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Article ; Online: Regulation of Body Temperature by the Nervous System.

Tan, Chan Lek / Knight, Zachary A

2018 Volume 98, Issue 1, Page(s) 31–48

Abstract: The regulation of body temperature is one of the most critical functions of the nervous system. Here we review our current understanding of thermoregulation in mammals. We outline the molecules and cells that measure body temperature in the periphery, ... ...

Abstract	The regulation of body temperature is one of the most critical functions of the nervous system. Here we review our current understanding of thermoregulation in mammals. We outline the molecules and cells that measure body temperature in the periphery, the neural pathways that communicate this information to the brain, and the central circuits that coordinate the homeostatic response. We also discuss some of the key unresolved issues in this field, including the following: the role of temperature sensing in the brain, the molecular identity of the warm sensor, the central representation of the labeled line for cold, and the neural substrates of thermoregulatory behavior. We suggest that approaches for molecularly defined circuit analysis will provide new insight into these topics in the near future.
MeSH term(s)	Animals ; Body Temperature/physiology ; Body Temperature Regulation/physiology ; Brain/physiology ; Homeostasis/physiology ; Humans ; Neural Pathways/physiology ; Thermosensing/physiology
Language	English
Publishing date	2018-04-05
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	808167-0
ISSN	1097-4199 ; 0896-6273
ISSN (online)	1097-4199
ISSN	0896-6273
DOI	10.1016/j.neuron.2018.02.022
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Article ; Online: Associations of predominant night-eating with plasma glycemic status and continuous glucose monitoring measures among pregnant women.

Loy, See Ling / Ku, Chee Wai / Zheng, Ruther Teo / Lim, Celeste Hong Fei / Chang, Ting Yu / Chen, Ling-Wei / Cheung, Yin Bun / Godfrey, Keith M / Tan, Kok Hian / Chong, Mary Foong-Fong / Chan, Jerry Kok Yen / Lek, Ngee / Yap, Fabian

Clinical nutrition (Edinburgh, Scotland)

2023 Volume 42, Issue 12, Page(s) 2320–2327

Abstract: Background & aims: To examine whether predominant night-eating, defined as more than 50% of total daily energy intake consumed between 1900 and 0659 h, is associated with glycemic outcomes in pregnancy.: Methods: This was a prospective cohort study ... ...

Abstract	Background & aims: To examine whether predominant night-eating, defined as more than 50% of total daily energy intake consumed between 1900 and 0659 h, is associated with glycemic outcomes in pregnancy. Methods: This was a prospective cohort study of 277 healthy pregnant women with complete 4-day dietary intake records at 18-24 weeks gestation, recruited from KK Women's and Children's Hospital, Singapore. Primary outcomes were fasting, 1-h, and 2-h plasma glucose after a 75-g oral glucose tolerance test at 24-28 weeks gestation. Secondary outcomes were gestational diabetes mellitus (GDM), fasting insulin, homeostasis model assessment of insulin resistance (HOMA2-IR), β-cell function (HOMA2-%B), and continuous glucose monitoring (CGM) measures. Glucose variables in continuous form were log Results: Predominant night-eating (11.6%) was associated with higher fasting glucose (geometric mean ratio (95% confidence interval) 1.05 (1.01, 1.08)) and 1-h glucose (1.11 (1.01, 1.21)), but not with 2-h glucose or GDM risk. Predominant night-eating women had lower fasting insulin (0.77 (0.63, 0.95)), lower HOMA2-IR (0.78 (0.64, 0.97)), and lower HOMA2-%B (0.77 (0.67, 0.89)) than their predominant day-eating counterparts. For CGM measures, predominant night-eating was associated with higher mean glucose (1.07 (1.00, 1.15)), higher glucose management indicator (1.05 (1.00, 1.10)), and higher overall glucose levels throughout 24 h (1.10 (1.02, 1.19)). All these associations were adjusted for socio-demographic, lifestyle factors, and diet composition. Conclusion: Predominant night-eating was mainly associated with less desirable glycemic outcomes during pregnancy. Future studies should explore dietary interventions aimed at reducing consumption of relatively more calories at night than day during pregnancy.
MeSH term(s)	Child ; Pregnancy ; Female ; Humans ; Blood Glucose/analysis ; Pregnant Women ; Prospective Studies ; Blood Glucose Self-Monitoring ; Diabetes, Gestational ; Insulin
Chemical Substances	Blood Glucose ; Insulin
Language	English
Publishing date	2023-10-11
Publishing country	England
Document type	Journal Article
ZDB-ID	604812-2
ISSN	1532-1983 ; 0261-5614
ISSN (online)	1532-1983
ISSN	0261-5614
DOI	10.1016/j.clnu.2023.10.009
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Article ; Online: Influence of red blood cell indices on HbA1c performance in detecting dysglycaemia in a Singapore preconception cohort study.

Loy, See Ling / Lin, Jinjie / Cheung, Yin Bun / Sreedharan, Aravind Venkatesh / Chin, Xinyi / Godfrey, Keith M / Tan, Kok Hian / Shek, Lynette Pei-Chi / Chong, Yap Seng / Leow, Melvin Khee-Shing / Khoo, Chin Meng / Lee, Yung Seng / Chan, Shiao-Yng / Lek, Ngee / Chan, Jerry Kok Yen / Yap, Fabian

Scientific reports

2021 Volume 11, Issue 1, Page(s) 20850

Abstract: Abnormalities of red blood cell (RBC) indices may affect glycated haemoglobin (HbA1c) levels. We assessed the influence of haemoglobin (Hb) and mean corpuscular volume (MCV) on the performance of HbA1c in detecting dysglycaemia among reproductive aged ... ...

Abstract	Abnormalities of red blood cell (RBC) indices may affect glycated haemoglobin (HbA1c) levels. We assessed the influence of haemoglobin (Hb) and mean corpuscular volume (MCV) on the performance of HbA1c in detecting dysglycaemia among reproductive aged women planning to conceive. Women aged 18-45 years (n = 985) were classified as normal (12 ≤ Hb ≤ 16 g/dL and 80 ≤ MCV ≤ 100 fL) and abnormal (Hb < 12 g/dL and/or MCV < 80 fL). The Area Under the Receiver Operating Characteristic (AUROC) curve was used to determine the performance of HbA1c in detecting dysglycaemic status (prediabetes and diabetes). There were 771 (78.3%) women with normal RBC indices. The AUROCs for the normal and abnormal groups were 0.75 (95% confidence interval 0.69, 0.81) and 0.80 (0.70, 0.90), respectively, and were not statistically different from one another [difference 0.04 (- 0.16, 0.08)]. Further stratification by ethnicity showed no difference between the two groups among Chinese and Indian women. However, Malay women with normal RBC indices displayed lower AUROC compared to those with abnormal RBC indices (0.71 (0.55, 0.87) vs. 0.98 (0.93, 1.00), p = 0.002). The results suggest that the performance of HbA1c in detecting dysglycaemia was not influenced by abnormal RBC indices based on low Hb and/or low MCV. However, there may be ethnic variations among them.
MeSH term(s)	Adult ; Blood Glucose/analysis ; Diabetes Mellitus/blood ; Diabetes Mellitus/diagnosis ; Diabetes Mellitus/epidemiology ; Erythrocyte Indices ; Female ; Fertilization ; Glycated Hemoglobin/analysis ; Hematologic Tests ; Humans ; Mass Screening ; Prediabetic State/blood ; Prediabetic State/diagnosis ; Prediabetic State/epidemiology ; ROC Curve ; Singapore/epidemiology ; Young Adult
Chemical Substances	Blood Glucose ; Glycated Hemoglobin A ; hemoglobin A1c protein, human
Language	English
Publishing date	2021-10-21
Publishing country	England
Document type	Clinical Trial ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-021-00445-w
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Article ; Online: Author Correction: Anthropometric measures and HbA1c to detect dysglycemia in young Asian women planning conception: The S-PRESTO cohort.

Scientific reports

2020 Volume 10, Issue 1, Page(s) 12744

Abstract: An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...

Abstract	An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Language	English
Publishing date	2020-07-24
Publishing country	England
Document type	Published Erratum
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-020-69653-0
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Article ; Online: Upregulation of Yy1 Suppresses Dilated Cardiomyopathy caused by Ttn insufficiency.

Liao, Dan / Chen, Weiming / Tan, Chia Yee / Wong, Jing Xuan / Chan, Pui Shi / Tan, Lek Wen / Foo, Roger / Jiang, Jianming

Scientific reports

2019 Volume 9, Issue 1, Page(s) 16330

Abstract: Truncating variants in TTN (TTNtv), coding for the largest structural protein in the sarcomere, contribute to the largest portion of familial and ambulatory dilated cardiomyopathy (DCM). TTN haploinsufficiency caused by TTNtv is suggested as the disease ... ...

Abstract	Truncating variants in TTN (TTNtv), coding for the largest structural protein in the sarcomere, contribute to the largest portion of familial and ambulatory dilated cardiomyopathy (DCM). TTN haploinsufficiency caused by TTNtv is suggested as the disease mechanism. However, it is unclear whether TTN insufficiency causes DCM. Moreover, it is unknown whether modulation of downstream pathways serves as a therapeutic strategy for DCM caused by TTN insufficiency. Here, we show that reduction of cardiac Ttn expression by adeno-associated virus mediated shRNA (Ttn shRNA) generated DCM in mouse, demonstrating impaired cardiac performance, enlarged left ventricle (LV) and reduced LV wall thickness. A screen of 10 dysregulated and selected genes identified that Yin Yang 1 (Yy1) significantly suppressed DCM caused by Ttn shRNA. Gene profiling by RNAseq showed Yy1 modulated cell growth related genes. Ttn insufficiency activated cardiomyocyte cell cycle reentry by upregulating of Ccnd1 and Ccnd2. Cardiomyocytes activated by Ttn insufficiency did not advance to S phase by EdU incorporation assay. Yy1 promoted cardiomyocyte cell cycle by further enhancing Ccnd1 and Ccnd2 and increasing DNA replication without undergoing cell division. Importantly, upregulation of Ccnd1 and Ccnd2 suppressed DCM caused by Ttn insufficiency. Our findings demonstrate that DCM caused by Ttn insufficiency can be treated by therapeutically promoting cardiac cell cycle.
MeSH term(s)	Cardiomyopathy, Dilated/genetics ; Cardiomyopathy, Dilated/pathology ; Cell Cycle/genetics ; HEK293 Cells ; Humans ; Myocytes, Cardiac/pathology ; Protein Kinases/genetics ; Up-Regulation ; YY1 Transcription Factor/genetics
Chemical Substances	YY1 Transcription Factor ; Yy1 protein, mouse ; Protein Kinases (EC 2.7.-) ; titin protein, mouse (EC 2.7.11.1)
Language	English
Publishing date	2019-11-08
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-019-52796-0
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Article ; Online: Upregulation of Yy1 Suppresses Dilated Cardiomyopathy caused by Ttn insufficiency

Dan Liao / Weiming Chen / Chia Yee Tan / Jing Xuan Wong / Pui Shi Chan / Lek Wen Tan / Roger Foo / Jianming Jiang

Scientific Reports, Vol 9, Iss 1, Pp 1-

2019 Volume 12

Abstract: Abstract Truncating variants in TTN (TTNtv), coding for the largest structural protein in the sarcomere, contribute to the largest portion of familial and ambulatory dilated cardiomyopathy (DCM). TTN haploinsufficiency caused by TTNtv is suggested as the ...

Abstract	Abstract Truncating variants in TTN (TTNtv), coding for the largest structural protein in the sarcomere, contribute to the largest portion of familial and ambulatory dilated cardiomyopathy (DCM). TTN haploinsufficiency caused by TTNtv is suggested as the disease mechanism. However, it is unclear whether TTN insufficiency causes DCM. Moreover, it is unknown whether modulation of downstream pathways serves as a therapeutic strategy for DCM caused by TTN insufficiency. Here, we show that reduction of cardiac Ttn expression by adeno-associated virus mediated shRNA (Ttn shRNA) generated DCM in mouse, demonstrating impaired cardiac performance, enlarged left ventricle (LV) and reduced LV wall thickness. A screen of 10 dysregulated and selected genes identified that Yin Yang 1 (Yy1) significantly suppressed DCM caused by Ttn shRNA. Gene profiling by RNAseq showed Yy1 modulated cell growth related genes. Ttn insufficiency activated cardiomyocyte cell cycle reentry by upregulating of Ccnd1 and Ccnd2. Cardiomyocytes activated by Ttn insufficiency did not advance to S phase by EdU incorporation assay. Yy1 promoted cardiomyocyte cell cycle by further enhancing Ccnd1 and Ccnd2 and increasing DNA replication without undergoing cell division. Importantly, upregulation of Ccnd1 and Ccnd2 suppressed DCM caused by Ttn insufficiency. Our findings demonstrate that DCM caused by Ttn insufficiency can be treated by therapeutically promoting cardiac cell cycle.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2019-11-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Maternal night-eating pattern and glucose tolerance during pregnancy: study protocol for a longitudinal study.

Loy, See Ling / Cheung, Yin Bun / Chong, Mary / Müller-Riemenschneider, Falk / Lek, Ngee / Lee, Y S / Tan, Kok Hian / Chern, Bernard / Yap, Fabian / Chan, Jerry

BMJ open

2019 Volume 9, Issue 10, Page(s) e030036

Abstract: Introduction: Coordinating eating schedules with day-night cycles has been shown to improve glucose regulation in adults, but its association with gestational glycaemia is less clear. A better understanding on how eating time can influence glucose ... ...

Abstract	Introduction: Coordinating eating schedules with day-night cycles has been shown to improve glucose regulation in adults, but its association with gestational glycaemia is less clear. A better understanding on how eating time can influence glucose levels in pregnancy may improve strategies for gestational glycaemic control. This study aims to examine the association of maternal night-eating pattern with glucose tolerance in the second trimester of pregnancy, and to investigate how lifestyle factors may be related to night-eating pattern. Methods and analysis: This is an observational longitudinal study that targets to recruit 200 pregnant women at 18-24 weeks' gestation from the KK Women's and Children's Hospital in Singapore. Data collection includes sociodemographics, lifestyle habits and obstetric information. Maternal dietary intake is collected using the 4-day food diary and food frequency questionnaire; while 24-hour physical activity, sedentary behaviour, sleep and light exposure are captured using the accelerometer at 18-24 weeks' gestation. Continuous glucose monitoring at 18-24 weeks' gestation, oral glucose tolerance test and insulin test at 24-28 weeks' gestation are performed to assess glycaemic outcomes. Multivariable generalised linear models will be used to analyse the association of maternal night-eating pattern (consumption of meal and snack during 1900-0659 hours) with glycaemic measures, and the associated factors of night-eating pattern, controlling for potential confounders. Recruitment began in March 2019 and is estimated to end in November 2020. Ethics and dissemination: Ethical approval has been granted by the Centralised Institutional Review Board of SingHealth, Singapore (reference 2018/2529). The results will be presented at conferences and disseminated in journal articles. Trial registration number: NCT03803345.
MeSH term(s)	Adult ; Blood Glucose/analysis ; Diabetes, Gestational/blood ; Diabetes, Gestational/physiopathology ; Diabetes, Gestational/psychology ; Feeding Behavior/physiology ; Feeding Behavior/psychology ; Female ; Glucose Tolerance Test ; Humans ; Longitudinal Studies ; Pregnancy ; Pregnancy Trimester, Second/blood ; Pregnancy Trimester, Second/physiology ; Pregnancy Trimester, Second/psychology ; Pregnancy Trimester, Third/blood ; Pregnancy Trimester, Third/physiology ; Pregnancy Trimester, Third/psychology
Chemical Substances	Blood Glucose
Language	English
Publishing date	2019-10-10
Publishing country	England
Document type	Journal Article ; Observational Study ; Research Support, Non-U.S. Gov't
ZDB-ID	2599832-8
ISSN	2044-6055 ; 2044-6055
ISSN (online)	2044-6055
ISSN	2044-6055
DOI	10.1136/bmjopen-2019-030036
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Article ; Online: Anthropometric measures and HbA1c to detect dysglycemia in young Asian women planning conception: The S-PRESTO cohort.

Scientific reports

2020 Volume 10, Issue 1, Page(s) 9228

Abstract: We investigated whether adding anthropometric measures to HbA1c would have stronger discriminative ability over HbA1c alone in detecting dysglycemia (diabetes and prediabetes) among Asian women trying to conceive. Among 971 Singaporean women, multiple ... ...

Abstract	We investigated whether adding anthropometric measures to HbA1c would have stronger discriminative ability over HbA1c alone in detecting dysglycemia (diabetes and prediabetes) among Asian women trying to conceive. Among 971 Singaporean women, multiple regression models and area under receiver-operating characteristic (AUROC) curves were used to analyze associations of anthropometric (weight, height, waist/hip circumferences, 4-site skinfold thicknesses) and HbA1c z-scores with dysglycemia (fasting glucose ≥6.1 mmol/L with 2-hour glucose ≥7.8 mmol/l). The prevalence of dysglycemia was 10.9%. After adjusting for sociodemographic/medical history, BMI (Odds Ratio [OR] = 1.62 [95%CI 1.32-1.99]), waist-to-height ratio (OR = 1.74 [1.39-2.17]) and total skinfolds (OR = 2.02 [1.60-2.55]) showed the strongest associations with dysglycemia but none outperformed HbA1c (OR = 4.09 [2.81-5.94]). After adjustment for history, adding BMI, waist-to-height ratio and total skinfolds (anthropometry trio) as continuous variables to HbA1c (AUROC = 0.80 [95%CI 0.75-0.85]) performed similarly to HbA1c alone (AUROC = 0.79 [0.74-0.84]). However, using clinically-defined thresholds without considering history, as in common clinical practice, BMI ≥ 23 kg/m
MeSH term(s)	Adolescent ; Adult ; Anthropometry ; Area Under Curve ; Asian Continental Ancestry Group ; Body Mass Index ; Cohort Studies ; Diabetes Mellitus/diagnosis ; Female ; Glucose Tolerance Test ; Glycated Hemoglobin A/analysis ; Humans ; Middle Aged ; Odds Ratio ; Prediabetic State/diagnosis ; ROC Curve ; Risk ; Sensitivity and Specificity ; Waist-Height Ratio ; Young Adult
Chemical Substances	Glycated Hemoglobin A
Language	English
Publishing date	2020-06-08
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-020-66147-x
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Article ; Online: Timeliness of Childhood Vaccination Coverage: the Growing Up in Singapore Towards Healthy Outcomes Study.

Loy, See Ling / Cheung, Yin Bun / Chan, Jerry Kok Yen / Soh, Shu E / Godfrey, Keith M / Tan, Kok Hian / Shek, Lynette Pei-Chi / Chong, Yap-Seng / Lek, Ngee / Yap, Fabian / Teoh, Oon Hoe / Yung, Chee Fu / Thoon, Koh Cheng

Prevention science : the official journal of the Society for Prevention Research

2020 Volume 21, Issue 3, Page(s) 283–292

Abstract: Studies investigating timeliness for childhood vaccination are limited especially in Asia. We examined the timeliness of vaccine administration and associated factors among infant and young children in Singapore. A total of 782 children born between ... ...

Abstract	Studies investigating timeliness for childhood vaccination are limited especially in Asia. We examined the timeliness of vaccine administration and associated factors among infant and young children in Singapore. A total of 782 children born between November 2009 and July 2011 from a prospective cohort in Singapore were studied. Vaccination records from birth to 24 months of age were obtained from the National Immunization Registry of Singapore. Multivariable logistic regression models were performed. By 2 years of age, 92.8% of children in our cohort experienced a delay in receiving 1 or more vaccine doses according to the recommended national immunization schedule. When vaccinations were reviewed by series for each vaccine, 15.6% received all vaccine series outside the recommended age ranges. Factors associated with receiving vaccination series outside the recommended ages included maternal aged ≤ 35 years (OR 2.00; 95% CI 1.09, 3.66), Malay (1.71; 1.01, 2.89) or Indian ethnicity (2.06; 1.19, 3.59), low monthly household income (1.91; 1.14, 3.18), having at least four children (3.46; 1.62, 7.38) and private (3.42; 1.80, 6.48) and multiple vaccination providers (3.91; 1.23, 12.48). These findings show an unacceptably high proportion of children experienced a delay in the receipt of their vaccinations. The identification of several demographic, socioeconomic, health-seeking behavioural and vaccine provider factors provides opportunities for targeted interventions to enhance the timeliness of childhood vaccination in Singapore.
MeSH term(s)	Adult ; Asia ; Child, Preschool ; Databases, Factual ; Female ; Humans ; Male ; Prospective Studies ; Singapore ; Surveys and Questionnaires ; Time Factors ; Vaccination Coverage ; Vaccines/administration & dosage
Chemical Substances	Vaccines
Language	English
Publishing date	2020-01-07
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2251270-6
ISSN	1573-6695 ; 1389-4986
ISSN (online)	1573-6695
ISSN	1389-4986
DOI	10.1007/s11121-019-01078-2
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Article ; Online: Near Infrared Fluorophore-Tagged Chloroquine in

Chan, Li Yan / Teo, Joshua Ding Wei / Tan, Kevin Shyong-Wei / Sou, Keitaro / Kwan, Wei Lek / Lee, Chi-Lik Ken

Molecules (Basel, Switzerland)

2018 Volume 23, Issue 10

Abstract: Chloroquine was among the first of several effective drug treatments against malaria until the onset of chloroquine resistance. In light of diminished clinical efficacy of chloroquine as an antimalarial therapeutic, there is potential in efforts to adapt ...

Abstract	Chloroquine was among the first of several effective drug treatments against malaria until the onset of chloroquine resistance. In light of diminished clinical efficacy of chloroquine as an antimalarial therapeutic, there is potential in efforts to adapt chloroquine for other clinical applications, such as in combination therapies and in diagnostics. In this context, we designed and synthesized a novel asymmetrical squaraine dye coupled with chloroquine (SQR1-CQ). In this study, SQR1-CQ was used to label live
MeSH term(s)	Antimalarials/chemistry ; Antimalarials/pharmacology ; Blood/parasitology ; Chloroquine/chemistry ; Chloroquine/pharmacology ; Cyclobutanes/chemistry ; Drug Resistance ; Fluorescent Dyes/chemistry ; Humans ; Inhibitory Concentration 50 ; Microscopy, Confocal ; Molecular Imaging ; Molecular Structure ; Phenols/chemistry ; Plasmodium falciparum/drug effects
Chemical Substances	Antimalarials ; Cyclobutanes ; Fluorescent Dyes ; Phenols ; squaraine ; Chloroquine (886U3H6UFF)
Language	English
Publishing date	2018-10-14
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	1413402-0
ISSN	1420-3049 ; 1431-5165 ; 1420-3049
ISSN (online)	1420-3049
ISSN	1431-5165 ; 1420-3049
DOI	10.3390/molecules23102635
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