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Seoul, South Korea
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Junsiri W.,Kasetsart University | Wongnarkpet S.,Kasetsart University | Chimnoi W.,Kasetsart University | Kengradomkij C.,Kasetsart University | And 3 more authors.
Tropical Biomedicine | Year: 2017

Leishmaniasis is a zoonotic disease that is a major public health problem in tropical countries caused by flagellate protozoa of the genus Leishmania. Domestic animals and wild rodents have been reported as natural reservoir hosts. Thailand is a non-endemic area for leishmaniasis but human cases have been reported sporadically, particularly in southern Thailand. The objective of the present study was to determine the seroprevalence of Leishmania infection in domestic animals in southern Thailand. Blood samples from 519 dogs, 250 cats, 113 rats, 19 shrews, 125 cattle, 95 buffaloes and spleen samples from 45 rats and 19 shrews were collected in Songkhla and Satun provinces. Seroreactivity to the Direct Agglutination Test (DAT) was found in 2.7% (14/519) of the dogs while 5.6% (14/250) of the cats were positive using ELISA. There were significant differences between positive samples based on adult age group in dogs and cats (χ2 = 5.396, P= 0.020, χ2 = 8.304, P = 0.004, respectively) and for the outdoor group in cats (χ2 = 6.956, P= 0.008). The results found low seroprevalence of Leishmania infection in both dogs and cats, but they could be natural reservoir hosts for leishmaniasis in southern Thailand. © 2017, Malaysian Society for Parasitology. All rights reserved.


Bae J.S.,Sogang University | Cheong H.S.,SNP Genetics Inc. | Chun J.-Y.,Sogang University | Park T.J.,Sogang University | And 9 more authors.
Ophthalmology | Year: 2010

Objective: To determine the association of identified copy number variations (CNVs) in whole genome with the risk of Avellino corneal dystrophy (ACD) in a Korean population. Design: Case-control study. Participants: A total of 146 patients with ACD and 226 control subjects. Methods: A total of 193 trios were genotyped by the Illumina HumanHapCNV370-Duo BeadChip (370 404 markers) (Illumina, Inc., San Diego, CA). The intensity signal (log R ratio) and allelic intensity ratio (B allele frequency) of each marker in all individuals were obtained by Illumina BeadStudio software (Illumina, Inc.). To obtain authentic CNVs in this study, we performed a family-based CNV validation and family-based boundary mapping using the PennCNV algorithm, which incorporates multiple factors, including total log R ratio, B allele frequency, and family information, based on an integrated hidden Markov model. Main Outcome Measures: Statistical comparison and identification of CNVs between case and control using family information. Results: We identified 27 267 individual trio CNVs with a median size of 16.2 kb, aggregated in 2245 CNV regions. Most of the identified trio CNVs in this study showed well-defined CNV boundaries and overlapped with those in the Database of Genomic Variants (DGV) (83.4% in number and 79.2% in length). With the common CNV regions (264 CNV regions >5%), we performed a family-based association test with the risk of ACD. Conclusions: Two CNV regions (chr6:29978470-29987783 and chr14:59896944-59916129) were significantly associated with the risk of ACD (P=0.05∼0.003 and P=0.008, respectively). This study describes the first results of a genome-wide association analysis of individual CNVs with the risk of ACD and shows that 2 novel CNV loci may be involved in the risk of ACD. © 2010 by the American Academy of Ophthalmology.


News Article | October 27, 2016
Site: www.eurekalert.org

SALT LAKE CITY -- More than 4,000 children and teens are diagnosed with brain cancer each year and the disease kills more children than any other cancer. Writing this week in the journal Cell Reports, researchers at Huntsman Cancer Institute (HCI) at the University of Utah report they have identified an existing group of drugs that appear to reduce or eliminate a certain subgroup of childhood brain cancers while sparing normal brain tissue. The research was conducted using a new zebrafish animal model system developed by the researchers, which closely resembles an aggressive subtype of pediatric brain tumors. "For many pediatric brain tumors no cell or animal model exist to test targeted, or personalized, medications that could significantly improve survival and alleviate the harmful side effects of conventional therapies," explains Rodney Stewart, PhD, an assistant professor in the Department of Oncological Sciences at the University of Utah and an HCI investigator. "Indeed, children with rare brain tumors have few options for life-saving treatment. Our hope is by creating this animal model we will be a step closer to finding effective therapies." The researchers studied a particularly aggressive pediatric brain tumor, known as primitive neuroectodermal tumors of the central nervous system (CNS-PNET) for which few animal or cell line models exist. Without an animal model or cell lines, Stewart explained, treatments could not be tested. Over the course of seven years, Stewart and his team worked to develop a model which, at the genomic level, closely modeled the human condition they hoped to study. "We spent a lot of time comparing brain tumors arising in fish with related human brain cancers at the molecular genetic level," Stewart says. "This is important because these childhood brain cancers are rare and as a result, there are few patient samples to study for comparisons." Human tissue samples were necessary, however, in order to construct a reliable model. "We needed to reach out to several groups," he explains, including Primary Children's Hospital in Salt Lake City and The Hospital for Sick Children in Toronto. Dr. Stewart credits discoveries announced by two other groups studying similar cancers that opened the way for his group to move forward. "They were able to re-classify CNS-PNET tumors into distinct subgroups at the molecular level. That opened up a new avenue for our team because that stratification made it possible for us to really nail down what the zebrafish brain tumor model represents." Using the model, Stewart's lab was able to test already existing compounds to see if they could find a targeted therapy that would work on one of the newly identified subgroups: the oligoneural or NB_FOXR2 CNS-PNET subgroup. Through work they had done to create the tumor model, they knew that a particular drug already in human clinical trials might work. "When we treated the fish with MEK inhibitors -- drugs that inhibit an enzyme -- they exhibited a remarkable response," says Stewart. "Not only was the tumor burden reduced, it completely eliminated the tumor in about 80% of the fish and those tumors have not come back. This is a durable response from a transient treatment. It's what we look for in cancer therapy, an effective drug that can be taken for a certain amount of time but, after the cancer is gone, patients can stop taking the drug and go on living their lives." Stewart is careful to emphasize that while the brain tumor type between fish and humans is similar, more studies are needed to determine if the results can be translated into the clinic. He would like to see his discovery in the hands of physicians as soon as possible. "Currently, the outcome for children with these cancers is deplorable. We don't want to wait much longer," he says. This study was done in partnership with collaborators at HCI including University of Utah faculty from the departments of pediatrics, pathology, neurosurgery, and oncological sciences; ARUP laboratories, Primary Children's Hospital, Salt Lake City; and the Hospital for Sick Children, Toronto. Funding for this work was provided by the Canadian Institute of Health Research, the American Cancer Society, National Institute of Health NIH P30 CA042014, and the Huntsman Cancer Foundation. About Huntsman Cancer Institute at the University of Utah Huntsman Cancer Institute (HCI) is one of the world's top academic research and cancer treatment centers. HCI manages the Utah Population Database -- the largest genetic database in the world, with more than 16 million records linked to genealogies, health records, and vital statistics. Using this data, HCI researchers have identified several cancer-causing genes, including the genes responsible for melanoma, colon and breast cancer. HCI is a member of the National Comprehensive Cancer Network (a 27-member alliance of the world's leading cancer centers) and is a National Cancer Institute-Designated Comprehensive Cancer Center. HCI treats patients with all forms of cancer and operates several high-risk clinics that focus on melanoma and breast, colon, and pancreas cancers. The HCI Cancer Learning Center for patient and public education contains one of the nation's largest collections of cancer-related publications. The institute is named after Jon M. Huntsman, a Utah philanthropist, industrialist, and cancer survivor.


Lee S.E.,Seoul National University | Cho H.-J.,Seoul National University | Lee H.-Y.,Seoul National University | Yang H.-M.,Seoul National University | And 16 more authors.
European Journal of Heart Failure | Year: 2014

Aims The Korean Acute Heart Failure registry (KorAHF) aims to evaluate the clinical characteristics, management, hospital course, and long-term outcomes of patients hospitalized for acute heart failure syndrome (AHFS) in Korea. Methods and results This is a prospective observational multicentre cohort study funded by the Korea National Institute of Health. Patients hospitalized for AHFS in 10 tertiary university hospitals across the country have been consecutively enrolled since March 2011. The study is expected to complete the scheduled enrolment of 5000 patients some time in 2014, and follow-up is planned through 2016. As of April 2012, the interim analysis of 2066 consecutive subjects was performed to understand the baseline characteristics of the population. The mean age was 69 ± 14 years; 55% were male; and 50% were de novo heart failure. The mean left ventricular ejection fraction (LVEF) was 40 ± 18%. Ischaemia was both the leading cause (38%) and the most frequent aggravating factor (26%) of AHFS. ACE inhibitors/ARBs and beta-blockers were prescribed at discharge in 65% and 51% of the patients, respectively. In-hospital mortality was 5.2%, and 0.9% of patients received urgent heart transplantation. Low blood pressure and azotaemia were the most important predictors of in-hospital mortality. The post-discharge 30-day and 180-day all-cause mortality were 1.2% and 9.2%, respectively. Conclusions Our analysis reveals that the prognosis of AHFS in Korea is poor and that there are specific features, including lower blood pressures at admission and lower rates of heart failure related to hypertension, compared with other registries. Adherence to current guidelines should be improved. © 2014 European Society of Cardiology.


Habib M.A.,Aga Khan University | Soofi S.,Aga Khan University | Sheraz A.,Aga Khan University | Bhatti Z.S.,Aga Khan University | And 6 more authors.
Vaccine | Year: 2015

Background: Polio eradication remains a challenge in Pakistan and the causes for the failure to eradicate poliomyelitis are complex. Undernutrition and micronutrient deficiencies, especially zinc deficiency, are major public health problems in Pakistan and could potentially affect the response to enteric vaccines, including oral poliovirus vaccine (OPV). Objective: To assess the impact of zinc supplementation among infants on immune response to oral poliovirus vaccine (OPV). Methods: A double-blind, randomized placebo-controlled trial was conducted in newborns (aged 0-14 days). Subjects were assigned to either receive 10. mg of zinc or placebo supplementation daily for 18 weeks. Both groups received OPV doses at birth, at 6 weeks, 10 weeks and 14 weeks. Data was collected on prior immunization status, diarrheal episodes, breastfeeding practices and anthropometric measurements at recruitment and at 6 and 18 weeks. Blood samples were similarly collected to determine the antibody response to OPV and for micronutrient analysis. Logistic regression was used to determine the relationship between seroconversion and zinc status. Results: Overall, 404 subjects were recruited. At recruitment, seropositivity was already high for poliovirus (PV) serotype 1 (zinc: 91.1%; control: 90.5%) and PV2 (90.0%; 92.7%), with lower estimates for PV3 (70.0%; 64.8%). By week 18, the proportion of subjects with measured zinc levels in the normal range (i.e. ≥60. μg/dL) was significantly greater in the intervention group compared to the control group (71.9%; 27.4%; p< 0.001). No significant difference in seroconversion was demonstrated between the groups for PV1, PV2, or PV3. Conclusions: There was no effect of zinc supplementation on OPV immunogenicity. These conclusions were confirmed when restricting the analysis to those with measured higher zinc levels. © 2014 Elsevier Ltd.


PubMed | National Institute of Health NIH, WHO, Aga Khan University and Centers for Disease Control and Prevention
Type: Journal Article | Journal: Vaccine | Year: 2015

Polio eradication remains a challenge in Pakistan and the causes for the failure to eradicate poliomyelitis are complex. Undernutrition and micronutrient deficiencies, especially zinc deficiency, are major public health problems in Pakistan and could potentially affect the response to enteric vaccines, including oral poliovirus vaccine (OPV).To assess the impact of zinc supplementation among infants on immune response to oral poliovirus vaccine (OPV).A double-blind, randomized placebo-controlled trial was conducted in newborns (aged 0-14 days). Subjects were assigned to either receive 10mg of zinc or placebo supplementation daily for 18 weeks. Both groups received OPV doses at birth, at 6 weeks, 10 weeks and 14 weeks. Data was collected on prior immunization status, diarrheal episodes, breastfeeding practices and anthropometric measurements at recruitment and at 6 and 18 weeks. Blood samples were similarly collected to determine the antibody response to OPV and for micronutrient analysis. Logistic regression was used to determine the relationship between seroconversion and zinc status.Overall, 404 subjects were recruited. At recruitment, seropositivity was already high for poliovirus (PV) serotype 1 (zinc: 91.1%; control: 90.5%) and PV2 (90.0%; 92.7%), with lower estimates for PV3 (70.0%; 64.8%). By week 18, the proportion of subjects with measured zinc levels in the normal range (i.e. 60 g/dL) was significantly greater in the intervention group compared to the control group (71.9%; 27.4%; p<0.001). No significant difference in seroconversion was demonstrated between the groups for PV1, PV2, or PV3.There was no effect of zinc supplementation on OPV immunogenicity. These conclusions were confirmed when restricting the analysis to those with measured higher zinc levels.


Muhammad N.,University of Peshawar | Saeed M.,University of Peshawar | Khan H.,Gandhara University | Haq I.,National Institute of Health NIH
Journal of Natural Medicines | Year: 2013

Viola betonicifolia (whole plant) has been used as a sedative and in various nervous disorders in Pakistani traditional medicines. The n-hexane extract of the whole plant of V. betonicifolia (HEVB) was investigated for neuropharmacological properties such as anxiolytic, muscle relaxant, sleep induction, antidepressant and sedative to ascertain its folk use. Anxiolytic activity was tested using the staircase test, while the muscle relaxing property of the extract was tested in various muscle relaxant paradigms, i.e. chimney test, traction test, rota rod and inclined plane. In anxiolytic and muscle relaxant tests, HEVB (0.3, 0.4 and 0.5 g/kg, i.p.), diazepam (1 mg/kg, i.p.) or distilled water (10 ml/kg i.p.) were administered 30, 60 and 90 min before performing the tests in mice. HEVB was also screened for a sleep-inducing effect. The antidepressant activity was determined by using the forced swimming test (FST), while line crossing in a special box was used for locomotor activity. HEVB showed a significant (P < 0.05) dose-dependent anxiolytic action in the staircase test. In muscle relaxant paradigms, a dose-dependent muscle relaxation was observed. For the phenobarbitone sleep induction test, HEVB notably (P < 0.05) reduced the latency time and increased the total sleeping duration. However, HEVB was devoid of any antidepressant activity, while the movements of mice were reduced significantly (P < 0.05) in locomotor activity. The results suggest that HEVB has anxiolytic, muscle relaxant, sleep-inducing (sedative) activity and, thus, provides pharmacological justification for the use of this plant as a sedative and for the relief of various nervous disorders. © 2012 The Japanese Society of Pharmacognosy and Springer.


Ahmed T.,University for Information Science and Technology | Hassan M.,National Institute of Health NIH | Malik F.,National Institute of Health NIH
Minerva Biotecnologica | Year: 2014

Aim. With a view to reduce waterborne diseases and to disinfect water from pathogens by the use of medicinal plant extracts, antibacterial properties of Adhatoda vasica (20mg/ml), Lawsonia alba (15 mg/ml), Myrtus communis (20mg/ml) and Plantago lanceolata (24 mg/ml) against seven waterborne bacterial strains were investigated. Methods. These waterborne bacterial strains were isolated and identified by API 20E method of identification. Lawsonia alba (15 mg/ml) showed the best results among the four tested plant extracts and was active against E. coli, Aeromonas hydrophila and Pseusomonas aerugonsa, Enterobacter cloacae, Serratia marcescens, and Cronobacter sakazakii. Adhatoda vasica (20 mg/ml). Myrtus communis (20 mg/ml), was active against Aeromonas hydrophila and Pseusomonas aerugonsa. Results. Different aqueous concentrations of four plant extracts Adhatoda vasica (20 mg/ml), Lawsonia alba (15 mg/ml), Myrtus communis (20 mg/ml) and Plantago lanceolata (24 mg/ml) showed pH 5.97, 4.62, 5.27 and 5.62 respectively. All the tested four plant extracts showed activity against Pseusomonas aerugonsa. Lawsonia alba (15 mg/ml) showed the best results (10-20 mm zones of inhibition against all the tested strains except Klebsiella pneumonia) among the four tested plants. Conclusion. Preliminary study show the use of Lawsonia alba and Adhatoda vasica against waterborne infectious diseases but there is a need to explore further for effective use of these plants against waterborne bacterial diseases.


Hayat K.,Pakistan Institute of Engineering and Applied Sciences | Khurshid A.,Pakistan Institute of Engineering and Applied Sciences | Khurshid A.,Quaid-i-Azam University | Rafiq M.A.,Pakistan Institute of Engineering and Applied Sciences | And 4 more authors.
Laser Physics Letters | Year: 2013

Nanoparticles are extensively used as efficient drug carriers in various biological studies. PEGylated barium manganate powder consisting of nanoparticles was synthesized using a hydrothermal technique. The nanoparticle morphology of the powder was confirmed via scanning electron microscopy. The average diameter of the nanoparticles was ∼90 nm. The x-ray diffraction pattern revealed that these nanoparticles consisted of single phase polycrystalline 2H-BaMnO3. The PEGylated BaMnO3 nanoparticles were loaded with 5-aminolevulinic acid (5-ALA) to evaluate their drug carrying potential. The toxicity of these nanoparticles was tested against the Hep2c cell line and found to be suitable for biological applications. It was seen that the drug uptake was a million times higher in the case of encapsulation compared to a conventional drug delivery system. This new formulation may find extensive use in nanomedicine as a multidrug delivery system. © 2013 Astro Ltd.


Muhammad N.,University of Peshawar | Saeed M.,University of Peshawar | Gilani S.N.,Laboratories Complex Peshawar | ul Haq I.,National Institute of Health NIH | Khan H.,University of Peshawar
Tropical Journal of Pharmaceutical Research | Year: 2012

Purpose: To evaluate the analgesic and anti-inflammatory activities of n-hexane extract of the whole plant of Viola betonicifolia Sm, family: Violaceace. Methods: The n-hexane fraction of Viola betonicifolia (VBHF) was tested for its analgesic and antiinflammatory activities (carrageenan-induced and histamine-induced edema models) in BALB/c mice. Results: VBHF exhibited significant (p < 0.01) analgesic and anti-inflammatory activity at test doses of 100, 200 and 300 mg/kg. The analgesic effect of VBHF was dose-dependent in acetic acid pain model while the extract was a weak analgesic at the dose of 300 mg/kg in hot plate and tail immersion test. Diclofenac sodium and tramadol showed better analgesic properties to the extract. Analgesia was not antagonized by naloxone in the hot plate model. Anti-inflammatory activity against carrageenan-induced edema was 60.8 %; however, histamine-induced inflammation was not antogonised by the extract. Conclusions: The extract has some analgesic and anti-inflammatory activities. This justifies its use in traditional medicine for pain of management. © Pharmacotherapy Group, Faculty of Pharmacy, University of Benin, Benin City, 300001 Nigeria. All rights reserved.

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