Upinder Kaur

Reactive oxygen species, redox signaling and neuroinflammation in Alzheimer's disease: the NF-κB connection.

Oxidative stress and inflammatory response are important elements of Alzheimers disease (AD) pathogenesis, but the role of redox signaling cascade and its cross-talk with inflammatory mediators have not been elucidated in details in this disorder. The review summarizes the facts about redox-signaling cascade in the cells operating through an array of kinases, phosphatases and transcription factors and their downstream components. The biology of NF-κB and its activation by reactive oxygen species (ROS) and proinflammatory cytokines in the pathogenesis of AD have been specially highlighted citing evidence both from post-mortem studies in AD brain and experimental research in animal or cell-based models of AD. The possibility of identifying new disease-modifying drugs for AD targeting NF-κBsignaling cascade has been discussed in the end.

Zoledronate Induced Hypocalcemia and Hypophosphatemia in Osteoporosis: A Cause of Concern

Zoledronate is a Nitrogen containing bisphosphonate (NBP) used in many conditions like osteoporosis, Pagets disease and hypercalcemia of malignancy. Unlike oral bisphosphonates, Zoledronate is not seen to be associated with gastroesophageal side effects but the drug is not free of certain rare but life threatening adverse effects like hypocalcemia and renal deterioration. Majority of cases of hypocalcemia with Zoledronate are seen in patients with underlying malignancy and are asymptomatic. Here we present a case of severe symptomatic hypocalcemia along with hypophosphatemia following zoledronate administration in an elderly male with a history of osteoporotic fracture.

Isoniazid Induced Metabolic Acidosis and Renal Dysfunction in an Elderly Patient with Chronic Renal Disease.

Metabolic acidosis is one of the common manifestations of Isoniazid toxicity but rare with normally used doses of the drug. Among anti tubercular drugs, rifampicin, streptomycin and capreomycin are commonly implicated in renal injury. Here we report the first case of metabolic acidosis and renal injury caused by isoniazid at normal prescribed dose.

Severe haematuria of lower urinary tract origin with low dose dabigatran use in three Indian elderly patients: unresolved issues in the safety of novel oral anticoagulants

Dabigatran is a newer oral direct thrombin inhibitor approved by the United States Food and Drug Administration and the European Medicines Agency (EMA). The proper dosage of the drug, the potential for adverse drug reactions and the nature of bleeds with use of this drug as with other novel oral anticoagulants (NOACs), in the elderly population are still areas of uncertainty. Despite the existence of a specific antibody, idarucizumab which is an antidote to dabigatran toxicity, management of dabigatran-induced bleeds is an undefined area especially in resource constrained settings. We report severe haematuria with dabigatran in three elderly Indian patients at the lowest recommended therapeutic dose and explore these grey zones in dabigatran therapy.

Morvan’s syndrome—is a pathogen behind the curtain?

Morvan’s syndrome is a rare syndrome of likely autoimmune etiology characterized by peripheral nerve hyperexcitability, dysautonomia, insomnia, and fluctuating delirium with prominent hallucinations. Since its first mention in 1890, less than 100 cases have been described in literature. The largest existing review includes details of 29 cases. This case series describes 4 cases (M = 4) of Morvan’s syndrome which presented between May and November 2017 to a single tertiary care referral teaching hospital in north India. All the four patients manifested behavioral abnormalities, sleep disturbances, hallucinations, autonomic dysfunction, and clinical signs of peripheral nerve hyperexcitability, mostly as myokymia. Two of the patients had Anti-CASPR2 (contactin-associated protein 2) antibodies. Three of them had electromyography features of peripheral nerve hyperexcitability and only one had elevated cerebrospinal fluid protein level. We hypothesize that Morvan’s syndrome and other less characterized autoimmune encephalitis/peripheral nervous system syndromes may have infectious triggers. A possible viral trigger may result in generation of autoantibodies which result in the typical manifestations. We base these hypotheses on the finding of four cases of an orphan disease within a short period of time in a limited geographical distribution.

Striatal hand in an elderly man with disseminated tuberculosis: An unusual first case: Letters to the Editor

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Delirium induced by albendazole-ivermectin combination: Report of the first case in an older patient: Letters to the Editor

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Deep Venous Thrombosis Associated with Thalidomide use in a Case of Steroid Dependent Erythema Nodosum Leprosum-a Management Conundrum

Thalidomide, previously banned owing to the issues of teratogenicity is being used and tested for a variety of dermatological and non dermatological conditions. The drug has been approved for the management of erythema nodosum leprosum [ENL] and multiple myeloma [MM]. The drug is commonly known to produce adverse effects like peripheral neuropathy and constipation. Deep vein thrombosis [DVT] is one of the serious adverse effects seen with thalidomide use, especially in malignancies and is relatively uncommon in non cancer settings like ENL. Method: Here we report a case of DVT occurring after 8 months of use of thalidomide in a young patient of 22 years age suffering from ENL. Result: The case highlights the problems faced in the management of refractory ENL and the treatment of DVT in the setting of multiple drug interactions and financial constraints. Conclusion: New guidelines are required regarding the prophylaxis and management of DVT associated with thalidomide use in non-malignant conditionsThalidomide, previously banned owing to the issues of teratogenicity is being used and tested for a variety of dermatological and non dermatological conditions. The drug has been approved for the management of ENL and Multiple myeloma. The drug is commonly known to produce adverse effects like peripheral neuropathy and constipation. Deep vein thrombosis (DVT) is one of the serious adverse effects seen with thalidomide use, especially in malignancies and is relatively uncommon in non cancer settings like ENL. Here we report a case of DVT induced after 8 months of use of thalidomide in a young patient of 22 years age suffering from ENL. The case also highlights the problems faced in the management of refractory ENL and the treatment of DVT in the setting of multiple drug interactions and financial constraints.

Orofacial dyskinesias by phenytoin in an elderly female: The dangers of poor therapeutic monitoring

Phenytoin iswell known for its antiepileptic role in themanagement of partial seizures, secondarily generalized tonic–clonic seizures (GTCSs), and status epilepticus. Its use has also been suggested for trigeminal neuralgia and arrhythmias. Therapeutic plasma concentration of phenytoin ranges from 10 to 20 μg/ml. Metabolism of phenytoin is complicated and changes from first order to zero order kinetics as the dose of phenytoin is increased [1,2]. Phenytoin toxicity can be the result of intentional overdose, misunderstanding of prescription or wrong prescription, altered metabolism, or physiology. It is characterized by nausea and neurological manifestations in the form of mental confusion, ataxia, drowsiness, dizziness, hallucinations, agitation, hyperreflexia or hyporeflexia, and nystagmus. Groups of individuals susceptible to phenytoin toxicity include neonates and elderly; those with hypoalbuminemia, uremia, liver dysfunction, and CYP2C9/2C19 polymorphisms; and patients on polypharmacy [3]. Orofacial dyskinesias are rare with phenytoin but documented. Being rarer than other neurological features of phenytoin intoxication, the diagnosis and treatmentmay be delayed. Children and young adults are seen to be the common victims. Here, we present an elderly female with atypical presentation of phenytoin toxicity in the form of excessive oral and lip movements, delirium, ataxia, and hallucinations.

MicroRNAs and cardiovascular medicine.

MicroRNAs are non-coding RNA sequences that act as regulators of gene expression. They are aberrantly expressed in many pathological conditions. Cardiovascular diseases are among the leading causes of morbidity and mortality in the general population. Various knock-in and knockdown approaches have shown abnormal signature patterns of microRNAs in cardiovascular conditions like cardiac hypertrophy, myocardial infarction, heart failure, arrhythmias and vascular proliferative diseases. Since a single microRNA targets many genes, modulating a single microRNA involved in a disease carries a possible risk of undesirable side effects. The review focuses on current understanding of microRNAs in cardiovascular conditions, the possible underlying mechanisms and various approaches of modulating microRNAs.