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INTRODUCTION: Most of the long-term care for older adults with chronic or debilitating illnesses is provided by unpaid family members or informal caregivers. There is limited information on caregiver burden among caregivers of older patients with cancer in India. Hence, we assessed the prevalence and severity of caregiver burden among caregivers of older Indian patients with cancer. MATERIALS AND METHODS: This was an observational study conducted at the geriatric oncology clinic at Tata Memorial Centre, Mumbai, India. Caregivers of patients aged 60 years and over with a diagnosis of cancer were assessed for caregiver burden using the Zarit Burden Interview. Descriptive statistics were used for demographic and clinical variables. Factors impacting caregiver burden were analyzed using multiple linear regression analysis. RESULTS: Caregiver burden was assessed among 127 caregivers of older Indian patients with cancer. The median patient age was 69 years (range 60-90). Most patients were men (75.6%). There were 33 female caregivers (26%), and 94 male caregivers (74%). The median caregiver burden score was 12 (IQR 6-20). Caregiver burden was "little/none" in 97 (76.4%), "mild-moderate" in 25 (19.7%), "moderate-severe" in four (3.1%) and "severe" in one (0.8%) of the caregivers assessed. On multivariate analysis, factors that significantly impacted caregiver burden scores were the presence of psychological issues in the patient and the caregiver's educational level. DISCUSSION: Caregiver burden was low among caregivers of older Indian patients with cancer seen at a single center. Caregivers of patients with psychological disorders, and those who had less schooling reported higher caregiver burden.
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Sobrecarga do Cuidador , Neoplasias , Idoso , Idoso de 80 Anos ou mais , Cuidadores/psicologia , Efeitos Psicossociais da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/terapia , Centros de Atenção TerciáriaRESUMO
Background: COVID-19 emerged as a global pandemic in 2020, spreading rapidly to most parts of the world. The proportion of infected individuals in a population can be reliably estimated via serosurveillance, making it a valuable tool for planning control measures. Our serosurvey study aimed to investigate SARS-CoV-2 seroprevalence in the urban population of Hyderabad at the end of the first wave of infections. Methods: This cross-sectional survey, conducted in January 2021 and including males and females aged 10 years and above, used multi-stage random sampling. 9363 samples were collected from 30 wards distributed over six zones of Hyderabad, and tested for antibodies against SARS-CoV-2 nucleocapsid antigen. Results: Overall seropositivity was 54.2%, ranging from 50% to 60% in most wards. Highest exposure appeared to be among those aged 30-39 and 50-59 years, with women showing greater seropositivity. Seropositivity increased with family size, with only marginal differences among people with varying levels of education. Seroprevalence was significantly lower among smokers. Only 11% of the survey subjects reported any COVID-19 symptoms, while 17% had appeared for COVID-19 testing. Conclusion: Over half the city's population was infected within a year of onset of the pandemic. However, â¼ 46% of people remained susceptible, contributing to subsequent waves of infection.
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BackgroundCOVID-19 emerged as a global pandemic in 2020, rapidly spreading to most parts of the world. The proportion of infected individuals in a population can be reliably estimated via sero-surveillance, making it a valuable tool for planning control measures. We conducted a serosurvey study to investigate SARS-CoV-2 seroprevalence in the urban population of Hyderabad at the end of the first wave of infections. MethodsThe cross-sectional survey conducted in January 2021 included males and females aged 10 years and above, selected by multi-stage random sampling. 9363 samples were collected from 30 wards distributed over 6 zones of Hyderabad and tested for antibodies against SARS-CoV-2 nucleocapsid antigen. ResultsOverall seropositivity was 54.2%, ranging from 50-60% in most wards. Highest exposure appeared to be among 30-39y and 50-59y olds, with women showing greater seropositivity. Seropositivity increased with family size, with only marginal differences among people with varying levels of education. Seroprevalence was significantly lower among smokers. Only 11% of the survey subjects reported any COVID-19 symptoms, while 17% had appeared for Covid testing. ConclusionOver half the citys population was infected within a year of onset of the pandemic. However, [~]46% people were still susceptible, contributing to subsequent waves of infection. Highlights National level serosurveys under-estimate localised prevalence in dense urban areas SARS-CoV-2 seroprevalence in Hyderabad city was 54.2% after the first wave A large proportion of the population remains at risk over a year into the pandemic
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BACKGROUND: Hypertension is one of the leading risk factors for cardiovascular, cerebrovascular, and renal disease. Its increasing prevalence and treatment costs influence the prescribing pattern among physicians. Drug utilization studies provide insights into the current prescribing practices and help us facilitate the rational use of drugs. We carried out the present study to assess the pattern of drug utilization in hypertensive patients. METHOD: Adults seeking treatment for hypertension were recruited. Prescriptions were studied for demographic and drug-use details. The World Health Organization indices for drug utilization were evaluated. The percentage of prescriptions adhering to the recent guidelines was determined. RESULTS: Enalapril was the most commonly prescribed drug. Monotherapy was used in 71.8% of the cases. However, 42% of the cases were newly diagnosed. The ratio of prescribed daily dose and defined daily dose showed underutilization of enalapril and atenolol and overutilization of amlodipine. About 87.5% of the prescriptions adhered to Eighth Joint National Committee guidelines. Most of the medications were available at the hospital pharmacy store and were prescribed by their generic names. Total 65.3% of the concomitant medications were not listed in the World Health Organization essential list of medicines. The average number of drugs prescribed was six. A median cost of 14.6 and 94.5 rupees was spent, respectively, on anti-hypertensive and concomitant medications per encounter. CONCLUSION: The adherence to the guideline was good. Polypharmacy can be reduced by avoiding the prescription of unnecessary medications and promoting the use of fixed-dose combinations.
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Anti-Hipertensivos/uso terapêutico , Uso de Medicamentos/estatística & dados numéricos , Fidelidade a Diretrizes/estatística & dados numéricos , Hipertensão/tratamento farmacológico , Polimedicação , Padrões de Prática Médica/estatística & dados numéricos , Anlodipino/uso terapêutico , Anti-Hipertensivos/economia , Atenolol/uso terapêutico , Estudos Transversais , Prescrições de Medicamentos/estatística & dados numéricos , Enalapril/uso terapêutico , Feminino , Humanos , Medicina Interna/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Ambulatório Hospitalar , Guias de Prática Clínica como Assunto , Centros de Atenção TerciáriaRESUMO
Exercise training results in dynamic changes in skeletal muscle blood flow and metabolism. Nitric oxide (NO) influences blood flow, oxidative stress, and glucose metabolism. Hsp90 interacts directly with nitric oxide synthases (NOS), increasing NOS activity and altering the balance of superoxide versus NO production. In addition, Hsp90 expression increases in various tissues following exercise. Therefore, we tested the hypothesis that exercise training increases Hsp90 expression as well as Hsp90/NOS association and NOS activity in skeletal muscle. Male, Sprague-Dawley rats were assigned to either a sedentary or exercise trained group (n = 10/group). Exercise training consisted of running on a motorized treadmill for 10 weeks at 30 m/min, 5% grade for 1 h. Western blotting revealed that exercise training resulted in a 1.9 +/- 0.1-fold increase in Hsp90 expression in the soleus muscle but no increase in neuronal nitric oxide synthase (nNOS), inducible nitric oxide synthase, or endothelial nitric oxide synthase (eNOS). Exercise training also resulted in a 3.4 +/- 1.0-fold increase in Hsp90 association with nNOS, a 2.3 +/- 0.4-fold increase association with eNOS measured by immunoprecipitation as well as a 1.5 +/- 0.3-fold increase in eNOS phosphorylation at Ser-1179. Total NOS activity measured by the rate of conversion of L-[(14)C]arginine to L-[(14)C]citrulline was increased by 1.42 +/- 0.9 fold in soleus muscle following exercise training compared to controls. In summary, a 10-week treadmill training program in rats results in a significant increase in total NOS activity in the soleus which may be due, in part, to increased NOS interaction with Hsp90 and phosphorylation. This interaction may play a role in altering muscle blood flow and skeletal muscle redox status.
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Proteínas de Choque Térmico HSP90/metabolismo , Contração Muscular , Músculo Esquelético/enzimologia , Óxido Nítrico Sintase/metabolismo , Esforço Físico , Animais , Masculino , Óxido Nítrico Sintase Tipo I , Óxido Nítrico Sintase Tipo II/metabolismo , Óxido Nítrico Sintase Tipo III , Fosforilação , Ratos , Ratos Sprague-Dawley , Regulação para CimaRESUMO
Tyr83 in endothelial nitric oxide synthase (eNOS) has been identified previously as a site of Src kinase-mediated phosphorylation of eNOS in bovine aortic endothelial cells (BAECs) that is phosphorylated in response to oxidant stress. In the present study, we have used a phospho-specific antibody to show that Tyr83 in eNOS is also phosphorylated in both BAECs and intact blood vessel segments in response to treatment with a variety of different eNOS-activating agonists, including thapsigargin, vascular endothelial growth factor, bradykinin, ATP, sphingosine-1-phosphate, estrogen, angiopoietin, and acetylcholine. Agonist stimulation of eNOS Tyr83 phosphorylation as well as agonist stimulation of endothelial NO release in BAECs is blocked by Src kinase inhibition by either 4-amino-5-(4-chlorophenyl)-7-(t-butyl) pyrazolo [3,4-d] pyrimidine (PP2) or by dominant negative Src. Mutation of Tyr83 to a nonphosphorylatable Phe blocks agonist stimulation of NO release from eNOS-reconstituted eNOS knockdown endothelial cells. Mutation of Tyr83 also attenuates agonist-induced relaxation of eNOS-reconstituted aortic rings from eNOS knockout mice. Phosphorylation of eNOS at Tyr83 thus appears to be a common covalent modification that is induced, not only by oxidant stress but also by other physiologically relevant extracellular signals known to be important in regulation of eNOS activity in vivo. Moreover, our results demonstrate an important role for Src-mediated phosphorylation of eNOS at Tyr83 in agonist stimulation of eNOS activation and vascular relaxation.
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Células Endoteliais/enzimologia , Fator A de Crescimento do Endotélio Vascular/farmacologia , Vasodilatação/fisiologia , Trifosfato de Adenosina/farmacologia , Angiopoietinas/farmacologia , Animais , Aorta/citologia , Bradicinina/farmacologia , Células COS , Bovinos , Chlorocebus aethiops , Células Endoteliais/citologia , Inibidores Enzimáticos/farmacologia , Estrogênios/farmacologia , Humanos , Rim/citologia , Lisofosfolipídeos/farmacologia , Masculino , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Óxido Nítrico Sintase Tipo III , Fosforilação/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Esfingosina/análogos & derivados , Esfingosina/farmacologia , Tapsigargina/farmacologia , Tirosina/metabolismo , Quinases da Família src/metabolismoRESUMO
Endothelial nitric oxide synthase (eNOS) catalyzes the conversion of L-arginine to L-citrulline and nitric oxide (NO), an important modulator of vascular function. eNOS is regulated post-translationally through phosphorylation/dephosphorylation at a number of specific phosphorylation sites including Ser-116 in the bovine eNOS sequence. Whether phosphorylation of eNOS at Ser-116 in endothelial cells is stimulatory or inhibitory has not previously been definitively determined. In this study we show that mimicking phosphorylation of eNOS at Ser-116 by Asp mutation reduces basal NO release from endothelial cells. Preventing phosphorylation at this site by Ala mutation increases the amount of NO release from endothelial cells in response to agonist stimulation. In addition, mimicking phosphorylation of Ser-116 increases eNOS association with caveolin-1 and reduces the vascular reactivity of intact aortic rings. eNOS phosphorylation at Ser-116, therefore, appears to contribute to negative modulation of eNOS activity and hence to regulation of vascular tone.
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Células Endoteliais/enzimologia , Óxido Nítrico Sintase Tipo III/metabolismo , Serina/metabolismo , Animais , Aorta Torácica/enzimologia , Aorta Torácica/fisiologia , Bovinos , Células Cultivadas , Células Endoteliais/citologia , Endotélio Vascular/citologia , Humanos , Técnicas In Vitro , Camundongos , Camundongos Knockout , Mutação , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo III/genética , Fosforilação , VasodilataçãoRESUMO
Endothelial NO synthase (eNOS) via the production of NO in the endothelium plays a key role in cardiovascular biology and is tightly regulated by co- and posttranslational mechanisms, phosphorylation, and protein-protein interactions. The cell division cycle 37 homolog (Cdc37) is a key heat shock protein 90 (Hsp90) cochaperone for protein kinase clients, and Akt/Hsp90 interaction is dependent on Cdc37. Because both Hsp90 and Akt are key eNOS regulatory proteins, we hypothesized that Cdc37 interacts with eNOS as part of the regulatory complex. In the present study, we demonstrate by coimmunoprecipitation and affinity purification in bovine aortic endothelial cells (BAECs) that Cdc37 is complexed with eNOS, Hsp90, and Akt. In addition, cell fractionation data indicate that Cdc37 is found in caveolae with eNOS. Further analysis by in vitro binding assays reveals a direct interaction between purified Cdc37 and eNOS. Incubation of purified Cdc37 with purified wild-type eNOS decreases eNOS activity in vitro. Overexpression of wild-type Cdc37 in BAECs inhibits eNOS activity and NO release, whereas overexpression of S13A-Cdc37 mutant in BAECs increases eNOS activity and NO release. Taken together, these data suggest that Cdc37 has a direct regulatory interaction with eNOS and may play an important role in mediating the eNOS protein complex formation as well as subsequent eNOS phosphorylation and activation.
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Proteínas de Choque Térmico HSP90/fisiologia , Óxido Nítrico Sintase Tipo III/metabolismo , Animais , Aorta , Bovinos , Células Cultivadas , Endotélio Vascular/enzimologia , Ativação Enzimática , Inibidores Enzimáticos , Proteínas de Choque Térmico HSP90/genética , Óxido Nítrico Sintase Tipo III/antagonistas & inibidores , Fosforilação , Proteínas Recombinantes de Fusão/farmacologia , Fator A de Crescimento do Endotélio Vascular/farmacologiaRESUMO
The endothelial nitric-oxide synthase (eNOS) is regulated in part by serine/threonine phosphorylation, but eNOS tyrosine phosphorylation is less well understood. In the present study we have examined the tyrosine phosphorylation of eNOS in bovine aortic endothelial cells (BAECs) exposed to oxidant stress. Hydrogen peroxide and pervanadate (PV) treatment stimulates eNOS tyrosine phosphorylation in BAECs. Phosphorylation is blocked by the Src kinase family inhibitor, 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine (PP2). Moreover, eNOS and c-Src can be coimmunoprecipitated from BAEC lysates by antibodies directed against either protein. Domain mapping and site-directed mutagenesis studies in COS-7 cells transfected with either eNOS alone and then treated with PV or cotransfected with eNOS and constitutively active v-Src identified Tyr-83 (bovine sequence) as the major eNOS tyrosine phosphorylation site. Tyr-83 phosphorylation is associated with a 3-fold increase in basal NO release from cotransfected cells. Furthermore, the Y83F eNOS mutation attenuated thapsigargin-stimulated NO production. Taken together, these data indicate that Src-mediated tyrosine phosphorylation of eNOS at Tyr-83 modulates eNOS activity in endothelial cells.
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Óxido Nítrico Sintase Tipo III/metabolismo , Tirosina/química , Quinases da Família src/fisiologia , Animais , Células COS , Cálcio/metabolismo , Bovinos , Células Cultivadas , Chlorocebus aethiops , Immunoblotting , Imunoprecipitação , Inflamação , Mutagênese Sítio-Dirigida , Óxido Nítrico/metabolismo , Fosforilação , Estrutura Terciária de Proteína , Pirimidinas/farmacologia , Fatores de Tempo , Transfecção , Tirosina/metabolismo , Quinases da Família src/metabolismoRESUMO
3-Hydroxy-3-methylglutaryl (HMG)-CoA reductase inhibitors, statins, provide beneficial effects independent of their lipid-lowering effects. One beneficial effect appears to involve acute activation of endothelial nitric oxide (NO) synthase (eNOS) and increased NO release. However, the mechanism of acute statin-stimulated eNOS activation is unknown. Therefore, we hypothesized that eNOS activation may be coupled to altered eNOS phosphorylation. Bovine aortic endothelial cells (BAECs), passages 2-6, were treated with either lovastatin or pravastatin from 0 to 30 min. eNOS phosphorylation was examined by Western blot by use of phosphospecific antibodies for Ser-1179, Ser-635, Ser-617, Thr-497, and Ser-116. Statin stimulation of BAECs increased eNOS phosphorylation at Ser-1179 and Ser-617, which was blocked by the phosphatidylinositol 3-kinase (PI3-kinase)/Akt inhibitor wortmannin, and at Ser-635, which was blocked by the protein kinase A (PKA) inhibitor KT-5720. Statin treatment of BAECs transiently increased NO release by fourfold, measured by cGMP accumulation, and was attenuated by N-nitro-l-arginine methyl ester, wortmannin, and KT-5720 but not by mevalonate. In conclusion, these data demonstrate that eNOS is acutely activated by statins independent of HMG-CoA reductase inhibition and that in addition to Ser-1179, eNOS phosphorylation at Ser-635 and Ser-617 through PKA and Akt, respectively, may explain, in part, a mechanism by which eNOS is activated in response to acute statin treatment.