Displaying publications 4681 - 4700 of 5566 in total

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  1. Mahdy MA, Alareqi LM, Abdul-Ghani R, Al-Eryani SM, Al-Mikhlafy AA, Al-Mekhlafi AM, et al.
    Infect Dis Poverty, 2017 Feb 13;6(1):26.
    PMID: 28190399 DOI: 10.1186/s40249-017-0243-0
    BACKGROUND: Toxoplasma gondii is a zoonotic coccidian parasite causing morbidity and mortality. In Yemen, T. gondii infection has been reported among pregnant women seeking healthcare in the main cities. However, no data are available on the prevalence of T. gondii infection and its associated risk factors among pregnant women in the rural communities of the country. Thus, the present study aimed to determine the seroprevalence of T. gondii and identify its risk factors among pregnant women in the rural communities of Taiz governorate, Yemen.

    METHODS: A total of 359 pregnant women living in the rural communities of Taiz governorate were enrolled in this study by house-to-house visits. Data were collected using a pre-designed questionnaire, and blood samples were collected and tested for the detection of anti- T. gondii IgM and IgG antibodies by enzyme-linked immunosorbent assay.

    RESULTS: The prevalence of T. gondii infection among pregnant women in this study was 46.2% (166/359). Bivariate analysis identified the age of  ≥ 30 years (odds ratio [OR] = 1.7; 95% confidence interval [CI] = 1.09-2.65, P = 0.019) and unimproved water sources (OR = 2.2; 95% CI = 1.10-4.55, P = 0.023) as factors associated with T. gondii infection among pregnant women. The multivariable analysis, however, identified unimproved water sources as an independent risk factor (adjusted OR = 2.4; 95% CI = 1.16-5.0, P = 0.018) associated with T. gondii infection among pregnant women.

    CONCLUSIONS: Pregnant women in the rural communities of Taiz, Yemen are at high risk of contracting T. gondii infection. Unimproved water sources (wells, water streams and water tanks) are significantly associated with T. gondii infection and should be considered in prevention and control strategies, especially among pregnant women.

    Matched MeSH terms: Antibodies, Protozoan/blood
  2. Chai HJ, Kiew LV, Chin Y, Norazit A, Mohd Noor S, Lo YL, et al.
    Int J Nanomedicine, 2017;12:577-591.
    PMID: 28144140 DOI: 10.2147/IJN.S111284
    BACKGROUND AND PURPOSE: Poly-l-glutamic acid (PG) has been used widely as a carrier to deliver anticancer chemotherapeutics. This study evaluates PG as a selective renal drug carrier.

    EXPERIMENTAL APPROACH: 3H-deoxycytidine-labeled PGs (17 or 41 kDa) and 3H-deoxycytidine were administered intravenously to normal rats and streptozotocin-induced diabetic rats. The biodistribution of these compounds was determined over 24 h. Accumulation of PG in normal kidneys was also tracked using 5-(aminoacetamido) fluorescein (fluoresceinyl glycine amide)-labeled PG (PG-AF). To evaluate the potential of PGs in ferrying renal protective anti-oxidative stress compounds, the model drug 4-(2-aminoethyl)benzenesulfonyl fluoride hydrochloride (AEBSF) was conjugated to 41 kDa PG to form PG-AEBSF. PG-AEBSF was then characterized and evaluated for intracellular anti-oxidative stress efficacy (relative to free AEBSF).

    RESULTS: In the normal rat kidneys, 17 kDa radiolabeled PG (PG-Tr) presents a 7-fold higher, while 41 kDa PG-Tr shows a 15-fold higher renal accumulation than the free radiolabel after 24 h post injection. The accumulation of PG-AF was primarily found in the renal tubular tissues at 2 and 6 h after an intravenous administration. In the diabetic (oxidative stress-induced) kidneys, 41 kDa PG-Tr showed the greatest renal accumulation of 8-fold higher than the free compound 24 h post dose. Meanwhile, the synthesized PG-AEBSF was found to inhibit intracellular nicotinamide adenine dinucleotide phosphate oxidase (a reactive oxygen species generator) at an efficiency that is comparable to that of free AEBSF. This indicates the preservation of the anti-oxidative stress properties of AEBSF in the conjugated state.

    CONCLUSION/IMPLICATIONS: The favorable accumulation property of 41 kDa PG in normal and oxidative stress-induced kidneys, along with its capabilities in conserving the pharmacological properties of the conjugated renal protective drugs, supports its role as a potential renal targeting drug carrier.

    Matched MeSH terms: Polyglutamic Acid/blood
  3. Tee BH, Hoe SZ, Cheah SH, Lam SK
    Biomed Res Int, 2016;2016:1361508.
    PMID: 27800486 DOI: 10.1155/2016/1361508
    Although Eurycoma longifolia has been studied for erectile function, the blood pressure- (BP-) lowering effect has yet to be verified. Hence, this study aims at investigating the BP-lowering properties of the plant with a view to develop an antihypertensive agent that could also preserve erectile function. Ethanolic root extract was partitioned by hexane, dichloromethane (DCM), ethyl acetate, butanol, and water. The DCM fraction, found to be potent in relaxing phenylephrine- (PE-) precontracted rat aortic rings, was further purified by column chromatography. Subfraction DCM-II, being the most active in relaxing aortae, was studied for effects on the renin-angiotensin and kallikrein-kinin systems in aortic rings. The effect of DCM-II on angiotensin-converting enzyme (ACE) activity was also evaluated in vitro. Results showed that DCM-II reduced (p < 0.05) the contractions evoked by angiotensin I and angiotensin II (Ang II). In PE-precontracted rings treated with DCM-II, the Ang II-induced contraction was attenuated (p < 0.05) while bradykinin- (BK-) induced relaxation enhanced (p < 0.001). In vitro, DCM-II inhibited (p < 0.001) the activity of ACE. These data demonstrate that the vasodilatory effect of DCM-II appears to be mediated via inhibition of Ang II type 1 receptor and ACE as well as enhancement of Ang II type 2 receptor activation and BK activity.
    Matched MeSH terms: Blood Pressure/drug effects
  4. Cheah HY, Kiew LV, Lee HB, Japundžić-Žigon N, Vicent MJ, Hoe SZ, et al.
    J Appl Toxicol, 2017 Nov;37(11):1268-1285.
    PMID: 28165137 DOI: 10.1002/jat.3437
    While nano-sized construct (NSC) use in medicine has grown significantly in recent years, reported unwanted side effects have raised safety concerns. However, the toxicity of NSCs to the cardiovascular system (CVS) and the relative merits of the associated evaluation methods have not been thoroughly studied. This review discusses the toxicological profiles of selected NSCs and provides an overview of the assessment methods, including in silico, in vitro, ex vivo and in vivo models and how they are related to CVS toxicity. We conclude the review by outlining the merits of telemetry coupled with spectral analysis, baroreceptor reflex sensitivity analysis and echocardiography as an appropriate integrated strategy for the assessment of the acute and chronic impact of NSCs on the CVS. Copyright © 2017 John Wiley & Sons, Ltd.
    Matched MeSH terms: Blood Pressure/drug effects
  5. Rahman R, Murthi P, Singh H, Gurusinghe S, Mockler JC, Lim R, et al.
    Pregnancy Hypertens, 2016 Oct;6(4):259-262.
    PMID: 27939463 DOI: 10.1016/j.preghy.2016.09.001
    Hydroxychloroquine is an anti-malarial drug which, due to its anti-inflammatory and immunomodulatory effects, is widely used for the treatment of autoimmune diseases. In a model of systemic lupus erythematosus hydroxychloroquine has been shown to exert protective endothelial effects. In this study, we aimed to investigate whether hydroxychloroquine was endothelial protective in an in vitro model of TNF-α and preeclamptic serum induced dysfunction. We showed that hydroxychloroquine significantly reduced the production of TNF-α and preeclamptic serum induced endothelin-1 (ET-1). Hydroxychloroquine also significantly mitigated TNF-α induced impairment of angiogenesis. These findings support the further assessment of hydroxychloroquine as an adjuvant therapy in preeclampsia.
    Matched MeSH terms: Pre-Eclampsia/blood
  6. Cong Y, Lentz MR, Lara A, Alexander I, Bartos C, Bohannon JK, et al.
    PLoS Negl Trop Dis, 2017 04;11(4):e0005532.
    PMID: 28388650 DOI: 10.1371/journal.pntd.0005532
    Nipah virus (NiV) is a paramyxovirus (genus Henipavirus) that emerged in the late 1990s in Malaysia and has since been identified as the cause of sporadic outbreaks of severe febrile disease in Bangladesh and India. NiV infection is frequently associated with severe respiratory or neurological disease in infected humans with transmission to humans through inhalation, contact or consumption of NiV contaminated foods. In the work presented here, the development of disease was investigated in the African Green Monkey (AGM) model following intratracheal (IT) and, for the first time, small-particle aerosol administration of NiV. This study utilized computed tomography (CT) and magnetic resonance imaging (MRI) to temporally assess disease progression. The host immune response and changes in immune cell populations over the course of disease were also evaluated. This study found that IT and small-particle administration of NiV caused similar disease progression, but that IT inoculation induced significant congestion in the lungs while disease following small-particle aerosol inoculation was largely confined to the lower respiratory tract. Quantitative assessment of changes in lung volume found up to a 45% loss in IT inoculated animals. None of the subjects in this study developed overt neurological disease, a finding that was supported by MRI analysis. The development of neutralizing antibodies was not apparent over the 8-10 day course of disease, but changes in cytokine response in all animals and activated CD8+ T cell numbers suggest the onset of cell-mediated immunity. These studies demonstrate that IT and small-particle aerosol infection with NiV in the AGM model leads to a severe respiratory disease devoid of neurological indications. This work also suggests that extending the disease course or minimizing the impact of the respiratory component is critical to developing a model that has a neurological component and more accurately reflects the human condition.
    Matched MeSH terms: Cytokines/blood
  7. Kiertiburanakul S, Boettiger D, Ng OT, Van Kinh N, Merati TP, Avihingsanon A, et al.
    AIDS Res Ther, 2017;14:27.
    PMID: 28484509 DOI: 10.1186/s12981-017-0151-1
    BACKGROUND: Abacavir and rilpivirine are alternative antiretroviral drugs for treatment-naïve HIV-infected patients. However, both drugs are only recommended for the patients who have pre-treatment HIV RNA <100,000 copies/mL. In resource-limited settings, pre-treatment HIV RNA is not routinely performed and not widely available. The aims of this study are to determine factors associated with pre-treatment HIV RNA <100,000 copies/mL and to construct a model to predict this outcome.

    METHODS: HIV-infected adults enrolled in the TREAT Asia HIV Observational Database were eligible if they had an HIV RNA measurement documented at the time of ART initiation. The dataset was randomly split into a derivation data set (75% of patients) and a validation data set (25%). Factors associated with pre-treatment HIV RNA <100,000 copies/mL were evaluated by logistic regression adjusted for study site. A prediction model and prediction scores were created.

    RESULTS: A total of 2592 patients were enrolled for the analysis. Median [interquartile range (IQR)] age was 35.8 (29.9-42.5) years; CD4 count was 147 (50-248) cells/mm3; and pre-treatment HIV RNA was 100,000 (34,045-301,075) copies/mL. Factors associated with pre-treatment HIV RNA <100,000 copies/mL were age <30 years [OR 1.40 vs. 41-50 years; 95% confidence interval (CI) 1.10-1.80, p = 0.01], body mass index >30 kg/m2(OR 2.4 vs. <18.5 kg/m2; 95% CI 1.1-5.1, p = 0.02), anemia (OR 1.70; 95% CI 1.40-2.10, p 350 cells/mm3(OR 3.9 vs. <100 cells/mm3; 95% CI 2.0-4.1, p 2000 cells/mm3(OR 1.7 vs. <1000 cells/mm3; 95% CI 1.3-2.3, p 25 yielded the sensitivity of 46.7%, specificity of 79.1%, positive predictive value of 67.7%, and negative predictive value of 61.2% for prediction of pre-treatment HIV RNA <100,000 copies/mL among derivation patients.

    CONCLUSION: A model prediction for pre-treatment HIV RNA <100,000 copies/mL produced an area under the ROC curve of 0.70. A larger sample size for prediction model development as well as for model validation is warranted.

    Matched MeSH terms: RNA, Viral/blood*
  8. Giribabu N, Karim K, Kilari EK, Salleh N
    J Ethnopharmacol, 2017 Jun 09;205:123-137.
    PMID: 28483637 DOI: 10.1016/j.jep.2017.05.002
    ETHNOPHARMACOLOGICAL RELEVANCE: Phylanthus niruri has been used to treat ailments related to the urogenital organs. In this study, this herb was hypothesized to help to ameliorate kidney disease in diabetes mellitus (DM).

    AIMS: To investigate P. niruri leaves aqueous extract (PN) effects on kidney functions, histopathological changes and levels of oxidative stress, inflammation, fibrosis, apoptosis and proliferation in DM.

    METHODS: PN was orally administered to streptozotocin-nicotinamide-induced male diabetic rats for 28 days. At the end of the treatment, fasting blood glucose (FBG) and kidney functions were measured. Kidney somatic index, histopathological changes and levels of RAGE, Nrf2, oxidative stress markers (TBARS, SOD, CAT and GPx), inflammatory markers (NFkβ-p65, Ikk-β, TNF-α, IL-1β and IL-6), apoptosis markers (caspase-3, caspase-9 and Bax), fibrosis markers (TGF-β1, VEGF and FGF-1) and proliferative markers (PCNA and Ki-67) were determined by biochemical assays, qPCR, Western blotting, immunohistochemistry or immunofluorescence.

    RESULTS: Administration of PN helps to maintain near normal FBG, creatinine clearance (CCr), blood urea nitrogen (BUN), BUN/Cr ratio, serum electrolytes, uric acid and urine protein levels in DM. Decreased RAGE, TBARS and increased Nrf2, SOD-1, CAT and GPx-1 were observed in PN-treated diabetic rat kidneys. Expression of inflammatory, fibrosis and apoptosis markers in the kidney reduced but expression of proliferative markers increased following PN treatment. Lesser histopathological changes were observed in the kidney of PN-treated diabetic rats.

    CONCLUSION: PN helps to preserve near normal kidney function and prevents histopathological changes via ameliorating oxidative stress, inflammation, fibrosis and apoptosis while enhancing proliferation of the kidney in DM.

    Matched MeSH terms: Blood Glucose; Blood Urea Nitrogen
  9. Najafi R, Hosseini A, Ghaznavi H, Mehrzadi S, Sharifi AM
    Brain Res Bull, 2017 May;131:117-122.
    PMID: 28373151 DOI: 10.1016/j.brainresbull.2017.03.013
    OBJECTIVE: Neuropathies are a nerve disorders that caused by diabetes. Neuropathy affects over 50% of diabetic patients. High blood glucose and their toxic byproducts are the main causes for nerve dysfunction. In the present study, we examined the neroprotective effects of cerium oxide (CeO2) nanoparticles in diabetic rats.

    METHOD: Rats divided into four groups: control group, diabetic group, the diabetic group treated with CeO2nanoparticle at a dose of 65mg/kg and diabetic group received CeO2nanoparticle at a dose of 85mg/kg. Diabetes was induced by single intraperitoneal injection of 65mg/kg streptozotocin (STZ). 8 weeks after the induction of diabetes, body weight and pain sensitivity in all groups were measured. The blood sample was collected for biochemical analysis. The dorsal root ganglion (DRG) neurons were isolated for histopathological stain and morphometric parameters studies.

    RESULTS: Reduction of body weight, total thiol molecules (TTM), total antioxidant power (TAP) and ADP/ATP ratio in diabetic rat was reversed by CeO2nanoparticles administration. We showed that lipid peroxidation (LPO) and nociception latency were significantly increased in STZ-treated rats and decreased after CeO2nanoparticles administration. DRG neurons showed obvious vacuole and various changes in diameter, area and the count of A and B cells in STZ-diabetic rat. CeO2nanoparticles improved the histopathology and morphological abnormalities of DRG neurons.

    CONCLUSION: Our study concluded the CeO2nanoparticles have a protective effect against the development of DN.

    Matched MeSH terms: Blood Glucose/drug effects
  10. Idris ZM, Chan CW, Mohammed M, Kalkoa M, Taleo G, Junker K, et al.
    Parasit Vectors, 2017 Apr 26;10(1):204.
    PMID: 28441959 DOI: 10.1186/s13071-017-2139-z
    BACKGROUND: Seroepidemiology can provide evidence for temporal changes in malaria transmission and is an important tool to evaluate the effectiveness of control interventions. During the early 2000s, Vanuatu experienced an acute increase in malaria incidence due to a lapse in funding for vector control. After the distribution of subsidised insecticide-treated nets (ITNs) resumed in 2003, malaria incidence decreased in the subsequent years. This study was conducted to find the serological evidence supporting the impact of ITN on exposure to Anopheles vector bites and parasite prevalence.

    METHODS: On Ambae Island, blood samples were collected from 231 and 282 individuals in 2003 and 2007, respectively. Parasite prevalence was determined by microscopy. Antibodies to three Plasmodium falciparum (PfSE, PfMSP-119, and PfAMA-1) and three Plasmodium vivax (PvSE, PvMSP-119, and PvAMA-1) antigens, as well as the Anopheles-specific salivary antigen gSG6, were detected by ELISA. Age-specific seroprevalence was analysed using a reverse catalytic modelling approach to estimate seroconversion rates (SCRs).

    RESULTS: Parasite rate decreased significantly (P 

    Matched MeSH terms: Antibodies, Protozoan/blood
  11. Goh DL, Chua KY, Chew FT, Liang RC, Seow TK, Ou KL, et al.
    J Allergy Clin Immunol, 2001 Jun;107(6):1082-7.
    PMID: 11398089
    BACKGROUND: We have previously described anaphylaxis induced by edible bird's nest (BN) and demonstrated that this condition is IgE mediated.

    OBJECTIVES: This study aimed at describing the immunochemical properties of the BN allergens. Comparative studies between 3 commercially available sources (according to the country of origin) of BN were also made.

    METHODS: Crude extracts of commercially available processed BN from Sarawak (Malaysia), Thailand, and Indonesia and fresh unprocessed BN from the caves of Sarawak were obtained by means of aqueous extraction. Specific IgE toward these sources were determined by using fluorescence allergosorbent tests (FASTs). Cross-reactivity studies between the 3 sources of commercially available processed BN were carried out by means of FAST inhibition. Immunochemical characterization by means of IgE immunoblot, periodate treatment, and heat stability studies were carried out on fresh unprocessed BN from Sarawak.

    RESULTS: Serum from allergic patients showed differences in IgE binding to the 3 sources of commercially available BN, with the highest levels of specific IgE recorded with the Sarawak source (P

    Matched MeSH terms: Immunoglobulin E/blood
  12. Kono Y, Tsukamoto K, Abd Hamid M, Darus A, Lian TC, Sam LS, et al.
    Am J Trop Med Hyg, 2001 5 19;63(1-2):94-101.
    PMID: 11358004
    A new virus named Sitiawan virus (SV) was isolated from sick broiler chicks in chicken embryos. The virus replicated well with cytopathogenic effect (CPE) in the chicken B-lymphocyte cell line LSCC-BK3. The virus was an enveloped RNA virus of approximately 41 nm in size with hemagglutinating activity (HA) to goose erythrocytes. It was cross-reactive with Japanese encephalitis virus (JEV), a member of flaviviruses by HA inhibition tests but not by cross-virus neutralization tests. The cDNA fragment of NS5 gene was amplified with primers corresponding to NS5 gene of flaviviruses. The nucleotide sequences were 92% homologous to Tembusu virus, a member of the mosquito-borne virus cluster of the genus Flavivirus. In cross-neutralization tests with Tembusu virus, antiserum to SV did not neutralize Tembusu virus, and antiserum to Tembusu virus neutralized more weakly to SV than against homologous virus. These results indicate that SV is a new virus which can be differentiated serologically from Tembusu virus but is otherwise similar with respect to nucleotide sequence. The virus causes encephalitis, growth retardation, and increased blood glucose levels in inoculated chicks.
    Matched MeSH terms: Poultry Diseases/blood
  13. Gibbs WW
    Sci. Am., 1999 Aug;281(2):80-7.
    PMID: 10443039
    Matched MeSH terms: Brain/blood supply
  14. Tee TS, Kamalanathan M, Suan KA, Chun SS, Ming HT, Yasin RM, et al.
    Am J Trop Med Hyg, 1999 Jul;61(1):73-7.
    PMID: 10432060
    The seroprevalence of Orientia tsutsugamushi, Rickettsia typhi, and TT118 spotted fever group (SFG) rickettsiae in 300 rubber estate workers in Slim River, Malaysia was determined in December 1996 and March 1997. In December, which was the wet season, 23.3%, 3.0%, and 57.3% of the population had antibodies detected against the three rickettsiae, respectively. The highest seropositive rate of 40% was detected for single infection with SFG rickettsiae, followed by a rate of 15.3% for both O. tsutsugamushi and SFG rickettsiae among the rubber estate workers. Subjects less than 21 years old had a lower seroprevalence of SFG rickettsiae compared with the other age groups. Indians had a higher seroprevalence of O. tsutsugamushi compared with other ethnic groups. Rubber tappers had a higher seroprevalence of SFG rickettsiae compared with other occupational groups. During the dry season in March 1997, there was a significant increase in the seroprevalence of R. typhi. The seroconversion rates for IgM against O. tsutsugamushi, R. typhi, and SFG rickettsiae were 5.7%, 12.3%, and 15.1%, respectively, during the four-month period. Significant variations of antibody titers towards the three rickettsiae was noted among subjects who were bled twice. This suggests a significant and continual exposure of rubber estate workers to the three rickettsiae.
    Matched MeSH terms: Antibodies, Bacterial/blood
  15. Yap SN, Phipps ME, Manivasagar M, Tan SY, Bosco JJ
    Lupus, 1999;8(4):305-10.
    PMID: 10413210 DOI: 10.1191/096120399678847876
    SLE is an autoimmune and polygenic disorder characterized by an accumulation and deposition of immune complexes. Several studies have indicated differential impact of FcgammaR polymorphism genotypes in different ethnic groups studied. The Fc receptor for IgG class IIA gene (FcgammaRIIA) occurs in two allelic forms. The allele FcgammaRIIA-H131 encodes a receptor with a histidine at the 131 amino acid position; the other allele FcgammaRIIA-R131 encodes an arginine. This polymorphism is believed to determine the affinity of the receptor for hIgG2 in immune complexes. FcgammaRIIA-H131 has a higher capacity for hIgG2 compared to FcgammaRIIA-R131 as measured by in vitro studies of insoluble immune complex clearance. We have investigated the polymorphism for FcgammaRIIA using a novel polymerase chain reaction-allele specific primer (PCR-ASP) method designed specifically to distinguish the two allelic forms. Our studies were based on 175 Chinese and 50 Malays SLE patients as well as 108 and 50 ethnically matched healthy controls for the respective groups. Analysis of the data (chi2 test with Yates correction factors and odds ratios) revealed that there were no significant differences between SLE patients and controls. We have not found evidence of a protective effect conferred by FcgammaRIIA-H131 in the ethnic groups studied.
    Matched MeSH terms: Immunoglobulin G/blood
  16. Kobayashi N, Thayan R, Sugimoto C, Oda K, Saat Z, Vijayamalar B, et al.
    Am J Trop Med Hyg, 1999 Jun;60(6):904-9.
    PMID: 10403318
    To characterize the dengue epidemic that recently occurred in Malaysia, we sequenced cDNAs from nine 1993-1994 dengue virus type-3 (DEN-3) isolates in Malaysia (DEN-3 was the most common type in Malaysia during this period). Nucleic acid sequences (720 nucleotides in length) from the nine isolates, encompassing the precursor of membrane protein (preM) and membrane (M) protein genes and part of the envelope (E) protein gene were aligned with various reference DEN-3 sequences to generate a neighbor-joining phylogenetic tree. According to the constructed tree, the nine Malaysian isolates were grouped into subtype II, which comprises Thai isolates from 1962 to 1987. Five earlier DEN-3 virus Malaysian isolates from 1974 to 1981 belonged to subtype I. The present data indicate that the recent dengue epidemic in Malaysia was due to the introduction of DEN-3 viruses previously endemic to Thailand.
    Matched MeSH terms: RNA, Viral/blood
  17. Monath TP
    PMID: 12082985
    Vaccination against JE ideally should be practiced in all areas of Asia where the virus is responsible for human disease. The WHO has placed a high priority on the development of a new vaccine for prevention of JE. Some countries in Asia (Japan, South Korea, North Korea, Taiwan, Vietnam, Thailand, and the PRC) manufacture JE vaccines and practice childhood immunization, while other countries suffering endemic or epidemic disease (India, Nepal, Laos, Cambodia, Bangladesh, Myanmar, Malaysia, Indonesia and the Philippines) have no JE vaccine manufacturing or policy for use. With the exception of the PRC, all countries practicing JE vaccination use formalin inactivated mouse brain vaccines, which are relatively expensive and are associated with rare but clinically significant allergic and neurological adverse events. New inactivated JE vaccines manufactured in Vero cells are in advanced preclinical or early clinical development in Japan, South Korea, Taiwan, and the PRC. An empirically derived, live attenuated vaccine (SA14-14-2) is widely used in the PRC. Trials in the PRC have shown SA14-14-2 to be safe and effective when administered in a two-dose regimen, but regulatory concerns over manufacturing and control have restricted international distribution. The genetic basis of attenuation of SA14-14-2 has been partially defined. A new live attenuated vaccine (ChimeriVax-JE) that uses a reliable flavivirus vaccine--yellow fever 17D--as a live vector for the envelope genes of SA14-14-2 virus is in early clinical trials and appears to be well tolerated and immunogenic after a single dose. Vaccinia and avipox vectored vaccines have also been tested clinically, but are no longer being pursued due to restricted effectiveness mediated by anti-vector immunity. Other approaches to JE vaccines--including naked DNA, oral vaccination, and recombinant subunit vaccines--have been reviewed.
    Matched MeSH terms: Antibodies, Viral/blood
  18. Liem LK, Choong LH, Woo KT
    Clin Biochem, 2002 May;35(3):181-7.
    PMID: 12074825
    OBJECTIVE: Dihydropyrimidine dehydrogenase (DPD) catalyzes the degradation of thymine, uracil, and the chemotherapeutic drug 5-Fluorouracil. In general reverse-phase high pressure liquid chromatography is the standard method for separating 5-[2-(14)C]Fluorouracil and 5-[2-(14)C]Fluoro-5,6-dihydrouracil. However, the use of 100% aqueous solution (as HPLC mobile phase) may collapse the C-18 bonded phase and result in a retention time shift. The aim of this study is to develop a rapid, reproducible, sensitive method for screening partial DPD deficiency in healthy volunteers.

    DESIGN AND METHODS: The activity of DPD was measured using 5-[2- (14)C]Fluorouracil (5-[2-(14)C]FUra) followed by separation of substrate and product 5-[2-(14)C]FUraH(2) with a 15 x 4.6 mm I.D., 5 microm particle size (d(p)) porous graphitic carbon (PGC) column (Hypercarb(R)) and HPLC with online detection of the radioactivity. This was standardized using the protein concentration of the cytosol (NanoOrange(R) Protein Quantitation).

    RESULTS: Complete baseline separation of 5-[2-(14)C]Fluorouracil (5-[2-(14)C]FUra) and 5-[2-(14)C]Fluoro-5,6-dihydrouracil (5-[2-(14)C]FUraH(2)) was achieved using a porous graphitic carbon (PGC) column. The detection limit for 5-[2-(14)C]FUraH(2) was 0.4 pmol.

    CONCLUSIONS: By using linear gradient separation (0.1% Trifluoroacetic acid [TFA] in water to 100% Methanol) protocols in concert with PGC columns (Hypercarb(R)), we have demonstrated that a PGC column has a distinct advantage over C-18 reverse phase columns in terms of column stability (pH 1-14). This method provides an improvement on the specific assay for DPD enzyme activity. It is rapid, reproducible and sensitive and can be used for routine screening for healthy and cancer patients for partial and profound DPD deficiency before treatment with 5- FUra.

    Matched MeSH terms: Oxidoreductases/blood*
  19. Rehman A, Rahman AR, Rasool AH
    J Hum Hypertens, 2002 Apr;16(4):261-6.
    PMID: 11967720
    The objective of this study was to examine the effect of angiotensin II (Ang II) and angiotensin II type 1 (AT(1)) receptor blockade on pulse wave velocity (PWV) in healthy humans. We studied nine young male volunteers in a double-blind randomised crossover design. Carotid-femoral PWV (an index of arterial stiffness) was measured by using a Complior machine. Subjects were previously treated for 3 days with once-daily dose of either a placebo or valsartan 80 mg. On the third day, they were infused with either placebo or 5 ng/kg/min of Ang II over 30 min. Subjects thus received placebo capsule + placebo infusion (P), valsartan + placebo infusion (V), placebo + Ang II infusion (A), and valsartan + Ang II infusion (VA) combinations. Heart rate (HR), blood pressure and PWV were recorded at baseline and then every 10 min during infusion and once after the end of infusion. There were significant increases in systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP) with A compared with P (P = 0.002, P = 0.002, P = 0.001 respectively). These rises in blood pressure were completely blocked by valsartan. A significant rise in PWV by A was seen compared with P (8.38 +/- 0.24 vs 7.48 +/- 0.24 m/sec, P = 0.013) and was completely blocked by valsartan; VA compared with P (7.27 +/- 0.24 vs 7.48 +/- 0.24 m/sec, P = NS). Multiple linear regression analysis showed that blockade of Ang II induced increase in blood pressure by valsartan contributed to only 30% of the total reduction in Ang II induced rise in PWV (R(2) = 0.306). The conclusions were that valsartan completely blocks the effect of Ang II on PWV. The effect of Ang II on PWV is mediated through AT(1)receptors. Reduction in PWV by Ang II antagonist is not fully explained by its pressure lowering effect of Ang II and may be partially independent of its effect on blood pressure.
    Matched MeSH terms: Blood Flow Velocity/drug effects*
  20. Zamri-Saad M, Effendy AW, Israf DA, Azmi ML
    Vet Microbiol, 1999 Mar 12;65(3):233-40.
    PMID: 10189198
    A study to determine the immunoglobulin and cellular responses in the respiratory tract of goats following intranasal exposures to formalin-killed Pasteurella haemolytica A2 was carried out. Forty-two goats were divided into two groups. Goats in Group 1 were subjected to double intranasal exposures to formalin-killed P. haemolytica A2 while goats in Group 2 were the unexposed control. Prior to and at weekly intervals post-exposure, three goats from each group were killed, serum samples were collected while the lungs were flushed with 50 ml normal saline before the right apical lobes were fixed in 10% buffered formalin. Both serum and lung lavage fluid were subjected to enzyme-linked immunosorbent assay (ELISA) to determine the levels of IgA, IgM and IgG while the formalin-fixed tissues were examined histologically. IgA levels in the lung lavage fluid increased rapidly to reach a significantly (p < 0.05) high level as early as Week 2 post-exposure and remained significantly (p < 0.05) high throughout the study period. The IgM levels increased at an intermediate rate to reach a significantly (p < 0.05) high level at Week 3 post-exposure before they decreased to an insignificant (p > 0.05) level the following week and the weeks thereafter. IgG levels increased gradually and only reached a significantly (p < 0.01) high level at Weeks 5 and 6 of the study. The size of the bronchus-associated lymphoid tissue (BALT) and the number of lymphocytes in BALT increased significantly from Week 2 and remained high thereafter. However, differences in the numbers of BALT were insignificant (p > 0.05) initially before becoming significantly (p < 0.05) high at Weeks 5 and 6. The BALT responses were parallel to those of imunoglobulins in the lung lavage fluid.
    Matched MeSH terms: Immunoglobulins/blood
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