its metabolites M1 and M2 in human plasma.
RESULTS: Analytes were gradiently separated on a C18 column and detected with a Sciex API 4000 MS/MS with an ESI source operated in the positive ion mode with deuterated PQ as internal standard. The response was linear in the range 3.9-2508nM with a runtime of 7.0min per sample. The method was applied to clinical samples from healthy volunteers.
CONCLUSION: This LC-MS/MS method for the simultaneous quantitation of PQ and two of its metabolites in plasma may prove helpful for assessment of metabolite safety issues in vivo.

Matched MeSH terms: Antimalarials/blood*; Quinolines/blood*
Fulltext Volumetric changes in the aging rat brain and its impact on cognitive and locomotor functions

Hamezah HS, Durani LW, Ibrahim NF, Yanagisawa D, Kato T, Shiino A, et al.

Exp Gerontol, 2017 12 01;99:69-79.
PMID: 28918364 DOI: 10.1016/j.exger.2017.09.008

Impairments in cognitive and locomotor functions usually occur with advanced age, as do changes in brain volume. This study was conducted to assess changes in brain volume, cognitive and locomotor functions, and oxidative stress levels in middle- to late-aged rats. Forty-four male Sprague-Dawley rats were divided into four groups: 14, 18, 23, and 27months of age. 1H magnetic resonance imaging (MRI) was performed using a 7.0-Tesla MR scanner system. The volumes of the lateral ventricles, medial prefrontal cortex (mPFC), hippocampus, striatum, cerebellum, and whole brain were measured. Open field, object recognition, and Morris water maze tests were conducted to assess cognitive and locomotor functions. Blood was taken for measurements of malondialdehyde (MDA), protein carbonyl content, and antioxidant enzyme activity. The lateral ventricle volumes were larger, whereas the mPFC, hippocampus, and striatum volumes were smaller in 27-month-old rats than in 14-month-old rats. In behavioral tasks, the 27-month-old rats showed less exploratory activity and poorer spatial learning and memory than did the 14-month-old rats. Biochemical measurements likewise showed increased MDA and lower glutathione peroxidase (GPx) activity in the 27-month-old rats. In conclusion, age-related increases in oxidative stress, impairment in cognitive and locomotor functions, and changes in brain volume were observed, with the most marked impairments observed in later age.

Matched MeSH terms: Malondialdehyde/blood; Biomarkers/blood
Fulltext Correlation of serum cartilage oligomeric matrix protein (COMP) and interleukin-16 (IL-16) levels with disease severity in primary knee osteoarthritis: A pilot study in a Malaysian population

Das Gupta E, Ng WR, Wong SF, Bhurhanudeen AK, Yeap SS

PLoS One, 2017;12(9):e0184802.
PMID: 28910372 DOI: 10.1371/journal.pone.0184802

OBJECTIVE: The aim of this study was to investigate the correlations between serum cartilage oligomeric matrix protein (COMP), interleukin-16 (IL-16) and different grades of knee osteoarthritis (KOA) in Malaysian subjects.

METHODS: Ninety subjects were recruited comprising 30 with Kellgren-Lawrence (K-L) grade 2 KOA, 27 with K-L grade 3 KOA, 7 with grade 4 KOA, and 30 healthy controls. All subjects completed the Western Ontario and McMaster Universities Arthritis Index (WOMAC) questionnaire. Serum COMP and IL-16 levels were measured using ELISA and their values log transformed to ensure a normal distribution.

RESULTS: There was no significant differences in levels of log serum COMP and IL-16 between healthy controls and KOA patients. There were no significant differences in the log serum COMP and IL-16 levels within the different K-L grades in the KOA patients. In KOA patients, log serum IL-16 levels significantly correlated with the WOMAC score (p = 0.001) and its subscales, pain (p = 0.005), stiffness (p = 0.019) and physical function (p<0.0001). Serum IL-16 levels were significantly higher in Malaysian Indians compared to Malays and Chinese (p = 0.024).

CONCLUSIONS: In this multi-ethnic Malaysian population, there was no difference in serum COMP and IL-16 levels between healthy controls and patients with KOA, nor was there any difference in serum COMP or IL-16 levels across the various K-L grades of KOA. However, there were significant inter-racial differences in serum IL-16 levels.

Matched MeSH terms: Interleukin-6/blood*; Cartilage Oligomeric Matrix Protein/blood*
Fulltext An internal audit of diabetes care for type 2 diabetic patients in a public hospital diabetes clinic in Malaysia

Hieng YC

Malays J Med Sci, 2017 Mar;24(2):55-60.
PMID: 28894404 MyJurnal DOI: 10.21315/mjms2017.24.2.7

INTRODUCTION: Earlier studies have identified a gap between guidelines and actual clinical diabetes care in Malaysia.
OBJECTIVE: We audited the quality of care for patients with type 2 diabetes mellitus (T2DM) attending our diabetes clinic at a public hospital.
METHODS: A structured review of the outpatient clinic cards, prescriptions and laboratory results was conducted for patients attending the diabetes clinic at Sibu Hospital in October and November 2014.
RESULTS: For the total of 233 patients who were audited, the levels of fasting blood sugar, blood pressure, body mass index and fasting lipid profile were satisfactory at 99.1%, 99.6%, 92.6% and 99.6% respectively. 79.7% of the subjects had had HbA1c performed at least once over the previous six months. Only 25.8% had annual foot screening, while the eye screening rate was 71.2% and the albuminuria screening rate was 93.6%. For outcome measures, the mean (SD) HbA1c level was 9.2% (1.91%), with 13 patients (6.7%) having HbA1c less than 6.5%; 36.4% of participants achieved BP < 130/80 mmHg; and 69.4% had LDL < 2.6 mmol/L. The majority of the patients were overweight or obese (91.4%).
CONCLUSIONS: Overall, the performance of diabetic care processes at our hospital was satisfactory, except for foot examination. The glycaemic and weight control among the subjects were suboptimal and warrant an optimised and comprehensive approach on the part of the management.

Study site: diabetes clinic at Sibu Hospital

Matched MeSH terms: Blood Glucose; Blood Pressure; Blood Pressure Determination
Toxicants in folk remedies: implications of elevated blood lead in an American-born infant due to imported diaper powder

Karwowski MP, Morman SA, Plumlee GS, Law T, Kellogg M, Woolf AD

Environ Geochem Health, 2017 Oct;39(5):1133-1143.
PMID: 27704308 DOI: 10.1007/s10653-016-9881-6

Though most childhood lead exposure in the USA results from ingestion of lead-based paint dust, non-paint sources are increasingly implicated. We present interdisciplinary findings from and policy implications of a case of elevated blood lead (13-18 mcg/dL, reference level <5 mcg/dL) in a 9-month-old infant, linked to a non-commercial Malaysian folk diaper powder. Analyses showed the powder contains 62 % lead by weight (primarily lead oxide) and elevated antimony [1000 parts per million (ppm)], arsenic (55 ppm), bismuth (110 ppm), and thallium (31 ppm). These metals are highly bioaccessible in simulated gastric fluids, but only slightly bioaccessible in simulated lung fluids and simulated urine, suggesting that the primary lead exposure routes were ingestion via hand-mouth transmission and ingestion of inhaled dusts cleared from the respiratory tract. Four weeks after discontinuing use of the powder, the infant's venous blood lead level was 8 mcg/dL. Unregulated, imported folk remedies can be a source of toxicant exposure. Additional research on import policy, product regulation, public health surveillance, and culturally sensitive risk communication is needed to develop efficacious risk reduction strategies in the USA. The more widespread use of contaminated folk remedies in the countries from which they originate is a substantial concern.

Matched MeSH terms: Lead/blood*; Hazardous Substances/blood
Fulltext Folate supplementation in people with sickle cell disease

Dixit R, Nettem S, Madan SS, Soe HH, Abas AB, Vance LD, et al.

Cochrane Database Syst Rev, 2016 Feb 16;2:CD011130.
PMID: 26880182 DOI: 10.1002/14651858.CD011130.pub2

BACKGROUND: Sickle cell disease is a group of disorders that affects haemoglobin, which causes distorted sickle- or crescent-shaped red blood cells. It is characterized by anaemia, increased susceptibility to infections and episodes of pain. The disease is acquired by inheriting abnormal genes from both parents, the combination giving rise to different forms of the disease. Due to increased erythropoiesis in people with sickle cell disease, it is hypothesized that they are at an increased risk for folate deficiency. For this reason, children and adults with sickle cell disease, particularly those with sickle cell anaemia, commonly take 1 mg of folic acid orally every day on the premise that this will replace depleted folate stores and reduce the symptoms of anaemia. It is thus important to evaluate the role of folate supplementation in treating sickle cell disease.
OBJECTIVES: To analyse the efficacy and possible adverse effects of folate supplementation (folate occurring naturally in foods, provided as fortified foods or additional supplements such as tablets) in people with sickle cell disease.
SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. We also conducted additional searches in both electronic databases and clinical trial registries.Date of last search: 07 December 2015.
SELECTION CRITERIA: Randomised, placebo-controlled trials of folate supplementation for sickle cell disease.
DATA COLLECTION AND ANALYSIS: Four review authors assessed the eligibility and risk of bias of the included trials and extracted and analysed the data included in the review. We used the standard Cochrane-defined methodological procedures.
MAIN RESULTS: One trial, undertaken in 1983, was eligible for inclusion in the review. This was a double-blind placebo-controlled quasi-randomised triaI of supplementation of folic acid in people with sickle cell disease. A total of 117 children with homozygous sickle cell (SS) disease aged six months to four years of age participated over a one-year period (analysis was restricted to 115 children).Serum folate measures, obtained after trial entry at six and 12 months, were available in 80 of 115 (70%) participants. There were significant differences between the folic acid and placebo groups with regards to serum folate values above 18 µg/l and values below 5 µg/l. In the folic acid group, values above 18 µg/l were observed in 33 of 41 (81 %) compared to six of 39 (15%) participants in the placebo (calcium lactate) group. Additionally, there were no participants in the folic acid group with serum folate levels below 5 µg/l, whereas in the placebo group, 15 of 39 (39%) participants had levels below this threshold. Haematological indices were measured in 100 of 115 (87%) participants at baseline and at one year. After adjusting for sex and age group, the investigators reported no significant differences between the trial groups with regards to total haemoglobin concentrations, either at baseline or at one year. It is important to note that none of the raw data for the outcomes listed above were available for analysis.The proportions of participants who experienced certain clinical events were analysed in all 115 participants, for which raw data were available. There were no statistically significant differences noted; however, the trial was not powered to investigate differences between the folic acid and placebo groups with regards to: minor infections, risk ratio 0.99 (95% confidence interval 0.85 to 1.15); major infections, risk ratio 0.89 (95% confidence interval 0.47 to 1.66); dactylitis, risk ratio 0.67 (95% confidence interval 0.35 to 1.27); acute splenic sequestration, risk ratio 1.07 (95% confidence interval 0.44 to 2.57); or episodes of pain, risk ratio 1.16 (95% confidence interval 0.70 to 1.92). However, the investigators reported a higher proportion of repeat dactylitis episodes in the placebo group, with two or more attacks occurring in 10 of 56 participants compared to two of 59 in the folic acid group (P < 0.05).Growth, determined by height-for-age and weight-for-age, as well as height and growth velocity, was measured in 103 of the 115 participants (90%), for which raw data were not available. The investigators reported no significant differences in growth between the two groups.The trial had a high risk of bias with regards to random sequence generation and incomplete outcome data. There was an unclear risk of bias in relation to allocation concealment, outcome assessment, and selective reporting. Finally, There was a low risk of bias with regards to blinding of participants and personnel. Overall the quality of the evidence in the review was low.There were no trials identified for other eligible comparisons, namely: folate supplementation (fortified foods and physical supplementation with tablets) versus placebo; folate supplementation (naturally occurring in diet) versus placebo; folate supplementation (fortified foods and physical supplementation with tablets) versus folate supplementation (naturally occurring in diet).
AUTHORS' CONCLUSIONS: One doubIe-blind, placebo-controlled triaI on folic acid supplementation in children with sickle cell disease was included in the review. Overall, the trial presented mixed evidence on the review's outcomes. No trials in adults were identified. With the limited evidence provided, we conclude that, while it is possible that folic acid supplementation may increase serum folate levels, the effect of supplementation on anaemia and any symptoms of anaemia remains unclear.Further trials may add evidence regarding the efficacy of folate supplementation. Future trials should assess clinical outcomes such as folate concentration, haemoglobin concentration, adverse effects and benefits of the intervention, especially with regards to sickle cell disease-related morbidity. Trials should include people with sickle cell disease of all ages and both sexes, in any setting. To investigate the effects of folate supplementation, trials should recruit more participants and be of longer duration, with long-term follow up, than the trial currently included in this review.

Matched MeSH terms: Anemia, Sickle Cell/blood; Folic Acid/blood
Leptospirosis in human: Biomarkers in host immune responses

Vk C, Ty L, Wf L, Ywy WS, An S, S Z, et al.

Microbiol Res, 2018 Mar;207:108-115.
PMID: 29458845 DOI: 10.1016/j.micres.2017.11.015

Leptospirosis remains one of the most widespread zoonotic diseases caused by spirochetes of the genus Leptospira, which accounts for high morbidity and mortality globally. Leptospiral infections are often found in tropical and subtropical regions, with people exposed to contaminated environments or animal reservoirs are at high risk of getting the infection. Leptospirosis has a wide range of clinical manifestations with non-specific signs and symptoms and often misdiagnosed with other acute febrile illnesses at early stage of infection. Despite being one of the leading causes of zoonotic morbidity worldwide, there is still a gap between pathogenesis and human immune responses during leptospiral infection. It still remains obscure whether the severity of the infection is caused by the pathogenic properties of the Leptospira itself, or it is a consequence of imbalance host immune factors. Hence, in this review, we seek to summarize the past and present milestone findings on the biomarkers of host immune response aspects during human leptospiral infection, including cytokine and other immune mediators. A profound understanding of the interlink between virulence factors and host immune responses during human leptospirosis is imperative to identify potential biomarkers for diagnostic and prognostic applications as well as designing novel immunotherapeutic strategies in future.

Matched MeSH terms: Biomarkers/blood; Cytokines/blood
Clinical efficacy and safety evaluation of tailoring iron chelation practice in thalassaemia patients from Asia-Pacific: a subanalysis of the EPIC study of deferasirox

Viprakasit V, Ibrahim H, Ha SY, Ho PJ, Li CK, Chan LL, et al.

Int J Hematol, 2011 Mar;93(3):319-328.
PMID: 21374076 DOI: 10.1007/s12185-011-0789-8

Although thalassaemia is highly prevalent in the Asia-Pacific region, clinical data on efficacy and safety profiles of deferasirox in patients from this region are rather limited. Recently, data from the multicentre Evaluation of Patients' Iron Chelation with Exjade (EPIC) study in 1744 patients with different anaemias has provided an opportunity to analyse 1115 thalassaemia patients, of whom 444 patients were from five countries in the Asia-Pacific region (AP) for whom thalassaemia management and choice of iron chelators were similar. Compared to the rest of the world (ROW), baseline clinical data showed that the AP group appeared to be more loaded with iron (3745.0 vs. 2822.0 ng/ml) and had a higher proportion on deferoxamine monotherapy prior to the study (82.9 vs. 58.9%). Using a starting deferasirox dose based on transfusional iron intake and tailoring it to individual patient response, clinical efficacy based on serum ferritin reduction in AP and ROW thalassaemia patients was similar. Interestingly, the AP group developed a higher incidence of drug-related skin rash compared to ROW (18.0 vs. 7.2%), which may indicate different pharmacogenetic backgrounds in the two populations. Our analysis confirms that, with appropriate adjustment of dose, deferasirox can be clinically effective across different regions, with manageable side effects.

Matched MeSH terms: Ferritins/blood; Thalassemia/blood
Fulltext Reduced red blood cell deformability in Plasmodium knowlesi malaria

Barber BE, Russell B, Grigg MJ, Zhang R, William T, Amir A, et al.

Blood Adv, 2018 02 27;2(4):433-443.
PMID: 29487058 DOI: 10.1182/bloodadvances.2017013730

The simian parasite Plasmodium knowlesi can cause severe and fatal human malaria. However, little is known about the pathogenesis of this disease. In falciparum malaria, reduced red blood cell deformability (RBC-D) contributes to microvascular obstruction and impaired organ perfusion. In P knowlesi infection, impaired microcirculatory flow has been observed in Macaca mulatta (rhesus macaques), unnatural hosts who develop severe and fatal disease. However, RBC-D has not been measured in human infection or in the natural host M fascicularis (long-tailed macaques). Using ektacytometry, we measured RBC-D in adults with severe and non-severe knowlesi and falciparum malaria and in healthy controls. In addition, we used micropipette aspiration to determine the relative stiffness of infected RBCs (iRBCs) and uninfected RBCs (uRBCs) in P knowlesi-infected humans and M fascicularis Ektacytometry demonstrated that RBC-D overall was reduced in human knowlesi malaria in proportion to disease severity, and in severe knowlesi malaria, it was comparable to that of severe falciparum malaria. RBC-D correlated inversely with parasitemia and lactate in knowlesi malaria and HRP2 in falciparum malaria, and it correlated with hemoglobin nadir in knowlesi malaria. Micropipette aspiration confirmed that in humans, P knowlesi infection increased stiffness of both iRBCs and uRBCs, with the latter mostly the result of echinocytosis. In contrast, in the natural host M fascicularis, echinocyte formation was not observed, and the RBC-D of uRBCs was unaffected. In unnatural primate hosts of P knowlesi, including humans, reduced deformability of iRBCs and uRBCs may represent a key pathogenic mechanism leading to microvascular accumulation, impaired organ perfusion, and anemia.

Matched MeSH terms: Malaria/blood*; Malaria, Falciparum/blood
Fulltext Neutrophil-lymphocyte ratios in the prognostication of primary non-metastatic nasopharyngeal carcinoma

Liew KY, Zulkiflee AB

Braz J Otorhinolaryngol, 2017 10 19;84(6):764-771.
PMID: 29128472 DOI: 10.1016/j.bjorl.2017.09.004

INTRODUCTION: Nasopharyngeal carcinoma is a geographically and racially variable disease which has a high incidence in Malaysia. Based on current concepts in tumour related inflammation the inflammatory marker, neutrophil-lymphocyte ratio was tested to find its relationship with prognosis in nasopharyngeal carcinoma.
OBJECTIVE: To investigate the effect of the neutrophil-lymphocyte ratio on prognosis in non-metastatic primary nasopharyngeal carcinoma patients and to further refine the cut off between high and low neutrophil-lymphocyte ratio values.
METHODS: The medical charts of patients with histologically confirmed nasopharyngeal carcinoma from 1st January 2005 until 31st December 2009 were reviewed retrospectively and theneutrophil-lymphocyte ratio was calculated to see if there was any association between their higher values with higher failure rates.
RESULTS: Records of 98 patients (n=98) were retrieved and reviewed. Only neutrophil-lymphocyte ratio (p=0.004) and tumor node metastasis staging (p=0.002) were significantly different between recurrent and non-recurrent groups, with the neutrophil-lymphocyte ratio being independent of tumor node metastasis staging (p=0.007). Treatment failure was significantly higher in the high neutrophil-lymphocyte ratio group (p=0.001). Disease free survival was also significantly higher in this group (p=0.000077).
CONCLUSION: High neutrophil-lymphocyte ratio values are associated with higher rates of recurrence and worse disease free survival in non-metastatic nasopharyngeal carcinoma patients undergoing primary curative treatment.

Matched MeSH terms: Neoplasm Recurrence, Local/blood*; Biomarkers, Tumor/blood
Fulltext Pre-transplantation serum ferritin as a prognostic marker in allogeneic haemopoietic stem cell transplant patients in a tertiary care hospital in Malaysia

Thambiah SC, George E, Samsudin IN, Hong LH, Chuo LL, Ramli N, et al.

Natl Med J India, 2016 May-Jun;29(3):136-140.
PMID: 27808061

BACKGROUND: The principal cause of iron overload in patients with haematological malignancies is recurrent red cell transfusions for anaemia. The serum ferritin level reflects the iron burden in the body, in the absence of inflammation or liver disease. In Malaysia, data are lacking on the association between pre-transplant serum ferritin levels and outcome after allogeneic haemopoietic stem cell transplant.

METHODS: We did a cross-sectional study using retrospective data of 106 post-allogeneic haemopoietic stem cell transplant patients (HLA-matched sibling) with haematological malignancies at Hospital Ampang to determine the relationship between pre-transplant serum ferritin levels and post-transplant outcome, post-transplant complications and survival time. Patients were divided into two groups according to the iron status: serum ferritin level >1000 μg/L (iron overload) and <1000 μg/L.

RESULTS: The median age for patients was 30.5 (18-58) years. The median pre-transplantation serum ferritin level and the prevalence of pre-transplantation iron overload were 2423 (408.2-7664) μg/L and 87.5%, respectively. No significant association was found between iron status and demographic factors, type of haematological malignancy and post-transplant complications. Although insignificant, patients with iron overload had a shorter survival time (36 months) compared to those with no iron overload (40 months). There was also no significant association between the iron status and post-transplant outcome. Significant post-transplant complications associated with post-transplant outcome were the need for total parenteral nutrition (TPN) (p=0.014) and chronic graft-versus-host disease (GVHD) (p=0.008). Similarly, significant associations were found between age group (p=0.003), TPN (p=0.035) and chronic GVHD (p=0.012) with survival time using Kaplan-Meir analysis. However, after Cox regression, only age group was found to be significantly associated with survival time (p=0.014).

CONCLUSION: Serum ferritin is an acute phase reactant and its levels increase in the presence of tissue necrosis and inflammation. Both these events occur in haematological malignancies. Although serum ferritin level is a non-invasive, relatively cost-effective, widely available and practical indicator of iron status, it is not specific to iron overload. Therefore, a true association between the serum ferritin level and iron burden is problematic in patients with haematological malignancies.

Matched MeSH terms: Ferritins/blood*; Biomarkers/blood*
Impact of late pregnancy haemoglobin A1c at 29-30 weeks' gestation on adverse pregnancy outcomes among women with pre-existing diabetes: a retrospective analysis

Yong SL, Ng BK, Mohd Yassin MAJ, Syed Zakaria SZ, Mohamed Ismail NA

J Obstet Gynaecol, 2018 May;38(4):461-465.
PMID: 29390907 DOI: 10.1080/01443615.2017.1372397

This study was to assess the relationship between late pregnancy haemoglobin A1C (HbA1C) at 29-30 weeks of gestation and adverse pregnancy outcomes (APOs) in 272 pregnant women with pre-existing diabetes. HbA1C ≥6.1% was associated with significantly increased risk of preterm delivery, Caesarean section, large for gestational age (LGA), neonatal respiratory distress, neonatal hypoglycaemia, and composite adverse neonatal outcome (p 5.6% (p = .039). Reduction of HbA1C cut-off from 6.1% to 5.6% improved the sensitivity but reduced the specificity for prediction of APOs. Overall, the receiver operating characteristic (ROC) curves demonstrated the moderate predictive value of late pregnancy HbA1C for APOs. In conclusion, elevated late pregnancy HbA1C levels at 29-30 gestational weeks had a negative impact on APOs in pregnant women with pre-existing diabetes. However, HbA1C cut-off levels of neither ≥6.1% nor >5.6% were ideal for predicting APOs. Impact statement What is already known on this subject: Poorly controlled diabetes is associated with adverse pregnancy outcomes (APOs). Periconceptual haemoglobin A1C (HbA1C) correlates well with the risk of foetal anomaly but is not predictive of APOs at time of delivery. New evidence suggested that late pregnancy HbA1C is predictive of APOs but the definitions of a late pregnancy gestational week and target HbA1C cutpoint remain in doubt. What the results of this study add: This study investigated the relationship between late pregnancy HbA1C levels at 29-30 weeks of gestation and the APOs among pregnant women with pre-existing diabetes. Late pregnancy HbA1C ≥ 6.1% correlated with the risk of APOs but the increased risk of pre-eclampsia only became significant at the lower cut-off of >5.6%. Reducing HbA1C cut-off from 6.1% to 5.6% improved the sensitivity but reduced the specificity for prediction of APOs. Overall, late pregnancy HbA1C had a moderate predictive value for APOs. What the implications are of these findings for clinical practice and/or further research: HbA1C cut-off levels of neither ≥6.1% nor >5.6% were ideal in predicting APOs among pregnant women with pre-existing diabetes. As HbA1C levels tend to drop in pregnancy, caution should be taken when interpreting HbA1C in pregnancy. More multi-centred studies are required to explore the respective glycaemic target for each APO and to determine the ideal timing for late pregnancy HbA1C measurement.

Matched MeSH terms: Pregnancy in Diabetics/blood*; Pregnancy Trimester, Third/blood*
Simultaneous determination of 25-hydroxyvitamin D2 and 25-hydroxyvitamin D3 in human serum by ultra performance liquid chromatography: An economical and validated method with bovine serum albumin

Chin SF, Osman J, Jamal R

Clin Chim Acta, 2018 Oct;485:60-66.
PMID: 29935177 DOI: 10.1016/j.cca.2018.06.024

A simple and economical method has been developed for simultaneous determination of human serum 25-hydroxyvitamin D2 (25OHD2) and 25-hydroxyvitamin D3 (25OHD3) using Ultra Performance Liquid Chromatography (UPLC). Non-human matrix of 4% BSA was used to construct the calibration curve and in quality control samples' preparation to avoid interference of the endogenous 25-hydroxyvitamin D (25OHD) present in the human serum. 25OHD2, 25OHD3 and dodecanophenone (internal standard, IS) were separated on a CORTECS solid-core particle column and monitored by photodiode array detector at wavelength of 265 nm within five min run time. The relationship between 25OHD concentration and peak area ratio (25OHD:IS) was linear over the range of 12.5 - 200 nM with mean correlation coefficients (r2) >0.998. The limit of detection (LOD) for 25OHD2 and 25OHD3 was 3.00 nM and 3.79 nM, while the lower limit of quantification (LLOQ) was 9.11 nM and 11.48 nM, respectively. High repeatability was obtained for both isomers with intra-day CV% <5.6% and <5.3% for inter-day assay. This method was further tested with a commercial lyophilized serum control with an accuracy of 92.87-108.31% and applied on 214 human serum samples. In summary, this validated method with BSA can be reliably applied for routine quantification of 25OHD in adults.

Matched MeSH terms: Calcifediol/blood*; 25-Hydroxyvitamin D 2/blood*
Fulltext Vitamin D non-sufficiency is prevalent in children with chronic liver disease in a tropical country

Lee WS, Jalaludin MY, Wong SY, Ong SY, Foo HW, Ng RT

Pediatr Neonatol, 2019 02;60(1):12-18.
PMID: 29680189 DOI: 10.1016/j.pedneo.2018.03.011

BACKGROUND: To determine vitamin D status in children with chronic liver disease (CLD) in a tropical country.
METHODS: Cross-sectional study in Malaysian children with CLD. Factors affecting serum vitamin D level (definition: deficient

Matched MeSH terms: Liver Diseases/blood; Vitamin D/blood
Improvement of bone turnover markers and bone mineral density following treatment of primary aldosteronism

Loh HH, Kamaruddin NA, Zakaria R, Sukor N

Minerva Endocrinol., 2018 Jun;43(2):117-125.
PMID: 28001017 DOI: 10.23736/S0391-1977.16.02553-0

BACKGROUND: Recent studies showed association between hyperaldosteronism and low bone density among patients with primary aldosteronism (PA) due to secondary hyperparathyroidism. Our objective is to assess bone turnover markers (BTM) and bone mineral density (BMD) of PA patients compared to essential hypertension.
METHODS: This was an open-label, prospective, case-controlled study, conducted over 12 months. Fifty-two consecutive patients referred for secondary hypertension were screened. Eighteen patients with confirmed PA (diagnosis based on the Endocrine Society clinical guideline) and seventeen matched controls with essential hypertension were recruited. BTM (CTX and P1NP), BMD, intact parathyroid hormone (iPTH), and bone profile were assessed at baseline and three months following treatment among the PA patients. Calcium intake was assessed using a validated questionnaire. Primary outcomes were the changes of bone markers and BMD following treatment of PA, and their relation to other parameters.
RESULTS: PA patients had significantly lower serum calcium and higher iPTH despite comparable vitamin D levels with control group. Both BTM were significantly higher among the PA group. BMD of lumbar spine, neck of femur and distal radius did not differ between groups. Three months following treatment, there were significant: 1) reduction in BTM; 2) improvement in the lumbar spine BMD; 3) reduction in iPTH level; and 4) increment of serum 25-OH vitamin D level.
CONCLUSIONS: Our findings support that bone loss and potential fracture risk among PA patients are likely a result of aldosterone-mediated secondary hyperparathyroidism. Patients with early PA may already exhibit increased bone turnover despite no significant changes in BMD.

Matched MeSH terms: Hyperaldosteronism/blood*; Biomarkers/blood*
Fulltext Ocular Blood Flow in Rabbits under Deep Anesthesia: A Real-Time Measurement Technique and Its Application in Characterizing Retinal Ischemia

Bhatti MS, Tang TB, Chen HC

Sci Rep, 2018 04 09;8(1):5713.
PMID: 29632320 DOI: 10.1038/s41598-018-24141-4

In this study, we reported a new technique based on laser speckle flowgraphy to record the ocular blood flow in rabbits under deep anesthesia, and proposed parameters to characterize retinal ischemia. We applied the proposed technique to study the correlation of blood flow between the eyes of normal non-anesthetized animals, and to characterize the occlusion of the internal carotid artery (ICA) and external carotid artery (ECA). We established a correlation in blood flow between the eyes of non-anesthetized animals, and derived two new parameters, namely, the laterality index and vascular perfusion estimate (VPE). Our experimental results from 16 eyes (of 13 New Zealand white rabbits) showed a reduction in ocular blood flow with a significant decrease in the VPE after the occlusion of the ECA (p blood flow was observed with the occlusion of the ICA. In conclusion, we demonstrated a means for the real-time measurement of the ocular blood flow in rabbits under deep anesthesia by using laser speckle flowgraphy and the VPE as an indicator of successful occlusion. The proposed technique might be applicable in quantifying the efficacy of new drugs and interventions for the treatment of retinal ischemia.

Matched MeSH terms: Eye/blood supply*; Regional Blood Flow
Au/Pd@rGO nanocomposite decorated with poly (L-Cysteine) as a probe for simultaneous sensitive electrochemical determination of anticancer drugs, Ifosfamide and Etoposide

Hatamluyi B, Lorestani F, Es'haghi Z

Biosens Bioelectron, 2018 Nov 30;120:22-29.
PMID: 30144642 DOI: 10.1016/j.bios.2018.08.008

The simultaneous measurement of the concentration of anticancer drugs with a fast, sensitive and accurate method in biological samples is a challenge for better monitoring of drug therapy and better determine the pharmacokinetics. An electrochemical sensor was developed for the simultaneous determination of anticancer drugs, Ifosfamide (IFO) and Etoposide (ETO) based on pencil graphite electrode modified with Au/Pd@rGO nanocomposite decorated with poly (L-Cysteine). Cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) were utilized to study the properties of the modified electrode. The electrochemical behavior of IFO and ETO on the Au/Pd@rGO@p(L-Cys) modified electrode was investigated by cyclic voltammetry and differential pulse voltammetry (DPV) techniques and the obtained results confirmed its efficiency for the individual and simultaneous sensing of IFO and ETO. After optimization of electrochemical parameters, the fabricated sensor presented excellent performance in simultaneous determination of IFO and ETO with a wide linear range from 0.10 to 90.0 μM and 0.01 to 40.0 μM and low detection limits (3 Sb/m) of 9.210 nM and 0.718 nM, respectively. In addition, this study proved that the constructed sensor could be useful to simultaneous analysis of IFO and ETO in biological samples and pharmaceutical compounds.

Matched MeSH terms: Etoposide/blood; Ifosfamide/blood
Fulltext Renal-limited AL amyloidosis - a diagnostic and management dilemma

Fuah KW, Lim CTS

BMC Nephrol, 2018 11 06;19(1):307.
PMID: 30400895 DOI: 10.1186/s12882-018-1118-8

BACKGROUND: Amyloidosis is a disorder caused by extracellular tissue deposition of insoluble fibrils which may result in a wide spectrum of symptoms depending upon their types, sites and amount of deposition. Amyloidosis can be divided into either systemic or localized disease.
CASE PRESENTATION: We present a case of a middle-aged gentleman who presented with persistent nephrotic syndrome with worsening renal function. Repeated renal biopsies showed the presence of renal-limited AL amyloidosis. Systemic amyloidosis workup was unremarkable apart from a slightly raised band of IgG lambda level with no associated immunoparesis. The nephrotic syndrome and renal histology did not improve over a 3-year period despite being given two courses of chemotherapies.
CONCLUSION: We hope that early recognition of this unusual localised presentation of renal- limited AL Amyloidosis and its poor response to conventional treatment can alert the nephrologist to the potential existence of this rare condition.

Matched MeSH terms: Amyloidosis/blood*; Nephrotic Syndrome/blood*
Fulltext Effects of weight loss intervention on body composition and blood pressure among overweight and obese women: findings from the MyBFF@home study

Fazliana M, Liyana AZ, Omar A, Ambak R, Mohamad Nor NS, Shamsudin UK, et al.

BMC Womens Health, 2018 07 19;18(Suppl 1):93.
PMID: 30066641 DOI: 10.1186/s12905-018-0592-2

BACKGROUND: Obesity is related to the increased incidence of hypertension and in healthy individuals, blood pressure changes with age and body mass. The aims of this paper were to evaluate the effectiveness of the weight loss intervention on body composition and blood pressure, and to evaluate the relationship between these factors among housewives in the MyBFF@home study.
METHODS: MyBFF@home intervention was a quasi-experimental study which involved 328 overweight and obese housewives aged 18-59 years old (Control group: 159, Intervention group: 169). Data of the control and intervention group (pre and post intervention who completed the body composition and blood pressure measurements were analysed. Body compositions were measured using the Body Impedance Analyser (InBody 720) and blood pressure (Systolic and Diastolic) was taken using the blood pressure monitoring device (Omron HEM 907) at baseline, 6 month and 12 month. Data analyses (Pearson's correlation test and ANOVA) were performed and analysed using SPSS Statistics for Windows, version 22.0.
RESULTS: Visceral fat area, fat mass and body fat percentage, were all significantly decreased in the intervention group compared to the control group after 6 month intervention (p blood pressure was reduced significantly by - 6.81 mmHg (95% CI: -9.72,-3.90; p blood pressure was significantly correlated with BMI (r = 0.19), waist circumference (r = 0.23), body fat mass (r = 0.22), body fat percentage (r = 0.18) visceral fat area (r = 0.22) and skeletal muscle mass (r = 0.14) with p blood pressure were detected in both groups.
CONCLUSION: There were significant changes in the body fat and systolic blood pressure over 6 month among the participants in the intervention group compared to the control group. However, both groups were unable to sustain the positive changes in the body fats during the maintenance phase. There was a relationship between the body composition and blood pressure during the weight loss intervention and weight loss maintenance phase. Participation among obese housewives in a community-based intervention programme led to the improvements in blood pressure and body composition.

Matched MeSH terms: Blood Pressure/physiology*; Blood Pressure Determination
Probiotic Lactobacillus plantarum P8 alleviated stress and anxiety while enhancing memory and cognition in stressed adults: A randomised, double-blind, placebo-controlled study

Lew LC, Hor YY, Yusoff NAA, Choi SB, Yusoff MSB, Roslan NS, et al.

Clin Nutr, 2019 10;38(5):2053-2064.
PMID: 30266270 DOI: 10.1016/j.clnu.2018.09.010

BACKGROUND & AIMS: To investigate the effects of probiotic in alleviation of stress in stressed adults, along our focus to identify and justify strain specificity on selected health benefits with a precisely targeted population.
METHODS: This 12-weeks randomized, double-blind and placebo-controlled study investigated the effects of a probiotic (Lactobacillus plantarum P8; 10 log CFU daily) on psychological, memory and cognition parameters in one hundred and three (P8 n = 52, placebo n = 51) stressed adults with mean age of 31.7 ± 11.1 years old. All subjects fulfilled the criteria of moderate stress upon diagnosis using the PSS-10 questionnaire.
RESULTS: At the end of study, subjects on P8 showed reduced scores of stress (mean difference 2.94; 95% CI 0.08 to 5.73; P = 0.048), anxiety (mean difference 2.82; 95% CI 0.35 to 5.30; P = 0.031) and total score (mean difference 8.04; 95% CI 0.73 to 15.30; P = 0.041) as compared to placebo after 4-weeks, as assessed by the DASS-42 questionnaire. Although plasma cortisol levels were only marginally different between placebo and P8 (mean difference 3.28 ug/dl; 95% CI -7.09 to 0.52; P = 0.090), pro-inflammatory cytokines such as IFN-γ (mean difference 8.07 pg/ml; 95% CI -11.2 to -4.93; P

Matched MeSH terms: Hydrocortisone/blood; Cytokines/blood

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