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Evaluation of dietary taste patterns as assessed by FFQ against 24-h recalls and biomarkers of exposure

van Langeveld AWB, Teo PS, Mars M, Feskens EJM, de Graaf C, de Vries JHM

Eur J Clin Nutr, 2019 01;73(1):132-140.
PMID: 30254242 DOI: 10.1038/s41430-018-0300-1

BACKGROUND/OBJECTIVE: Taste is of key importance in food choice and dietary patterns, but studies on taste profiles are limited. We previously assessed dietary taste patterns by 24 h recalls (24hR), but for epidemiological studies food frequency questionnaires (FFQ) may also be suitable. This study compared dietary taste patterns based on FFQ against 24hR and biomarkers of exposure.
SUBJECTS/METHODS: A taste database including 467 foods' sweet, sour, bitter, salt, umami and fat sensation values was combined with food intake data to assess dietary taste patterns: the contribution to energy intake of 6 taste clusters. The FFQ's reliability was assessed against 3-d 24hR and urinary biomarkers for sodium (Na) and protein intake (N) in Dutch men (n = 449) and women (n = 397) from the NQplus validation study (mean age 53 ± 11 y, BMI 26 ± 4 kg/m2).
RESULTS: Correlations of dietary taste patterns ranged from 0.39-0.68 between FFQ and 24hR (p
Temperature dependence of the Raman spectrum of 1-(4-chlorophenyl)-3-(2-thienyl)prop-2-en-1-one

de Toledo TA, da Costa RC, Al-Maqtari HM, Jamalis J, Pizani PS

Spectrochim Acta A Mol Biomol Spectrosc, 2017 Jun 05;180:9-17.
PMID: 28259100 DOI: 10.1016/j.saa.2017.02.051

The heterocyclic chalcone containing thiophene ring 1-(4-chlorophenyl)-3-(2-thienyl)prop-2-en-1-one, C13H9ClOS was synthesized and investigated using experimental techniques such as nuclear magnetic resonance (1H and 13C NMR), Fourier transform infrared spectroscopy (FTIR) at room temperature, differential scanning calorimeter (DSC) from room temperature to 500K and Raman scattering at the temperature range 10-413K in order to study its structure and vibrational properties as well as stability and possible phase transition. Density functional theory (DFT) calculations were performed to determine the vibrational spectrum viewing to improve the knowledge of the material properties. A reasonable agreement was observed between theoretical and experimental Raman spectrum taken at 10K since anharmonic effects of the molecular motion is reduced at low temperatures, leading to a more comprehensive assignment of the vibrational modes. Increasing the temperature up to 393K, was observed the typical phonon anharmonicity behavior associated to changes in the Raman line intensities, line-widths and red-shift, in special in the external mode region, whereas the internal modes region remains almost unchanged due its strong chemical bonds. Furthermore, C13H9ClOS goes to melting phase transition in the temperature range 393-403K and then sublimates in the temperature range 403-413K. This is denounced by the disappearance of the external modes and the absence of internal modes in the Raman spectra, in accordance with DSC curve. The enthalpy (ΔH) obtained from the integration of the endothermic peak in DSC curve centered at 397K is founded to be 121.5J/g.
Alpha lipoic acid possess dual antioxidant and lipid lowering properties in atherosclerotic-induced New Zealand White rabbit

Zulkhairi A, Zaiton Z, Jamaluddin M, Sharida F, Mohd TH, Hasnah B, et al.

Biomed Pharmacother, 2008 Dec;62(10):716-22.
PMID: 18538528 DOI: 10.1016/j.biopha.2006.12.003

There is accumulating data demonstrated hypercholesterolemia and oxidative stress play an important role in the development of atherosclerosis. In the present study, a protective activity of alpha-lipoic acid; a metabolic antioxidant in hypercholesterolemic-induced animals was investigated. Eighteen adult male New Zealand White (NZW) rabbit were segregated into three groups labelled as group K, AT and ALA (n=6). While group K was fed with normal chow and acted as a control, the rest fed with 100 g/head/day with 1% high cholesterol diet to induce hypercholesterolemia. 4.2 mg/body weight of alpha lipoic acid was supplemented daily to the ALA group. Drinking water was given ad-libitum. The study was designed for 10 weeks. Blood sampling was taken from the ear lobe vein at the beginning of the study, week 5 and week 10 and plasma was prepared for lipid profile estimation and microsomal lipid peroxidation index indicated with malondialdehyde (MDA) formation. Animals were sacrificed at the end of the study and the aortas were excised for intimal lesion analysis. The results showed a significant reduction of lipid peroxidation index indicated with low MDA level (p<0.05) in ALA group compared to that of the AT group. The blood total cholesterol (TCHOL) and low density lipoprotein (LDL) levels were found to be significantly low in ALA group compared to that of the AT group (p<0.05). Histomorphometric intimal lesion analysis of the aorta showing less of atheromatous plaque formation in alpha lipoic acid supplemented group (p<0.05) compared to that of AT group. These findings suggested that apart from its antioxidant activity, alpha lipoic acid may also posses a lipid lowering effect indicated with low plasma TCHOL and LDL levels and reduced the athero-lesion formation in rabbits fed a high cholesterol diet.
Fulltext Twenty Years of the Malaysian Association of Medical Physics: Looking Back to Move Forwards

Zin, H. M.

Physics and Technology in Medicine, 2020;1(2):1-6.
MyJurnal

The Malaysian Association of Medical Physics (MAMP) was set up in the year 2000 to promote and further develop the field that was relatively new in Malaysia. The article briefly summarises key developments in medical physics since the first discovery of x-rays in 1895. The resulted rapid progress in the field was also highlighted and related to the pace of development in Malaysia. Key activities organised by MAMP were also addressed. The international practices related to the field and the profession were highlighted and compared to the current status in Malaysia. Although the field has progressed well in the country, there are several gaps identified to further improve the field and the profession in Malaysia.
Fulltext Three new pancreatic cancer susceptibility signals identified on chromosomes 1q32.1, 5p15.33 and 8q24.21

Zhang M, Wang Z, Obazee O, Jia J, Childs EJ, Hoskins J, et al.

Oncotarget, 2016 Oct 11;7(41):66328-66343.
PMID: 27579533 DOI: 10.18632/oncotarget.11041

Genome-wide association studies (GWAS) have identified common pancreatic cancer susceptibility variants at 13 chromosomal loci in individuals of European descent. To identify new susceptibility variants, we performed imputation based on 1000 Genomes (1000G) Project data and association analysis using 5,107 case and 8,845 control subjects from 27 cohort and case-control studies that participated in the PanScan I-III GWAS. This analysis, in combination with a two-staged replication in an additional 6,076 case and 7,555 control subjects from the PANcreatic Disease ReseArch (PANDoRA) and Pancreatic Cancer Case-Control (PanC4) Consortia uncovered 3 new pancreatic cancer risk signals marked by single nucleotide polymorphisms (SNPs) rs2816938 at chromosome 1q32.1 (per allele odds ratio (OR) = 1.20, P = 4.88x10 -15), rs10094872 at 8q24.21 (OR = 1.15, P = 3.22x10 -9) and rs35226131 at 5p15.33 (OR = 0.71, P = 1.70x10 -8). These SNPs represent independent risk variants at previously identified pancreatic cancer risk loci on chr1q32.1 ( NR5A2), chr8q24.21 ( MYC) and chr5p15.33 ( CLPTM1L- TERT) as per analyses conditioned on previously reported susceptibility variants. We assessed expression of candidate genes at the three risk loci in histologically normal ( n = 10) and tumor ( n = 8) derived pancreatic tissue samples and observed a marked reduction of NR5A2 expression (chr1q32.1) in the tumors (fold change -7.6, P = 5.7x10 -8). This finding was validated in a second set of paired ( n = 20) histologically normal and tumor derived pancreatic tissue samples (average fold change for three NR5A2 isoforms -31.3 to -95.7, P = 7.5x10 -4-2.0x10 -3). Our study has identified new susceptibility variants independently conferring pancreatic cancer risk that merit functional follow-up to identify target genes and explain the underlying biology.
Determination of trans- and cis-urocanic acid in relation to histamine, putrescine, and cadaverine contents in tuna (Auxis Thazard) at different storage temperatures

Zare D, Muhammad K, Bejo MH, Ghazali HM

J Food Sci, 2015 Feb;80(2):T479-83.
PMID: 25586500 DOI: 10.1111/1750-3841.12752

Scombroid fish poisoning is usually associated with consumption of fish containing high levels of histamine. However, reports indicate that some cases have responded to antihistamine therapy while ingested histamine levels in these cases were low. Potentiation of histamine toxicity by some biogenic amines, and release of endogenous histamine by other compounds such as cis-urocanic acid (UCA) are some hypotheses that have been put forth to explain this anomaly. Very little is known about the effects of storage conditions on the production of both UCA isomers and biogenic amines in tuna. Thus, the production of trans- and cis-UCA, histamine, putrescine, and cadaverine in tuna during 15 d of storage at 0, 3, and 10 °C and 2 d storage at ambient temperature were monitored. The initial trans- and cis-UCA contents in fresh tuna were 2.90 and 1.47 mg/kg, respectively, whereas the levels of putrescine and cadaverine were less than 2 mg/kg, and histamine was not detected. The highest levels of trans- and cis-UCA were obtained during 15 d storage at 3 °C (23.74 and 21.79 mg/kg, respectively) while the highest concentrations of histamine (2796 mg/kg), putrescine (220.32 mg/kg) and cadaverine (1045.20 mg/kg) were obtained during storage at room temperature, 10 and 10 °C, respectively. Histamine content increased considerably during storage at 10 °C whereas trans- and cis-UCA contents changed slightly. The initial trans-UCA content decreased during storage at ambient temperature. Thus, unlike histamine, concentrations of trans- and cis-UCA did not result in elevated levels during storage of tuna.
Changes in urocanic acid, histamine, putrescine and cadaverine levels in Indian mackerel (Rastrelliger kanagurta) during storage at different temperatures

Zare D, Muhammad K, Bejo MH, Ghazali HM

Food Chem, 2013 Aug 15;139(1-4):320-5.
PMID: 23561112 DOI: 10.1016/j.foodchem.2012.12.040

Histamine, putrescine cadaverine and cis-urocanic acid (UCA) have all been implicated or suggested in scombroid fish poisoning. However, there is little information on UCA especially during storage. Changes in their contents during storage of whole Indian mackerel at 0, 3±1, 10±1 for up to 15 days and 23±2°C for up to 2 days were monitored. Fresh muscles contained 14.83 mg/kg trans-UCA, 2.23 mg/kg cis-UCA and 1.86 mg/kg cadaverine. Histamine and putrescine were not detected. After 15 days at 0 and 3°C, trans-UCA content increased to 52.83 and 189.51 mg/kg, respectively, and decreased to <2 mg/kg at the other two temperatures. Storage at 10°C also resulted in an increase in trans-UCA after 3 days, only to decrease after 6 days. The concentration of cis-UCA increased nearly 13-fold after 15 days at 0 and 3°C, decreased at 10°C and remained unchanged at 23°C. Histamine, putrescine and cadaverine levels increased significantly (P value<0.05) at all temperatures especially at 23°C.
Assessing the quality of sardine based on biogenic amines using a fuzzy logic model

Zare D, Ghazali HM

Food Chem, 2017 Apr 15;221:936-943.
PMID: 27979297 DOI: 10.1016/j.foodchem.2016.11.071

There is an increasing concern about the quality and quality assessment procedures of seafood. In the present study, a model to assess fish quality based on biogenic amine contents using fuzzy logic model (FLM) is proposed. The fish used was sardine (Sardinella sp.) where the production of eight biogenic amines was monitored over fifteen days of storage at 0, 3 and 10°C. Based on the results, histamine, putrescine and cadaverine were selected as input variables and twelve quality grades were considered for quality of fish as output variables for the FLM. Input data were processed by rules established in the model and were then defuzzified according to defined output variables. Finally, the quality of fish was evaluated using the designed model and Pearson correlation between storage times with quality of fish showed r=0.97, 0.95 and 1 for fish stored at 0, 3 and 10°C, respectively.
Fulltext Dietary polyphenol intake in Europe: the European Prospective Investigation into Cancer and Nutrition (EPIC) study

Zamora-Ros R, Knaze V, Rothwell JA, Hémon B, Moskal A, Overvad K, et al.

Eur J Nutr, 2016 Jun;55(4):1359-75.
PMID: 26081647 DOI: 10.1007/s00394-015-0950-x

BACKGROUND/OBJECTIVES: Polyphenols are plant secondary metabolites with a large variability in their chemical structure and dietary occurrence that have been associated with some protective effects against several chronic diseases. To date, limited data exist on intake of polyphenols in populations. The current cross-sectional analysis aimed at estimating dietary intakes of all currently known individual polyphenols and total intake per class and subclass, and to identify their main food sources in the European Prospective Investigation into Cancer and Nutrition cohort.
METHODS: Dietary data at baseline were collected using a standardized 24-h dietary recall software administered to 36,037 adult subjects. Dietary data were linked with Phenol-Explorer, a database with data on 502 individual polyphenols in 452 foods and data on polyphenol losses due to cooking and food processing.
RESULTS: Mean total polyphenol intake was the highest in Aarhus-Denmark (1786 mg/day in men and 1626 mg/day in women) and the lowest in Greece (744 mg/day in men and 584 mg/day in women). When dividing the subjects into three regions, the highest intake of total polyphenols was observed in the UK health-conscious group, followed by non-Mediterranean (non-MED) and MED countries. The main polyphenol contributors were phenolic acids (52.5-56.9 %), except in men from MED countries and in the UK health-conscious group where they were flavonoids (49.1-61.7 %). Coffee, tea, and fruits were the most important food sources of total polyphenols. A total of 437 different individual polyphenols were consumed, including 94 consumed at a level >1 mg/day. The most abundant ones were the caffeoylquinic acids and the proanthocyanidin oligomers and polymers.
CONCLUSION: This study describes the large number of dietary individual polyphenols consumed and the high variability of their intakes between European populations, particularly between MED and non-MED countries.
Fulltext Energy and macronutrient intake and risk of differentiated thyroid carcinoma in the European Prospective Investigation into Cancer and Nutrition study

Zamora-Ros R, Rinaldi S, Tsilidis KK, Weiderpass E, Boutron-Ruault MC, Rostgaard-Hansen AL, et al.

Int J Cancer, 2016 Jan 01;138(1):65-73.
PMID: 26190646 DOI: 10.1002/ijc.29693

Incidence rates of differentiated thyroid carcinoma (TC) have increased in many countries. Adiposity and dietary risk factors may play a role, but little is known on the influence of energy intake and macronutrient composition. The aim of this study was to investigate the associations between TC and the intake of energy, macronutrients, glycemic index (GI) and glycemic load in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. The study included 477,274 middle-age participants (70.2% women) from ten European countries. Dietary data were collected using country-specific validated dietary questionnaires. Total carbohydrates, proteins, fats, saturated, monounsaturated and polyunsaturated fats (PUFA), starch, sugar, and fiber were computed as g/1,000 kcal. Multivariable Cox regression was used to calculate multivariable adjusted hazard ratios (HR) and 95% confidence interval (CI) by intake quartile (Q). After a mean follow-up time of 11 years, differentiated TC was diagnosed in 556 participants (90% women). Overall, we found significant associations only with total energy (HRQ4 vs .Q1 , 1.29; 95% CI, 1.00-1.68) and PUFA intakes (HRQ4 vs .Q1 , 0.74; 95% CI, 0.57-0.95). However, the associations with starch and sugar intake and GI were significantly heterogeneous across body mass index (BMI) groups, i.e., positive associations with starch and GI were found in participants with a BMI ≥ 25 and with sugar intake in those with BMI
Selecting a probability distribution for extreme rainfall series in Malaysia

Zalina MD, Desa MN, Nguyen VT, Kassim AH

Water Sci Technol, 2002;45(2):63-8.
PMID: 11890166

This paper discusses the comparative assessment of eight candidate distributions in providing accurate and reliable maximum rainfall estimates for Malaysia. The models considered were the Gamma, Generalised Normal, Generalised Pareto, Generalised Extreme Value, Gumbel, Log Pearson Type III, Pearson Type III and Wakeby. Annual maximum rainfall series for one-hour resolution from a network of seventeen automatic gauging stations located throughout Peninsular Malaysia were selected for this study. The length of rainfall records varies from twenty-three to twenty-eight years. Model parameters were estimated using the L-moment method. The quantitative assessment of the descriptive ability of each model was based on the Probability Plot Correlation Coefficient test combined with root mean squared error, relative root mean squared error and maximum absolute deviation. Bootstrap resampling was employed to investigate the extrapolative ability of each distribution. On the basis of these comparisons, it can be concluded that the GEV distribution is the most appropriate distribution for describing the annual maximum rainfall series in Malaysia.
Fulltext Malaysian cockle (Anadara granosa) allergy: Identification of IgE-binding proteins and effects of different cooking methods

Zailatul HM, Rosmilah M, Faizal B, Noormalin A, Shahnaz M

Trop Biomed, 2015 Jun;32(2):323-34.
PMID: 26691261 MyJurnal

The purpose of this study was to evaluate the effect of different cooking methods on the allergenicity of cockle and to identify proteins most frequently bound by IgE antibodies using a proteomics approach. Raw, boiled, fried and roasted extracts of the cockle were prepared. The protein profiles of the extracts were obtained by separation using sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and 2-dimensional gel electrophoresis (2-DE). IgE-immunoblotting was then performed with the use of individual sera from patients with cockle allergy and the major IgE-binding proteins were analyzed by mass-spectrometry. SDS-PAGE of raw extract showed 13 protein bands. Smaller numbers of protein bands were detected in the boiled, fried and roasted extracts. The 2-DE gel profile of the raw extract further separated the protein bands to ~50 protein spots with molecular masses between 13 to 180 kDa and isoelectric point (pI) values ranging from 3 to 10. Immunoblotting of raw extract exhibited 11 IgE-binding proteins with two proteins of 36 and 40 kDa as the major IgE-binding proteins, while the boiled extract revealed 3 IgE-binding proteins. Fried and roasted extracts only showed a single IgE-binding protein at 36 kDa. 2-DE immunoblotting of raw extract demonstrated 5 to 20 IgE reactive spots. Mass spectrometry analysis led to identification of 2 important allergens, tropomyosin (36 kDa) and arginine kinase (40 kDa). Heated extracts showed a reduction in the number of IgE-reactive bands compared with raw extract, which suggest that thermal treatment can be used as a tool in attempting to reduce cockle allergenicity. The degree of allergenicity of cockle was demonstrated in the order raw > boiled > fried ≈ roasted. Two important allergens reacting with more than 50% of patients' sera identified using mass spectrometric approaches were tropomyosin and arginine kinase. Thus, allergens found in this study would help in component based diagnosis, management of cockle allergic patients and to the standardisation of allergenic test products as tools in molecular allergology.
Fulltext Gracilis muscle as neoanal sphincter for faecal incontinence

Zailani MH, Azmi MN, Deen KI

Med J Malaysia, 2010 Mar;65(1):66-7.
PMID: 21265253 MyJurnal

Faecal incontinence is a debilitating chronic clinical condition which may affect the patient and care givers. Modality of treatment is based on severity of the symptoms as well as the anatomical defect itself, availability of resources and expertise. We describe a modified technique of dynamic graciloplasty as neoanal sphincter for the treatment severe faecal incontinence who has failed previous over lapping sphincteroplasty. In our modified version, instead of using implanted intramuscular electrodes and subcutaneous neurostimulator to provide continuous stimulation, the patient will undergo an external stimulation on the nerve of transplanted gracilis periodically and concurrent biofeedback therapy. We believe the technique is relatively easy to learn and very cost effective without any electrodes or neurostimulator related complications.
Progression of malaria induced pathogenicity during chloroquine therapy

Zaid OI, Abd Majid R, Sidek HM, Noor SM, Abd Rachman-Isnadi MF, Bello RO, et al.

Trop Biomed, 2020 Mar 01;37(1):29-49.
PMID: 33612716

Treatment Failure with chloroquine is one of the challenges that faced the dedicated efforts to eradicate malaria This study aims at investigating the impact of treatment failure with chloroquine on the progression of the disease-induced histo-pathogenic and immunogenic outcomes. To achieve this, Rane's protocol with modifications was applied on a model of Plasmodium berghei ANKA infected ICR mice to determine the dose response curve of chloroquine and to screen the treatment impact on the disease progression. Chloroquine was given at 1, 5, 10, 15 and 20 mg/kg once the parasitemia reached to 20-30% (the experimental initiation point). During the subsequent days, the mice were monitored for changes in the clinical signs, hematology parameters and the progress of the parasitemia until the parasitemia reached to 60-70% (the experimental termination point) or up to 10 days after chloroquine administration in case of achieving a complete eradication of the parasite. At the end, the mice were exsanguinated and their blood and organs were collected for the biochemistry and the histology study. A complete eradication of the parasite was achieved at 20 mg/kg while recrudescence was observed at the lower doses. At 1 mg/kg, the parasite growth was comparable to that of the positive control. The histo-pathogenic and immunogenic changes were stronger in the groups that experienced recrudescence (at 5 and 10 mg/kg). All in all, the study highlights the possibility of having a worsened clinical condition when chloroquine is given at its sub-therapeutic doses during malaria treatment.
The effect of mitragynine on extracellular activity of brain dopamine and its metabolites

Yusoff NHM, Hassan Z, Murugaiyah V, Müller CP

Brain Res Bull, 2022 01;178:1-8.
PMID: 34774992 DOI: 10.1016/j.brainresbull.2021.11.002

Kratom, derived from the plant Mitragyna speciosa (M. speciosa) Korth is a traditional psychoactive preparation widely used in Southeast Asia and increasingly in the rest of the world. Use and abuse of Kratom preparations can be attributed to mitragynine (MIT), the main psychoactive compound isolated from its leaves. While MIT may have beneficial effects as a recreational drug, for pain management, and for opiate withdrawal, it may have an addiction potential at higher doses. However, its action in the reward system of the brain is currently unknown. This study investigated how mitragynine (10 mg/kg, i.p.) affects extracellular activity of dopamine (DA) and its metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the prefrontal cortex (PFC), nucleus accumbens (NAc) and caudate putamen (CPu) of the brain, compared to morphine (MOR; 10 mg/kg, i.p.) and methamphetamine (METH; 10 mg/kg, i.p.). Using in-vivo microdialysis in freely moving rats, we found a significant increase of extracellular DA after MOR and METH, but not after MIT in all three brain regions. MIT led to a significant increase of DOPAC and/or HVA in these brain regions while MOR and METH had only moderate effects. These findings suggest a strong and prolonged effect of MIT on DA synthesis/metabolism, but not on extracellular DA activity, which may limit the addiction risk of MIT, in contrast to MOR and METH.
Baclofen blocks the acquisition and expression of mitragynine-induced conditioned place preference in rats

Yusoff NHM, Mansor SM, Müller CP, Hassan Z

Behav Brain Res, 2018 06 01;345:65-71.
PMID: 29499286 DOI: 10.1016/j.bbr.2018.02.039

Mitragynine is the major alkaloid found in the leaves of M. speciosa Korth (Rubiaceae), a plant that is native to Southeast Asia. This compound has been used, either traditionally or recreationally, due to its psychostimulant and opioid-like effects. Recently, mitragynine has been shown to exert conditioned place preference (CPP), indicating the rewarding and motivational properties of M. speciosa. Here, the involvement of GABAB receptors in mediating mitragynine reward is studied using a CPP paradigm in rats. First, we examined the effects of GABAB receptor agonist baclofen (1.25, 2.5 and 5 mg/kg) on the acquisition of mitragynine (10 mg/kg)-induced CPP. Second, the involvement of GABAB receptors in the expression of mitragynine-induced CPP was tested. We found that the acquisition of mitragynine-induced CPP could be blocked by higher doses (2.5 and 5 mg/kg) of baclofen. Baclofen at a high dose inhibited locomotor activity and caused a CPP. Furthermore, we found that baclofen (2.5 and 5 mg/kg) also blocked the expression of mitragynine-induced CPP. These findings suggest that both, the acquisition and expression of mitragynine's reinforcing properties is controlled by the GABAB receptor.
Opioid receptors mediate the acquisition, but not the expression of mitragynine-induced conditioned place preference in rats

Yusoff NHM, Mansor SM, Müller CP, Hassan Z

Behav Brain Res, 2017 08 14;332:1-6.
PMID: 28559179 DOI: 10.1016/j.bbr.2017.05.059

Mitragynine is the main psychoactive ingredient of the herbal drug preparation Kratom (Ketum), derived from the plant Mitragyna speciosa. Kratom is a widely abused drug in Southeast Asian and has a psychostimulant profile at low-medium doses, while high doses have opioidergic effects. Mitragynine was shown to possess opiate receptor affinity. However, its role in the behavioural effects of mitragynine is unclear. Here we asked whether the reinforcing effects of mitragynine are mediated by opiate receptors using a conditioned place preference (CPP) paradigm in rats. In the first experiment we tested the effects of the opiate receptor antagonist naloxone (0.1, 0.3 and 1.0mg/kg) on the acquisition of mitragynine (10mg/kg)-induced CPP. In the second experiment, we tested the involvement of opiate receptors in the expression of mitragynine-induced CPP in rats. We found that naloxone suppresses the acquisition of mitragynine-induced CPP. This effect was already evident at a dose of naloxone (0.1mg/kg) which, by itself, had no conditioned place aversion (CPA) effect. Higher doses of naloxone induced a CPA and blocked mitragynine-induced CPP. In contrast, naloxone had no effect on the expression of mitragynine-induced CPP. These findings suggest that the acquisition, but not the expression of the reinforcing effects of mitragynine is mediated by opiate receptors.
Abuse potential and adverse cognitive effects of mitragynine (kratom)

Yusoff NH, Suhaimi FW, Vadivelu RK, Hassan Z, Rümler A, Rotter A, et al.

Addict Biol, 2016 Jan;21(1):98-110.
PMID: 25262913 DOI: 10.1111/adb.12185

Mitragynine is the major psychoactive alkaloid of the plant kratom/ketum. Kratom is widely used in Southeast Asia as a recreational drug, and increasingly appears as a pure compound or a component of 'herbal high' preparations in the Western world. While mitragynine/kratom may have analgesic, muscle relaxant and anti-inflammatory effects, its addictive properties and effects on cognitive performance are unknown. We isolated mitragynine from the plant and performed a thorough investigation of its behavioural effects in rats and mice. Here we describe an addictive profile and cognitive impairments of acute and chronic mitragynine administration, which closely resembles that of morphine. Acute mitragynine has complex effects on locomotor activity. Repeated administration induces locomotor sensitization, anxiolysis and conditioned place preference, enhances expression of dopamine transporter- and dopamine receptor-regulating factor mRNA in the mesencephalon. While there was no increase in spontaneous locomotor activity during withdrawal, animals showed hypersensitivity towards small challenging doses for up to 14 days. Severe somatic withdrawal signs developed after 12 hours, and increased level of anxiety became evident after 24 hours of withdrawal. Acute mitragynine independently impaired passive avoidance learning, memory consolidation and retrieval, possibly mediated by a disruption of cortical oscillatory activity, including the suppression of low-frequency rhythms (delta and theta) in the electrocorticogram. Chronic mitragynine administration led to impaired passive avoidance and object recognition learning. Altogether, these findings provide evidence for an addiction potential with cognitive impairments for mitragynine, which suggest its classification as a harmful drug.
Role of supraspinal vasopressin neurones in the effects of atrial natriuretic peptide on sympathetic nerve activity

Yusof AP, Yusoff NH, Suhaimi FW, Coote JH

Auton Neurosci, 2009 Jun 15;148(1-2):50-4.
PMID: 19349212 DOI: 10.1016/j.autneu.2009.03.005

The aim of the present study was to determine if paraventricular-spinal vasopressin neurones participate in the sympatho-inhibitory effects of systemically administered atrial natriuretic peptide (ANP) on renal sympathetic nerve activity (RSNA). Experiments were carried out on male Sprague-Dawley rats anesthetized with 1.3 g/kg urethane. Changes in mean arterial pressure (mm Hg), heart rate (beats per minute) and RSNA (%) were measured following intravenous bolus administration of ANP (250 ng, 500 ng and 5 microg). Intrathecal application of selective V 1a receptor antagonist was performed to test for the involvement of supraspinal vasopressin pathways in mediating the effect on sympathetic outflow evoked by intravenous ANP administration. The results obtained demonstrated that both low and high doses of ANP caused renal sympathoinhibition (250 ng; - 7.5 +/- 1%, 500 ng; - 14.2 +/- 1%, 5 microg; - 16.4 +/- 2%), concomitant with vasodilation and bradycardia. After spinal vasopressin receptor blockade, the inhibitory effects of ANP were prevented and there was a small renal sympatho-excitation (250 ng; + 1.7 +/- 0.2%, 500 ng; + 6.1 +/- 0.03%, 5 microg; + 8.0 +/- 0.03%, P < 0.05). Therefore, the renal sympathetic nerve inhibition elicited by circulating ANP is dependent on the efficacy of a well established supraspinal vasopressin pathway. Since supraspinal vasopressin neurones without exception excite renal sympathetic neurones, it is suggested that ANP elicits this effect by activating cardiac vagal afferents that inhibit the spinally projecting vasopressin neurones at their origin in the paraventricular nucleus of the hypothalamus.
Does abuse in late life worsen sleep quality? A two-year prospective cohort study among rural older adults

Yunus RM, Hairi NN, Yuen C, Sooryanarayana R, Hairi F, Ismail N, et al.

Int J Geriatr Psychiatry, 2019 01;34(1):60-66.
PMID: 30230023 DOI: 10.1002/gps.4986

BACKGROUND: Elder abuse and neglect (EAN) is a growing public health problem, and numerous adverse health effects of abuse in late life have been documented. Little is known, however, about the impact of elder abuse on sleep quality. This study examines the longitudinal relationship between EAN and sleep quality.

METHODS: This was a 2-year prospective cohort study involving 1927 older adults in a rural Malaysian district, Kuala Pilah. A multi-stage cluster sampling strategy was employed. After 2 years, 1189 respondents were re-assessed. EAN was determined using the modified Conflict Tactic Scale, while sleep quality was measured using the Pittsburgh Sleep Quality Index (PSQI).

RESULTS: The prevalence of elder abuse was 8.1% (95% CI:6.9,9.3). Longitudinal analysis using generalized estimating equations showed that elder abuse contributed to higher PSQI scores (B:0.49, 95% CI:0.17,0.58). Sub-analyses demonstrated that psychological abuse and neglect had significant longitudinal relationships with increase of PSQI scores, while other subtypes did not.

CONCLUSION: Abuse in late life, particularly psychological abuse and neglect, result in greater PSQI scores. Even though this may imply decline in sleep quality, our findings were not considered clinically significant as they did not exceed the clinical cut-off score of five. Nevertheless, sleep quality is an important determinant of health and a predictor of mortality among older adults; thus, understanding its relationship with abuse is useful to health care providers and policy-makers in improving health services and upgrading preventive measures.

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