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Minocycline Protects Against Lipopolysaccharide-Induced Cognitive Impairment and Oxidative Stress: Possible Role of the CREB-BDNF Signaling Pathway

Qaid EYA, Abdullah Z, Zakaria R, Long I

Neurochem Res, 2023 May;48(5):1480-1490.
PMID: 36509985 DOI: 10.1007/s11064-022-03842-3

The oxidative stress-induced dysregulation of the cyclic AMP response element-binding protein- brain-derived neurotrophic factor (CREB-BDNF) cascade has been linked to cognitive impairment in several studies. This study aimed to investigate the effect of minocycline on the levels of oxidative stress markers, CREB, and BDNF in lipopolysaccharide (LPS)-induced cognitive impairment. Fifty adult male Sprague Dawley rats were divided randomly into five groups. Group 1 was an untreated control group. Groups 2, 3, 4 and 5 were treated concurrently with LPS (5 mg/kg, i.p) once on day 5 and normal saline (0.7 ml/rat, i.p) or minocycline (25 and 50 mg/kg, i.p) or memantine (10 mg/kg, i.p) once daily from day 1 until day 14, respectively. From day 15 to day 22 of the experiment, Morris Water Maze (MWM) was used to evaluate learning and reference memory in rats. The levels of protein carbonyl (PCO), malondialdehyde (MDA), catalase (CAT), and superoxide dismutase (SOD) were determined by enzyme-linked immunosorbent assay (ELISA). CREB and BDNF expression and density were measured by immunohistochemistry and western blot analysis, respectively. LPS administration significantly increased escape latency to the hidden platform with decreased travelled distance, swimming speed, target crossings and time spent in the target quadrant. Besides, the hippocampal tissue of LPS rats showed increased levels of PCO and MDA, decreased levels of CAT and SOD, and reduced expression and density of BDNF and CREB. Treatment with minocycline reversed these effects in a dose-dependent manner, comparable to the effects of memantine. Both doses of minocycline treatment protect against LPS-induced cognitive impairment by reducing oxidative stress and upregulating the CREB-BDNF signalling pathway in the rat hippocampus.
Fulltext Minocycline Attenuates Lipopolysaccharide-Induced Locomotor Deficit and Anxiety-like Behavior and Related Expression of the BDNF/CREB Protein in the Rat Medial Prefrontal Cortex (mPFC)

Abdo Qaid EY, Abdullah Z, Zakaria R, Long I

Int J Mol Sci, 2022 Nov 03;23(21).
PMID: 36362262 DOI: 10.3390/ijms232113474

Neuroinflammation following lipopolysaccharide (LPS) administration induces locomotor deficits and anxiety-like behaviour. In this study, minocycline was compared to memantine, an NMDA receptor antagonist, for its effects on LPS-induced locomotor deficits and anxiety-like behaviour in rats. Adult male Sprague Dawley rats were administered either two different doses of minocycline (25 or 50 mg/kg/day, i.p.) or 10 mg/kg/day of memantine (i.p.) for 14 days four days prior to an LPS (5 mg/kg, i.p.) injection. Locomotor activity and anxiety-like behaviour were assessed using the open-field test (OFT). The phosphorylated tau protein level was measured using ELISA, while the expression and density of brain-derived neurotrophic factor (BDNF) and cAMP response element-binding (CREB) protein in the medial prefrontal cortex (mPFC) were measured using immunohistochemistry and Western blot, respectively. Minocycline treatment reduced locomotor deficits and anxiety-like behaviour associated with reduced phosphorylated tau protein levels, but it upregulated BDNF/CREB protein expressions in the mPFC in a comparable manner to memantine, with a higher dose of minocycline having better benefits. Minocycline treatment attenuated LPS-induced locomotor deficits and anxiety-like behaviour in rats and decreased phosphorylated tau protein levels, but it increased the expressions of the BDNF/CREB proteins in the mPFC.
Melatonin effects on Plasmodium life cycle: new avenues for therapeutic approach

Srinivasan V, Ahmad AH, Mohamed M, Zakaria R

Recent Pat Endocr Metab Immune Drug Discov, 2012 May;6(2):139-47.
PMID: 22537380

Malaria remains a global health problem affecting more than 515 million people all over the world including Malaysia. It is on the rise, even within unknown regions that previous to this were free of malaria. Although malaria eradication programs carried out by vector control programs are still effective, anti-malarial drugs are also used extensively for curtailing this disease. But resistance to the use of anti-malarial drugs is also increasing on a daily basis. With an increased understanding of mechanisms that cause growth, differentiation and development of malarial parasites in rodents and humans, new avenues of therapeutic approaches for controlling the growth, synchronization and development of malarial parasites are essential. Within this context, the recent discoveries related to IP3 interconnected signalling pathways, the release of Ca2+ from intracellular stores of Plasmodium, ubiquitin protease systems as a signalling pathway, and melatonin influencing the growth and differentiation of malarial parasites by its effects on these signalling pathways have opened new therapeutic avenues for arresting the growth and differentiation of malarial parasites. Indeed, the use of melatonin antagonist, luzindole, has inhibited the melatonin's effect on these signalling pathways and thereby has effectively reduced the growth and differentiation of malarial parasites. As Plasmodium has effective sensors which detect the nocturnal plasma melatonin concentrations, suppression of plasma melatonin levels with the use of bright light during the night or by anti-melatonergic drugs and by using anti-kinase drugs will help in eradicating malaria on a global level. A number of patients have been admitted with regards to the control and management of malarial growth. Patents related to the discovery of serpentine receptors on Plasmodium, essential for modulating intra parasitic melatonin levels, procedures for effective delivery of bright light to suppress plasma melatonin levels and thereby arresting the growth and elimination of malarial parasites from the blood of the host are all cited in the paper. The purpose of the paper is to highlight the importance of melatonin acting as a cue for Plasmodium faciparum growth and to discuss the ways of curbing the effects of melatonin on Plasmodium growth and for arresting its life cycle, as a method of eliminating the parasite from the host.
Management Options and Outcome of Cerebral Arteriovenous Malformation in Pregnancy: Case Series

Teik CK, Basri NI, Abdul Karim AK, Azrai Abu M, Ahmad MF, Abdul Ghani NA, et al.

Arch Iran Med, 2019 06 01;22(6):340-343.
PMID: 31356101

Cerebral arteriovenous malformation (AVM) is a rare entity with an estimated prevalence of 0.01-0.05% in the general population. We reviewed hospital obstetric records during 2010-2017 and reported a case series of six patients with cerebral AVM in pregnancy, of which five patients had successful pregnancy, and one maternal mortality.
Malaria, anti malarial drugs and the role of melatonin

Srinivasan V, Mohamed M, Zakaria R, Ahmad AH

Infect Disord Drug Targets, 2012 Oct;12(5):371-9.
PMID: 23082960

Malaria, one of the most deadly diseases of our time affects more than 200 million people across the globe and is responsible for about one million deaths annually. Until recently Plasmodium falciparum has been the main cause for malarial infection in human beings but now Plasmodium knowlesi from Malaysia remains as one of the most virulent parasite spreading fast not only in Malaysia but in different parts of the world. Hence there is urgent need for the global fight to control malaria. Global malaria eradication program by use of insecticide spraying has resulted in good response in the past. Treatment of malaria infected patients with anti-malarial drugs has helped to eliminate malarial infections successfully but with increased resistance displayed by malarial parasites to these drugs there is resurgence of malaria caused both by drug resistance as well as by infection caused by new malarial species like Plasmodium knowlesi. With recent advances on molecular studies on malarial parasites it is now clear that the pineal hormone melatonin acts as a cue for growth and development of Plasmodium falciparum. Same may be true for Plasmodium knowlesi also. Hence treatment modalities that can effectively block the action of melatonin on Plasmodium species during night time by way of using either bright light therapy or use of melatonin receptor blocking can be considered as useful approaches for eliminating malarial infection in man.
MRI-based brain structural changes following radiotherapy of Nasopharyngeal Carcinoma: A systematic review

Voon NS, Lau FN, Zakaria R, Md Rani SA, Ismail F, Manan HA, et al.

Cancer Radiother, 2021 Feb;25(1):62-71.
PMID: 33414057 DOI: 10.1016/j.canrad.2020.07.008

PURPOSE: Nasopharyngeal carcinoma (NPC) radiotherapy (RT) irradiates parts of the brain which may cause cerebral tissue changes. This study aimed to systematically review the brain microstructure changes using MRI-based measures, diffusion tensor imaging (DTI), diffusion kurtosis imaging (DKI) and voxel-based morphometry (VBM) and the impact of dose and latency following RT.
METHODS: PubMed and Scopus databases were searched based on PRISMA guideline to determine studies focusing on changes following NPC RT.
RESULTS: Eleven studies fulfilled the inclusion criteria. Microstructural changes occur most consistently in the temporal region. The changes were correlated with latency in seven studies; fractional anisotropy (FA) and gray matter (GM) volume remained low even after a longer period following RT and areas beyond irradiation site with reduced FA and GM measures. For dosage, only one study showed correlation, thus requiring further investigations.
CONCLUSION: DTI, DKI and VBM may be used as a surveillance tool in detecting brain microstructural changes of NPC patients which correlates to latency and brain areas following RT.
Fulltext Lucio Phenomenon: Sequelae of Neglected Leprosy

Ya SNC, Muhamad R, Zakaria R, Ishak A, Abdullah WNHW

Korean J Fam Med, 2021 May;42(3):245-249.
PMID: 31968408 DOI: 10.4082/kjfm.19.0068

Lucio phenomenon is a potentially fatal leprosy reaction seen in pure, primitive, and diffuse form of lepromatous leprosy. It is a globally restricted phenomenon that occurs in Mexico and Costa Rica; however, sporadic cases have been reported elsewhere. We report a rare case of a 50-year-old Indonesian, who resided in Malaysia for the past 33 years, which presented with extensive ulcers on all four limbs for 3 weeks, as well as a 16-year history of skin changes and alopecia. Full evaluation established the diagnosis of lepromatous leprosy with Lucio phenomenon. Delay in diagnosis leads to significant disabilities and disease transmission within the community. Therefore, primary care practitioners, even in non-endemic countries, should be wary of this atypical feature of leprosy to prevent complications since it is a highly curable disease.
Fulltext Long-term effects of honey on cardiovascular parameters and anthropometric measurements of postmenopausal women

Ab Wahab SZ, Nik Hussain NH, Zakaria R, Abdul Kadir A, Mohamed N, Tohit NM, et al.

Complement Ther Med, 2018 Dec;41:154-160.
PMID: 30477832 DOI: 10.1016/j.ctim.2018.08.015

OBJECTIVE: To investigate the long-term effects of Tualang Honey versus Honey Cocktail (mixture of honey, bee bread, and royal jelly) on cardiovascular markers and anthropometric measurements of postmenopausal women.
METHODS: We conducted a randomised, double blinded, two-armed parallel study comparing 20 g/day of Tualang Honey versus 20 g/day Honey Cocktail among postmenopausal women aged 45-65 years. The cardiovascular parameters and anthropometrics measurements were assessed at baseline, 6 months, and 12 months of the intervention.
RESULTS: 100 subjects were successfully randomised into the groups. There was a significant decrease in the diastolic blood pressure from 77.92 mmHg at baseline to 73.45 mmHg at 12 months (F-statistic = 2.55, p-value = 0.047) in the Tualang Honey group compared to Honey Cocktail. There was also a significant decrease in the fasting blood sugar from 6.11 mmol/L at baseline to 5.71 mmol/L at 12 months (F-statistic = 4.03, p-value = 0.021) in the Tualang Honey group compared to the Honey Cocktail group. The body mass index remained unchanged at 27 kg/m2 (F-statistic = 1.60, p-value = 0.010) throughout 12 months of the intervention in the Honey Cocktail group.
CONCLUSION: Subjects who received Honey Cocktail showed remarkable effects on body mass index. However, Tualang Honey supplementation showed superior effect in lowering diastolic blood pressure and fasting blood sugar compared to Honey Cocktail. Further studies are required to ascertain the underlying mechanism(s) of Tualang Honey and Honey Cocktail on each observed parameter.
Fulltext Long-term assessment of an innovative mangrove rehabilitation project: case study on Carey Island, Malaysia

Motamedi S, Hashim R, Zakaria R, Song KI, Sofawi B

ScientificWorldJournal, 2014;2014:953830.
PMID: 25097894 DOI: 10.1155/2014/953830

Wave energy and storm surges threaten coastal ecology and nearshore infrastructures. Although coastal structures are conventionally constructed to dampen the wave energy, they introduce tremendous damage to the ecology of the coast. To minimize environmental impact, ecofriendly coastal protection schemes should be introduced. In this paper, we discuss an example of an innovative mangrove rehabilitation attempt to restore the endangered mangroves on Carey Island, Malaysia. A submerged detached breakwater system was constructed to dampen the energy of wave and trap the sediments behind the structure. Further, a large number of mangrove seedlings were planted using different techniques. Further, we assess the possibility of success for a future mangrove rehabilitation project at the site in the context of sedimentology, bathymetry, and hydrogeochemistry. The assessment showed an increase in the amount of silt and clay, and the seabed was noticeably elevated. The nutrient concentration, the pH value, and the salinity index demonstrate that the site is conducive in establishing mangrove seedlings. As a result, we conclude that the site is now ready for attempts to rehabilitate the lost mangrove forest.
Lipopolysaccharide-induced memory impairment in rats: a model of Alzheimer's disease

Zakaria R, Wan Yaacob WM, Othman Z, Long I, Ahmad AH, Al-Rahbi B

Physiol Res, 2017 09 22;66(4):553-565.
PMID: 28406691

Alzheimer's disease (AD) is a primary cause of dementia in the middle-aged and elderly worldwide. Animal models for AD are widely used to study the disease mechanisms as well as to test potential therapeutic agents for disease modification. Among the non-genetically manipulated neuroinflammation models for AD, lipopolysaccharide (LPS)-induced animal model is commonly used. This review paper aims to discuss the possible factors that influence rats' response following LPS injection. Factors such as dose of LPS, route of administration, nature and duration of exposure as well as age and gender of animal used should be taken into account when designing a study using LPS-induced memory impairment as model for AD.
Fulltext Letter in Reply: Gender Differences and Obesity Influence on Pulmonary Function Parameters

Zakaria R, Harif N, Ahmad AH

Oman Med J, 2020 Jan;35(1):e101.
PMID: 32128260 DOI: 10.5001/omj.2020.19
Fulltext Larvicidal efficacy screening of Anacardaciae crude extracts on the dengue hemorrhagic vector, Aedes aegypti

Zuharah WF, Fadzly N, Ali Y, Zakaria R, Juperi S, Asyraf M, et al.

Trop Biomed, 2014 Jun;31(2):297-304.
PMID: 25134898 MyJurnal

Vector-borne diseases are still rife because of the re-emergence of diseases transmitted by mosquitoes. The objective of this paper is to evaluate the larvicidal efficacy of crude leaf extract of Mangifera indica, Gluta renghas, and Melanochyla fasciculiflora against vector of dengue hemorrhagic fever, Aedes aegypti. These plant species are endemic species and widely distributed in Malaysian forests. Leaves of Ma. indica, G. renghas and M. fascculiflora were collected from Teluk Bahang National Park, Penang Malaysia. Fractions of leaves were segregated, air-dried, powdered and extracted using Soxhlet with methanol. The solvent was removed by using rotary evaporator to obtain the crude extract. Using WHO standard larval bioassay test method, third instar larvae of Aedes aegypti were exposed to concentration ranging from 200- 4500 ppm of methanol extract for all plant species. Larval mortality was observed after 24 hours exposure. The highest susceptibility and toxicity was recorded by Mangifera indica with the lowest concentration at 800 ppm followed by M. fasciculiflora and G. renghas. This indicates that crude plant extract is very effective in killing Ae. aegypti mosquitoes. This finding may lead to new low cost alternative, environmentally friendly method for mosquito control programs. To our knowledge, this is the first report on larvicidal bioefficacy from endemic Malaysian plants.
Fulltext Knowledge, Attitude, and Stigma on Tuberculosis and the Associated Factors for Attitude Among Tuberculosis Contacts in Malaysia

Loh SY, Zakaria R, Mohamad N

Medeni Med J, 2023 Mar 28;38(1):45-53.
PMID: 36974481 DOI: 10.4274/MMJ.galenos.2023.14478

OBJECTIVE: Tuberculosis (TB) is an old disease and it has infected millions of people worldwide. Since it is a highly infectious disease, many people became TB contact due to prolonged exposure to a person with TB infection. This group of people is at a higher risk of getting latent and active TB infection, hence a vulnerable group for active TB screening. This study explored the factors that determined the attitude score, the level of knowledge, attitude, and stigma (KAS) regarding TB disease among TB contact.
METHODS: This cross-sectional study used a validated KAS questionnaire, performed among 338 TB contacts from 5 health clinics in Kedah, Malaysia. The respondents were selected via convenience sampling. Simple and multiple linear regressions were used to analyze the data.
RESULTS: The mean KAS scores of participants are 73.5% [standard deviation (SD)=17.06], 83.0% (SD=10.33), and 67.0% (SD=16.72), respectively. Higher income (p=0.001), better knowledge score (p<0.001), and higher stigma score (p=0.003) are the significant associated factors for the attitude score.
CONCLUSIONS: This study revealed that most of the TB contacts have good knowledge and constructive attitude toward TB prevention and screening, but their level of stigma on TB is high. The implementation of TB education and intervention programs among TB contacts are required especially among low-income groups.
Fulltext Investigation on the Effects of the Formation of a Silver "Flower-Like Structure" on Graphene

Zakaria R, Yusoff SFAZ, Law KC, Lim CS, Ahmad H

Nanoscale Res Lett, 2017 Dec;12(1):50.
PMID: 28101853 DOI: 10.1186/s11671-016-1793-y

In this report, we experimentally investigate the formation of "flower-like silver structures" on graphene. Using an electrochemical deposition technique with deposition times of 2.5 and 5 min, agglomerations of silver nanoparticles (AgNPs) were deposited on the graphene surfaces, causing the formation of "flower-like structures" on the graphene substrate. Localized surface plasmon resonance (LSPR) was observed in the interaction between the structures and the graphene substrate. The morphology of the samples was observed using a field-emission scanning electron microscope (FESEM) and Raman spectroscopy. Thereafter, the potential of the flower-like Ag microstructures on graphene for use in Raman spectroscopic applications was examined. The signal showed a highest intensity value after a deposition time of 5 min, as portrayed by the intense local electromagnetic fields. For a better understanding, the CST Microwave Studio software, based on the finite element method (FEM), was applied to simulate the absorption characteristics of the structures on the graphene substrate. The absorption peak was redshifted due to the increment of the nanoparticle size.
Fulltext Investigation of Surface Plasmon Resonance (SPR) in MoS2- and WS2-Protected Titanium Side-Polished Optical Fiber as a Humidity Sensor

Zakaria R, Zainuddin NAM, Leong TC, Rosli R, Rusdi MF, Harun SW, et al.

Micromachines (Basel), 2019 Jul 11;10(7).
PMID: 31336745 DOI: 10.3390/mi10070465

In this paper, we report the effects of a side-polished fiber (SPF) coated with titanium (Ti) films in different thicknesses, namely 5 nm, 13 nm, and 36 nm, protected by a thin layer of transition metal dichalcogenides (TMDCs) such as molybdenum disulfide (MoS2) and tungsten disulfide (WS2), which provide ultra-sensitive sensor-based surface plasmon resonance (SPR) covering from the visible to mid-infrared region. The SPF deposited with Ti exhibits strong evanescent field interaction with the MoS2 and WS2, and good optical absorption, hence resulting in high-sensitivity performance. Incremental increases in the thickness of the Ti layer contribute to the enhancement of the intensity of transmission with redshift and broad spectra. The findings show that the optimum thickness of Ti with 36 nm combined with MoS2 causes weak redshifts of the longitudinal localized surface plasmon resonance (LSPR) mode, while the same thickness of Ti with WS2 causes large blueshifts. The redshifts are possibly due to a reduced plasmon-coupling effect with the excitonic region of MoS2. The observed blueshifts of the LSPR peak position are possibly due to surface modification between WS2 and Ti. Changing the relative humidity from 58% to 88% only elicited a response in Ti/MoS2. Thus, MoS2 shows more sensitivity on 36-nm thickness of Ti compared with WS2. Therefore, the proposed fiber-optic sensor with integration of 2D materials is capable of measuring humidity in any environment.
Insight into potential mechanisms of hypobaric hypoxia-induced learning and memory deficit - Lessons from rat studies

Qaid E, Zakaria R, Sulaiman SF, Yusof NM, Shafin N, Othman Z, et al.

Hum Exp Toxicol, 2017 Dec;36(12):1315-1325.
PMID: 28111974 DOI: 10.1177/0960327116689714

Impairment of memory is one of the most frequently reported symptoms during sudden hypoxia exposure in human. Cortical atrophy has been linked to the impaired memory function and is suggested to occur with chronic high-altitude exposure. However, the precise molecular mechanism(s) of hypoxia-induced memory impairment remains an enigma. In this work, we review hypoxia-induced learning and memory deficit in human and rat studies. Based on data from rat studies using different protocols of continuous hypoxia, we try to elicit potential mechanisms of hypobaric hypoxia-induced memory deficit.
In Vitro Efficacy of Aqueous and Methanol Extract of Cassia siamea Against the Motility of Caenorhabditis elegans

Gagman HA, Him NAIIN, Ahmad H, Sulaiman SF, Zakaria R, Termizi FHM

Trop Life Sci Res, 2020 Oct;31(3):145-159.
PMID: 33214861 DOI: 10.21315/tlsr2020.31.3.10

Gastrointestinal nematode infections can cause great losses in revenue due to decrease livestock production and animal death. The use of anthelmintic to control gastrointestinal nematode put a selection pressure on nematode populations which led to emergence of anthelmintic resistance. Because of that, this study was carried out to investigate the efficacy of aqueous and methanol extract of Cassia siamea against the motility of C. elegans Bristol N2 and C. elegans DA1316. Caenorhabditis elegans Bristol N2 is a susceptible strain and C. elegans DA1316 is an ivermectin resistant strain. In vitro bioassay of various concentrations of (0.2, 0.6, 0.8, 1.0 and 2.0 mg mL-1) aqueous and methanol extracts of C. siamea was conducted against the motility of L4 larvae of C. elegans Bristol N2 and C. elegans DA1316. The L4 larvae were treated with 0.02 μg mL-1 of ivermectin served as positive control while those in M9 solution served as negative control. The activity of the extracts was observed after 24 h and 48 h. A significant difference was recorded in the extract performance compared to control at (P < 0.001) after 48 h against the motility of the larvae of both strains. The methanol extracts inhibited the motility of C. elegans Bristol N2 by 86.7% as well as DA1316 up to 84.9% at 2.0 mg mL-1 after 48 h. The methanol extract was more efficient than aqueous extract (P < 0.05) against the motility of both strains of C. elegans. Cassia siamea may be used as a natural source of lead compounds for the development of alternative anthelmintic against parasitic nematodes as well ivermectin resistant strains of nematodes.
Fulltext In Silico Analyses and Cytotoxicity Study of Asiaticoside and Asiatic Acid from Malaysian Plant as Potential mTOR Inhibitors

Zulkipli NN, Zakaria R, Long I, Abdullah SF, Muhammad EF, Wahab HA, et al.

Molecules, 2020 Sep 02;25(17).
PMID: 32887218 DOI: 10.3390/molecules25173991

Natural products remain a popular alternative treatment for many ailments in various countries. This study aimed to screen for potential mammalian target of rapamycin (mTOR) inhibitors from Malaysian natural substance, using the Natural Product Discovery database, and to determine the IC50 of the selected mTOR inhibitors against UMB1949 cell line. The crystallographic structure of the molecular target (mTOR) was obtained from Protein Data Bank, with Protein Data Bank (PDB) ID: 4DRI. Everolimus, an mTOR inhibitor, was used as a standard compound for the comparative analysis. Computational docking approach was performed, using AutoDock Vina (screening) and AutoDock 4.2.6 (analysis). Based on our analysis, asiaticoside and its derivative, asiatic acid, both from Centella asiatica, revealed optimum-binding affinities with mTOR that were comparable to our standard compound. The effect of asiaticoside and asiatic acid on mTOR inhibition was validated with UMB1949 cell line, and their IC50 values were 300 and 60 µM, respectively, compared to everolimus (29.5 µM). Interestingly, this is the first study of asiaticoside and asiatic acid against tuberous sclerosis complex (TSC) disease model by targeting mTOR. These results, coupled with our in silico findings, should prompt further studies, to clarify the mode of action, safety, and efficacy of these compounds as mTOR inhibitors.
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.
Improvement in immediate memory after 16 weeks of tualang honey (Agro Mas) supplement in healthy postmenopausal women

Othman Z, Shafin N, Zakaria R, Hussain NH, Mohammad WM

Menopause, 2011 Nov;18(11):1219-24.
PMID: 21926932 DOI: 10.1097/gme.0b013e31821e2044

The aim of this study was to evaluate the verbal learning and memory performance of postmenopausal women who received tualang honey (Agro Mas) in comparison with women receiving estrogen plus progestin therapy and untreated controls.

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