Burden of Wet Age-Related Macular Degeneration and Its Economic Implications in Singapore in the Year 2030

Purpose: To estimate the prevalence of wet age-related macular degeneration (AMD) in Singapore in the year 2030. This projection will help in planning appropriate care provision and build health services capacity to cater to the increasing healthcare demand in 2030.

Methods: The number of AMD patients aged 40–79 years from all Singaporeans was estimated using prevalence rates from a local study and using the United Nations population projections for Singapore to 2030. Age-specific mortality was accounted for. Additionally, two main scenarios were presented: (1) Projected number of wet AMD cases if patients were not taking preventive antioxidant vitamins; (2) projected number of wet AMD cases if patients were taking preventive antioxidant vitamins. Based on these scenarios, the economic burden was calculated. The number of quality-adjusted life years (QALYs) gained as a result of improvement in visual acuity (VA) due to anti-vascular endothelial growth factor (VEGF) treatment was also calculated.

Results: An estimated growth of 42% in the number of wet AMD cases is expected by 2030. The estimated economic burden of wet AMD in 2030 for scenarios 1 and 2 is Singapore $203.1 million and $162.9 million, respectively. The QALYs gained as a result of improved VA from wet AMD treatment ranged from 10,114.4 to 14,058.8 over a 5-year period for the 2030 cohort.

Conclusion: The burden of wet AMD is set to increase over the next 15 years. Appropriate measures to build healthcare capacity and plan for this expected surge in patients should be a priority in Singapore.     

Development of the nephrotic syndrome during treatment of Crohn's disease with adalimumab

We report a patient with Crohn's disease who presented with renal insufficiency and the nephrotic syndrome after initiating therapy with adalimumab. Renal biopsy showed stages 2 to 3 membranous glomerulonephritis, and immunostaining showed glomerular deposition of immunoglobulin G and C3. The patient's serum creatinine decreased after discontinuation of adalimumab, and treatment with prednisone and mycophenolic acid reversed his proteinuria. The pathogenesis of glomerular disease induced by antitumor necrosis factor antibodies is uncertain, and the potential roles of the generation of autoantibodies, development of antiadalimumab antibodies, and the interaction of adalimumab with glomerular tumor necrosis factor are discussed.     

Candidate placental biomarkers for intrauterine alcohol exposure

Background: Fetal alcohol spectrum disorder (FASD) is a leading cause of nongenetic mental retardation and other neurodevelopmental deficits. Earlier diagnosis of FASD would greatly improve prognosis for individuals and families affected by this disorder. Here, we identify candidate placental biomarkers in an animal model of FASD that recapitulates many aspects of human FASD. Methods: Pregnant Sprague‐Dawley (SD) females were assigned to 1 of 3 diet groups on gestation day 8 (G8): Ethanol (E), Pair‐fed (PF) or Control (C). E dams received ethanol‐containing liquid diet and PF dams received isocaloric liquid diet in an amount that matched the paired E dam’s diet consumption the previous day. Control dams received laboratory chow and water ad libitum. Whole placentae from individual fetuses were collected on gestational day 21 (G21) for analyses. Western blotting and quantitative real‐time RT‐PCR were used to measure protein and mRNA levels of placental iodothyronine deiodinase III (Dio3), thyroid hormone receptor α1 (TRα1), and glucocorticoid receptor (GR). Placental mRNA levels of insulin‐like growth factor 2 (Igf‐2), pleckstrin homology‐like domain family A member 2 (Phlda2), and cyclin‐dependent kinase inhibitor 1C (Cdkn1c) were also measured. Results: Placental protein and mRNA levels from ethanol (E)‐consuming dams showed the following changes: increased Dio3, decreased TRα1, and decreased GR compared to both C and PF dams. Placental mRNA levels of intrauterine growth restriction (IUGR) markers Igf‐2, Phlda2, and Cdkn1c were altered similarly in PF and E dams. Conclusions: We propose the specific pattern of increased Dio3 and decreased TRα1 and GR protein levels in the placenta as selective biomarker for intrauterine alcohol exposure.     

Symptom screening among HIV-infected pregnant women is acceptable and has high negative predictive value for active tuberculosis

We evaluated tuberculosis (TB) screening among 799 human immunodeficiency virus (HIV)-infected pregnant women in India. Eleven (1.4%) had active TB. The negative predictive value of screening using cough, fever, night sweats, or weight loss was 99.3%. Tuberculin skin test and targeted chest radiography provided no substantial benefit. TB symptom screening, as recommended by the World Health Organization, is effective for ruling out TB in HIV-infected pregnant women.     

Anemia of Chronic Disease and Chronic Periodontitis: Does Periodontal Therapy Have an Effect on Anemic Status?

Background: As the periodontal tissues mount an immune inflammatory response to bacteria and their products, the systemic challenge with these agents also induces a major vascular response. Certain inflammatory cytokines produced during periodontal inflammation can depress erythropoietin production leading to the development of anemia. The aim of this study is to investigate whether patients with chronic periodontitis have an anemic status, and subsequently, to analyze the effect of non‐surgical periodontal therapy on the anemic status of subjects over a 6‐month period. Methods: A total of 187 patients with chronic periodontitis participated in the study. After red blood cell analyses, 60 patients with hemoglobin concentrations below reference ranges entered into the second part of the study in which patients were treated with non‐surgical periodontal therapy. Clinical parameters and red blood cell analyses were repeated at 3 and 6 months. Results: In the first part of the study, 33.6% of patients had hemoglobin concentrations below normal reference ranges. In the second part of the study, all red blood cell parameters and clinical parameters showed statistical improvements over a 6‐month period. Conclusion: The present study strengthens the hypothesis that chronic periodontitis may lead to anemia and provides evidence that non‐surgical periodontal therapy can improve the anemic status of patients with chronic periodontitis with greater improvement in females.     

Neuroprotective efficacy of curcumin in arsenic induced cholinergic dysfunctions in rats

Our recent studies have shown that curcumin protects arsenic induced neurotoxicity by modulating oxidative stress, neurotransmitter levels and dopaminergic system in rats. As chronic exposure to arsenic has been associated with cognitive deficits in humans, the present study has been carried out to implore the neuroprotective potential of curcumin in arsenic induced cholinergic dysfunctions in rats. Rats treated with arsenic (sodium arsenite, 20mg/kg body weight, p.o., 28 days) exhibited a significant decrease in the learning activity, assessed by passive avoidance response associated with decreased binding of (3)H-QNB, known to label muscarinic-cholinergic receptors in hippocampus (54%) and frontal cortex (27%) as compared to controls. Decrease in the activity of acetylcholinesterase in hippocampus (46%) and frontal cortex (33%), staining of Nissl body, immunoreactivity of choline acetyltransferase (ChAT) and expression of ChAT protein in hippocampal region was also observed in arsenic treated rats as compared to controls. Simultaneous treatment with arsenic and curcumin (100mg/kg body weight, p.o., 28 days) increased learning and memory performance associated with increased binding of (3)H-QNB in hippocampus (54%), frontal cortex (25%) and activity of acetylcholinesterase in hippocampus (41%) and frontal cortex (29%) as compared to arsenic treated rats. Increase in the expression of ChAT protein, immunoreactivity of ChAT and staining of Nissl body in hippocampal region was also observed in rats simultaneously treated with arsenic and curcumin as compared to those treated with arsenic alone. The results of the present study suggest that curcumin significantly modulates arsenic induced cholinergic dysfunctions in brain and also exhibits neuroprotective efficacy of curcumin.     

Memantine reduces mania-like symptoms in animal models

Memantine, a selective antagonist of the N-methyl-D-aspartate receptor, is approved for the treatment of moderate to severe Alzheimer's disease. Ion dysregulation is thought to be involved in the pathophysiology of bipolar illness, suggesting that memantine may be effective in treating bipolar manic and/or depressive episodes. We utilized two preclinical models of mania that mimic pathophysiologic changes seen in bipolar illness to examine the potential efficacy of memantine in the treatment of this disorder. Locomotor hyperactivity of male Sprague-Dawley rats in an open field was induced with intracerebroventricular (ICV) administration of 10⁻³ M ouabain. Memantine (2.5, 5 or 7.5 mg/kg), lithium (6.75 mEq/kg), or vehicle were administered acutely via intraperitoneal injection immediately prior to ouabain, then chronically for 7 days (oral memantine 20, 30, and 40 mg/kg/day in water; lithium 2.4 g/kg food). In a second model of bipolar disorder, cycling between population spikes and epileptiform bursts was investigated in rat hippocampal slices treated with ouabain (3.3 μM) alone or in combination with memantine (0.5, 1.0, and 5.0 μM). Ouabain-induced hyperlocomotion was normalized with acute and chronic lithium and chronic use of memantine. Memantine delayed the onset of ouabain-induced-cycling in hippocampal slices. Memantine may have antimanic properties.     

Improvement of brain energy metabolism and cholinergic functions contributes to the beneficial effects of silibinin against streptozotocin induced memory impairment

Recently, silibinin, a clinically used hepatoprotectant, has been reported to prevent amyloid beta induced memory impairment by reducing oxidative stress and inflammation in mice brain. However, the exact mechanism of neuroprotective effect of silibinin has not been properly studied especially in context of brain energy metabolism and cholinergic functions, the essential factors that undergo impairment in Alzheimer's disease. Therefore, the present study investigated the effect of silibinin on impairment in memory, brain energy metabolism and cholinergic function following intracerebral (IC) streptozotocin (STZ) administration in mice. STZ (0.5 mg/kg), administered twice at an interval of 48 h, caused significant memory impairment tested by Morris water maze. Further, STZ significantly decreased ATP and increased synaptosomal calcium level in mice brain. Increased oxidative and nitrosative stress was also observed in IC STZ injected mice brain. STZ IC induced memory impairment is associated with increased activity and mRNA expression of acetylcholinesterase (AChE) and decreased α-7 nicotinic acetylcholine receptor (α-7-nAChR) mRNA expression in mice brain. Pretreatment with silibinin (100 and 200 mg/kg, po) attenuated STZ induced memory impairment by reducing oxidative and nitrosative stress and synaptosomal calcium ion level. Further, silibinin dose dependently restored ATP level indicating improvement in brain energy metabolism. The activity and mRNA expression of AChE was restored by silibinin. Moreover, α-7-nAChR mRNA expression was significantly increased by silibinin in STZ treated mice brain. The present study clearly demonstrates that beneficial effects of silibinin in STZ induced memory impairment in mice is due to improvement in brain energy metabolism and cholinergic function.