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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.
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CONTEXT: Carbon monoxide, also known as the "silent killer," is a colorless, odorless, tasteless, and non-irritable gas that, when inhaled, enters the bloodstream and lungs, binds with the hemoglobin, and blocks oxygen from reaching tissues and cells. In this work, the monolayer MoSe2-based CO gas sensors were designed using density functional theory calculation with several dopants including Al, Au, Pd, Ni, Cu, and P. Here, Cu and P were found to be the best dopants, with adsorption energies of -0.67 eV (Cu) and -0.54 eV (P) and recovery times of 1.66 s and 13.8 ms respectively. Cu conductivity for CO adsorption was found to be 2.74 times that of CO2 adsorption in the 1.0-2.26 eV range. P displayed the highest selectivity, followed by Pd and Ni. The dopants, Pd and Ni, were found suitable for building CO gas scavengers due to their high recovery times of 9.76 × 1020 s and 2.47 × 1011 s. Similarly, the adsorption of CO2 on doped monolayer MoSe2 was also investigated. In this study, it is found that monolayer MoSe2 could be employed to create high-performance CO sensors in a CO2-rich environment. METHOD: The electrical characteristics of all doped MoSe2 monolayers are obtained using a DFT calculation with the PBE-GGA method from the Quantum ESPRESSO package. The self-consistent field (SCF) computations were performed using a 7 × 7 × 1 k-point grid and a norm-conserving pseudo potential (NCPP) file. To determine electrical conductivity, the semi-classical version of Boltzmann transport theory, implemented in the Boltz Trap code, was used.
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Here, we have synthesized and characterized three visible light responsive terpyridine based-Re(I)-tricarbonyl complexes; [Re(CO)3(ph-tpy)Cl] (Retp1), [Re(CO)3(an-tpy)Cl] (Retp2), and [Re(CO)3(py-tpy)Cl] (Retp3) where ph-tpy = 4'-phenyl-2,2':6',2â³-terpyridine; an-tpy = 4'-anthracenyl-2,2':6',2â³-terpyridine, py-tpy = 4'-pyrenyl-2,2':6',2â³-terpyridine. The structures of Retp1 and Retp2 were confirmed from the SC-XRD data, indicating distorted octahedral structures. Unlike traditional PDT agents, these complexes generated reactive oxygen species (ROS) via type I and type II pathways and oxidized redox crucial NADH (reduced nicotinamide adenine dinucleotide) upon visible light exposure. Retp3 showed significant mitochondrial localization and demonstrated photoactivated anticancer activity (IC50 â¼ 2 µM) by inducing ROS-mediated cell death in cancer cells selectively (photocytotoxicity Index, PI > 28) upon compromising mitochondrial function in A549 cells. Their diagnostic capabilities were ultimately assessed using clinically relevant 3D multicellular tumor spheroids (MCTs).
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Antineoplásicos , Complexos de Coordenação , NAD , Oxirredução , Piridinas , Espécies Reativas de Oxigênio , Rênio , Humanos , Espécies Reativas de Oxigênio/metabolismo , NAD/química , NAD/metabolismo , Piridinas/química , Piridinas/farmacologia , Complexos de Coordenação/química , Complexos de Coordenação/farmacologia , Complexos de Coordenação/síntese química , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Rênio/química , Rênio/farmacologia , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/síntese química , Luz , Ensaios de Seleção de Medicamentos Antitumorais , Fotoquimioterapia , Estrutura Molecular , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células A549 , Linhagem Celular TumoralRESUMO
Photoactive metal complexes of bioessential transition metal ions with natural chelators are gaining interest as photocytotoxic agents for cancer photodynamic therapy (PDT). We report six new cobalt(III) complexes with a mixed-ligand formulation [Co(B)2(L)](ClO4)2 (Co1-Co6), where B represents a N,N-donor α-diimine ligand, namely, phenanthroline (phen; Co1, Co2), dipyrido[3,2-d:2',3'-f]quinoxaline (dpq; Co3, Co4), and dipyrido[3,2-a:2',3'-c]phenazine (dppz; Co5, Co6), and L is the monoanionic form of the naturally occurring flavonoids chrysin (chry; Co1, Co3, Co5) and silibinin (sili; Co2, Co4, Co6). Complexes displayed a d-d absorption band within 500-700â nm and exhibited excellent dark and photostability in solution. Cytotoxicity studies indicated significant activity of Co5 and Co6 against cervical (HeLa) and lung (A549) cancer cells under visible light (400-700â nm) irradiation giving low micromolar IC50 values (2.3-3.4â µM, phototoxicity index~15-30). The complexes demonstrated notably low toxicity against normal HPL1D lung epithelial cells. Flow cytometry assay revealed an apoptotic mode of cell damage triggered by the complexes when irradiated. ROS generation assay indicated the involvement of singlet oxygen species in the cell death mechanism when irradiated with light. Overall, complexes Co5 and Co6 with coordinated dipyridophenazine and flavonoid ligands are potential candidates for cancer PDT applications.
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We have red-shifted the light absorbance property of a Re(I)-tricarbonyl complex via distant conjugation of a ferrocene moiety and developed a novel complex ReFctp, [Re(Fctp)(CO)3Cl], where Fctp = 4'-ferrocenyl-2,2':6',2â³-terpyridine. ReFctp showed green to red light absorption ability and blue emission, indicating its potential for photodynamic therapy (PDT) application. The conjugation of ferrocene introduced ferrocene-based transitions, which lie at a higher wavelength within the PDT therapeutic window. The time-dependent density functional theory and excited state calculations revealed an efficient intersystem crossing for ReFctp, which is helpful for PDT. ReFctp elicited both PDT type I and type II pathways for reactive oxygen species (ROS) generation and facilitated NADH (1,4-dihydro-nicotinamide adenine dinucleotide) oxidation upon exposure to visible light. Importantly, ReFctp showed effective penetration through the layers of clinically relevant 3D multicellular tumor spheroids and localized primarily in mitochondria (Pearson's correlation coefficient, PCC = 0.65) of A549 cancer cells. ReFctp produced more than 20 times higher phototoxicity (IC50 â¼1.5 µM) by inducing ROS generation and altering mitochondrial membrane potential in A549 cancer cells than the nonferrocene analogue Retp, [Re(CO)3(tp)Cl], where tp = 2,2':6',2â³-terpyridine. ReFctp induced apoptotic mode of cell death with a notable photocytotoxicity index (PI, PI = IC50dark/IC50light) and selectivity index (SI, SI = normal cell's IC50dark/cancer cell's IC50light) in the range of 25-33.
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Antineoplásicos , Compostos Ferrosos , Luz , Metalocenos , Compostos Ferrosos/química , Compostos Ferrosos/farmacologia , Humanos , Metalocenos/química , Metalocenos/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Antineoplásicos/efeitos da radiação , Antineoplásicos/síntese química , Espécies Reativas de Oxigênio/metabolismo , Teoria da Densidade Funcional , Fotoquimioterapia , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/efeitos da radiação , Fármacos Fotossensibilizantes/síntese química , Complexos de Coordenação/química , Complexos de Coordenação/farmacologia , Complexos de Coordenação/efeitos da radiação , Complexos de Coordenação/síntese química , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Luz VermelhaRESUMO
Herein, we have compared the effectivity of light-based photoactivated cancer therapy and ultrasound-based sonodynamic therapy with Re(I)-tricarbonyl complexes (Re1-Re3) against cancer cells. The observed photophysical and TD-DFT calculations indicated the potential of Re1-Re3 to act as good anticancer agents under visible light/ultrasound exposure. Re1 did not display any dark- or light- or ultrasound-triggered anticancer activity. However, Re2 and Re3 displayed concentration-dependent anticancer activity upon light and ultrasound exposure. Interestingly, Re3 produced 1O2 and OH⢠on light/ultrasound exposure. Moreover, Re3 induced NADH photo-oxidation in PBS and produced H2O2. To the best of our knowledge, NADH photo-oxidation has been achieved here with the Re(I) complex for the first time in PBS. Additionally, Re3 released CO upon light/ultrasound exposure. The cell death mechanism revealed that Re3 produced an apoptotic cell death response in HeLa cells via ROS generation. Interestingly, Re3 showed slightly better anticancer activity under light exposure compared to ultrasound exposure.
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Antineoplásicos , Fenantrolinas , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Ligantes , Células HeLa , Fenantrolinas/química , Fenantrolinas/farmacologia , Rênio/química , Rênio/farmacologia , Complexos de Coordenação/farmacologia , Complexos de Coordenação/química , Complexos de Coordenação/síntese química , Complexos de Coordenação/efeitos da radiação , Apoptose/efeitos dos fármacos , Luz , Espécies Reativas de Oxigênio/metabolismo , Terapia por Ultrassom , Fotoquimioterapia , Ensaios de Seleção de Medicamentos Antitumorais , Neoplasias/tratamento farmacológicoRESUMO
Chronic wounds have long been a significant public health concern, but the true impact of these wounds is unknown since research designs and measuring techniques vary, leading to inconsistent estimates. The definition of a wound is a loss of epithelial continuity caused by damage to the tissue. The following conditions can cause chronic wounds: panniculitis, pyoderma gangrenosum, traumatic, neurological, metabolic, hematologic, neoplastic, or infection-related. The growing global incidence of diabetes and the aging population necessitate greater attention to chronic wounds. Regrettably, it is sad that significant healthcare institutions have overlooked wound research. The study of health-related illnesses and occurrences in particular populations, including their distribution, frequency, and determinants, and the application of this research to control health problems.
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The relentless increase in drug resistance of platinum-based chemotherapeutics has opened the scope for other new cancer therapies with novel mechanisms of action (MoA). Recently, photocatalytic cancer therapy, an intrusive catalytic treatment, is receiving significant interest due to its multitargeting cell death mechanism with high selectivity. Here, we report the synthesis and characterization of three photoresponsive Ru(II) complexes, viz., [Ru(ph-tpy)(bpy)Cl]PF6 (Ru1), [Ru(ph-tpy)(phen)Cl]PF6 (Ru2), and [Ru(ph-tpy)(aip)Cl]PF6 (Ru3), where, ph-tpy = 4'-phenyl-2,2':6',2â³-terpyridine, bpy = 2,2'-bipyridine, phen = 1,10-phenanthroline, and aip = 2-(anthracen-9-yl)-1H-imidazo[4,5-f][1,10] phenanthroline, showing photocatalytic anticancer activity. The X-ray crystal structures of Ru1 and Ru2 revealed a distorted octahedral geometry with a RuN5Cl core. The complexes showed an intense absorption band in the 440-600 nm range corresponding to the metal-to-ligand charge transfer (MLCT) that was further used to achieve the green light-induced photocatalytic anticancer effect. The mitochondria-targeting photostable complex Ru3 induced phototoxicity with IC50 and PI values of ca. 0.7 µM and 88, respectively, under white light irradiation and ca. 1.9 µM and 35 under green light irradiation against HeLa cells. The complexes (Ru1-Ru3) showed negligible dark cytotoxicity toward normal splenocytes (IC50s > 50 µM). The cell death mechanistic study revealed that Ru3 induced ROS-mediated apoptosis in HeLa cells via mitochondrial depolarization under white or green light exposure. Interestingly, Ru3 also acted as a highly potent catalyst for NADH photo-oxidation under green light. This NADH photo-oxidation process also contributed to the photocytotoxicity of the complexes. Overall, Ru3 presented multitargeting synergistic type I and type II photochemotherapeutic effects.
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Antineoplásicos , Complexos de Coordenação , Luz , Piridinas , Rutênio , Humanos , Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Catálise , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Complexos de Coordenação/síntese química , Complexos de Coordenação/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Luz Verde , Células HeLa , Estrutura Molecular , Processos Fotoquímicos , Piridinas/química , Piridinas/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Rutênio/química , Rutênio/farmacologiaRESUMO
The increase in antibacterial drug resistance is threatening global health conditions. Recently, antibacterial photodynamic therapy (aPDT) has emerged as an effective antibacterial treatment with high cure gain. In this work, three Zn(II) complexes viz., [Zn(en)(acac)Cl] (1), [Zn(bpy)(acac)Cl] (2), [Zn(en)(cur)Cl] (3), where en=ethylenediamine (1 and 3), bpy=2,2'-bipyridine (2), acac=acetylacetonate (1 and 2), cur=curcumin monoanionic (3) were developed as aPDT agents. Complexes 1-3 were synthesized and fully characterized using NMR, HRMS, FTIR, UV-Vis. and fluorescence spectroscopy. The HOMO-LUMO energy gap (Eg), and adiabatic splittings (ΔS1-T1 and ΔS0-T1 ) obtained from DFT calculation indicated the photosensivity of the complexes. These complexes have not shown any potent antibacterial activity under dark conditions but the antibacterial activity of these complexes was significantly enhanced upon light exposure (MIC value up to 0.025â µg/mL) due to their light-mediated 1 O2 generation abilities. The molecular docking study suggested that complexes 1-3 interact efficiently with DNA gyrase B (PDB ID: 4uro). Importantly, 1-3 did not show any toxicity toward normal HEK-293 cells. Overall, in this work, we have demonstrated the promising potential of Zn(II) complexes as effective antibacterial agents under the influence of visible light.
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Complexos de Coordenação , Curcumina , Fotoquimioterapia , Humanos , Curcumina/farmacologia , Simulação de Acoplamento Molecular , Complexos de Coordenação/química , Teoria da Densidade Funcional , Células HEK293 , Antibacterianos/farmacologia , Antibacterianos/química , Zinco/químicaRESUMO
Background: Thyroid dysfunction (TD) is considered a common cause of secondary hypertension (HT). Therefore, correcting TD may help in quicker and sustained achievement of desired blood pressure goals. However, there is a paucity of literature from India which estimates the relationship of HT with TD. Objectives: The objective of the study was to estimate the prevalence of TD with HT and to identify associated factors among Indian population. Materials and Methods: The survey data of the National Family Health Survey 4 (NFHS-4), conducted in India during 2015-2016, were analyzed using R statistical software for estimating the relationship between a history of HT and TD among women (N = 687246) aged 15-49 years and men (N = 108492) aged 15-54 years. Descriptive statistical tests and logistic regression were applied. Results: Among the persons suffering from the TD, the prevalence of HT was 32.8%, which was significantly higher than the prevalence of HT (21.9%) in euthyroid individuals. Further, the prevalence of TD was higher among hypertensive adults (2.5%) compared to nonhypertensive (1.5%). Conclusions: The study reported a higher prevalence of TD among the hypertensive persons and higher prevalence of HT among cases of TD. Therefore, screening for thyroid disorders should be routinely considered for better management of HT.
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Hipertensão , Doenças da Glândula Tireoide , Masculino , Adulto , Humanos , Feminino , Prevalência , Índia/epidemiologia , Doenças da Glândula Tireoide/epidemiologia , Doenças da Glândula Tireoide/diagnóstico , Hipertensão/epidemiologia , Fatores de Risco , Inquéritos EpidemiológicosRESUMO
Herein, five novel polypyridyl-based Co(III) complexes of Schiff bases, viz., [Co(dpa)(L1)]Cl (1), [Co(dpa)(L2)]Cl (2), [Co(L3)(L2)]Cl (3), [Co(L3)(L1)]Cl (4), and [Co(L4)(L1)]Cl (5), where dpa (dipicolylamine) = bis(2-pyridylmethyl)amine; H2L1 = (E)-2-((2-hydroxybenzylidene)amino)phenol; H2L2 = (E)-5-(hydroxymethyl)-4-(((2-hydroxyphenyl)imino)methyl)-2-methylpyridin-3-ol; L3 = 4'-phenyl-2,2':6',2''-terpyridine (ph-tpy); and L4 = 4'-ferrocenyl-2,2':6',2''-terpyridine (Fc-tpy), were synthesized and characterized. Complexes 1, 3, and 4 were structurally characterized by single-crystal XRD, indicating an octahedral CoIIIN4O2 coordination core. The absorption bands of these complexes were observed in the visible range with a λmax at â¼430-485 nm. Complex 5 displayed an extra absorption band near 545 nm because of a ferrocene moiety. These absorptions in the visible region reflect the potential of the complexes to act as visible-light antimicrobial photodynamic therapy (aPDT) agents. All of these complexes showed reactive oxygen species (ROS)-mediated antibacterial effects against S. aureus (Gram-positive) and E. coli (Gram-negative bacteria) upon low-energy visible light (0.5 J cm-2, 400-700 nm) exposure. Additionally, 1-5 did not show any toxicity toward A549 (Human Lung adenocarcinoma) cells, reflecting their selective bacteria-killing abilities.
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Complexos de Coordenação , Vitamina B 6 , Humanos , Piridinas/farmacologia , Piridinas/química , Bases de Schiff/farmacologia , Bases de Schiff/química , Staphylococcus aureus , Escherichia coli , Antibacterianos/farmacologia , Vitaminas , Complexos de Coordenação/farmacologia , Complexos de Coordenação/químicaRESUMO
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.
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Vacinas contra COVID-19 , COVID-19 , Dengue , Humanos , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinas contra COVID-19/administração & dosagem , Vacinação , Dengue/epidemiologia , Índia/epidemiologiaRESUMO
In antimalarial drug development research, overcoming drug resistance has been a major challenge for researchers. Nowadays, several drugs like chloroquine, mefloquine, sulfadoxine, and artemisinin are used to treat malaria. But increment in drug resistance has pushed researchers to find novel drugs to tackle drug resistance problems. The idea of using transition metal complexes with pharmacophores as ligands/ligand pendants to show enhanced antimalarial activity with a novel mechanism of action has gained significant attention recently. The advantages of metal complexes include tunable chemical/physical properties, redox activity, avoiding resistance factors, etc. Several recent reports have successfully demonstrated that the metal complexation of known organic antimalarial drugs can overcome drug resistance by showing enhanced activities than the parent drugs. This review has discussed the fruitful research works done in the past few years falling into this criterion. Based on transition metal series (3d, 4d, or 5d), the antimalarial metal complexes have been divided into three broad categories (3d, 4d, or 5d metal-based), and their activities have been compared with the similar control complexes as well as the parent drugs. Furthermore, we have also commented on the potential issues and their possible solution for translating these metal-based antimalarial complexes into the clinic.
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Antimaláricos , Complexos de Coordenação , Malária Falciparum , Malária , Humanos , Antimaláricos/farmacologia , Antimaláricos/uso terapêutico , Complexos de Coordenação/farmacologia , Complexos de Coordenação/uso terapêutico , Malária/tratamento farmacológico , Cloroquina/farmacologia , Mefloquina/uso terapêutico , Resistência a Medicamentos , Plasmodium falciparum , Malária Falciparum/tratamento farmacológicoRESUMO
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.
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COVID-19 , Hipotireoidismo , Doenças Musculoesqueléticas , Idoso , Feminino , Humanos , ChAdOx1 nCoV-19 , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Índia/epidemiologia , SARS-CoV-2 , Vacinação/efeitos adversosRESUMO
Four new CoII complexes, [Co(bpy)2 (acac)]Cl (1), [Co(phen)2 (acac)]Cl (2), [Co(bpy)2 (cur)]Cl (3), [Co(phen)2 (cur)]Cl (4), where bpy=2,2'-bipyridine (1 and 3), phen=1,10-phenanthroline (2 and 4), acac=acetylacetonate (1 and 2), cur=curcumin monoanion (3 and 4) have been designed, synthesized and fully characterized. The X-ray crystal structures of 1 and 2 indicated that the CoN4 O2 core has a distorted octahedral geometry. The photoactivity of these complexes was tuned by varying the π conjugation in the ligands. Curcumin complexes 3 and 4 had an intense absorption band near 435â nm, which made them useful as visible-light photodynamic therapy agents; they also showed fluorescence with λem ≈565â nm. This fluorescence was useful for studying their intracellular uptake and localization in MCF-7 breast cancer cells. The acetylacetonate complexes (1 and 2) were used as control complexes to understand the role of curcumin. The white-light-triggered anticancer profiles of the cytosol targeting complexes 3 and 4 were investigated in detail. These non-dark toxic complexes displayed significant apoptotic photo-cytotoxicity (under visible light) against MCF-7 cells through ROS generation. The control complexes 1 and 2 did not induce significant cell death in the light or dark. Interestingly, 1-4 produced a remarkable antibacterial response upon light exposure. Overall, the reported results here can increase the boundary of the CoII -based anticancer and antibacterial drug development.
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Antineoplásicos , Complexos de Coordenação , Curcumina , Fotoquimioterapia , Humanos , Curcumina/farmacologia , Curcumina/química , Hidroxibutiratos , Pentanonas , Antineoplásicos/farmacologia , Antineoplásicos/química , Complexos de Coordenação/farmacologia , Complexos de Coordenação/química , Antibacterianos/farmacologiaRESUMO
Sonodynamic therapy (SDT) for cancer treatment is gaining attention owing to its non-invasive property and ultrasound's (US) deep tissue penetration ability. In SDT, US activates the sonosensitizer at the target deep-seated tumors to generate reactive oxygen species (ROS), which ultimately damage tumors. However, drawbacks such as insufficient ROS production, aggregation of sonosensitizer, off-target side effects, etc., of the current organic/nanomaterial-based sonosensitizers limit the effectiveness of cancer SDT. Very recently, metal complexes with tunable physiochemical properties (such as sonostability, HOMO to LUMO energy gap, ROS generation ability, aqueous solubility, emission, etc.) have been devised as effective sonosensitizers, which could overcome the limitations of organic/nanomaterial-based sonosensitizers. This concept introduces all the reported metal-based sonosensitizers and delineates the prospects of metal complexes in cancer sonodynamic therapy. This new concept of metal-based sonosensitizer can deliver next-generation cancer drugs.
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Antineoplásicos , Complexos de Coordenação , Neoplasias , Terapia por Ultrassom , Humanos , Espécies Reativas de Oxigênio , Complexos de Coordenação/farmacologia , Complexos de Coordenação/uso terapêutico , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Linhagem Celular TumoralRESUMO
Recently, interest has been given to developing photocatalytic anticancer drugs. This area of research is dominated by metal complexes. Here, we report the potential of lysosome/mitochondria targeting cyanine appended bipyridine compounds as the organic photocatalytic anticancer agents. The organocatalyst (bpyPCN) not only exhibits light-induced NADH oxidation but also generates intracellular ROS to demonstrate anticancer activity. This is the first example of organic compound induced catalytic NADH photo-oxidation in an aqueous solution and in cancer cells.
Assuntos
Antineoplásicos , Complexos de Coordenação , Neoplasias , 2,2'-Dipiridil/farmacologia , Oxirredução , NAD , Antineoplásicos/farmacologiaRESUMO
The current analysis is a part of an ongoing observational study that began in February 2021 in the Sir Sunder Lal Hospital (Varanasi, Uttar Pradesh) in northern India and is expected to continue until June 2022. This analysis aimed to delineate the clinical presentation and risk factors of occurrence and severity of COVID-19 in vaccinated individuals. The study enrolled health-care workers and the elderly receiving the COVID-19 vaccine at one of three centers linked to the study hospital. The participants received the ChAdOx1 nCoV-19 (Oxford-AstraZeneca) vaccine based on the chimpanzee adenovirus platform (manufactured in India by the Serum Institute of India). The adenovirus codes for the spike (S) protein of SARS-CoV-2. Participants were contacted by phone at pre-decided intervals and questioned about the occurrence of COVID-19, clinical presentation, severity, and persistence of symptoms. A logistic regression analysis was performed to predict the risk factors of occurrence and severity of COVID-19. Of the 1,500 participants included in the analysis, 418 developed COVID-19 (27.9%). Fever was the most common symptom (72%), followed by cough (34%) and rhinitis (26%). Cardiovascular involvement was seen in more than 2% of individuals, and 11% had post-COVID-19 complaints. Regression analysis showed 1.6 times greater odds of contracting the disease in females and in those younger than 40 years, 1.4 times greater odds in individuals who were overweight, and 2.9 times greater odds in those receiving only one dose, compared with respective comparators. Individuals receiving two doses at a gap of ≤ 30 days had 6.7 times greater odds of infection than those receiving at a > 60-day interval. There was no association between COVID-19 occurrence in the vaccinees and pre-vaccination history of SARS-CoV-2 infection. Males were at a 3.6 times greater risk, and persons with preexisting lung disease-mainly asthma-had a 5.9 times greater risk of experiencing moderate to severe COVID-19 than comparators. While an extended interval between the two vaccine doses seems to be a better strategy, gender differences and an association of asthma phenotypes with COVID-19 need to be explored.
Assuntos
Asma , COVID-19 , COVID-19/epidemiologia , Vacinas contra COVID-19 , ChAdOx1 nCoV-19 , Feminino , Humanos , Masculino , SARS-CoV-2 , VacinaçãoRESUMO
Background There is paucity of real-world data on COVID-19 vaccine effectiveness from cohort designs. Variable vaccine performance has been observed in test-negative case-control designs. There is also scarce real-world data of health issues in individuals receiving vaccines after prior COVID-19, and of adverse events of significant concern (AESCs) in the vaccinated. Methods: A cohort study was conducted from July 2021 to December 2021 in a tertiary hospital of North India. The primary outcome was vaccine effectiveness against COVID-19 during the second wave in India. Secondary outcomes were AESCs, and persistent health issues in those receiving COVID-19 vaccines. Regression analyses were performed to determine risk factors of COVID-19 outcomes and persistent health issues. Results: Of the 2760 health care workers included, 2544 had received COVID-19 vaccines, with COVISHIELD (rChAdOx1-nCoV-19 vaccine) received by 2476 (97.3%) and COVAXIN (inactivated SARS-CoV-2 vaccine) by 64 (2.5%). A total of 2691 HCWs were included in the vaccine effectiveness analysis, and 973 COVID-19 events were reported during the period of analysis. Maximum effectiveness of two doses of vaccine in preventing COVID-19 occurrence was 17% across three different strategies of analysis adopted for robustness of data. One-dose recipients were at 1.27-times increased risk of COVID-19. Prior SARS-CoV-2 infection was a strong independent protective factor against COVID-19 (aOR 0.66). Full vaccination reduced moderate-severe COVID-19 by 57%. Those with lung disease were at 2.54-times increased risk of moderate-severe COVID-19, independent of vaccination status. AESCs were observed in 33/2544 (1.3%) vaccinees, including one case each of myocarditis and severe hypersensitivity. Individuals with hypothyroidism were at 5-times higher risk and those receiving a vaccine after recovery from COVID-19 were at 3-times higher risk of persistent health issues. Conclusions: COVID-19 vaccination reduced COVID-19 severity but offered marginal protection against occurrence. The possible relationship of asthma and hypothyroidism with COVID-19 outcomes necessitates focused research. With independent protection of SARS-CoV-2 infection, and high-risk of persistent health issues in individuals receiving vaccine after recovery from SARS-CoV-2 infection, the recommendation of vaccinating those with prior SARS-CoV-2 infection needs reconsideration.
RESUMO
Immunotherapy has made great progress in clinical cancer treatment in recent years, but its therapeutic efficacy is significantly limited by the lack of immunogenicity in the tumor microenvironment. Pyroptosis is a type of programmed cell death in which the dying cancer cells produce inflammatory cytokines to relieve the immuno-suppressive microenvironment and thus increase anti-tumor immunity. Reactive oxygen species (ROS) produced during photodynamic therapy (PDT) are one of the efficient activators that induce pyroptosis. Recently, a few photosensitizers have emerged with the ability to induce immunogenic cancer cell death via pyroptosis, opening a new field for PDT. This highlight introduces the latest research on antitumor strategies achieved by the combination of immunotherapy and photodynamic therapy through photo-pyroptosis.