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Banerjee P.,Institute of Post Graduate Medical and Educational Research | Sahoo A.,Institute of Post Graduate Medical and Educational Research | Anand S.,Institute of Post Graduate Medical and Educational Research | Bir A.,ICARE Institute of Medical science and Research | Chakrabarti S.,ICARE Institute of Medical science and Research
Journal of Alzheimer's Disease | Year: 2016

The altered metabolism of iron impacts the brain function in multiple deleteriousways during normal aging as well as in Alzheimer's disease.We have shown in this study that chelatable iron accumulates in the aged rat brain along with overexpression of transferrin receptor 1 (TfR1) and ferritin, accompanied by significant alterations in amyloid-β (Aβ) peptide homeostasis in the aging brain, such as an increased production of the amyloid-β protein precursor, a decreased level of neprilysin, and increased accumulation of Aβ42. When aged rats are given daily the iron chelator, deferasirox, over a period of more than 4 months starting from the 18th month, the age-related accumulation of iron and overexpression of TfR1 and ferritin in the brain are significantly prevented. More interestingly, the chelator treatment also considerably reverses the altered Aβ peptide metabolism in the aging brain implying a significant role of iron in the latter phenomenon. Further, other results indicate that iron accumulation results in oxidative stress and the activation of NFB in the aged rat brain, which are also reversed by the deferasirox treatment. The analysis of the results together suggests that iron accumulation and oxidative stress interact at multiple levels that include transcriptional and post-transcriptional mechanisms to bring about changes in the expression levels of TfR1 and ferritin and also alterations in Aβ peptide metabolism in the aging rat brain. The efficacy of deferasirox in preventing age-related changes in iron and Aβ peptide metabolism in the aging brain, as shown here, has obvious therapeutic implications for Alzheimer's disease. © 2016 - IOS Press and the authors. All rights reserved.


PubMed | Institute of Post Graduate Medical and Educational Research and ICARE Institute of Medical science and Research
Type: Journal Article | Journal: Journal of Alzheimer's disease : JAD | Year: 2015

The altered metabolism of iron impacts the brain function in multiple deleterious ways during normal aging as well as in Alzheimers disease. We have shown in this study that chelatable iron accumulates in the aged rat brain along with overexpression of transferrin receptor 1 (TfR1) and ferritin, accompanied by significant alterations in amyloid- (A) peptide homeostasis in the aging brain, such as an increased production of the amyloid- protein precursor, a decreased level of neprilysin, and increased accumulation of A42. When aged rats are given daily the iron chelator, deferasirox, over a period of more than 4 months starting from the 18th month, the age-related accumulation of iron and overexpression of TfR1 and ferritin in the brain are significantly prevented. More interestingly, the chelator treatment also considerably reverses the altered A peptide metabolism in the aging brain implying a significant role of iron in the latter phenomenon. Further, other results indicate that iron accumulation results in oxidative stress and the activation of NF-B in the aged rat brain, which are also reversed by the deferasirox treatment. The analysis of the results together suggests that iron accumulation and oxidative stress interact at multiple levels that include transcriptional and post-transcriptional mechanisms to bring about changes in the expression levels of TfR1 and ferritin and also alterations in A peptide metabolism in the aging rat brain. The efficacy of deferasirox in preventing age-related changes in iron and A peptide metabolism in the aging brain, as shown here, has obvious therapeutic implications for Alzheimers disease.


Banerjee A.,ICARE Institute of Medical science and Research | Banerjee A.,Medical Education and Research | Khemka V.K.,ICARE Institute of Medical science and Research | Khemka V.K.,Medical Education and Research | And 4 more authors.
International Journal of Alzheimer's Disease | Year: 2015

Alzheimer's disease (AD), the major cause of dementia worldwide, is characterized by progressive loss of memory and cognition. The sporadic form of AD accounts for nearly 90% of the patients developing this disease. The last century has witnessed significant research to identify various mechanisms and risk factors contributing to the complex etiopathogenesis of AD by analyzing postmortem AD brains and experimenting with animal and cell culture based models. However, the treatment strategies, as of now, are only symptomatic. Accumulating evidences suggested a significant association between vitamin D deficiency, dementia, and AD. This review encompasses the beneficial role of vitamin D in neurocognition and optimal brain health along with epidemiological evidence of the high prevalence of hypovitaminosis D among aged and AD population. Moreover, disrupted signaling, altered utilization of vitamin D, and polymorphisms of several related genes including vitamin D receptor (VDR) also predispose to AD or AD-like neurodegeneration. This review explores the relationship between this gene-environmental influence and long term vitamin D deficiency as a risk factor for development of sporadic AD along with the role and rationale of therapeutic trials with vitamin D. It is, therefore, urgently warranted to further establish the role of this potentially neuroprotective vitamin in preventing and halting progressive neurodegeneration in AD patients. © 2015 Anindita Banerjee et al.


PubMed | M G M Medical College And L S K Hospital, R G Kar Medical College And Hospital, West Dermatology, Jawaharlal Institute of Postgraduate Medical Education & Research and 2 more.
Type: Journal Article | Journal: Indian journal of pharmacology | Year: 2017

Epidermal dermatophyte infections most commonly manifest as tinea corporis or tinea cruris. Topical azole antifungals are commonly used in their treatment but literature suggests that most require twice-daily application and provide lower cure rates than the allylamine antifungal terbinafine. We conducted a head-to-head comparison of the effectiveness of the once-daily topical azole, sertaconazole, with terbinafine in these infections.We conducted a randomized, observer-blind, parallel group study (Clinical Trial Registry India [CTRI]/2014/09/005029) with adult patients of either sex presenting with localized lesions. The clinical diagnosis was confirmed by potassium hydroxide smear microscopy of skin scrapings. After baseline assessment of erythema, scaling, and pruritus, patients applied either of the two study drugs once daily for 2 weeks. If clinical cure was not seen at 2 weeks, but improvement was noted, application was continued for further 2 weeks. Patients deemed to be clinical failure at 2 weeks were switched to oral antifungals.Overall 88 patients on sertaconazole and 91 on terbinafine were analyzed. At 2 weeks, the clinical cure rates were comparable at 77.27% (95% confidence interval [CI]: 68.52%-86.03%) for sertaconazole and 73.63% (95% CI 64.57%-82.68%) for terbinafine (Despite the limitations of an observer-blind study without microbiological support, the results suggest that once-daily topical sertaconazole is as effective as terbinafine in localized tinea infections.


PubMed | Institute of Medical science & SUM Hospital, Central Institute of Psychiatry and ICARE Institute of Medical science and Research
Type: Journal Article | Journal: Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology | Year: 2016

Clozapine is a gold standard medication and drug of choice in refractory schizophrenia. Among many of its fatal side effects, delirium is less reported and inconsistently recognized by clinicians. We here present a case of delirium which emerged during retreatment with clozapine in a patient of paranoid schizophrenia. A patient diagnosed with paranoid schizophrenia, was restarted on clozapine after he left medications and became symptomatic. He was delirious on 22nd day after clozapine was restarted. Clozapine was stopped and the patient was managed with standard treatment for delirium. After one week interval, clozapine was restarted. Delirium was not noted till 6 weeks of his hospital stay. Clozapine induced central anticholinergic toxicity or clozapine induced seizure might cause delirium in index case. Limited literature exist delirium with clozapine. Clinicians must have high index of suspicion to detect delirium during clozapine therapy. More researches should focus to explore the association between delirium and clozapine.


PubMed | Training Co ordinator Project HIFAZAT Central Institute of Psychiatry, ICARE Institute of Medical science and Research and Central Institute of Psychiatry
Type: Journal Article | Journal: Industrial psychiatry journal | Year: 2015

Cavum septum pellucidum (CSP) is a neurodevelopmental anomaly, which is commonly reported in schizophrenia patients. Various symptoms of schizophrenia, including thought disturbances have been associated with CSP. We present a rare case of undifferentiated schizophrenia with CSP who presented with self-mutilating behaviors.


Chakrabarti S.,Post Graduate Institute of Medical Education and Research | Khemka V.K.,Post Graduate Institute of Medical Education and Research | Banerjee A.,Post Graduate Institute of Medical Education and Research | Banerjee A.,ICARE Institute of Medical science and Research | And 3 more authors.
Aging and Disease | Year: 2015

Alzheimer's disease (AD), the major cause of dementia among the elderly world-wide, manifests in familial and sporadic forms, and the latter variety accounts for the majority of the patients affected by this disease. The etiopathogenesis of sporadic AD is complex and uncertain. The autopsy studies of AD brain have provided limited understanding of the antemortem pathogenesis of the disease. Experimental AD research with transgenic animal or various cell based models has so far failed to explain the complex and varied spectrum of AD dementia. The review, therefore, emphasizes the importance of AD related risk factors, especially those with metabolic implications, identified from various epidemiological studies, in providing clues to the pathogenesis of this complex disorder. Several metabolic risk factors of AD like hypercholesterolemia, hyperhomocysteinemia and type 2 diabetes have been studied extensively both in epidemiology and experimental research, while much less is known about the role of adipokines, pro-inflammatory cytokines and vitamin D in this context. Moreover, the results from many of these studies have shown a degree of variability which has hindered our understanding of the role of AD related risk factors in the disease progression. The review also encompasses the recent recommendations regarding clinical and neuropathological diagnosis of AD and brings out the inherent uncertainty and ambiguity in this area which may have a distinct impact on the outcome of various population-based studies on AD-related risk factors.


PubMed | ICARE Institute of Medical science and Research and Post Graduate Institute of Medical Education and Research
Type: | Journal: International journal of Alzheimer's disease | Year: 2015

Alzheimers disease (AD), the major cause of dementia worldwide, is characterized by progressive loss of memory and cognition. The sporadic form of AD accounts for nearly 90% of the patients developing this disease. The last century has witnessed significant research to identify various mechanisms and risk factors contributing to the complex etiopathogenesis of AD by analyzing postmortem AD brains and experimenting with animal and cell culture based models. However, the treatment strategies, as of now, are only symptomatic. Accumulating evidences suggested a significant association between vitamin D deficiency, dementia, and AD. This review encompasses the beneficial role of vitamin D in neurocognition and optimal brain health along with epidemiological evidence of the high prevalence of hypovitaminosis D among aged and AD population. Moreover, disrupted signaling, altered utilization of vitamin D, and polymorphisms of several related genes including vitamin D receptor (VDR) also predispose to AD or AD-like neurodegeneration. This review explores the relationship between this gene-environmental influence and long term vitamin D deficiency as a risk factor for development of sporadic AD along with the role and rationale of therapeutic trials with vitamin D. It is, therefore, urgently warranted to further establish the role of this potentially neuroprotective vitamin in preventing and halting progressive neurodegeneration in AD patients.


PubMed | Mahatma Gandhi University and ICARE Institute of Medical science and Research
Type: Journal Article | Journal: Aging and disease | Year: 2016

The research on aging and age-related diseases, especially the neurodegenerative diseases, is on the fast track. However, the results have so far not been translated to actual benefit for the patients in terms of treatment or diagnosis of age-related degenerative diseases including those of the CNS. As far as the prevention of the cognitive decline during non-pathological aging is concerned, there is nothing much to offer other than calorie restriction and physical exercise. Needless to say, the benefits are not up to our expectations. However, over the years at the experimental level it has been possible to identify several cellular and molecular mechanisms that are intricately associated with aging in general and neurodegenerative diseases in particular. These include oxidative stress and altered redox-signaling, mitochondrial dysfunction, inflammation, proteotoxicity and altered gene expressions. These inter-dependent pathways mediate cellular senescence and often culminate in programmed cell death like apoptosis and autophagy, and in the context of brain these changes are manifested clinically as cognitive decline and pathologically as neurodegeneration. This special issue provides the readers with glimpses of this complex scenario from different angles primarily in the context of brain and also attempts to identify the potential drug targets against neurodegenerative diseases.


PubMed | ICARE Institute of Medical science and Research
Type: Case Reports | Journal: Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology | Year: 2017

Steroid withdrawal syndrome (SWS) following steroid dependence is becoming a common clinical condition. It may be associated with body image disorder. Though selective serotonin reuptake inhibitors (SSRIs) are found to be effective SWS associated depression, data for this clinical condition is limited. We present a case of SWS associated with body image disorder which improved with mirtazapine. Mirtazapine might be better option than SSRIs in this subgroup of patients for its noradrenergic property and better gastrointestinal profile. More research should explore its efficacy in this clinical condition.

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