243 research outputs found
Cinnamon: A Multifaceted Medicinal Plant
Cinnamon (Cinnamomum zeylanicum, and Cinnamon cassia), the eternal tree of tropical medicine, belongs to the Lauraceae family.
Cinnamon is one of the most important spices used daily by people all over the world. Cinnamon primarily contains vital oils and
other derivatives, such as cinnamaldehyde, cinnamic acid, and cinnamate. In addition to being an antioxidant, anti-inflammatory,
antidiabetic, antimicrobial, anticancer, lipid-lowering, and cardiovascular-disease-lowering compound, cinnamon has also been
reported to have activities against neurological disorders, such as Parkinson’s and Alzheimer’s diseases. This review illustrates the
pharmacological prospective of cinnamon and its use in daily life
Genetic polymorphisms of cyp3a4 and cyp2c8 in heal thy volunteers administered with repaglinide
Repaglinide is a novel prandial glucose regulator (PGR) for the treatment of
type 2 diabetes mellitus. Repaglinide is mainly metabolised in the liver by CYP3A4
and CYP2C8 enzymes. The objective of the present study is to investigate the
effects of the CYP3A4 and CYP2CB genotypes on the pharmacokinetics of
repaglinide in 121 healthy Malaysian subjects.
The study protocol was approved by our local Research and Ethics
Committee, School of Medical Sciences, Universiti Sains Malaysia. Initially, a new
HPLC method using a simple liquid-liquid extraction for the determination of
repaglinide in human serum was developed and later validated. Then, PCR methods
were optimized to detect CYP3A4 and CYP2CB genetic polymorphisms among
healthy Malaysian subjects.
Each subject received 4 mg of oral repaglinide. Six blood samples per
individual were taken (0 min, 30 min, 60 min, 120 min, 180 min and 240 min) for
repaglinide's serum concentration determination by using HPLC. NPAG was then
used to determine population pharmacokinetic parameter values of repaglinide.
The developed HPLC method was selective and calibration curves of
repaglinide were found to be linear in the concentration range of 20-200 ng/ml. The
limits of detection (LOD) and quantification (LOQ) were 10 ng/ml and 20 ng/ml,
respectively. The inter-day precision was from 5.21% to 11.84o/o while the intra-day
precision ranged from 3.90°/o to 6.67%. The inter-day accuracy ranged between
89. 95°/o and 105. 75o/o with the intra-day accuracy ranging from 92.37% to 1 04.66°/o.
No mutations were detected for the CYP3A4*4 and CYP3A4*5 alleles. The
frequency of the CYP3A4*18 allele was 2.07o/o. All five subjects with CYP3A4*18
mutations were found to be heterozygous. For CYP2C8, the allele frequency for both
CYP2C8*2 and *3 was 0.4°/o while the allele frequency for CYP2C8*5 was 4.13°/o. All
subjects with mutations were found to be heterozygous.
No mutation was detected for the CYP2C8*4 allele. CYP2CB and CYP3A4
genotypes were not significantly associated with changes in the blood glucose
lowering effect of repaglinide. On the other hand, the CYP3A4 genotype significantly
influenced repaglinide's pharmacokinetics where the mean elimination rate constant
(kel) was 34°/o lower (p = 0.04) and the mean half-life (t112) was 133% longer (p =
0.04) i.n .. subjects having the CYP3A4*1/*18 genotype compared to those having the
CYP3A4*11*1 genotype.
In conclusion, CYP3A4 activity plays an important role in influencing
repaglinide's pharmacokinetics. Therefore, subjects having CYP3A4*11*18 may need
to receive lower doses of repaglinide
Folic acid supplementation is not the sole factor in determining neural tube defects: The possible role of autoantibodies
Neural tube defects (NTDs) are severe but common congenital malformations. Neonates who suffer from NTDs may experience long-term complications throughout their lives. These NTD complications which have been reduced worldwide are primarily due to environmental and genetic factors. Multicenter NTD studies conducted in Malaysia report a prevalence ranging from 0.79 to 1.29 per 1000 live births based on NTD etiologies, such as anti-epileptic drug consumption and maternal folate levels. In addition, intervention studies concluded that daily consumption of 400 μg of folic acid effectively reduced NTD risk; however, this data has not been robustly tested on the entire population due to the inefficiency of the three interrelated folate transport mechanisms and autoantibody generation. In this review, we evaluated the studies indicating that folic acid supplementation may not be the sole factor in reducing NTD incidence and that autoantibodies may have an important role in the NTD etiological pathway.Key words: Neural tube defect, folic acid, methylenetetrahydrofolate reductase (MTHFR), Malaysia, anti-epileptic, folate transport mechanisms, autoantibodie
Genetic polymorphisms of CYP 3A4 & CYP2C8 in healthy volunteers title of project administered with repaglinide
Repaglinide is a novel prandial glucose regulator (PG R) for the treatment of
type 2 diabetes mellitus. Repaglinide is mainly metabolised in the liver by CYP3A4
and CYP2C8 enzymes. The objective of the present study is to investigate the
effects of the CYP3A4 and CYP2CB genotypes on the pharmacokinetics of
repaglinide in 121 healthy Malaysian subjects.
The study protocol was approved by our local Research and Ethics
Committee, School of Medical Sciences, Universiti Sains Malaysia. Initially, a new
HPLC method using a simple liquid-liquid extraction for the determination of
repaglinide in human serum was developed and later validated. Then, PCR methods
were optimized to detect CYP3A4 and CYP2CB genetic polymorphisms among
healthy Malaysian subjects.
Each subject received 4 mg of oral repaglinide. Six blood samples per
individual were taken (0 min, 30 min, 60 min, 120 min, 180 min and 240 min) for
repaglinide's serum concentration determination by using HPLC. NPAG was then
'
used to determine population pharmacokinetic parameter values of repaglinide.
The developed HPLC method was selective and calibration curves of
repaglinide were found to be linear in the concentration range of 20-200 ng/ml. The
limits of detection (LOD) and quantification (LOQ) were 10 ng/ml and 20 ng/ml,
respectively. The inter-day precision was from 5.21%, to 11.84°/o while the intra-day
precision ranged from 3.90%, to 6.67°/o. The inter-day accuracy ranged between
89.95% and 105.75%> with the intra-day accuracy ranging from 92.37°/o to 104.66%.
No mutations were detected for the CYP3A4*4 and CYP3A4*5 alleles. The
frequency of the CYP3A4*18 allele was 2.07o/o. All five subjects with CYP3A4*18
mutations were found to be heterozygous. For CYP2C8, the allele frequency for both
CYP2C8*2 and *3 was 0.4°/o while the allele frequency for CYP2C8*5 was 4.13o/o. All
subjects with mutations were found to be heterozygous.
No mutation was detected for the CYP2C8*4 allele. CYP2C8 and CYP3A4
genotypes were not significantly associated with changes in the blood glucose
lowering effect of repaglinide. On the other hand, the CYP3A4 genotype significantly
influenced repaglinide's pharmacokinetics where the mean elimination rate constant
(kel) was 34% lower (p = 0.04) and the mean half-life (t112) was 133°/o longer (p =
0.04) i.n subjects having the CYP3A4*11*18 genotype compared to those having the
CYP3A4*11*1 genotype.
In conclusion, CYP3A4 activity plays an important role in influencing
'
repaglinide's pharmacokinetics. Therefore, subjects having CYP3A4*11*18 may need
to receive lower doses of repaglinide
Cinnamon: A Multifaceted Medicinal Plant
Cinnamon (Cinnamomum zeylanicum, and Cinnamon cassia), the eternal tree of tropical medicine, belongs to the Lauraceae family. Cinnamon is one of the most important spices used daily by people all over the world. Cinnamon primarily contains vital oils and other derivatives, such as cinnamaldehyde, cinnamic acid, and cinnamate. In addition to being an antioxidant, anti-inflammatory, antidiabetic, antimicrobial, anticancer, lipid-lowering, and cardiovascular-disease-lowering compound, cinnamon has also been reported to have activities against neurological disorders, such as Parkinson’s and Alzheimer’s diseases. This review illustrates the pharmacological prospective of cinnamon and its use in daily life
A New Nested Allele-Specific Multiplex Polymerase Chain Reaction Method for Haplotyping of VKORC1 Gene to Predict Warfarin Sensitivity
The vitamin K epoxide reductase complex 1 gene (VKORC1) is commonly assessed to predict warfarin sensitivity. In this study, a
new nested allele-specific multiplex polymerase chain reaction (PCR) method that can simultaneously identify single nucleotide
polymorphisms (SNPs) at VKORC1 381, 861, 5808, and 9041 for haplotype analysiswas developed and validated. ExtractedDNAwas
amplified in the first PCR DNA, which was optimized by investigating the effects of varying the primer concentrations, annealing
temperature, magnesium chloride concentration, enzyme concentration, and the amount of DNA template. The amplification
products produced from the first round of PCR were used as templates for a second PCR amplification in which both mutant
and wild-type primers were added in separate PCR tubes, followed by optimization in a similar manner. The final PCR products
were resolved by agarose gel electrophoresis and further analysed by using a VKORC1 genealogic tree to infer patient haplotypes.
Fifty patients were identified to have H1H1, one had H1H2, one had H1H7, 31 had either H1H7 or H1H9, one had H1H9, eight had
H7H7, and one had H8H9 haplotypes. This is the first method that is able to infer VKORC1 haplotypes using only conventional
PCR methods
Rhinacanthus nasutus
The present study was conducted to evaluate the therapeutic efficacy of Rhinacanthus nasutus (R. nasutus) on mitochondrial and cytosolic enzymes in streptozotocin-induced diabetic rats. The rats were divided into five groups with 6 rats in each group. The methanolic extract of R. nasutus was orally administered at a dose of 200 mg/kg/day, and glibenclamide was administered at a dose of 50 mg/kg/day. All animals were treated for 30 days and were sacrificed. The activities of both intra- and extramitochondrial enzymes including glucose-6-phosphate dehydrogenase (G6PDH), succinate dehydrogenase (SDH), glutamate dehydrogenase (GDH), and lactate dehydrogenase (LDH) were measured in the livers of the animals. The levels of G6PDH, SDH, and GDH were significantly reduced in the diabetic rats but were significantly increased after 30 days of R. nasutus treatment. The increased LDH level in diabetic rats exhibited a significant reduction after treatment with R. nasutus. These results indicate that the administration of R. nasutus altered the activities of oxidative enzymes in a positive manner, indicating that R. nasutus improves mitochondrial energy production. Our data suggest that R. nasutus should be further explored for its role in the treatment of diabetes mellitus
Antiproliferative effect of methanolic extraction of tualang honey on human keloid fibroblasts
<p>Abstract</p> <p>Background</p> <p>Keloid is a type of scar which extends beyond the boundaries of the original wound. It can spread to the surrounding skin by invasion. The use of Tualang honey is a possible approach for keloid treatment. The objective of this study was to determine the antiproliferative effect of methanolic extraction of Tualang honey to primary human keloid fibroblasts and to identify the volatile compounds in methanol extraction of Tualang honey.</p> <p>Methods</p> <p>Crude Tualang honey was extracted with methanol and then dried using rota vapor to remove remaining methanol from honey. Normal and keloid fibroblasts were verified and treated with the extracted honey. Cell proliferation was tested with [3-(4,5-dimethylthiazol-2-yi)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt] (MTS) assay. Extraction of Tualang honey using methanol was carried out and the extracted samples were analysed using gas chromatography-mass spectrometry (GC-MS). The result was analysed using SPSS and tested with Kruskal-Wallis and Mann-Whitney tests.</p> <p>Results</p> <p>Methanolic extraction of honey has positive anti proliferative effect on keloid fibroblasts in a dose-dependent manner. The presence of fatty acids such as palmitic acid, stearic acid, oleic acid, linoleic acid and octadecanoic acid may contribute to the anti-proliferative effect in keloid fibroblasts.</p> <p>Conclusions</p> <p>The methanolic honey extraction has an antiproliferative effect on keloid fibroblasts and a range of volatile compounds has been identified from Tualang honey. The antiproliferative effect of keloid fibroblasts towards Tualang honey may involve cell signaling pathway. Identifying other volatile compounds from different organic solvents should be carried out in future.</p
Trigeminal Neuralgia, Glossopharyngeal Neuralgia, and Myofascial Pain Dysfunction Syndrome: An Update
Neuropathic pain is a common phenomenon that affects millions of people worldwide. Maxillofacial structures consist of various
tissues that receive frequent stimulation during food digestion.The unique functions (masticatory process and facial expression)
of the maxillofacial structure require the exquisite organization of both the peripheral and central nervous systems. Neuralgia is
painful paroxysmal disorder of the head-neck region characterized by some commonly shared features such as the unilateral pain,
transience and recurrence of attacks, and superficial and shock-like pain at a trigger point.These types of pain can be experienced
after nerve injury or as a part of diseases that affect peripheral and central nerve function, or they can be psychological. Since
the trigeminal and glossopharyngeal nerves innervate the oral structure, trigeminal and glossopharyngeal neuralgia are the most
common syndromes following myofascial pain dysfunction syndrome. Nevertheless, misdiagnoses are common. The aim of this
review is to discuss the currently available diagnostic procedures and treatment options for trigeminal neuralgia, glossopharyngeal
neuralgia, and myofascial pain dysfunction syndrome
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