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1.
Indian J Radiol Imaging ; 34(4): 714-725, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39318578

RESUMEN

The World Health Organization has declared "with great hope" an end to COVID-19 as a public health emergency. The vaccination drive that started in December 2020 played a crucial role in controlling the pandemic. However, the pace at which COVID-19 vaccines were developed and deployed for general population use led to vaccine hesitancy, largely owing to concerns regarding the safety and efficacy of the vaccines. Radiology has been instrumental in demonstrating the extent of pulmonary involvement and identification of the complications of COVID-19, and the same holds true for vaccine-related complications. This review summarizes the existing body of radiological literature regarding the efficacy, adverse events, and imaging pitfalls that accompany the global rollout of various COVID-19 vaccines.

2.
Artículo en Inglés | MEDLINE | ID: mdl-39046529

RESUMEN

Older adults are vulnerable to adverse drug reactions (ADRs) and drug-drug interactions (DDIs). Evidence on clinically manifest DDIs in older outpatients is scanty. The present study aims to report clinically manifest DDIs, their risk factors, and preventive measures. A subgroup analysis of a 6-year (2015-2021) long prospective study was conducted in a tertiary hospital in North India. Older outpatients with ADRs constituted the study participants. Among 933 ADRs reported in 10,400 patient registrations, clinically manifest DDIs were involved in 199 (21.3%). DDIs accounted for 29.9%, 26.5%, and 21.3% of drug-related metabolic, vascular, and nervous system disorders, respectively. Movement disorders (n = 18), hypotension (n = 16), and hypoglycemia (n = 15) were the most common manifestations. Eighty-six percent of DDIs were of the pharmacodynamic type, and 13.1% were immune-mediated. Around 35% of DDIs resulted in hospitalization, with hyponatremia, movement disorder, and renal impairment as the common reasons. Older adults with Parkinsonism, infection, coronary artery disease, neuropsychiatric disease, and diabetes mellitus, respectively, had 3.28, 2.85, 1.97, 1.76, and 1.80 times higher odds of DDIs. Those receiving ≥ 10 drugs had 5.31 times higher odds of DDIs compared to individuals receiving 1-4 drugs. "Avoiding the causative drug," "optimal monitoring of the patient," and "start-low and go-slow" policy together could prevent 85% of DDIs. In conclusion, every fifth case of ADRs and nearly one third of ADR-related hospitalizations in older adults are related to DDIs. Movement disorder, hypotension, and hypoglycemia are the common manifestations. A holistic approach with drug omission, optimal patient monitoring, and slow titration of therapy can prevent significant DDIs in older adults.

4.
Free Radic Res ; 58(3): 217-228, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38572725

RESUMEN

Ferroptosis has been characterized as a form of iron-dependent regulated cell death accompanied by an accumulation of reactive oxygen species and lipid oxidation products along with typical morphological alterations in mitochondria. Ferroptosis is activated by diverse triggers and inhibited by ferrostatin-1 and liproxstatin-1, apart from iron chelators and several antioxidants, and the process is implicated in multiple pathological conditions. There are, however, certain ambiguities about ferroptosis, especially regarding the final executioner of cell death subsequent to the accumulation of ROS. This study uses a typical inducer of ferroptosis such as erastin on SH-SY5Y cells, and shows clearly that ferroptotic death of cells is accompanied by the loss of mitochondrial membrane potential and intracellular ATP content along with an accumulation of oxidative stress markers. All these are prevented by ferrostatin-1 and liproxstatin-1. Additionally, cyclosporine A prevents mitochondrial alterations and cell death induced by erastin implying the crucial role of mitochondrial permeability transition pore (mPTP) activation in ferroptotic death. Furthermore, an accumulation of α-synuclein occurs during erastin induced ferroptosis which can be inhibited by ferrostatin-1 and liproxstatin-1. When the knock-down of α-synuclein expression is performed by specific siRNA treatment of SH-SY5Y cells, the mitochondrial impairment and ferroptotic death of the cells induced by erastin are markedly prevented. Thus, α-synuclein through the involvement of mPTP appears to be the key executioner protein of ferroptosis induced by erastin, but it needs to be verified if it is a generalized mechanism of ferroptosis by using other inducers and cell lines.


Asunto(s)
Ferroptosis , Mitocondrias , Piperazinas , alfa-Sinucleína , Humanos , alfa-Sinucleína/metabolismo , Muerte Celular/efectos de los fármacos , Línea Celular Tumoral , Ferroptosis/efectos de los fármacos , Mitocondrias/metabolismo , Mitocondrias/efectos de los fármacos , Piperazinas/farmacología , Especies Reactivas de Oxígeno/metabolismo
5.
Clin Drug Investig ; 44(4): 223-250, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38460077

RESUMEN

Despite advances in the management of type 2 diabetes mellitus (T2DM), one-third of patients with diabetes do not achieve the desired glycemic goal. Considering this inadequacy, many agents that activate glucokinase have been investigated over the last two decades but were withdrawn before submission for marketing permission. Dorzagliatin is the first glucokinase activator that has been granted approval for T2DM, only in China. As overstimulation of glucokinase is linked with pathophysiological disturbances such as fatty liver and cardiovascular issues and a loss of therapeutic efficacy with time. This review aims to highlight the benefits of glucokinase activators vis-à-vis the risks associated with chronic enzymatic activation. We discuss the multisystem disturbances expected with chronic activation of the enzyme, the lessons learned with glucokinase activators of the past, the major efficacy and safety findings with dorzagliatin and its pharmacological properties, and the status of other glucokinase activators in the pipeline. The approval of dorzagliatin in China was based on the SEED and the DAWN trials, the major pivotal phase III trials that enrolled patients with T2DM with a mean glycosylated hemoglobin of 8.3-8.4%, and a mean age of 53-54.5 years from multiple sites in China. Patients with uncontrolled diabetes, cardiac diseases, organ dysfunction, and a history of severe hypoglycemia were excluded. Both trials had a randomized double-blind placebo-controlled phase of 24 weeks followed by an open-label phase of 28 weeks with dorzagliatin. Drug-naïve patients with T2DM with a disease duration of 11.7 months were enrolled in the SEED trial while the DAWN trial involved patients with T2DM with a mean duration of 71.5 months and receiving background metformin therapy. Compared with placebo, the decline in glycosylated hemoglobin at 24 weeks was more with dorzagliatin with an estimated treatment difference of - 0.57% in the SEED trial and - 0.66% in the DAWN trial. The desired glycosylated hemoglobin (< 7%) was also attained at more than two times higher rates with dorzagliatin. The glycemic improvement was sustained in the SEED trial but decreased over 52 weeks in the DAWN trial. Hyperlipidemia was observed in 12-14% of patients taking dorzagliatin versus 9-11% of patients receiving a placebo. Additional adverse effects noticed over 52 weeks with dorzagliatin included an elevation in liver enzymes, hyperuricemia, hyperlacticacidemia, renal dysfunction, and cardiovascular disturbances. Considering the statistically significant improvement in glycosylated hemoglobin with dorzagliatin in patients with T2DM, the drug may be given a chance in treatment-naïve patients with a shorter disease history. However, with the waning therapeutic efficacy witnessed in patients with long-standing diabetes, which was also one of the potential concerns with previously tested molecules, extended studies involving patients with chronic and uncontrolled diabetes are needed to comment upon the long-term therapeutic performance of dorzagliatin. Likewise, evidence needs to be generated from other countries, patients with organ dysfunction, a history of severe hypoglycemia, cardiac diseases, and elderly patients before extending the use of dorzagliatin. Apart from monitoring lipid profiles, long-term safety studies of dorzagliatin should involve the assessment of serum uric acid, lactate, renal function, liver function, and cardiovascular parameters.


Asunto(s)
Diabetes Mellitus Tipo 2 , Cardiopatías , Hipoglucemia , Pirazoles , Humanos , Anciano , Persona de Mediana Edad , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemiantes/efectos adversos , Hemoglobina Glucada , Glucoquinasa , Insuficiencia Multiorgánica/inducido químicamente , Insuficiencia Multiorgánica/tratamiento farmacológico , Ácido Úrico , Hipoglucemia/inducido químicamente , Hipoglucemia/tratamiento farmacológico , Cardiopatías/inducido químicamente , Cardiopatías/tratamiento farmacológico , Glucemia , Ensayos Clínicos Controlados Aleatorios como Asunto
6.
Curr Drug Saf ; 2024 03 20.
Artículo en Inglés | MEDLINE | ID: mdl-38523545

RESUMEN

INTRODUCTION: Prescribing cascade is a condition in which a drug administered to a patient causes an adverse reaction that is misinterpreted as a new condition, resulting in the addition of a new drug. CASE PRESENTATION: Here, we report the case of an elderly female patient who suffered from metabolic, neurologic, and urinary consequences of a prescribing cascade of antiemetic, antiepileptic, and dopaminergic drugs. While levosulpiride caused Parkinsonian symptoms, the dopaminergic drugs and valproate caused refractory hyponatremia followed by altered sensorium, and clidinium contributed to urinary retention. CONCLUSION: The case highlights the need to be vigilant for adverse consequences of the prescribing cascade, especially for antiemetic drugs, such as levosulpiride, because of its propensity to induce extrapyramidal reactions in older patients. In cases of refractory hyponatremia, a trial of de-challenge of valproate and dopaminergic drugs should be considered. The identification and removal of the culprit drugs can rescue the patient from a disabling cycle of adverse drug reactions.

7.
Geriatr Gerontol Int ; 24 Suppl 1: 285-291, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37577765

RESUMEN

AIM: Drug-related problems (DRPs) are a common cause of hospitalization in older patients. So far, these issues have been studied in hospitalized settings, and evidence on patterns and outcomes of DRPs, such as adverse drug reactions, is relatively scarce in older outpatients. The main aim of this study was to provide a comprehensive description and possible solutions for DRPs in older adults in outpatient settings. METHODS: The study was carried out from January 2015 to September 2021 in a tertiary hospital in north India. Patients aged ≥50 years with DRPs were enrolled. DRPs causing hospitalization, drug interactions and drug-disease interactions were identified, along with preventive measures. RESULTS: Of 10 400 patients registered, 1031 DRPs occurred in 666 patients (9.9%). Adverse drug reactions were the major DRPs (n = 933, 8.9%). Metabolic disorders were the commonest DRP in individuals aged ≥65 years compared with gastrointestinal disorders in the 50-64 years group. Drug interactions and drug-disease interactions contributed to 20.1% and 7.9% of patients, respectively. Nearly 15.8% of DRPs directly led to hospitalization, with drug-induced metabolic disturbances and movement disorders as the common causes. The Naranjo scale was not applicable in 35.3% of patients, and drug interactions were the commonest cause. Frequent monitoring, omission of unnecessary drugs, slow titration and proper instructions on therapy, together, could avoid one-third of DRPs. CONCLUSION: One out of 10 prescriptions of older outpatients carries a DRP. New-onset metabolic and neurological disturbances should prompt a thorough drug history. A multifaceted holistic approach can prevent significant drug-related morbidity and requires future evaluation. Geriatr Gerontol Int 2024; 24: 285-291.


Asunto(s)
Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Pacientes Ambulatorios , Humanos , Anciano , Estudios Prospectivos , Centros de Atención Terciaria , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Interacciones Farmacológicas , Farmacéuticos
8.
Clin Drug Investig ; 44(1): 1-10, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38095822

RESUMEN

The approval of lecanemab by the US Food and Drug Administration has been touted as a defining moment in the treatment of Alzheimer's disease. Lecanemab, an anti-amyloid beta monoclonal antibody, is the first Alzheimer's disease drug targeting amyloid beta that has shown statistically significant cognitive benefits in phase III trials. However, there have been many questions raised over the clinical relevance of the otherwise minimal cognitive improvements. Furthermore, its rapid approval has been mired in controversy, in addition to the reports of adverse events such as amyloid-related imaging abnormalities and several deaths of participants in the lecanemab trials. Here, we analyze the evidence supporting lecanemab as an amyloid beta therapy and also discuss the concerns raised about its efficacy and safety.


Asunto(s)
Enfermedad de Alzheimer , Estados Unidos , Humanos , Enfermedad de Alzheimer/tratamiento farmacológico , Péptidos beta-Amiloides , Anticuerpos Monoclonales Humanizados/efectos adversos , Sistemas de Liberación de Medicamentos
9.
BMJ Open ; 13(12): e077530, 2023 12 27.
Artículo en Inglés | MEDLINE | ID: mdl-38151275

RESUMEN

OBJECTIVES: To identify factors associated with malnutrition (undernutrition and overnutrition) and determine appropriate cut-off values for mid-arm circumference (MAC) and calf circumference (CC) among community-dwelling Indian older adults. DESIGN: Data from the first wave of harmonised diagnostic assessment of dementia for Longitudinal Ageing Study in India (LASI-DAD) were used. Various sociodemographic factors, comorbidities, geriatric syndromes, childhood financial and health status were included. Anthropometric measurements included body mass index (BMI), MAC and CC. SETTING: Nationally representative cohort study including 36 Indian states and union territories. PARTICIPANTS: 4096 older adults aged >60 years from LASI DAD. OUTCOME MEASURES: The outcome variable was BMI, categorised as low (<18.5 kg/m2), normal (18.5-22.9 kg/m2) and high (>23 kg/m2). The cut-off values of MAC and CC were derived using ROC curve with BMI as the gold standard. RESULTS: 902 (weighted percentage 20.55%) had low BMI, 1742 (44.25%) had high BMI. Undernutrition was associated with age, wealth-quintile and impaired cognition, while overnutrition was associated with higher education, urban living and comorbidities such as hypertension, diabetes and chronic heart disease. For CC, the optimal lower and upper cut-offs for males were 28.1 cm and >31.5 cm, respectively, while for females, the corresponding values were 26 cm and >29 cm. Similarly, the optimal lower and upper cut-offs for MAC in males were 23.9 cm and >26.9 cm, and for females, they were 22.5 cm and >25 cm. CONCLUSION: Our study identifies a high BMI prevalence, especially among females, individuals with higher education, urban residents and those with comorbidities. We establish gender-specific MAC and CC cut-off values with significant implications for healthcare, policy and research. Tailored interventions can address undernutrition and overnutrition in older adults, enhancing standardised nutritional assessment and well-being.


Asunto(s)
Antropometría , Desnutrición , Hipernutrición , Anciano , Femenino , Humanos , Masculino , Envejecimiento , Índice de Masa Corporal , Estudios de Cohortes , Estudios Transversales , India/epidemiología , Desnutrición/diagnóstico , Desnutrición/epidemiología , Persona de Mediana Edad , Valores de Referencia
10.
Daru ; 2023 Nov 14.
Artículo en Inglés | MEDLINE | ID: mdl-37962835

RESUMEN

INTRODUCTION: Typical antipsychotics are known to produce extrapyramidal side effects such as drug induced parkinsonism, acute dystonia, akathisia, tardive dyskinesias and rabbit syndrome. Rabbit syndrome is characterized by vertical rhythmic motion of the mouth and lips, resembling chewing movements of a rabbit. REASON FOR THE REPORT: Rabbit syndrome seen in patients on antidopaminergic therapies is characterized by vertical rhythmic movements of perioral region, has a late onset, and characteristically spares the tongue. The main aim of the report is to highlight atypical manifestation of antipsychotic associated Rabbit syndrome in the presence of a serotonergic antidepressant. An elderly patient presented with atypical rabbit syndrome with relatively acute onset, horizontal movements of jaw and marked tongue involvement after haloperidol-escitalopram initiation. OUTCOME: The patient improved with discontinuation of antipsychotic. The tongue involvement was believed to be secondary to escitalopram use.

12.
Am J Trop Med Hyg ; 109(6): 1290-1297, 2023 12 06.
Artículo en Inglés | MEDLINE | ID: mdl-37903443

RESUMEN

Dengue experienced a rise in disease burden in 2021 in specific regions of India. We aimed to explore the risk factors of dengue occurrence and severity in the post-COVID-19 and post-COVID-19 vaccination era and performed an exploratory analysis involving participants from two prior observational studies conducted from February 2021 to April 2022 in a tertiary hospital in North India. Health care workers constituted the majority of the study participants. Individuals were stratified into five groups based on COVID-19 infection and timing of vaccination: COVID-No Vaccine, Vaccine-No COVID (VNC), COVID After Vaccine (CAV), Vaccine After COVID (VAC), and No Vaccine-No COVID (NVNC) groups. The occurrence of laboratory-confirmed dengue and severe forms of dengue were the main outcomes of interest. A total of 1,701 participants (1,520 vaccinated, 181 unvaccinated) were included. Of these, symptomatic dengue occurred in 133 (7.8%) and was "severe" in 42 (31.6%) cases. Individuals with a history of COVID-19 in 2020 had a 2-times-higher odds of developing symptomatic dengue (P = 0.002). The VAC group had 3.6 (P = 0.019)-, 2 (P = 0.002)-, and 1.9 (P = 0.01)-times-higher odds of developing symptomatic dengue than the NVNC, VNC, and CAV groups, respectively. The severity of dengue was not affected by COVID-19 vaccination but with marginal statistical significance, a 2-times-higher risk of severe dengue was observed with any COVID-19 of the past (P = 0.08). We conclude that COVID-19 may enhance the risk of developing symptomatic dengue. Future research should explore the predisposition of COVID-19-recovered patients toward other viral illnesses. Individuals receiving COVID-19 vaccines after recovering from COVID-19 particularly seem to be at greater risk of symptomatic dengue and need long-term watchfulness. Possible mechanisms, such as antibody-dependent enhancement or T-cell dysfunction, should be investigated in COVID-19-recovered and vaccinated individuals.


Asunto(s)
Vacunas contra la COVID-19 , COVID-19 , Dengue , Humanos , COVID-19/epidemiología , COVID-19/prevención & control , Vacunas contra la COVID-19/administración & dosificación , Vacunación , Dengue/epidemiología , India/epidemiología
13.
Am J Trop Med Hyg ; 109(5): 1137-1140, 2023 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-37696514

RESUMEN

Nocardiosis is a rare opportunistic infection mostly affecting the lungs, brain, or skin of immunocompromised individuals. Most pulmonary nocardiosis patients present with nonspecific clinical features such as productive cough, exertional dyspnea, and fever. The disease is uncommonly suspected, especially in tuberculosis-endemic regions, and clinical diagnosis is often delayed, resulting in high mortality. Pulmonary nocardiosis in apparently immunocompetent individuals is uncommon. Here, we present the case of an elderly gentleman with a background history of poorly controlled diabetes but no history of systemic steroid use who presented with worsening symptoms of chronic obstructive pulmonary disease in the form of productive cough and dyspnea. The patient had diffuse crepitations in bilateral lung fields and an arterial oxygen saturation of 86% at admission. Sputum microscopy revealed gram-positive filamentous bacteria that could be successfully cultured and identified as Nocardia amamiensis on 16S ribosomal RNA sequencing. Contrast-enhanced computed tomography of the lungs revealed cavitary nodules and consolidation. The patient responded well to treatment with specific antibiotics based on sensitivity patterns. Because of the nonspecific clinical and radiological findings in pulmonary nocardiosis, a high index of suspicion is required, especially in tuberculosis-endemic regions.


Asunto(s)
Nocardiosis , Enfermedad Pulmonar Obstructiva Crónica , Tuberculosis , Masculino , Humanos , Anciano , Tos , Nocardiosis/diagnóstico , Nocardiosis/tratamiento farmacológico , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Disnea , Tuberculosis/complicaciones
14.
Gerontol Geriatr Med ; 9: 23337214231194965, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37743872

RESUMEN

Malnutrition in low- and middle-income countries causes cognitive decline and other health problems. Harmonized Diagnostic Assessment of Dementia for Longitudinal Aging Study in India (LASI DAD) is an extensive study on late-life cognition and dementia. This study examines the link between nutrition and cognitive abilities in older adults using data from the LASI DAD. We conducted descriptive statistics on nutritional parameters (body-mass index, waist-hip ratio, and Mini-Nutritional Assessment), cognitive functions, and socio-demographic variables in 2,892 adults aged ≥60 years. Cognitive domains assessed included delayed recall, orientation, language, executive function, abstract reasoning, and attention. Cognitive impairment was defined as impaired performance in two or more domains. Mean age was 69.3 ± 7.1 years, 52.9% were female, and 57.5% were illiterate. Low body-mass index (adjusted OR: 1.88, p < .001), at risk of malnutrition (adjusted OR: 1.89, p < .001) and malnourished (adjusted OR: 2.86, p < .001) on Mini-Nutritional Assessment were associated with the presence of cognitive impairment. Better cognitive performance was associated with increased body mass index (adjusted OR: 0.74, p-.03), hemoglobin (adjusted OR: 0.91, p-.006), and serum albumin (adjusted OR: 0.38, p < .001). This study shows that nutritional status assessed by anthropometric measures and blood markers is strongly linked to cognitive performance in older adults.

15.
Drug Saf ; 46(6): 553-563, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-37133805

RESUMEN

INTRODUCTION: Various vaccines for protection against COVID-19 were provided emergency approval in late 2020 to early 2021. There is a scarcity of long-term safety data for many of these. OBJECTIVE: The main aim of this study is to provide the one-year safety results of the ChAdOx1-nCoV-19/AZD1222 vaccine and determine the risk factors of adverse events of special interest (AESIs) and persistent AESIs. METHODS: This was a prospective observational study conducted from February 2021 to April 2022 in a tertiary hospital in North India and its two associated centers. Health care workers, other frontline workers, and the elderly vaccinated with the ChAdOx1-nCoV-19 vaccine constituted the study population. Individuals were contacted telephonically at pre-decided intervals for one year and health issues of significant concern were recorded. Atypical adverse events developing after a booster dose of the COVID-19 vaccine were assessed. Regression analysis was conducted to determine risk factors of AESI occurrence and determinants of AESIs persisting for at least one month at the time of final telephonic contact. RESULTS: Of 1650 individuals enrolled, 1520 could be assessed at one-year post-vaccination. COVID-19 occurred in 44.1% of participants. Dengue occurred in 8% of participants. The majority of the AESIs belonged to the MedDRA® SOC of musculoskeletal disorders (3.7% of 1520). Arthropathy (knee joint involvement) was the most common individual AESI (1.7%). Endocrinal disorders such as thyroid abnormalities and metabolic disorders such as newly diagnosed diabetes developed in 0.4% and 0.3% of individuals, respectively. Regression analysis showed females, individuals with a pre-vaccination history of COVID-19, diabetes, hypothyroidism, and arthropathy had 1.78-, 1.55-, 1.82-, 2.47- and 3.9-times higher odds of AESI development. Females and individuals with hypothyroidism were at 1.66- and 2.23-times higher risk of persistent AESIs. Individuals receiving the vaccine after COVID-19 were at 2.85- and 1.94 times higher risk of persistent AESIs compared, respectively, to individuals with no history of COVID-19 and individuals developing COVID-19 after the vaccine. Among participants receiving a booster dose of the COVID-19 vaccine (n = 185), 9.7% developed atypical adverse events of which urticaria and new-onset arthropathy were common. CONCLUSION: Nearly half of the ChAdOx1-nCoV-19 vaccine recipients developed COVID-19 over one year. Vigilance is warranted for AESIs such as musculoskeletal disorders. Females, individuals with hypothyroidism, diabetes, and pre-vaccination history of COVID-19 are at higher risk of adverse events. Vaccines received after natural SARS-CoV-2 infection may increase the risk of persistence of adverse events. Sex and endocrinal differences and timing of the COVID-19 vaccine with respect to natural infection should be explored as determinants of AESIs in the future. Pathogenetic mechanisms of vaccine-related adverse events should be investigated along with comparisons with an unvaccinated arm to delineate the overall safety profile of COVID-19 vaccines.


Asunto(s)
COVID-19 , Hipotiroidismo , Enfermedades Musculoesqueléticas , Anciano , Femenino , Humanos , ChAdOx1 nCoV-19 , COVID-19/epidemiología , COVID-19/prevención & control , Vacunas contra la COVID-19/efectos adversos , India/epidemiología , SARS-CoV-2 , Vacunación/efectos adversos
16.
Pharmacol Rep ; 75(2): 482-489, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36849757

RESUMEN

BACKGROUND: Inhibitors of glucose transporters are being explored as potential anti-cancer drugs. Decreased cerebral glucose utilization with reduced levels of several glucose transporters is also an important pathogenic signature of neurodegeneration of Alzheimer's disease, but its exact role in the pathogenesis of this disease is not established. We explored in an experimental model if inhibitors of glucose transporters could lead to altered amyloid-beta homeostasis, mitochondrial dysfunction, and neuronal death, which are relevant in the pathogenesis of Alzheimer's disease. METHODS: SH-SY5Y cells (human neuroblastoma cell line) were exposed to an inhibitor (WZB117) of several types of glucose transporters. We examined the effects of glucose hypometabolism on SH-SY5Y cells in terms of mitochondrial functions, production of reactive oxygen species, amyloid-beta homeostasis, and neural cell death. The effect of ß-hydroxybutyrate in ameliorating the effects of WZB117 on SH-SY5Y cells was also examined. RESULTS: We observed that exposure of SH-SY5Y cells to WZB117 caused mitochondrial dysfunction, increased production of reactive oxygen species, loss of cell viability, increased expression of BACE 1, and intracellular accumulation of amyloid ß peptide (Aß42). All the effects of WZB117 could be markedly prevented by co-treatment with ß-hydroxybutyrate. Cyclosporine A, a blocker of mitochondrial permeability transition pore (mPTP) activation, could not prevent cell death caused by WZB117. CONCLUSION: Results in this neuroblastoma model have implications for the pathogenesis of Alzheimer's disease and warrant further explorations of WZB117 in primary cultures of neurons and experimental animal models.


Asunto(s)
Enfermedad de Alzheimer , Neuroblastoma , Animales , Humanos , Péptidos beta-Amiloides/toxicidad , Péptidos beta-Amiloides/metabolismo , Enfermedad de Alzheimer/tratamiento farmacológico , Ácido 3-Hidroxibutírico/farmacología , Ácido 3-Hidroxibutírico/uso terapéutico , Especies Reactivas de Oxígeno/metabolismo , Glucosa , Línea Celular Tumoral , Fragmentos de Péptidos/metabolismo
17.
Alzheimers Dement ; 19(7): 2898-2912, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-36637034

RESUMEN

INTRODUCTION: Prior estimates of dementia prevalence in India were based on samples from selected communities, inadequately representing the national and state populations. METHODS: From the Longitudinal Aging Study in India (LASI) we recruited a sample of adults ages 60+ and administered a rich battery of neuropsychological tests and an informant interview in 2018 through 2020. We obtained a clinical consensus rating of dementia status for a subsample (N = 2528), fitted a logistic model for dementia status on this subsample, and then imputed dementia status for all other LASI respondents aged 60+ (N = 28,949). RESULTS: The estimated dementia prevalence for adults ages 60+ in India is 7.4%, with significant age and education gradients, sex and urban/rural differences, and cross-state variation. DISCUSSION: An estimated 8.8 million Indians older than 60 years have dementia. The burden of dementia cases is unevenly distributed across states and subpopulations and may therefore require different levels of local planning and support. HIGHLIGHTS: The estimated dementia prevalence for adults ages 60+ in India is 7.4%. About 8.8 million Indians older than 60 years live with dementia. Dementia is more prevalent among females than males and in rural than urban areas. Significant cross-state variation exists in dementia prevalence.


Asunto(s)
Demencia , Masculino , Femenino , Humanos , Demencia/epidemiología , Prevalencia , Envejecimiento , Pruebas Neuropsicológicas , India/epidemiología
18.
Sci Data ; 10(1): 45, 2023 01 20.
Artículo en Inglés | MEDLINE | ID: mdl-36670106

RESUMEN

The Harmonized Diagnostic Assessment of Dementia for the Longitudinal Aging Study in India (LASI-DAD) is a nationally representative in-depth study of cognitive aging and dementia. We present a publicly available dataset of harmonized cognitive measures of 4,096 adults 60 years of age and older in India, collected across 18 states and union territories. Blood samples were obtained to carry out whole blood and serum-based assays. Results are included in a venous blood specimen datafile that can be linked to the Harmonized LASI-DAD dataset. A global screening array of 960 LASI-DAD respondents is also publicly available for download, in addition to neuroimaging data on 137 LASI-DAD participants. Altogether, these datasets provide comprehensive information on older adults in India that allow researchers to further understand risk factors associated with cognitive impairment and dementia.


Asunto(s)
Disfunción Cognitiva , Demencia , Anciano , Humanos , Envejecimiento , Demencia/genética , Genómica , Estudios Longitudinales , India
19.
Curr Drug Saf ; 18(1): 103-106, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-35579125

RESUMEN

INTRODUCTION: COVID-19 vaccine-induced serious adverse reactions are rare. Hypereosinophilia syndrome with myocarditis has not been reported earlier following BBV152 vaccine administration. CASE PRESENTATION: A young man without any co-morbidities presented with persistent periorbital swelling along with itchy swelling over fingers, resting tachycardia, and exertional breathlessness following the first dose of an inactivated SARS-CoV-2 vaccine (BBV152, COVAXIN). On investigation, the patient had elevated blood eosinophils (maximum 21.5% with an absolute eosinophil count of 2767/mm3) and myocarditis (Lake Louise Criteria). He was successfully treated with steroids and supportive treatment. CONCLUSION: This is the first reported case of hyper-eosinophilia syndrome after COVAXIN administration. Prior history of the allergic disease may be a predisposing factor in this case. Hypereosinophilia can present with variable symptoms. In the current case, myocarditis was present with persistent resting tachycardia and dyspnea. Steroid and antiallergic drugs may be successful for the treatment of vaccine-induced hyper-eosinophilia with myocarditis. Increased vigilance is needed for such adverse events.


Asunto(s)
Vacunas contra la COVID-19 , COVID-19 , Eosinofilia , Miocarditis , Humanos , Masculino , COVID-19/prevención & control , Vacunas contra la COVID-19/efectos adversos , Eosinofilia/inducido químicamente , Miocarditis/inducido químicamente , Miocarditis/diagnóstico , SARS-CoV-2 , Vacunación
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