Department of Biochemistry, Faculty of Medicine, National University of Singapore, Kent Ridge Crescent, Singapore.
1. Myricetin is a natural bioflavonoid whose occurrence in nature is widespread among plants. 2. It has been demonstrated to possess both antioxidative properties and prooxidative properties. 3. It is a potent anticarcinogen and antimutagen, although it has been shown to promote mutagenesis with the use of the Ames Test. 4. Its therapeutic potential and benefits in cardiovascular diseases and diabetes mellitus also are reviewed.
Myricetin Increases Hepatic Peroxisome Proliferator-Activated Receptor α Protein Expression and Decreases Plasma Lipids and Adiposity in Rats.
School of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, China Medical University, Taichung, Taiwan.
The aim of this study was to investigate the antiobesity and antihyperlipidaemic effects of myricetin. Myricetin exhibited a significant concentration-dependent decrease in the intracellular accumulation of triglyceride in 3T3-L1 adipocytes. The high-fat diet (HFD)-fed rats were dosed orally with myricetin or fenofibrate, once daily for eight weeks. Myricetin (300 mg kg(-1) per day) displayed similar characteristics to fenofibrate (100 mg kg(-1) per day) in reducing lowered body weight (BW) gain, visceral fat-pad weights and plasma lipid levels of HFD-fed rats. Myricetin also reduced the hepatic triglyceride and cholesterol contents, as well as lowered hepatic lipid droplets accumulation and epididymal adipocyte size in HFD-fed rats. Myricetin and fenofibrate reversed the HFD-induced down-regulation of the hepatic peroxisome proliferator activated receptor (PPAR)α. HFD-induced decreases of the hepatic protein level of acyl-CoA oxidase and cytochrome P450 isoform 4A1 were up-regulated by myricetin and fenofibrate. The elevated expressions of hepatic sterol regulatory element binding proteins (SREBPs) of HFD-fed rats were lowered by myricetin and fenofibrate. These results suggest that myricetin suppressed BW gain and body fat accumulation by increasing the fatty acid oxidation, which was likely mediated via up-regulation of PPARα and down-regulation of SREBP expressions in the liver of HFD-fed rats.
Myricetin Ameliorates Defective Post-Receptor Insulin Signaling via β-Endorphin Signaling in the Skeletal Muscles of Fructose-Fed Rats.
Department of Internal Medicine, Pao Chien Hospital, Ping Tung City, China.
β-Endorphin plays a major role in the amelioration of insulin resistance. The present study documents that myricetin (3,5,7,3', 4', 5'-hexahydroxyflavone) ameliorates insulin resistance by enhancing β-endorphin production in insulin-resistant rats. The rats were induced for insulin resistance by feeding them a diet containing 60% fructose for 6 weeks. The degree of insulin resistance was measured by the homeostasis model assessment of basal insulin resistance (HOMA-IR). The plasma levels of insulin and β-endorphin were measured by an enzyme-linked immunosorbent assay. The insulin receptor-related signaling mediators in the soleus muscles of rats were evaluated by immunoprecipitation or immunoblotting. Myricetin was injected daily (1 mg kg(-1) per injection, thrice daily) for 14 days. Consequently, the high-glucose plasma levels in fructose-fed rats decreased significantly concomitant with an increase in plasma β-endorphin. The reduction of the elevated HOMA-IR index following treatment with myricetin was subsequently inhibited by the administration of β-funaltrexamine hydrochloride (β-FNA) at doses sufficient to block μ-opioid receptors (MOR). The myricetin treatment was also observed to affect the phosphorylation of the insulin receptor, insulin receptor substrate-1, Akt and Akt substrate of 160 kDa, with subsequent effects on glucose-transporter subtype 4 translocation, all of which were blocked by β-FNA pretreatment. These results indicated that enhancement of β-endorphin secretion, which in turn leads to peripheral MOR activation, is involved in the action of myricetin on the amelioration of impaired signaling intermediates downstream of insulin receptors.
Department of Chemistry, Quaid-i-Azam University, Islamabad, Pakistan. firstname.lastname@example.org
Phytochemical investigation of the leaves of Astragalus beckari yielded four flavonol aglycones, namely kaempferol, quercetin, 5-deoxy kaempferol and fisitin. These isolated compounds were then synthesised in the laboratory using the Algar-Flyn-Oyamad reaction. Antioxidant activity of both the isolated and synthesised flavonoids was compared using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay method. The isolated flavonoids were found to be more active.
Total phenolic compounds, flavonoids, and radical scavenging activity of 21 selected tropical plants.
Food Biotechnology & Functional Food Lab., Faculty of Food Science and Technology, Univ. Putra Malaysia, Serdang Selangor, Malaysia.
Free radical scavenging activity of 21 tropical plant extracts was evaluated using 1,1-diphenyl-2-picrylhydrazyl assay (DPPH). Total phenolic compounds and flavonoids were determined using Folin-Ciocalteu and HPLC, respectively. Results of the study revealed that all the plants tested exhibited excellent antioxidant activity with IC(50) in the range of 21.3 to 89.6 microg/mL. The most potent activity was demonstrated by Cosmos caudatus (21.3 microg/mL) and Piper betle (23.0 microg/mL) that are not significantly different than that of -tocopherol or BHA. L. inermis extract was found to consist of the highest concentration of phenolics, catechin, epicatechin, and naringenin. High content of quercetin, myricetin, and kaempferol were identified in Vitex negundo, Centella asiatica, and Sesbania grandiflora extracts, respectively. Luteolin and apigenin, on the other hand, were found in Premna cordifolia and Kaempferia galanga extracts. Strong correlation (R = 0.8613) between total phenolic compounds and total flavonoids (R = 0.8430) and that of antioxidant activity of the extracts were observed. The study revealed that phenolic, in particular flavonoids, may be the main contributors to the antioxidant activity exhibited by the plants. PRACTICAL APPLICATION: Potent antioxidant from natural sources is of great interest to replace the use of synthetic antioxidants. In addition, some of the plants have great potential to be used in the development of functional ingredients/foods that are currently in demand for the health benefits associated with their use.
Myricetin Inhibits Akt Survival Signaling and Induces Bad-mediated Apoptosis in a Low Dose Ultraviolet (UV)-B-irradiated HaCaT Human Immortalized Keratinocytes.
College of Natural Sciences, Department of Biological Sciences, Pusan National University.
Deregulation of cell survival pathways and resistance to apoptosis are generally accepted as crucial aspects of tumorigenesis. As in many tumors, increasing occurrence of human skin cancer and other conflicting effects of solar ultraviolet (UV) radiation enhance the demand for novel chemoprevention agents. Myricetin, a naturally occurring phytochemical, is potent in anti-cancer promoting activity and affords to the chemopreventive potential of several healthy-foods, including fruits and vegetables. We demonstrate here that myricetin inhibits Akt activity to induce apoptosis in a low dose (;repairable dose') UVB-irradiated keratinocytes. Treatment of UVB-irradiated HaCaT cells with an apoptosis-inducing concentration of myricetin (20 muM) resulted in a decrease in phosphorylation of Akt leading to inhibition of its kinase activity. Myricetin treatment also caused a decrease in phosphorylation of Bad (a pro-apoptotic protein), a direct target of Akt in signaling pathway. Interaction between Bad and 14-3-3beta was reduced markedly in UVB-irradiated cells upon a treatment with myricetin. Comparable to these results, myricetin treatment promoted mitochondrial translocation of Bad, loss of the mitochondrial membrane potential, and release of the mitochondrial apoptotic proteins including cytochrome c, Smac, and AIF. Ectopic expression of constitutively active Akt granted statistically significant protection against myricetin-induced apoptosis. In addition, myricetin-induced apoptosis in UVB-irradiated cells was notably attenuated in the presence of caspase inhibitors. Together, these results indicate that myricetin might take on potent chemopreventive activity by inhibiting the Akt-mediated survival signaling axis in UVB-induced skin carcinogenesis.
J Vet Sci. 2010 Mar ;11 (1):51-8 20195065
National Veterinary Research and Quarantine Service, Anyang 430-757, Korea.
The methanol extract from the leaves of Petasites japonicus Maxim (PJ) was studied for its (anti-)mutagenic effect with the SOS chromotest and reverse mutation assay. The (anti-)carcinogenic effects were evaluated by the cytotoxicity on human cancer line cells and by the function and the expression of gap junctions in rat liver epithelial cell. PJ extracts significantly decreased spontaneous beta-galactosidase activity and beta-galactosidase activity induced by a mutagen, ICR, in Salmonella (S.) typhimurium TA 1535/pSK 1002. All doses of the extract (0.08-100 mg/plate) decreased the reversion frequency induced by benzo (alpha)pyrene (BaP) in S. typhimurium TA 98. It decreased not only the spontaneous reversion frequency but also that induced by BaP in S. typhimurium TA 100. PJ extract showed greater cytotoxic effects on human stomach, colon and uterus cancer cells than on other cancer cell types and normal rat liver epithelial cells. Dye transfers though gap junctions were significantly increased by PJ extracts at concentrations greater than 200 microg/mL and the inhibition of dye transfer by 12-O-tetradecanoylphorobol-13-acetate (TPA) was obstructed in all concentrations of PJ. PJ significantly increased the numbers of gap junction protein connexin 43, and increased the protein expression decreased by TPA in a dose-dependent manner. Based on these findings, PJ is suggested to contain antimutagenic and anticarcionogenic compounds.
Separation and Purification of Phenolic Acids and Myricetin from Black Currant by High Speed Countercurrent Chromatography.
Xinjiang Key Laboratory of Plant Resources and Natural Products Chemistry, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Urumqi, China.
Black currant is an important material for food industry, but little research has been reported on the isolation of phenolic acids because of their low content. In present study, high-speed countercurrent chromatography (HSCCC) has been successfully used for the preparative isolation of the minor phenolic compounds from the ethyl acetate extracts of black currant fruit. The HSCCC separation was performed with a two-phase solvent system composed of n-hexane/EtOAc/MeOH/H(2)O (5:15:4:7 v/v) at a flow rate of 1.5 mL/min. From 500 mg crude sample 0.8 mg of protocatechuic acid, 1.0 mg of caffeic acid, 0.5 mg of 4-hydroxybenzoic acid and 2.5 mg of myricetin were purified by one-step HSCCC operation,. Their chemical structures were confirmed by MS and NMR.
Flavonoids as protein kinase inhibitors for cancer chemoprevention: direct binding and molecular modeling.
The United Graduate School of Agricultural Sciences, Faculty of Agriculture, Kagoshima University, Kagoshima City, Japan.
Protein kinases play crucial roles in the regulation of multiple cell signaling pathways and cellular functions. Deregulation of protein kinase function has been implicated in carcinogenesis. The inhibition of protein kinases has emerged as an important target for cancer chemoprevention and therapy. Accumulated data revealed that flavonoids exert chemopreventive effects through acting at protein kinase signaling pathways, more than as conventional hydrogen-donating antioxidants. Recent studies show that flavonoids can bind directly to some protein kinases, including Akt/protein kinase B (Akt/PKB), Fyn, Janus kinase 1 (JAK1), mitogen-activated protein kinase kinase 1 (MEK1), phosphoinositide 3-kinase (PI3K), mitogen-activated protein (MAP) kinase kinase 4 (MKK4), Raf1, and zeta chain-associated 70-kDa protein (ZAP-70) kinase, and then alter their phosphorylation state to regulate multiple cell signaling pathways in carcinogenesis processes. In this review, we report recent results on the interactions of flavonoids and protein kinases, especially their direct binding and molecular modeling. The data suggest that flavonoids act as protein kinase inhibitors for cancer chemoprevention that were thought previously as conventional hydrogen-donating antioxidant. Moreover, the molecular modeling data show some hints for creating natural compound-based protein kinase inhibitors for cancer chemoprevention and therapy.
Phenolic compounds prevent Alzheimer's pathology through different effects on the amyloid-beta aggregation pathway.
Department of Neurology and Neurobiology of Aging, Kanazawa University Graduate School of Medical Science, Takara-machi, Kanazawa, Japan.
Inhibition of amyloid-beta (Abeta) aggregation is an attractive therapeutic strategy for Alzheimer's disease (AD). Certain phenolic compounds have been reported to have anti-Abeta aggregation effects in vitro. This study systematically investigated the effects of phenolic compounds on AD model transgenic mice (Tg2576). Mice were fed five phenolic compounds (curcumin, ferulic acid, myricetin, nordihydroguaiaretic acid (NDGA), and rosmarinic acid (RA)) for 10 months from the age of 5 months. Immunohistochemically, in both the NDGA- and RA-treated groups, Abeta deposition was significantly decreased in the brain (P < 0.05). In the RA-treated group, the level of Tris-buffered saline (TBS)-soluble Abeta monomers was increased (P < 0.01), whereas that of oligomers, as probed with the A11 antibody (A11-positive oligomers), was decreased (P < 0.001). However, in the NDGA-treated group, the abundance of A11-positive oligomers was increased (P < 0.05) without any change in the levels of TBS-soluble or TBS-insoluble Abeta. In the curcumin- and myricetin-treated groups, changes in the Abeta profile were similar to those in the RA-treated group, but Abeta plaque deposition was not significantly decreased. In the ferulic acid-treated group, there was no significant difference in the Abeta profile. These results showed that oral administration of phenolic compounds prevented the development of AD pathology by affecting different Abeta aggregation pathways in vivo. Clinical trials with these compounds are necessary to confirm the anti-AD effects and safety in humans.
United Graduate School of Agricultural Sciences, Kagoshima University, Korimoto 1-21-24, Kagoshima City, 890-0065, Japan.
Akt, a serine/threonine kinase, is a critical regulator in many cellular processes including cell growth, proliferation, and apoptosis. In this study, we found that myricetin, a typical flavonol existing in many fruits and vegetables, could directly target Akt to inhibit cell transformation. Binding assay revealed that myricetin bound to Akt directly by competing with ATP. In vitro and ex vivo data confirmed that myricetin inhibited the phosphorylation and kinase activity of Akt. Molecular modeling suggested that myricetin easily docks to the ATP-binding site of Akt with hydrogen bonds. Signaling analysis data further demonstrated that myricetin inhibited Akt-mediated activator protein-1 (AP-1) transactivation, cyclin D1 expression and cell transformation. Overall, our results indicate that Akt is a direct target for myricetin to inhibit cell transformation.
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Department of Biochemistry, Faculty of Medicine, National University of Singapore, Republic of Singapore.
In our previous study, we found that myricetin, a naturally occurring bioflavonoid, was able to stimulate glucose transport in rat adipocytes and enhance insulin-stimulated lipogenesis. We report here that after 2 days of treatment with myricetin (3 mg/12 h), hyperglycemia in diabetic rats was reduced by 50% and the hypertriglyceridemia that is often associated with diabetes was normalised. Treatment with myricetin increased hepatic glycogen and glucose-6-phosphate content. It increased hepatic glycogen synthase I activity without having any effect on total glycogen synthase nor phosphorylase a activity. It lowered phosphorylase a activity in the muscle. Thus, the hypoglycemic effect of myricetin is likely to be due to its effect on glycogen metabolism. There was no indication of serious hepatotoxicity with myricetin treatment and therefore, myricetin could be of therapeutic potential in diabetes.
Insulinomimetic effects of myricetin on lipogenesis and glucose transport in rat adipocytes but not glucose transport translocation.
Department of Biochemistry, Faculty of Medicine, National University of Singapore, Singapore.
Myricetin is a naturally occurring flavonol that is commonly found in tea, berries, fruits, and medicinal plants. It mimics insulin in stimulating lipogenesis and glucose transport in rat adipocytes in vitro. It was found to stimulate lipogenesis in rat adipocytes and enhance the stimulatory effect of insulin. The EC50 was estimated to be about 65 microM. Myricetin did not have any effect on insulin receptor autophosphorylation nor on the tyrosine kinase activity of the receptor. However, myricetin stimulated both D-glucose and D-3-O-methylglucose uptake in rat adipocytes. The Vmax of glucose transport was increased, but the Km did not change significantly. Immunoblot analysis of Glut4 in rat adipocyte plasma membrane showed that the stimulation of glucose transport was not a consequence of glucose transporter translocation. Instead, the stimulation in glucose uptake probably was due to a change in the intrinsic activity of the glucose transporter possibly caused by alterations in membrane fluidity or transporter-lipid interactions as a result of the insertion of myricetin into the membrane bilayer. Thus, myricetin may have therapeutic potential in the management of non-insulin-dependent diabetes mellitus by stimulating glucose uptake without the presence of fully functional insulin receptor.
Tannic acid inhibits insulin-stimulated lipogenesis in rat adipose tissue and insulin receptor function in vitro.
Department of Biochemistry, National University of Singapore.
Tannins occur naturally in relatively abundant amounts in fruits, herbal medicines and common beverages. Thus an understanding of how these polyphenols affect peptide hormone action is of importance. We report here that tannic acid (a hydrolysable tannin) inhibits insulin-stimulated lipogenesis in rat adipose tissue in vitro, with an IC50 estimated to be about 350 microM. However, its monomer, gallic acid, did not show a similar inhibitory effect at concentrations up to 1 mM. The inhibition by tannic acid was less evident with higher concentrations of bovine serum albumin in the incubation buffer. This was attributed to the formation of a tannin-protein complex between bovine serum albumin and tannic acid. In a binding assay, it was observed that the specific binding of insulin to its receptor was not inhibited by tannic acid in the concentration range 0-200 microM. However, insulin-stimulated autophosphorylation of the insulin receptor, and receptor-associated tyrosine kinase phosphorylation of RR-SRC peptide, were inhibited by tannic acid at concentrations as low as 25 microM. Our data do not support the current speculation that tannins affect the activity of peptide hormones by binding to them. Therefore, our finding opens up a new perspective in the understanding of the mode of action of tannins on such hormones.
Department of Nutrition and Dietetics, Faculty of Medicine and Health Sciences, 43400 UPM Serdang, Selangor, Malaysia. email@example.com
INTRODUCTION Quality drinking water should be free from harmful levels of impurities such as heavy metals and other inorganic elements. METHODS Samples of tap water collected from 24 locations in Peninsular Malaysia were determined for inorganic element content. Minerals and heavy metals were analysed by spectroscopy methods, while non-metal elements were analysed using test kits. RESULTS Minerals and heavy metals determined were sodium, magnesium, potassium, calcium, chromium, manganese, iron, nickel, copper, zinc, arsenic, cadmium and lead while the non-metal elements were fluoride, chloride, nitrate and sulphate. Most of the inorganic elements found in the samples were below the maximum permitted levels recommended by inter-national drinking water standard limits, except for iron and manganese. Iron concentration of tap water from one of the locations was higher than the standard limit. CONCLUSION In general, tap water from different parts of Peninsular Malaysia had low concentrations of heavy metals and inorganic elements.
Enterovirus 71 encephalomyelitis and Japanese encephalitis can be distinguished by topographic distribution of inflammation and specific intraneuronal detection of viral antigen and RNA.
K T Wong, K Y Ng, K C Ong, W F Ng, S K Shankar, A Mahadevan, B Radotra, I J Su, G Lau, A E Ling, K P Chan, P Macorelles, S Vallet, M J Cardosa, A Desai, V Ravi, N Nagata, H Shimizu, T Takasaki
Faculty of Medicine, University of Malaya, Kuala Lumpur Universiti Sarawak Malaysia, Kuching, Malaysia Yan Chai Hospital, Hong Kong, China NIMHANS, Bangalore PGIMER, Chandigarh, India National Cheng Kung University, Taichung, Taiwan Centre for Forensic Science Singapore General Hospital, Singapore Centre Hospitalier Universitaire, Brest, France National Institute of Infectious Diseases, Tokyo, Japan.
K. T. Wong, K. Y. Ng, K. C. Ong, W. F. Ng, S. K. Shankar, A. Mahadevan, B. Radotra, I. J. Su, G. Lau, A. E. Ling, K. P. Chan, P. Macorelles, S. Vallet, M. J. Cardosa, A. Desai, V. Ravi, N. Nagata, H. Shimizu and T. Takasaki (2012) Neuropathology and Applied Neurobiology38, 443-453 Enterovirus 71 encephalomyelitis and Japanese encephalitis can be distinguished by topographic distribution of inflammation and specific intraneuronal detection of viral antigen and RNA Aims: To investigate if two important epidemic viral encephalitis in children, Enterovirus 71 (EV71) encephalomyelitis and Japanese encephalitis (JE) whose clinical and pathological features may be nonspecific and overlapping, could be distinguished. Methods: Tissue sections from the central nervous system of infected cases were examined by light microscopy, immunohistochemistry and in situ hybridization. Results: All 13 cases of EV71 encephalomyelitis collected from Asia and France invariably showed stereotyped distribution of inflammation in the spinal cord, brainstem, hypothalamus, cerebellar dentate nucleus and, to a lesser extent, cerebral cortex and meninges. Anterior pons, corpus striatum, thalamus, temporal lobe, hippocampus and cerebellar cortex were always uninflamed. In contrast, the eight JE cases studied showed inflammation involving most neuronal areas of the central nervous system, including the areas that were uninflamed in EV71 encephalomyelitis. Lesions in both infections were nonspecific, consisting of perivascular and parenchymal infiltration by inflammatory cells, oedematous/necrolytic areas, microglial nodules and neuronophagia. Viral inclusions were absent. Conclusions: Immunohistochemistry and in situ hybridization assays were useful to identify the causative virus, localizing viral antigens and RNA, respectively, almost exclusively to neurones. The stereotyped distribution of inflammatory lesions in EV71 encephalomyelitis appears to be very useful to help distinguish it from JE.
Patholog Res Int. 2011 ;2011 :567248 21961078
Department of Pathology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
Zoonoses as causes of human infections have been increasingly reported, and many of these are viruses that cause central nervous system infections. This paper focuses on the henipaviruses (family Paramyxoviridae, genus henipavirus) that have recently emerged to cause severe encephalitis and systemic infection in humans and animals in the Asia-Pacific region. The pathological features in the human infections comprise vasculopathy (vasculitis, endothelial multinucleated syncytia, thrombosis, etc.) and parenchymal cell infection in the central nervous system, lung, kidney, and other major organs. Most animals naturally or experimentally infected show more or less similar features confirming the dual pathogenetic mechanism of vasculopathy-associated microinfarction and direct extravascular parenchymal cell infection as causes of tissue injury. The most promising animal models include the hamster, ferret, squirrel monkey, and African green monkey. With increasing evidence of infection in the natural hosts, the pteropid bats and, hence, probable future outbreaks in many more countries, a greater awareness of henipavirus infection in both humans and animals is imperative.
Synergism between hydrogen sulfide (H(2)S) and nitric oxide (NO) in vasorelaxation induced by stonustoxin (SNTX), a lethal and hypotensive protein factor isolated from stonefish Synanceja horrida venom.
Department of Biochemistry, National University of Singapore, Blk MD4A, 10 Kent Ridge Crescent, Singapore.
Stonustoxin (SNTX) is a 148 kDa, dimeric, hypotensive and lethal protein factor isolated from the venom of the stonefish Synanceja horrida. SNTX (10-320 ng/ml) progressively causes relaxation of endothelium-intact, phenylephrine (PE)-precontracted rat thoracic aortic rings. The SNTX-induced vasorelaxation was inhibited by L-N(G)-nitro arginine methyl ester (L-NAME), suggesting that nitric oxide (NO) contributes to the SNTX-induced response. Interestingly, D, L-proparglyglycine (PAG) and beta-cyano-L-alanine (BCA), irreversible and competitive inhibitors of cystathionine-gamma-lyase (CSE) respectively, also inhibited SNTX-induced vasorelaxation, indicating that H(2)S may also play a part in the effect of SNTX. The combined use of L-NAME with PAG or BCA showed that H(2)S and NO act synergistically in effecting SNTX-induced vasorelaxation.
A comparison of 5% dextrose in 0.9% normal saline versus non-dextrose-containing crystalloids as the initial intravenous replacement fluid in elective surgery.
Department of Anaesthesia, Singapore General Hospital.
Intravenous fluid replacement in adult elective surgery is often initiated with dextrose-containing fluids. We sought to determine if this practice resulted in significant hyperglycaemia and if there was a risk of hypoglycaemia if non-dextrose-containing crystalloids were used instead. We conducted a randomized controlled trial in 50 non-diabetic adult patients undergoing elective surgery which did not involve entry into major body cavities, large fluid shifts, or require administration of >500 ml of intravenous fluid in the first two hours of peri-operative care. Patients received 500 ml of either 5% dextrose in 0.9% normal saline, lactated Ringer's solution, or 0.9% normal saline over 45 to 60 minutes. Plasma glucose, electrolytes and osmolarity were measured prior to infusion, and at 15 minutes and one hour after completion of infusion. None of the patients had preoperative hypoglycaemia despite average fasting times of almost 13 hours. Patients receiving lactated Ringer's and normal saline remained normoglycaemic throughout the study period. Patients receiving dextrose saline had significantly elevated plasma glucose 15 minutes after completion of infusion (11.1 (9.9-12.2, 95% CI) mmol/l). Plasma glucose exceeded 10 mmol/l in 72% of patients receiving dextrose saline. There was no significant difference in plasma glucose between the groups at one hour after infusion, but 33% of patients receiving DS had plasma glucose > or = 8 mmol/l. We conclude that initiation of intravenous fluid replacement with dextrose-containing solutions is not required to prevent hypoglycaemia in elective surgery. On the contrary, a relatively small volume of 500 ml causes significant, albeit transient, hyperglycaemia, even in non-diabetic patients.
Cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations in Asians with chronic pulmonary disease: a pilot study.
Nicola S P Ngiam, Samuel S Chong, Lynette P C Shek, Denise L M Goh, K C Ong, S Y Chng, G H Yeo, Daniel Y T Goh
Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, 5, Lower Kent Ridge Road, Singapore 119074, Singapore. firstname.lastname@example.org
BACKGROUND Little is known about the relationship between cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations in Asian patients and severe asthma or idiopathic bronchiectasis. We investigated this potential relationship in the Singaporean Chinese. METHODS Twenty patients with chronic pulmonary disease, 14 with severe asthma and 6 with idiopathic bronchiectasis, were screened for CFTR mutations by direct gene sequencing. The frequencies of identified putative mutations were compared against 40 unaffected controls and 96 unselected population samples. RESULTS Three missense mutations (I125T, I556V, and Q1352H) and 1 splice site variant (intron 8 12TG5T) were identified in a total of 10 patients, representing a combined mutant/variant allele frequency of 0.25. These alleles were also observed in the controls, but at a significantly lower allele frequency of 0.09 (P<0.01). Furthermore, the I125T mutation was significantly associated with the idiopathic bronchiectasis sub-group (P<0.05). CONCLUSIONS The significantly higher frequency of CFTR mutations among patients with chronic pulmonary disease compared with unaffected controls suggests that these mutations may increase risk for disease. The association of I125T with idiopathic bronchiectasis alone suggests that different mutations predispose to different disease.
Medical Education Unit, Yong Loo Lin School of Medicine, National University of Singapore,#01-08 Clinical Research Centre, 10 Medical Drive, Singapore 117597. email@example.com
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Formaldehyde-based resins have been used to create permanent-press finishes on fabrics since the 1920s. These resins have been shown to be potent sensitizers in some patients, leading to allergic contact dermatitis. This review summarizes the history of formaldehyde textile resin use, the diagnosis and management of allergic contact dermatitis from these resins, and current regulation of formaldehyde resins in textiles.
Department of Chemistry and School of Pharmacy, Analytical and Biological Chemistry Research Facility, University College Cork, Cork, Ireland.
The synthesis and structural characterization of a series of oxides of stigmasterol is described providing a valuable series of reference standards for these oxides, analogous to the cholesterol oxidation products (COPs) which have been shown to have detrimental biological effects. Biological evaluation of the oxides of phytosterols is significant in the context of increased dietary use of phytosterols in the drive to reduce cholesterol absorption.
The introduction and nature of the limited list are described, and both the early and longer term effects discussed. Although it was produced for economic reasons, the limited list has not been shown to have lowered drug costs overall.
Department of Pediatric Gastroenterology and Growth, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran. firstname.lastname@example.org
Celiac disease has been shown to be associated with type 1 diabetes mellitus. We conducted this study to determine the frequency of celiac disease in a group of Iranian diabetic children. Ninety-six patients with type 1 diabetes mellitus were tested for anti-tissue transglutaminase antibodies. Six patients (6.25%) were seropositive, and histopathological changes were compatible with celiac disease in intestinal biopsy.
Department of Physics and Astronomy, University of Nebraska-Lincoln, Lincoln Nebraska 68588, USA.
The Aharonov-Bohm (AB) effect is a purely quantum mechanical effect. The original (classified as type-I) AB-phase shift exists in experimental conditions where the electromagnetic fields and forces are zero. It is the absence of forces that makes the AB effect entirely quantum mechanical. Although the AB-phase shift has been demonstrated unambiguously, the absence of forces in type-I AB effects has never been shown. Here, we report the observation of the absence of time delays associated with forces of the magnitude needed to explain the AB-phase shift for a macroscopic system.
Use of overpressurized thin-layer chromatography (OPTLC) for the separation of amino-acids and polypeptides.
Chemical Works of Gedeon Richter Ltd, 1475 Budapest, Gyömröi u. 19-21, Hungary.
Overpressurized thin-layer chromatography (OPTLC) has been used for the separation of amino-acids and polypeptides. The effects of the ratio of pyridine to acetic acid as well as that of butanol to water on the selectivity and efficiency of separation have been investigated in detail. The influence of the nature of organic solvents in the eluent has also been studied. The optimal conditions have been elaborated and the practical applicability in pharmaceutical analysis of the separation system has been demonstrated.
Rebecca C Painter, Tessa J Roseboom, Patrick M M Bossuyt, Clive Osmond, David J P Barker, O P Bleker
Department of Clinical Epidemiology and Biostatistics, Academic Medical Center at the University of Amsterdam, P.O. Box 22660, 1100 DD, Meibergdreef 9, 1105, Amsterdam, AZ, The Netherlands. email@example.com
Prenatal famine exposure has previously been shown to be associated with cardiovascular disease and type II diabetes in adulthood. In the current study, we could not demonstrate an effect of prenatal exposure to famine in 2254 term singletons born during the 1944-1945 Dutch famine on adult mortality up to the age of 57 years. Follow-up of this cohort will resolve whether famine exposure is linked to increased adult mortality.
Department of Biological and Biomedical Sciences, Aga Khan University, Stadium road, Karachi, Pakistan. firstname.lastname@example.org
The ATP-binding cassette transporter 1 (ABCA1) is a trans-membrane peptide that is involved in the lipidification of ApoA-I. ABCA1 gene was initially implicated in Tangier disease and familial hypoalphalipoproteinemia and has been shown to be associated with coronary artery disease and atherosclerosis as well. Recently, a haplotype in ABCA1 gene was associated with increased risk of type II diabetes mellitus (DM). In this report, a relationship between ApoA-I, DM and ABCA1 has been emphasized.
Cold Spring Harbor Laboratory, NY 11724, USA. email@example.com
RNAi has shown great potential for use as a tool for biological discovery, analysis and therapeutics. The involvement of the RNAi pathway in post-transcription silencing, transcriptional silencing and epigenetic silencing as well as its use as a tool for forward genetics and therapeutics throws up several bioinformatics challenges. This paper delineates several areas of research and reviews work that has already been done, the tools that are available and the challenges that lie ahead.
Clin Calcium. 2003 Jul ;13 (7):911-4 15775167
Department of Hygienic Sciences, Kobe Pharmaceutical University.
2MD [2-methylene-19-nor-(20S)-1alpha, 25 (OH)(2)D(3)] is a bone-selective vitamin D analog that has been developed on the basis of structure-function study. The bone-selective action of the analog has been tested and confirmed both in vitro and in vivo and its clinical application as a medication for bone diseases is anticipated although its adverse effects remain unclear.