Diabetic nephropathy (DN) is a hyperglycemia-induced progressivedevelopment of renal insufficiency. Excessive glucose can increase mitochondrialreactive oxygen species (ROS) and induce cell damage, causing mitochondrial dysfunction.Our previous study indicated that cilostazol (CTZ) can reduce ROS levelsand decelerate DN progression in streptozotocin (STZ)-induced type 1 diabetes.This study investigated the potential mechanisms of CTZ in rats with DN and in highglucose-treated mesangial cells. Male Sprague–Dawley rats were fed 5 mg/kg/day ofCTZ after developing STZ-induced diabetes mellitus. Electron microscopy revealedthat CTZ reduced the thickness of the glomerular basement membrane and improvedmitochondrial morphology in mesangial cells of diabetic kidney. CTZ treatmentreduced excessive kidney mitochondrial DNA copy numbers induced by hyperglycemiaand interacted with the intrinsic pathway for regulating cell apoptosis as anantiapoptotic mechanism. In high-glucose-treated mesangial cells, CTZ reduced ROSproduction, altered the apoptotic status, and down-regulated transforming growthfactor beta (TGF-) and nuclear factor kappa light chain enhancer of activated B cells(NF-B). Base on the results of our previous and current studies, CTZ decelerationof hyperglycemia-induced DN is attributable to ROS reduction and thereby maintenanceof the mitochondrial function and reduction in TGF- and NF-B levels.

Diabetic nephropathy (DN) is a hyperglycemia-induced progressivedevelopment of renal insufficiency. Excessive glucose can increase mitochondrialreactive oxygen species (ROS) and induce cell damage, causing mitochondrial dysfunction.Our previous study indicated that cilostazol (CTZ) can reduce ROS levelsand decelerate DN progression in streptozotocin (STZ)-induced type 1 diabetes.This study investigated the potential mechanisms of CTZ in rats with DN and in highglucose-treated mesangial cells. Male Sprague–Dawley rats were fed 5 mg/kg/day ofCTZ after developing STZ-induced diabetes mellitus. Electron microscopy revealedthat CTZ reduced the thickness of the glomerular basement membrane and improvedmitochondrial morphology in mesangial cells of diabetic kidney. CTZ treatmentreduced excessive kidney mitochondrial DNA copy numbers induced by hyperglycemiaand interacted with the intrinsic pathway for regulating cell apoptosis as anantiapoptotic mechanism. In high-glucose-treated mesangial cells, CTZ reduced ROSproduction, altered the apoptotic status, and down-regulated transforming growthfactor beta (TGF-) and nuclear factor kappa light chain enhancer of activated B cells(NF-B). Base on the results of our previous and current studies, CTZ decelerationof hyperglycemia-induced DN is attributable to ROS reduction and thereby maintenanceof the mitochondrial function and reduction in TGF- and NF-B levels.

BACKGROUND: There is limited literature in the management of chronic urticaria in children. Treatment algorithms are generally extrapolated from adult studies. OBJECTIVE: Utility of a weight and age-based algorithm for antihistamines in management of chronic spontaneous urticaria (CSU) in childhood. To document associated factors that predict for step of control of CSU and time taken to attain control of symptoms in children. METHODS: A workgroup comprising of allergists, nurses, and pharmacists convened to develop a stepwise treatment algorithm in management of children with CSU. Sequential patients presenting to the paediatric allergy service with CSU were included in this observational, prospective study. RESULTS: Ninety-eight patients were recruited from September 2012 to September 2013. Majority were male, Chinese with median age 4 years 7 months. A third of patients with CSU had a family history of acute urticaria. Ten point two percent had previously resolved CSU, 25.5% had associated angioedema, and 53.1% had a history of atopy. A total of 96.9% of patients achieved control of symptoms, of which 91.8% achieved control with cetirizine. Fifty percent of all the patients were controlled on step 2 or higher. Forty-seven point eight percent of those on step 2 or higher were between 2 to 6 years of age compared to 32.6% and 19.6% who were 6 years and older and lesser than 2 years of age respectively. Eighty percent of those with previously resolved CSU required an increase to step 2 and above to achieve chronic urticaria control. CONCLUSION: We propose a weight- and age-based titration algorithm for different antihistamines for CSU in children using a stepwise approach to achieve control. This algorithm may improve the management and safety profile for paediatric CSU patients and allow for review in a more systematic manner for physicians dealing with CSU in children.
Adult ; Angioedema ; Asian Continental Ancestry Group ; Cetirizine ; Child ; Histamine Antagonists ; Humans ; Hypersensitivity ; Male ; Pharmacists ; Prospective Studies ; Urticaria

The incidence of diabetes mellitus is increasing among companion animals. This disease has similar characteristics in both humans and animals. Diabetes is frequently identified as an independent risk factor for infections associated with increased mortality. In the present study, homozygous diabetic (db/db) mice were infected with Listeria (L.) monocytogenes and then treated with the anti-diabetic drug exendin-4, a glucagon-like peptide 1 analogue. In aged db/db mice, decreased CD11b+ macrophage populations with higher lipid content and lower phagocytic activity were observed. Exendin-4 lowered high lipid levels and enhanced phagocytosis in macrophages from db/db mice infected with L. monocytogenes. Exendin-4 also ameliorated obesity and hyperglycemia, and improved ex vivo bacteria clearance by macrophages in the animals. Liver histology examined during L. monocytogenes infection indicated that abscess formation was much milder in exendin-4-treated db/db mice than in the control animals. Moreover, mechanistic studies demonstrated that expression of ATP binding cassette transporter 1, a sterol transporter, was higher in macrophages isolated from the exendin-4-treated db/db mice. Overall, our results suggest that exendin-4 decreases the risk of infection in diabetic animals by modifying the interaction between intracellular lipids and phagocytic macrophages.
ATP-Binding Cassette Transporters/metabolism ; Age Factors ; Animals ; Blood Chemical Analysis ; Cholesterol/metabolism ; Diabetes Mellitus, Type 2/*drug therapy/genetics ; Dyslipidemias/drug therapy/genetics ; Female ; Hyperglycemia/drug therapy/genetics ; Hypoglycemic Agents/*therapeutic use ; Injections, Intraperitoneal ; *Lipid Metabolism/drug effects ; Listeria monocytogenes/*drug effects/immunology ; Listeriosis/*drug therapy/immunology/microbiology ; Macrophages/drug effects/*metabolism ; Mice ; Obesity/drug therapy/genetics ; Peptides/*therapeutic use ; Phagocytosis/drug effects ; Venoms/*therapeutic use

INTRODUCTIONThis study evaluates determinants, expectations, association with quality of life (QOL) and doctor's awareness of Complementary and Alternative Medicine (CAM) use in Singapore cancer patients.

MATERIAL AND METHODSWe interviewed 316 patients visiting the Cancer Centre of the National University Hospital on behaviour, attitudes and expectations towards CAM and assessed QOL via Euroqol Questionnaire (EQ-5D). Medical information was obtained from oncologists.

RESULTSOne hundred and seventy-three patients (55%) reported CAM use after cancer diagnosis. Chinese ethnicity, tertiary education, age <65 years and previous CAM use were independent predictors of CAM use. Fifty-one per cent of CAM users informed their doctors about their use and 15% of doctors reported to be aware of CAM use in these patients. Thirty-seven per cent believed CAM to be equally or more effective than conventional cancer therapies and 78% expected at least basic knowledge about CAM from their oncologists. Twenty-fi ve per cent of patients reported concurrent use of oral CAM and chemotherapy, of which oncologists were unaware in 86% of cases. CAM users had higher EuroQol utility scores than non-CAM users (0.79 versus 0.73, respectively, P = 0.03), in particularly those aged >or=65 years and those with stage IV disease.

CONCLUSIONSingapore cancer patients show high prevalence of CAM use, high expectations regarding its effectiveness and doctors' knowledge on CAM and many use it concurrently with chemotherapy or radiotherapy. Since oncologists are generally unaware of CAM use in their patients, doctor-patient communication on CAM use needs to be improved. The association of CAM use and higher QOL scores in some subgroups deserves further exploration.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Complementary Therapies ; utilization ; Female ; Humans ; Interviews as Topic ; Male ; Middle Aged ; Neoplasms ; therapy ; Quality of Life ; Singapore ; Surveys and Questionnaires ; Young Adult

AIMTo complete comprehensive haplotype analysis of USP26 for both fertile and infertile men.

METHODSTwo hundred infertile men with severe oligospermia or non-obstructive azoospermia were subjected to sequence analysis for the entire coding sequences of the USP26 gene. Two hundred men with proven fertility were genotyped by primer extension methods. Allele/genotype frequencies, linkage disequilibrium (LD) characteristics and haplotypes of fertile men were compared with infertile men.

RESULTSThe allele frequencies of five single nucleotide polymorphisms (370-371insACA, 494T>C, 576G>A, ss6202791C>T, 1737G>A) were significantly higher in infertile patients than control subjects. The major haplotypes in infertile men were TACCGA (28% of the population), TGCCGA (15%), TACCAA (8%), TGCCAA (6%), TATCAA (5%) and CATCAA (5%). The major haplotypes for the control subjects were TACCGA (58% of the population), CACCGA (7%), CATCGA (6%) and TGCCGA (5%). Haplotypes TGCCGA, TATCAA, CATCAA, CATCGC, TACCAA and TGCCAA were over-transmitted in patients with spermatogenic defect, whereas haplotypes TACCGA, CACCGA, and CATCGA were under-transmitted in these patients.

CONCLUSIONSome USP26 alleles and haplotypes are associated with spermatogenic defect in the Han nationality in Taiwan, China.

Adult ; Alleles ; Azoospermia ; epidemiology ; genetics ; Cysteine Endopeptidases ; genetics ; DNA Primers ; Gene Frequency ; Genetic Variation ; Genotype ; Haplotypes ; Humans ; Infertility, Male ; epidemiology ; genetics ; Linkage Disequilibrium ; Male ; Multigene Family ; Oligospermia ; epidemiology ; genetics ; Polymorphism, Genetic ; Spermatogenesis ; genetics ; physiology ; Taiwan ; epidemiology

BACKGROUND: The prevalence of peanut allergy (PA) among children has increased significantly over the past decade. Even though the prevalence of PA in Singapore is considered low, peanut is the top trigger for food-induced anaphylaxis in Singaporean children.OBJECTIVE: To describe the demographic characteristics and clinical features of children with PA.METHODS: This is a 5-year retrospective review of children diagnosed with PA based on clinical history coupled with a positive skin prick test to peanut or positive oral food challenge results.RESULTS: There were 269 patients (53.9% males) with a clinical diagnosis of PA. The median age at first allergic presentation for the PA group was 24 months old, with interquartile range of 13–39 months. The most common form of peanut introduced was roasted peanut. The rate of peanut anaphylaxis was 7.1%. Concomitant tree nut sensitization was found in 32.3% of this cohort, predominantly to cashew nut. Majority of them have a personal history of atopy – 75.8% with eczema, 63.6% with allergic rhinitis, and 19.7% with asthma.CONCLUSION: This is the first large review of peanut-allergic children in Singapore. Prospective population-based studies are needed to establish the true prevalence and risk factors associated with the development of this potentially life-threatening condition.
Anacardium ; Anaphylaxis ; Arachis ; Asia ; Asthma ; Child ; Cohort Studies ; Diagnosis ; Eczema ; Humans ; Nuts ; Peanut Hypersensitivity ; Prevalence ; Prospective Studies ; Retrospective Studies ; Rhinitis, Allergic ; Risk Factors ; Singapore ; Skin ; Trees

Bipolar disorder (BD) is a major psychiatric disorder that is easily misdiagnosed. Patient adherence to a treatment regimen is of utmost importance for successful outcomes in BD. Several trials of antipsychotics suggested that depot antipsychotics, including long-acting first- and second-generation agents, are effective in preventing non-adherence, partial adherence, and in reducing relapse in BD. Various long-acting injectable (LAI) antipsychotics are available, including fluphenazine decanoate, haloperidol decanoate, olanzapine pamoate, risperidone microspheres, paliperidone palmitate, and aripiprazole monohydrate. Due to the increasing number of BD patients receiving LAI antipsychotics, treatment guidelines have been developed. However, the clinical applicability of LAI antipsychotics remains a global cause for concern, particularly in Asian countries. Expert physicians from Taiwan participated in a consensus meeting, which was held to review key areas based on both current literature and clinical practice. The purpose of this meeting was to generate a practical and implementable set of recommendations for LAI antipsychotic use to treat BD; target patient groups, dosage, administration, and adverse effects were considered. Experts recommended using LAI antipsychotics in patients with schizophrenia, rapid cycling BD, BD I, and bipolar-type schizoaffective disorder. LAI antipsychotic use was recommended in BD patients with the following characteristics: multiple episodes and low adherence; seldom yet serious episodes; low adherence potential per a physician's clinical judgment; preference for injectable agents over oral agents; and multiple oral agent users still experiencing residual symptoms.
Antipsychotic Agents* ; Asian Continental Ancestry Group ; Bipolar Disorder* ; Consensus* ; Fluphenazine ; Haloperidol ; Humans ; Judgment ; Microspheres ; Patient Compliance ; Psychotic Disorders ; Recurrence ; Risperidone ; Schizophrenia ; Taiwan ; Aripiprazole ; Paliperidone Palmitate

Food allergy is defined as reaction to a food which has an immunologic mechanism. Its prevalence is increasing in children globally and is therefore of increasing clinical importance. A useful clinical approach is to distinguish food allergic reactions by the timing of clinical reaction in relation to food exposure and classified as immediate (generally IgE-mediated) and delayed (generally non-IgE-mediated), with the exception of eczema and eosinophilic gastrointestinal disease, which, when associated with food allergy may be associated with either mechanism. This review is aimed at providing the clinician with a Singaporean perspective on the clinical approach and management of these disorders.
Breast Feeding ; Child ; Child, Preschool ; Eczema ; diagnosis ; immunology ; Food Hypersensitivity ; diagnosis ; prevention & control ; Humans ; Hypersensitivity, Delayed ; diagnosis ; prevention & control ; Immunoglobulin E ; blood ; Infant ; Infant, Newborn ; Skin Test End-Point Titration

The Singapore Health Services cluster (SingHealth) radiology film archives are a valuable repository of local radiological cases dating back to the 1950s. Some of the cases in the archives are of historical medical interest, i.e. cerebral angiography in the workup of patients with hemiplegia. Other cases are of historical social interest, being conditions seen during earlier stages of Singapore's development, i.e. bound feet. The archives form a unique portal into the development of local radiology as well as the national development of Singapore. A selection from the archives is published in 2020 in commemoration of the 20th anniversary of the formation of SingHealth, the 55th National Day of Singapore, and the 125th anniversary of the International Day of Radiology. This pictorial essay comprises cardiovascular, respiratory and neurological cases from the archives.