Unique case of a geminated supernumerary tooth with trifid crown

Ather, Amber,Ather, Hunaiza,Sheth, Sanket Milan,Muliya, Vidya Saraswathi Korean Academy of Oral and Maxillofacial Radiology 2012 Imaging Science in Dentistry Vol.42 No.3

Gemination, a relatively uncommon dental anomaly, is characterized by its peculiar representation as a tooth with a bifid crown and a common root and root canal. It usually occurs in primary dentition. To come across gemination in a supernumerary tooth is a rare phenomenon. The purpose of this paper is to present a unique case of hyperdontia wherein gemination in an impacted supernumerary tooth resulted in a trifid crown unlike the usual bifid crown. The role of conventional radiographs as well as computed tomography, to accurately determine the morphology and spatial location, and to arrive at a diagnosis, is also emphasized in this paper.

Unique case of a geminated supernumerary tooth with trifid crown

Amber Ather,Hunaiza Ather,Sanket Milan Sheth,Vidya Saraswathi Muliya 대한구강악안면방사선학회 2012 Imaging Science in Dentistry Vol.42 No.3

Gemination, a relatively uncommon dental anomaly, is characterized by its peculiar representation as a tooth with a bifid crown and a common root and root canal. It usually occurs in primary dentition. To come across gemination in a supernumerary tooth is a rare phenomenon. The purpose of this paper is to present a unique case of hyperdontia wherein gemination in an impacted supernumerary tooth resulted in a trifid crown unlike the usual bifid crown. The role of conventional radiographs as well as computed tomography, to accurately determine the morphology and spatial location, and to arrive at a diagnosis, is also emphasized in this paper.

Endoplasmic Reticulum Stress: Implications for Neuropsychiatric Disorders

Ather Muneer,Rana Mozammil Shamsher Khan 전남대학교 의과학연구소 2019 전남의대학술지 Vol.55 No.1

The Endoplasmic reticulum (ER), an indispensable sub-cellular component of the eukaryotic cell carries out essential functions, is critical to the survival of the organism. The chaperone proteins and the folding enzymes which are multi-domain ER effectors carry out 3-dimensional conformation of nascent polypeptides and check misfolded protein aggregation, easing the exit of functional proteins from the ER. Diverse conditions, for instance redox imbalance, alterations in ionic calcium levels, and inflammatory signaling can perturb the functioning of the ER, leading to a build-up of unfolded or misfolded proteins in the lumen. This results in ER stress, and aiming to reinstate protein homeostasis, a well conserved reaction called the unfolded protein response (UPR) is elicited. Equally, in protracted cellular stress or inadequate compensatory reaction, UPR pathway leads to cell loss. Dysfunctional ER mechanisms are responsible for neuronal degeneration in numerous human diseases, for instance Alzheimer’s, Parkinson’s and Huntington’s diseases. In addition, mounting proof indicates that ER stress is incriminated in psychiatric diseases like major depressive disorder, bipolar disorder, and schizophrenia. Accumulating evidence suggests that pharmacological agents regulating the working of ER may have a role in diminishing advancing neuronal dysfunction in neuropsychiatric disorders. Here, new findings are examined which link the foremost mechanisms connecting ER stress and cell homeostasis. Furthermore, a supposed new pathogenic model of major neuropsychiatry disorders is provided, with ER stress proposed as the pivotal step in disease development.

Telomere Biology in Mood Disorders: An Updated, Comprehensive Review of the Literature

Ather Muneer,Fareed Aslam Minhas 대한정신약물학회 2019 CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE Vol.17 No.3

Major psychiatric disorders are linked to early mortality and patients afflicted with these ailments demonstrate an increased risk of developing physical diseases that are characteristically seen in the elderly. Psychiatric conditions like major depressive disorder, bipolar disorder and schizophrenia may be associated with accelerated cellular aging, indicated by shortened leukocyte telomere length (LTL), which could underlie this connection. Telomere shortening occurs with repeated cell division and is reflective of a cell’s mitotic history. It is also influenced by cumulative exposure to inflammation and oxidative stress as well as the availability of telomerase, the telomere-lengthening enzyme. Precariously short telomeres can cause cells to undergo senescence, apoptosis or genomic instability; shorter LTL correlates with compromised general health and foretells mortality. Important data specify that LTL may be reduced in principal psychiatric illnesses, possibly in proportion to exposure to the ailment. Telomerase, as measured in peripheral blood monocytes, has been less well characterized in psychiatric illnesses, but a role in mood disorder has been suggested by preclinical and clinical studies. In this manuscript, the most recent studies on LTL and telomerase activity in mood disorders are comprehensively reviewed, potential mediators are discussed, and future directions are suggested. An enhanced comprehension of cellular aging in psychiatric illnesses could lead to their re-conceptualizing as systemic ailments with manifestations both inside and outside the brain. At the same time this paradigm shift could identify new treatment targets, helpful in bringing about lasting cures to innumerable sufferers across the globe.

Kynurenine Pathway of Tryptophan Metabolism in Neuropsychiatric Disorders: Pathophysiologic and Therapeutic Considerations

Ather Muneer 대한정신약물학회 2020 CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE Vol.18 No.4

Under physiological conditions 95% of the ingested essential amino acid tryptophan is metabolized by the kynurenine pathway (KP) to yield the ubiquitous co-enzyme nicotinamide adenine dinucleotide, fulfilling cellular energy requirements. Importantly, the intermediaries of KP exert crucial effects throughout the body, including the central nervous system. Besides, KP metabolites are implicated in diverse disease processes such as inflammation/immune disorders, endocrine/metabolic conditions, cancers and neuropsychiatric diseases. A burgeoning body of research indicates that the KP plays a pathogenic role in major psychiatric diseases like mood disorders and schizophrenia. Triggered by inflammatory processes, the balance between neurotoxic and neuroprotective branches of the KP is disturbed. In preclinical models these discrepancies result in behaviors reminiscent of depression and psychosis. In clinical samples, recent studies are discovering key kynurenine pathway abnormalities which incriminate it in the pathogenesis of the main psychiatric disorders. Harnessing this knowledge has the potential to find disease biomarkers helpful in identifying and prognosticating neuropsychiatric disorders. Concurrently, earnest research efforts directed towards manipulating the KP hold the promise of discovering novel pharmacological agents that have therapeutic value. In this manuscript, an in-depth appraisal of the extant literature is done to understand the working of KP as this applies to neuropsychiatric disorders. It is concluded that this pathway plays an overarching role in the development of major psychiatric disorders, the KP metabolites have the potential to serve as disease markers and new medications based on KP modulation can bring lasting cures for patients suffering from these intractable conditions.

The Discovery of Clinically Applicable Biomarkers for Bipolar Disorder: A Review of Candidate and Proteomic Approaches

Ather Muneer 전남대학교 의과학연구소 2020 전남의대학술지 Vol.56 No.3

Bipolar disorder (BD) is a severe psychiatric condition which affects innumerable people across the globe. The etiopathogenesis of BD is multi-faceted with genetic, environmental and psychosocial factors playing a role. Hitherto, the diagnosis and management of BD are purely on empirical grounds as we lack confirmed biomarkers for this condition. In this regard, hypothesis-driven investigations have been unable to identify clinically applicable biomarkers, steering the field towards newer technologies. Innovative, state-of-the-art techniques like multiplex immunoassays and mass spectrometry can potentially investigate the entire proteome. By detecting up or down regulated proteins, novel biomarkers are identified and new postulates about the etiopathogenesis of BD are specified. Hence, biological pathways are uncovered which are involved in the initiation and advancement of the disease and new therapeutic targets are identified. In this manuscript, the extant literature is thoroughly reviewed and the latest findings on candidate BD biomarkers are provided, followed by an overview of the proteomic approaches. It was found that due to the heterogeneous nature of BD no single biomarker is feasible, instead a panel of tests is more likely to be useful. With the application of latest technologies, it is expected that validated biomarkers will be discovered which will be useful as diagnostic tools and help in the delivery of individually tailored therapies to the patients.

The Neurobiology of Bipolar Disorder: An Integrated Approach

Ather Muneer 전남대학교 의과학연구소 2016 전남의대학술지 Vol.52 No.1

Bipolar disorder is a heterogeneous condition with myriad clinical manifestations andmany comorbidities leading to severe disabilities in the biopsychosocial realm. The objectiveof this review article was to underline recent advances in knowledge regardingthe neurobiology of bipolar disorder. A further aim was to draw attention to new therapeutictargets in the treatment of bipolar disorder. To accomplish these goals, an electronicsearch was undertaken of the PubMed database in August 2015 of literature publishedduring the last 10 years on the pathophysiology of bipolar disorder. A wide-rangingevaluation of the existing work was done with search terms such as “mood disordersand biology,” “bipolar disorder and HPA axis,” “bipolar disorder and cytokines,” “mooddisorders and circadian rhythm,” “bipolar disorder and oxidative stress,” etc. This endeavorshowed that bipolar disorder is a diverse condition sharing neurobiologicalmechanisms with major depressive disorder and psychotic spectrum disorders. Thereis convincing evidence of crosstalk between different biological systems that act in adeleterious manner causing expression of the disease in genetically predisposedindividuals. Inflammatory mediators act in concert with oxidative stress to dysregulatehormonal, metabolic, and circadian homeostasis in precipitating and perpetuating theillness. Stress, whether biologically or psychologically mediated, is responsible for theinitiation and progression of the diathesis. Bipolar spectrum disorders have a stronggenetic component; severe life stresses acting through various paths cause the illnessphenotype.

Aripiprazole in the Treatment of Refractory Mood Disorders: A Case Series

Ather Muneer 대한정신약물학회 2014 CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE Vol.12 No.2

Major depressive disorder and bipolar disorders are among the commonest neuropsychiatric conditions, affecting persons ofboth sexes which belong to all age groups. Comorbidity is the rule rather than the exception; anxiety spectrum disorders, somatoformdisorders, eating disorders and substance use disorders frequently co-exist with mood disorders. Catatonia is a seriouscomplication of the latter and every patient with a severe affective exacerbation should be assessed for the presence of catatonicsigns and symptoms. In a significant minority of patients, symptoms show treatment resistance; many patients experience severehopelessness and suicidal ideation, causing high rates of morbidity and mortality in afflicted individuals. Pharmacological managementis challenging and currently available psychotropic agents often fall short of inducing remission. Second generationantipsychotics have been shown in a number of studies as having an antidepressant and mood stabilizing effect. Aripiprazoleis a novel antipsychotic which is being increasingly used in difficult to treat mood disorders patients. Several controlled anduncontrolled studies have shown the efficacy and safety of this medication in subjects of all ages. Here a case series of threepatients is presented who suffered from refractory mood disorders but responded to aripiprazole with complete remission ofaffective symptoms.

Bipolar Disorder: Role of Inflammation and the Development of Disease Biomarkers

Ather Muneer 대한신경정신의학회 2016 PSYCHIATRY INVESTIGATION Vol.13 No.1

Bipolar disorder is a severe and enduring psychiatric condition which in many cases starts during early adulthood and follows a relapsing and remitting course throughout life. In many patients the disease follows a progressive path with brief periods of inter-episode recovery, sub-threshold symptoms, treatment resistance and increasing functional impairment in the biopsychosocial domains. Knowledge about the neurobiology of bipolar disorder is increasing steadily and evidence from several lines of research implicates immuno-inflammatory mechanisms in the brain and periphery in the etiopathogenesis of this illness and its comorbidities. The main findings are an increase in the levels of proinflammatory cytokines during acute episodes with a decrease in neurotrophic support. Related to these factors are glial cell dysfunction, neuro-endocrine abnormalities and neurotransmitter aberrations which together cause plastic changes in the mood regulating areas of the brain and neuroprogression of the bipolar diathesis. Research in the above mentioned areas is providing an opportunity to discover novel biomarkers for the disease and the field is reaching a point where major breakthroughs can be expected in the not too distant future. It is hoped that with new discoveries fresh avenues will be found to better treat an otherwise recalcitrant disease.

Pharmacotherapy of Acute Bipolar Depression in Adults: An Evidence Based Approach

Ather Muneer 대한가정의학회 2016 Korean Journal of Family Medicine Vol.37 No.3

In the majority of cases of bipolar disorder, manic episodes are usually brief and typically responsive to currentlyavailable psychopharmacological agents. In contrast, depressive manifestations are more prevalent and persistent,and can present as major depressive/mixed episodes or residual interepisode symptoms. The depressive phase isoften associated with other neuropsychiatric conditions, such as anxiety spectrum disorders, substance use disorders,stressor-related disorders, and eating disorders. It is viewed as a systemic disease with associated ailmentssuch as metabolic syndrome, diabetes mellitus, and cardiovascular disease. There is an increased rate of mortalitynot only from suicide, but also from concomitant physical illness. This scenario is made worse by the fact that depressivesymptoms, which represent the main disease burden, are often refractory to existing psychotropic drugs. As such, there is a pressing need for novel agents that are efficacious in acute depressive exacerbations, and alsohave applicable value in preventing recurrent episodes. The rationale of the present review is to delineate the pharmacotherapyof the depressive phase of bipolar disorder with medications for which there is evidence in the formof observational, open-label, or double-blind randomized controlled studies. In the treatment of acute bipolar depressionin adults, a comprehensive appraisal of the extant literature reveals that among mood stabilizers, the mostrobust proof of efficacy exists for divalproex sodium; while atypical antipsychotics, which include olanzapine, quetiapine,lurasidone, and cariprazine, are also effective, as demonstrated in controlled trials.