Poly(amidoamine) dendrimers (PAMAM) are well-defined, highly branched, nanoscale macromolecules with numerous active amine groups on the surface. PAMAM dendrimer can enhance the solubility of hydrophobic drugs, and with numerous reactive groups on the surface PAMAM dendrimer can be engineered with various functional groups for specific targeting ability. However, in physiological conditions, these amine groups are toxic to cells and limit the application of PAMAM. In the recent years, polyethylene glycol (PEG) conjugation has been the most widely used approach to reduce the toxicity of the active group on dendrimer surface. PEG molecules are known to be inert, non-immunogenic, and non-antigenic with a significant water solubility. PEGylated PAMAM-mediated delivery could not only overcome the limitations of dendrimer such as drug leakage, immunogenicity, hemolytic toxicity, systemic cytotoxicity but they also have the ability to enhance the solubilization of hydrophobic drugs and facilitates the potential for DNA transfection, siRNA delivery and tumor targeting. This review focuses on the recent developments on the application and influence of PEGylation on various biopharmaceutical properties of PAMAM dendrimers.
STATEMENT OF SIGNIFICANCE: It is well established that dendrimers have demonstrated promising potentials for drug delivery. However, the inherent toxicity poses challenges for its clinical translation. In this regard, PEGylation has helped mitigate some of the toxicity concerns of dendrimers and have paved the way forward for testing its translational potentials. The review is a collection of articles demonstrating the utility of PEGylation of the most studied PAMAM dendrimers. To our knowledge, this is a first such attempt to draw reader's attention, specifically, towards PEGylated PAMAM dendrimers.
Nano-formulations of medicinal drugs have attracted the interest of many researchers for drug delivery applications. These nano-formulations enhance the properties of conventional drugs and are specific to the targeted delivery site. Dendrimers, polymeric nanoparticles, liposomes, nano-emulsions and micelles are some of the nano-formulations that are gaining prominence in pharmaceutical industry for enhanced drug formulation. Wide varieties of synthesis methods are available for the preparation of nano-formulations to deliver drugs in biological system. The choice of synthesis methods depend on the size and shape of particulate formulation, biochemical properties of drug, and the targeted site. This article discusses recent developments in nano-formulation and the progressive impact on pharmaceutical research and industries. Additionally, process challenges relating to consistent generation of nano-formulations for drug delivery are discussed.
The biofilm degradation of Aggregatibacter actinomycetemcomitans is essential as a complete periodontal disease therapy, and here we show the effects of potential probiotic bacteria such as Lactobacillus spp. for the biofilm of several serotypes of A. actinomycetemcomitans strains. Eight of the 13 species showed the competent biofilm degradation of ≥ 90% reduction in biofilm values in A. actinomycetemcomitans Y4 (serotype b) as well as four of the seven species for the biofilm of A. actinomycetemcomitans OMZ 534 (serotype e). In contrast, the probiotic bacteria did not have a big impact for the degradation of A. actinomycetemcomitans SUNY 75 (serotype a) biofilm. The dispersed A. actinomycetemcomitans Y4 cells through the biofilm detachment were still viable and plausible factors for the biofilm degradation were not due to the lactic acid and low pH conditions. The three enzymes, protease, lipase, and amylase may be responsible for the biofilm degradation; in particular, lipase was the most effective enzyme for the biofilm degradation of A. actinomycetemcomitans Y4 along with the protease activity which should be also important for the other serotypes. Remarkable lipase enzyme activities were detected from some of the potential probiotics and a supporting result using a lipase inhibitor presented corroborating evidence that lipase activity is one of the contributing factors for biofilm degradation outside of the protease which is also another possible factor for the biofilm of the other serotype of A. actinomycetemcomitans strains. On the other hand, the biofilm of A. actinomycetemcomitans SUNY 75 (serotype a) was not powerfully degraded by the lipase enzyme because the lipase inhibitor was slightly functional for only two of potential probiotics.
The predictability of neurocognitive outcomes in patients with traumatic brain injury is not straightforward. The extent and nature of recovery in patients with mild traumatic brain injury (mTBI) are usually heterogeneous and not substantially explained by the commonly known demographic and injury-related prognostic factors despite having sustained similar injuries or injury severity. Hence, this study evaluated the effects and association of the Brain Derived Neurotrophic Factor (BDNF) missense mutations in relation to neurocognitive performance among patients with mTBI. 48 patients with mTBI were prospectively recruited and MRI scans of the brain were performed within an average 10.1 (SD 4.2) hours post trauma with assessment of their neuropsychological performance post full Glasgow Coma Scale (GCS) recovery. Neurocognitive assessments were repeated again at 6 months follow-up. The paired t-test, Cohen's d effect size and repeated measure ANOVA were performed to delineate statistically significant differences between the groups [wildtype G allele (Val homozygotes) vs. minor A allele (Met carriers)] and their neuropsychological performance across the time point (T1 = baseline/ admission vs. T2 = 6th month follow-up). Minor A allele carriers in this study generally performed more poorly on neuropsychological testing in comparison wildtype G allele group at both time points. Significant mean differences were observed among the wildtype group in the domains of memory (M = -11.44, SD = 10.0, p = .01, d = 1.22), executive function (M = -11.56, SD = 11.7, p = .02, d = 1.05) and overall performance (M = -6.89 SD = 5.3, p = .00, d = 1.39), while the minor A allele carriers showed significant mean differences in the domains of attention (M = -11.0, SD = 13.1, p = .00, d = .86) and overall cognitive performance (M = -5.25, SD = 8.1, p = .01, d = .66).The minor A allele carriers in comparison to the wildtype G allele group, showed considerably lower scores at admission and remained impaired in most domains across the timepoints, although delayed signs of recovery were noted to be significant in the domains attention and overall cognition. In conclusion, the current study has demonstrated the role of the BDNF rs6265 Val66Met polymorphism in influencing specific neurocognitive outcomes in patients with mTBI. Findings were more detrimentally profound among Met allele carriers.
This study aims to design a vertical handover prediction method to minimize unnecessary handovers for a mobile node (MN) during the vertical handover process. This relies on a novel method for the prediction of a received signal strength indicator (RSSI) referred to as IRBF-FFA, which is designed by utilizing the imperialist competition algorithm (ICA) to train the radial basis function (RBF), and by hybridizing with the firefly algorithm (FFA) to predict the optimal solution. The prediction accuracy of the proposed IRBF-FFA model was validated by comparing it to support vector machines (SVMs) and multilayer perceptron (MLP) models. In order to assess the model's performance, we measured the coefficient of determination (R2), correlation coefficient (r), root mean square error (RMSE) and mean absolute percentage error (MAPE). The achieved results indicate that the IRBF-FFA model provides more precise predictions compared to different ANNs, namely, support vector machines (SVMs) and multilayer perceptron (MLP). The performance of the proposed model is analyzed through simulated and real-time RSSI measurements. The results also suggest that the IRBF-FFA model can be applied as an efficient technique for the accurate prediction of vertical handover.
Neuromyelitis optica (NMO) is a rare disorder in children
with variable presentation. We report a 7-year-old boy who
presented with bilateral retrobulbar optic neuritis and
responded very well to treatment. He was also positive for
aquaporin 4 (AQP4) antibodies, which is part of an emerging
endophenotype within autoimmune neurological disorders
in childhood.
MeSH terms: Autoantibodies; Eye; Humans; Male; Neuromyelitis Optica; Optic Neuritis; Autoimmune Diseases of the Nervous System; Aquaporin 4; Endophenotypes
Introduction: Biomedical research has traditionally been the
domain of developed countries. We aim to study the effects
of the increased focus on biomedical and medical research
on level 1-4 publications in several industrialised and newly
industrialised countries endowed with petroleum and gas
resources.
Methods: We identified all level 1-4 publications from
01/01/1994 to 31/12/2013 via PubMed using advanced
options. The population and GDP (current US$) data from
1994-2013 were obtained through data provided by the
World Bank and the raw data was normalised based on
these two indicators.
Results: From 1994-2013, Saudi Arabia and Malaysia were
responsible for the highest absolute number of level 1 to 4
biomedical and medical research publications with 2551 and
1951 publications respectively. When normalised to
population, Kuwait and Qatar had the highest publication
rates, with 7.84 and 3.99 publications per 100,000
inhabitants respectively in a five yearly average. Kuwait
produced the largest number of publications per billion
(current US$) of GDP, at 2.92 publications, followed by
Malaysia at 2.82 publications in a five yearly average.
Conclusion: The population size of a country as well as GDP
can influence the number of level 1-4 publications in some
countries. More importantly, effective government policy
which stimulates research as well as a culture which actively
promotes research as shown by Malaysia have proven to
have a larger influence on the amount of level 1-4 biomedical
and medical publications.
MeSH terms: Government; Guanosine Diphosphate; Kuwait; Malaysia; Petroleum; Population Density; Publications; Publishing; Qatar; Saudi Arabia; United Nations; Developed Countries; Biomedical Research; PubMed
We report herein the clinical presentation and diagnosis of scrub typhus in three
patients attending a teaching hospital in Malaysia. Three genetic variants belonged to the
Karp and Gilliam strains of O. tsutsugamushi were amplified from the acute blood samples of
the patients by a nested polymerase chain reaction assay. The circulation of different genetic
variants of O. tsutsugamushi strains might complicate the presentation and severity of scrub
typhus. Loop-PCR is a promising diagnostic tool for rapid diagnosis of scrub typhus.
Orang Asli communities are known as aborigines of peninsular Malaysia who are
underprivileged and also known to be carriers of many different parasitic infections. However,
the possible burden of cysticercosis (caused by Taenia solium larvae or Cysticercus cellulosae)
has never been explored in these communities. Objective of this study was to explore the
seroprevalence of human cysticercosis among Orang Asli (subgroups: Semelai, Semai Pahang,
Temuan, Orang Kuala, Temiar, Semai Perak, and Mah Meri) communities. In this preliminary
study, both male and female of all age groups (1 to 68 years) were screened for T. solium
larvae specific antibodies in sera employing a commercially procured IgG-ELISA kit. Sera
from a total of 522 randomly chosen Orang Asli individuals were screened between July to
December 2013. A total of 20 (3.8%) subjects were diagnosed positive for anti-Cysticercus
antibodies (95% CI: 2.5% – 5.8%; χ2=17.8; p
This is the first Malaysian study to determine the trend and risk factors of Toxoplasma
gondii infection in HIV and non-HIV among prisoners in terms of socio-demographic and
behavioural characteristics, clinical presentations and haematological distributions. Blood
samples from 303 participants, comprising 133 HIV positive and 170 HIV negative inmates
were collected in EDTA and plain tubes. Two mls of each blood sample in plain tubes were
centrifuged at 1500 rpm for 10 minutes and the sera obtained were subjected to ELISA for
detection of Toxoplasma IgM and IgG antibody towards Toxoplasma antigen. Seropositive
samples for Toxoplasma IgM or both Toxoplasma IgM and IgG were further tested with
Novalisa Toxoplasma gondii IgG avidity test to rule out acute from latent infections. Blood
in EDTA tubes were sent to Clinical Diagnostic Lab (CDL), University Malaya Medical Centre
(UMMC), Kuala Lumpur for complete blood count and differential count analysis. Overall
seroprevalence of anti-T. gondii antibodies was detected in 41.9% (127 out of 303) of the
participants. Anti-T. gondii antibodies was detected in 63.2% (84 out of 133) of HIV positive
subjects and in 25.3% (43 out of 170) of HIV negative subjects. Seroprevalence of anti-T.
gondii antibodies was significantly higher in HIV positive than in HIV negative subjects (OR
= 5.06; 95% CI = 3.09-8.30; p < 0.001). The rate of T. gondii seropositivity increased significantly
in those aged 40 years and above, HIV positive individuals and those with history of drug
abuse. White blood cells (WBCs), neutrophils and basophils counts decreased significantly in
those infected with Toxoplasma. Creating awareness about T. gondii infection and follow-up
of their status is recommended. Moreover, screening of T. gondii infection in HIV-infected
individuals should be considered for better treatment and management, including control and
prevention.
Laboratory colonised mosquitoes are usually maintained on vitamin B complex
fortified sucrose solution, however only few studies were conducted to evaluate the effects
of such practice. This study aimed to determine the effects of different concentrations of
sucrose solution fortified with and without 1% vitamin B complex on the longevity and
reproductive potential of adult female of a local strain of Culex quinquefasciatus Say. Two
arms of studies were carried out separately and each arm was triplicated. In one arm,
concentrations of sucrose solution at 0%, 1%, 3%, 5% and 10% fortified with 1% Vitamin B
complex were fed to the mosquitoes, while in the other arm, similar sucrose concentrations
were used but without 1% vitamin B complex. Adult Cx. quinquefasciatus maintained on 5%
sucrose solution fortified with 1% vitamin B complex exhibited significant extended vitality
and longevity in stimulating ovarian development, compared with other vitamin fortified
sucrose concentrations (p
The increase of the burden of dengue and chikungunya and the relative failure of
traditional vector control strategies have highlighted the need to develop new control methods.
RIDL-SIT, a vector control method based on the release of engineered male mosquitoes, has
shown promising results from field trials conducted in the Cayman Islands and Brazil. In large
scale use, a small proportion of females might be released along with the males. Such females
are potential virus vectors; here we investigate the vertical transmission of dengue and
chikungunya of homozygous OX513A females.We provided females of OX513A-My1 and a
wild type comparator strain with blood meals artificially infected with dengue serotype 1, 2,
3, 4 or chikungunya viruses. For 14 days post-feeding, eggs laid by females were collected.
Larvae and their mothers were first tested by qRT-PCR, then by inoculation on cell cultures to
search for infectious viral particles. We found no significant difference between the minimum
infection rate of OX513A-My1 and wild type females. We also discussed the potential number
of females being released, a fraction of the female wild population. Consequently, we conclude
that there are no evidence that OX513A-My females, if released into the environment, would
cause more harm than their wild counterparts.
Detailed reports regarding the distribution and activity of extended-spectrum
beta-lactamase (ESBL)-producing Klebsiella pneumoniae isolates are currently not widely
available in the Malaysian setting. This study was conducted to determine the ESBL genes
distribution rate, phenotypic detection, and antimicrobial susceptibility patterns among betalactam
resistant Klebsiella pneumoniae isolated from a Malaysian district hospital.
K. pneumoniae isolates were collected from a microbiology laboratory at Hospital
Pakar Sultanah Fatimah, Malaysia. Following exclusion and inclusion criteria, 141 isolates
were selected for this study. K. pneumoniae was identified by phenotypic method, whilst
antibiotics’ susceptibility patterns were determined by the Kirby-Bauer method, as described
in Clinical Laboratory Standard Institute (CLSI) guidelines (Oxoid, UK; Becton-Dickenson,
USA). Detection of Ambler Group A ESBL gene (blaSHV, blaTEM, blaCTX-M-1, blaCTX-M-2, blaCTX-M-8,
blaCTX-M-9, and blaCTX-M-25) was done using polymerase chain reaction (PCR).
ESBL genes were found in 85.8% of K. pneumoniae (121 of 141) isolates. Only blaSHV,
blaTEM, blaCTX-M-1, and blaCTX-M-9 were detected among K. pneumoniae isolates with distribution
rates of 75.2% (106 of 141), 41.1% (58 of 141), 44% (62 of 141), and 0.7% (1 of 141), respectively.
There was no blaCTX-M-2, blaCTX-M-8, or blaCTX-M-25 detected from any isolates in this study.
Sequencing of representative amplicons revealed blaSHV as SHV-12, blaTEM as TEM-1,
blaCTX-M-1 as CTX-M-15, and blaCTX-M-9 as CTX-M-18. The phenotypic detection rate of ESBL was
71.6% (101 of 141), whilst 9.2% (13 of 141) were positive for carbapenemase. AmpC betalactamase
was detected in 22% (31 of 141) of all isolates. Antibiotic resistance was between
44.6% (netilmicin) and 97.2% (cefotaxime).
Based on ESBL genes distribution, blaSHV was a predominant gene found in one of
Malaysian district hospitals, notwithstanding having blaTEM, blaCTX-M-1, and blaCTX-M-9. Despite
carrying multiple ESBL genes, some strains were positive for carbapenemase or AmpC betalactamase,
which resulted in high antimicrobial resistance rates.
Toxoplasmosis is a worldwide endemic zoonotic infection caused by the obligate
coccidian parasite Toxoplasma gondii. To assess the seroprevalence of T. gondii infection
among hospital population of Hospital Universiti Sains Malaysia (HUSM), a cross-sectional
study was conducted using serum samples of 102 participants. Samples were screened for
the presence of anti-Toxoplasma IgG and IgM antibodies by enzyme-linked immunosorbent
assay (ELISA). Only one sample recorded as IgM positive (0.98%) (1/102; 95% CI = 0.02–
5.34%), whereas 44.12% (45/102; 95% CI = 34.29–54.29%) were IgG positive. The study showed
that seroprevalence of toxoplasmosis significantly differs between age groups (p < 0.001),
with high prevalence of T. gondii infection (37.8%) among patients aged less than one month.
Moreover, the study indicated a significant difference in the prevalence of toxoplasmosis
between males and females. Additionally, a significant dependent relationships were observed
(p = 0.003), when the reasons of toxoplasma serology request was considered, and the
highest prevalence (59.6%) observed in congenital toxoplasmosis. In conclusion, the
seroprevalence of toxoplasmosis in our study group was high. The study provides preliminary
information about the seroprevalence and epidemiology of T. gondii infection among the
hospital population in HUSM.
The rat lungworm Angiostrongylus cantonensis, a zoonotic parasite, is known to
be responsible for eosinophilic meningitis and meningoencephalitis in humans in many countries
worldwide. Another congener A. malaysiensis is a potential pathogen. Rodents as natural
definitive host of the parasites are abundant and globally widespread. In this study, the
prevalence of Angiostrongylus infection in wild rats was investigated in twenty-four provinces
of Thailand during the period December 2011 to June 2014. Of the 669 wild rats sampled, 46
(6.88%) were infected with Angiostrongylus lungworms. The rodents harbouring A.
cantonensis worms included Bandicota indica, Bandicota savilei, Rattus exulans, Rattus
norvegicus, Rattus rattus complex and Rattus tiomanicus, and those harbouring A.
malaysiensis were B. savilei, Rattus losea, R. norvegicus and R. rattus complex. No parasite
was recovered from Maxomys surifer (n=11), Mus musculus (n=1), Niviventer fulvescens
(n=2), Rattus argentiventer (n=4), Rattus nitidus (n=3) and Sundamys muelleri (n=3). In
positive rats, the incidence of infection with Angiostrongylus lungworms was variable among
host species and provinces. There were also considerable variation in the proportion of male
and female worms among rodent hosts and localities. Two hundred and thirty-five of the
collected worms were male and 282 were female. The mean worm burden in the positive rats
was 11.24 and ranged from 1 to 61. 81.82% (423/517) of the adult worms were morphologically
identified as A. cantonensis, and 18.18% (94/517) were A malaysiensis. One R. rattus from
Prachuap Khiri Khan had mixed infection of A. cantonensis and A. malaysiensis (10 worms of
each species). The overall number of male (202) and female (221) A. cantonensis worms was
not significantly different (χ2 = 0.86, 0.50 > P > 0.30). However, the overall number of male
(33) and female (61) A. malaysiensis worms was significantly different (χ2 = 8.34, P < 0.01).
The present study added one new definitive host (R. tiomanicus) for A. cantonensis and two
new definitive hosts (B. savilei and R. losea) for A. malaysiensis in Thailand. Our data update
and contribute significantly to existing knowledge of the geographical distribution of A.
cantonensis in wild rats in Thailand and confirm the occurrence of A. malaysiensis throughout
the country.
Emergence of chloroquine (CQ) resistance among different strains
of Plasmodium falciparum is the worst incident that has ever faced the dedicated efforts to
eradicate malaria. The main cause of CQ resistance is over-activity of the pumping mechanism
that ousts CQ outside the DV. This urged the scientists to look for other alternatives or
adjuvants that augment its action. CQ The study aimed to test the potential of five coumarin
derivatives, namely; umbeliferon, esculetin, scopoletine, herniarin and 3-aminocoumarine to
inhibit plasmodium growth and reverse CQ resistance in Plasmodium falciparum K1 and
3D7. They are highly ubiquitous in nature and are famous by their diverse pharmacological
effects. SYBRE green-1 based drug sensitivity assay was used to screen the effect of CQ and
each coumarin on the parasite growth and isobologram technique was to assess the interaction
of the coumarins with CQ. Effect of each coumarin on both RBCs and Vero cells stability as
well as on RBCs fragility were screened to exclude any toxic impact on normal cells. On the
other hand, their effect on hemozoin formation was screened to investigate about their
molecular mechanism. For molecular characterization, Their antioxidant properties were
determined using the conventional in vitro tests and their characters were obtained from
Molinspiration Simulation Software. Results showed that all of them were safe to human
cells, have weak to moderate plasmodial growth inhibitory effect and only umbeliferon, 3-
aminocoumarin and esculetin has interacted effectively with CQ. These actions are neither
correlated with hemozoin formation inhibition nor to the antioxidant mechanisms. Further
studies recommended to investigate the mechanism of their action. Overall, all the tested
coumarins are not ideal to be used in the conventional malaria therapy and only umbeliferon,
3-aminocoumarin and esculetin can be suggested to potentiate CQ action.
The emergence of research about the biological effects of electromagnetic field (EMF) have growing concern among
researchers. The aim of this study was to investigate the effects on the brain of rats periodically exposed to 0.1 mT EMF.
Total 24 adult male Sprague Dawley rats were subdivided randomly to 4 groups: 2 control groups (C1 6 hours: 6 h/
day for 5 days; C2 20 hours: 20 h/day for 5 days) and 2 treatment groups which exposed to 0.1 mT EMF (T1 6 hours:
6 h/day for 5 days; T2 20 hours: 20 h/day for 5 days). A significant decrease in the pyramidal cell number was higher
as the exposure duration to EMF was extended (T1, p
Kefungsian mobiliti dalam kalangan populasi warga emas merupakan elemen yang penting bagi kualiti hidup yang
lebih bermakna. Penilaian adalah penting untuk memastikan langkah-langkah sewajarnya boleh diambil demi
mengesan perubahan dalam kefungsian mobiliti. Terdapat pelbagai jenis penilaian mobiliti namun kebanyakan
kajian kebolehpercayaan ulang semula alat penilaian ini adalah berdasarkan kajian luar negara. Oleh itu, kajian
ini adalah untuk menentukan kebolehpercayaan tiga alat penilaian status kefungsian mobiliti terutama aktiviti fizikal
dalam kalangan warga emas. Seramai 60 orang warga emas dengan min umur 76.32 tahun dan sisihan piawai 8.66
terlibat dalam kajian kebolehpercayaan uji-ulang semula bagi tiga jenis alat penilaian; Ujian Berjalan Enam Minit
[Six-Minute Walk Test (6MWT)], Ujian Bangun dan Berjalan [Timed Up and Go Test (TUG)], Ujian Duduk-Berdiri [Sitto-Stand
Test (STS)]. Bacaan di ambil sebanyak dua kali dengan selang masa seminggu antara penilaian pertama dan
kedua. Korelasi Intra-Kelas [Intraclass Correlation (ICC)], Had Keserasian [Limits of Agreement (LOA)] dan Ralat
Pengukuran Piawai [Standard Error of Measurement (SEM)] dan diikuti kombinasi ketiga-tiga kaedah telah digunakan
dalam analisa data. Hasil kajian menunjukkan ketiga-tiga alat penilaian menggunakan metodologi analisis statistik
ICC, LOA, SEM dan kombinasi ketiga-tiga metodologi tersebut menunjukkan nilai kebolehpercayaan yang tinggi. Nilai
ICC bagi kesemua alat penilaian aktiviti melebihi 0.90 (ICC=0.94-0.99). Graf LOA menunjukkan wujudnya suatu tahap
kebolehpercayaan bagi kesemua alat penilaian aktiviti manakala peratus SEM pula merekodkan nilai kurang dari
10% (SEM%=0.95%-9.95%). Kesimpulannya, ketiga-tiga alat penilaian mempunyai ketekalan yang tinggi dan sesuai
digunakan sebagai salah satu alat penilaian kefungsian mobiliti bagi warga emas di Malaysia.