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The existent pre-clinical models of Parkinson's disease do not simultaneously recapitulate severe degeneration of dopamine neurons and the occurrence of alpha-synuclein (aSyn) aggregation in one study system. In this study, we injected aSyn pre-formed fibrils (PFF) and 6-hydroxydopamine (6-OHDA) unilaterally into the striatum of C57BL/6 wild-type male mice at an interval of 2 weeks to induce aggregation of aSyn protein and trigger the loss of dopamine neurons simultaneously in one model and studied the behavioural effects of the combination in these mice. 6-OHDA was tested at three different doses, and 2 µg of 6-OHDA combined with PFF-induced aSyn aggregation was found to produce the most optimal disease phenotype. At 14 weeks timepoint, mice injected with a combination of PFF and 6-OHDA sustained significant damage to the nigrostriatal pathway and exhibited aSyn-positive aggregation. Our data suggest that the neurons that formed large aSyn aggregates were particularly vulnerable to 6-OHDA-induced degeneration. We also demonstrate the manifestation of a relatively aggressive pathology in 2- to 4-month-old mice, as compared to younger 7- to 9-week-old ones. Furthermore, cerebral dopamine neurotrophic factor (CDNF) administered intrastriatally rescued dopamine neurons and motor behaviour of the animals to some extent from 6-OHDA toxicity. However, no such effect could be seen in the novel 6-OHDA + PFFs combination model. For the first time, we demonstrate the combined effect of PFF and 6-OHDA simultaneously in one model. We further discuss the scope for further optimizing this combination model to develop it as a promising pre-clinical platform for drug screening and development.
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Doença de Parkinson , alfa-Sinucleína , Animais , Masculino , Camundongos , alfa-Sinucleína/metabolismo , Modelos Animais de Doenças , Dopamina/metabolismo , Neurônios Dopaminérgicos/metabolismo , Camundongos Endogâmicos C57BL , Fatores de Crescimento Neural/metabolismo , Fatores de Crescimento Neural/farmacologia , Oxidopamina , Doença de Parkinson/metabolismoRESUMO
Prevention of inflammatory angiogenesis is critical for suppressing chronic inflammation and inhibiting inflammatory tissue damage. Angiogenesis is particularly detrimental to the cornea because pathologic growth of new blood vessels can lead to marked vision impairment and even loss of vision. The expression of proinflammatory cytokines by injured tissues exacerbates the inflammatory cascade, including angiogenesis. IL-36 cytokine, a subfamily of the IL-1 superfamily, consists of three proinflammatory agonists, IL-36α, IL-36ß, and IL-36γ, and an IL-36 receptor antagonist (IL-36Ra). Data from the current study indicate that human vascular endothelial cells constitutively expressed the cognate IL-36 receptor. The current investigation, for the first time, characterized the direct contribution of IL-36γ to various angiogenic processes. IL-36γ up-regulated the expression of vascular endothelial growth factors (VEGFs) and their receptors VEGFR2 and VEGFR3 by human vascular endothelial cells, suggesting that IL-36γ mediates the VEGF-VEGFR signaling by endothelial cells. Moreover, by using a naturally occurring antagonist IL-36Ra in a murine model of inflammatory angiogenesis, this study demonstrated that blockade of endogenous IL-36γ signaling results in significant retardation of inflammatory angiogenesis. The current investigation on the proangiogenic function of IL-36γ provides novel evidence of the development of IL-36γ-targeting strategies to hamper inflammatory angiogenesis.
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Doenças da Córnea , Células Endoteliais , Interleucina-1 , Neovascularização Patológica , Fator A de Crescimento do Endotélio Vascular , Animais , Humanos , Camundongos , Doenças da Córnea/genética , Doenças da Córnea/imunologia , Doenças da Córnea/patologia , Citocinas , Células Endoteliais/metabolismo , Interleucina-1/genética , Interleucina-1/metabolismo , Neovascularização Patológica/genética , Neovascularização Patológica/imunologia , Neovascularização Patológica/patologia , Receptores de Fatores de Crescimento do Endotélio Vascular/genética , Receptores de Fatores de Crescimento do Endotélio Vascular/imunologia , Receptor 2 de Fatores de Crescimento do Endotélio VascularRESUMO
A molecular hallmark in Parkinson's disease (PD) pathogenesis are α-synuclein aggregates. Cerebral dopamine neurotrophic factor (CDNF) is an atypical growth factor that is mostly resident in the endoplasmic reticulum but exerts its effects both intracellularly and extracellularly. One of the beneficial effects of CDNF can be protecting neurons from the toxic effects of α-synuclein. Here, we investigated the effects of CDNF on α-synuclein aggregation in vitro and in vivo. We found that CDNF directly interacts with α-synuclein with a KD = 23 ± 6 nM and reduces its auto-association. Using nuclear magnetic resonance (NMR) spectroscopy, we identified interaction sites on the CDNF protein. Remarkably, CDNF reduces the neuronal internalization of α-synuclein fibrils and induces the formation of insoluble phosphorylated α-synuclein inclusions. Intra-striatal CDNF administration alleviates motor deficits in rodents challenged with α-synuclein fibrils, though it did not reduce the number of phosphorylated α-synuclein inclusions in the substantia nigra. CDNF's beneficial effects on rodent behavior appear not to be related to the number of inclusions formed in the current context, and further study of its effects on the aggregation mechanism in vivo are needed. Nonetheless, the interaction of CDNF with α-synuclein, modifying its aggregation, spreading, and associated behavioral alterations, provides novel insights into the potential of CDNF as a therapeutic strategy in PD and other synucleinopathies.
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Fatores de Crescimento Neural/química , Fatores de Crescimento Neural/metabolismo , Doença de Parkinson/fisiopatologia , Substância Negra/metabolismo , alfa-Sinucleína/química , alfa-Sinucleína/metabolismo , Animais , Sítios de Ligação , Linhagem Celular , Modelos Animais de Doenças , Dopamina/metabolismo , Humanos , Espectroscopia de Ressonância Magnética , Masculino , Camundongos , Modelos Moleculares , Doença de Parkinson/metabolismo , Fosforilação , Cultura Primária de Células , Agregados Proteicos , Ligação Proteica , Conformação Proteica , RatosRESUMO
Colchicine site inhibitors are microtubule destabilizers having promising role in cancer therapeutics. In the current study, four such indanone derivatives (t1, t9, t14 and t17) with 3,4,5-trimethoxyphenyl fragment (ring A) and showing significant microtubule destabilization property have been explored. The interaction mechanism and conformational modes triggered by binding of these indanone derivatives and combretastatin at colchicine binding site (CBS) of αß-tubulin dimer were studied using molecular dynamics (MD) simulation, principle component analysis and free energy landscape analysis. In the MD results, t1 showed binding similar to colchicine interacting in the deep hydrophobic core at the CBS. While t9, t14 and t17 showed binding conformation similar to combretastatin, with ring A superficially binding at the CBS. Results demonstrated that ring A played a vital role in binding via hydrophobic interactions and got anchored between the S8 and S9 sheets, H8 helix and T7 loop at the CBS. Conformational modes study revealed that twisting and bending conformational motions (as found in the apo system) were nearly absent in the ligand bound systems. Absence of twisting motion might causes loss of lateral contacts in microtubule, thus promoting microtubule destabilization. This study provides detailed account of microtubule destabilization mechanism by indanone ligands and combretastatin, and would be helpful for designing microtubule destabilizers with higher activity.
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Indanos/química , Microtúbulos/química , Simulação de Dinâmica Molecular , Moduladores de Tubulina/química , Bibenzilas/química , Sítios de Ligação , Isomerismo , Ligantes , Conformação Molecular , Análise de Componente Principal , Ligação Proteica , Relação Estrutura-Atividade , TermodinâmicaRESUMO
The purpose of the present study was to study the synergy potential of gallic acid-based derivatives in combination with conventional antibiotics using multidrug resistant cultures of Escherichia coli. Gallic acid-based derivatives significantly reduced the MIC of tetracycline against multidrug resistant clinical isolate of E. coli. The best representative, 3-(3',4,'5'-trimethoxyphenyl)-4,5,6-trimethoxyindanone-1, an indanone derivative of gallic acid, was observed to inhibit ethidium bromide efflux and ATPase which was also supported by in silico docking. This derivative extended the post-antibiotic effect and decreased the mutation prevention concentration of tetracycline. This derivative in combination with TET was able to reduce the concentration of TNFα up to 18-fold in Swiss albino mice. This derivative was nontoxic and well tolerated up to 300 mg/kg dose in subacute oral toxicity study in mice. This is the first report of gallic acid-based indanone derivative as drug resistance reversal agent acting through ATP-dependent efflux pump inhibition.
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Antibacterianos/farmacologia , Sinergismo Farmacológico , Inibidores Enzimáticos/farmacologia , Escherichia coli/efeitos dos fármacos , Ácido Gálico/farmacologia , Indanos/farmacologia , Tetraciclina/farmacologia , Administração Oral , Animais , Modelos Animais de Doenças , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Ácido Gálico/administração & dosagem , Ácido Gálico/efeitos adversos , Indanos/administração & dosagem , Indanos/efeitos adversos , Macrófagos/efeitos dos fármacos , Camundongos , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Choque Séptico/prevenção & controleRESUMO
Tubulin is a well established target for anticancer drug development. Lignans and neolignans were synthesized as tubulin interacting agents. Neolignans 10 and 19 exhibited significant anticancer activity against MCF-7 and MDAMB-231 human breast cancer cell lines. Both the compounds effectively induced stabilization of microtubule at 4 and 20 µM concentrations respectively. Neolignan 10 induced G2/M phase arrest in MCF-7 cells. Docking experiments raveled that 10 and 19 occupied the same binding pocket of paclitaxel with some difference in active site amino acids and good bioavailability of both the compounds. In in vivo acute oral toxicity 10 was well tolerated up to 300 mg/kg dose in Swiss-albino mice.
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Antineoplásicos/síntese química , Ácidos Cumáricos/síntese química , Lignanas/síntese química , Tubulina (Proteína)/química , Administração Oral , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Sítios de Ligação , Peso Corporal/efeitos dos fármacos , Linhagem Celular Tumoral , Ácidos Cumáricos/química , Ácidos Cumáricos/farmacologia , Feminino , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Meia-Vida , Humanos , Lignanas/química , Lignanas/farmacologia , Pontos de Checagem da Fase M do Ciclo Celular/efeitos dos fármacos , Células MCF-7 , Masculino , Camundongos , Simulação de Acoplamento Molecular , Estabilidade Proteica , Estrutura Terciária de Proteína , Tubulina (Proteína)/metabolismoRESUMO
PURPOSE: To assess outcomes of keratoplasty performed in patients diagnosed with keratitis caused by Pythium insidiosum (PI). DESIGN: Retrospective review. METHODS: Preoperative, intra operative and post operative data of patients diagnosed with PI keratitis and who underwent keratoplasty for their condition from January 2020 to December 2021 were collected from the central patient database of a tertiary eye care hospital in India. The data were analyzed for anatomic success, elimination of infection, graft survival, incidence of repeat keratoplasty, final visual acuity and varied complications. RESULTS: In total, 16 eyes underwent penetrating keratoplasty for PI keratitis during the study period. Mean time to keratoplasty from onset of symptoms was 31.3 days and mean graft size was 10.4 mm. Nine out of the 16 cases had recurrence of infection following surgery, seven of which required a repeat keratoplasty for elimination of infection. Mean graft size for repeat keratoplasty performed in recurrent cases was 11.7 mm. Globe was successfully salvaged in 14 out of 16 patients (87.5 %). Three grafts remained clear at 6-month follow up while 11 grafts failed. Mean improvement in uncorrected visual acuity from 2.32 to 2.04 logMAR was observed at last follow up. Endo-exudates, graft infiltration, graft dehiscence, secondary glaucoma and retinal detachment were the various complications noted after keratoplasty. CONCLUSION: PI keratitis is a tenacious and potentially blinding condition. Keratoplasty remains the choice of treatment in this condition, however recurrence of disease and graft failure are common. Large sized grafts, meticulous per-operative removal of infection, adjuvant cryotherapy, and intraoperative and post operative use of antibiotics can help in improving outcome of keratoplasty in these patients.
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Ceratoplastia Penetrante , Pitiose , Centros de Atenção Terciária , Acuidade Visual , Humanos , Índia/epidemiologia , Estudos Retrospectivos , Masculino , Feminino , Adulto , Ceratoplastia Penetrante/métodos , Pessoa de Meia-Idade , Pitiose/diagnóstico , Pitiose/cirurgia , Ceratite/diagnóstico , Ceratite/cirurgia , Ceratite/microbiologia , Ceratite/epidemiologia , Sobrevivência de Enxerto , Seguimentos , Pythium/isolamento & purificação , Adulto Jovem , Córnea/cirurgia , Córnea/patologia , Córnea/parasitologia , Córnea/microbiologia , Resultado do Tratamento , Idoso , Infecções Oculares Parasitárias/cirurgia , Infecções Oculares Parasitárias/diagnóstico , Infecções Oculares Parasitárias/parasitologia , Infecções Oculares Parasitárias/epidemiologia , AdolescenteRESUMO
PURPOSE: To determine the visual outcome and postoperative complications of cataract surgery in patients with ocular surface disorders (OSDs). SETTING: Tertiary eyecare center in North India. DESIGN: Retrospective observational study. METHODS: Patients with various OSDs with stabilized ocular surfaces who underwent cataract surgery during this period and had a minimum postoperative follow-up of 6 weeks were included. The primary outcome measures were postoperative corrected distance visual acuity (CDVA) at 6 weeks, best CDVA achieved, and postoperative complications. RESULTS: The study included 20 men and 24 women. A total of 55 eyes were evaluated: Stevens-Johnson syndrome (SJS) 35 eyes, ocular cicatricial pemphigoid (OCP) 4 eyes, 8 eyes with dry eye disease (DED), 6 eyes with chemical injury and 2 eyes with vernal keratoconjunctivitis (VKC). The mean duration of OSD was 33.9 ± 52.17 months. The median preoperative CDVA was 2.0 (interquartile range [IQR], 1.45 to 2.0). The median CDVA ever achieved was 0.50 (IQR, 0.18 to 1.45) at 2 months and the median CDVA at 6 weeks was 0.6 (IQR, 0.3 to 1.5). Maximum improvement in CDVA was noted in patients with DED and SJS and the least in OCP. Phacoemulsification was performed in 47.27% eyes with intraoperative complications noted in 9% eyes. Postoperative surface complications occurred in 12 (21.82%) eyes. Other postoperative complications occurred in 9 (16%) eyes. CONCLUSIONS: Cataract surgery outcome can be visually rewarding in patients with OSDs provided ocular surface integrity is adequately maintained preoperatively and postoperatively.
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Background and Aim: As oral submucous fibrosis (OSMF) is a chronic progressive disorder, the treatment is based on the severity of the disease. Surgical treatment is the only choice for grade III and grade IV OSMF cases because the patient can neither clean his/her mouth nor properly chew. The resulting soft tissue defect requires resurfacing with various well-vascularized tissues such as extraoral flaps, intraoral flaps, microvascular flaps, and allografts that have been used. Reconstruction of the resultant defects proved to be challenging. Till date, none of the flaps has been proven to be effective and is universally accepted for the treatment of OSMF because of various drawbacks of the available techniques. This study was conducted to know whether an endoscopic-assisted platysma flap is associated with better outcomes in terms of ease of operation and postoperative function than the conventional approach. Materials and Methods: This study included 40 patients of grade III and grade IV OSMF reporting to the outpatient department of oral and maxillofacial surgery in a tertiary center of North India. These patients were divided randomly into two groups. Group I and Group II had 20 patients each, undergoing endoscopic-assisted platysma flap and non-endoscopic-assisted platysma flap for reconstruction after resection of OSMF bands, respectively. Data were analyzed for the mouth opening, operating time, flap viability, congestion of neck and oral cavity, signs of inflammation, neurologic assessment, and measurement of the drain. Results: The results showed significant increase in mouth opening from the preoperative value to the values immediately after surgery and at 24 h, 1 week, 15 days, 1 month, 3 months, and 6 months after surgery in both the study groups. Reduced bleeding incidence was found in group I compared to group II, with better postoperative outcomes noted during follow-up. But the mean intraoperative time of the subjects in group I was 130.80 ± 5.5.908 min and in group II was 105.74 ± 2. 491 min. Increased time taken in group I may be due to the long learning curve. Conclusion: The present study concluded that the Endoscope-assisted technique has a key role during supra and subplatysmal dissection to allow for better accessibility, handling, and visibility of the flap and its orientation in relation to the underlying structures to avoid postoperative complications and to overcome the drawback of platysma myocutaneous flap in reconstruction of OSMF defects.
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Parkinson's disease (PD) is characterized by the loss of nigrostriatal dopamine (DA) neurons and the presence of alpha-synuclein (αSyn)-positive Lewy body (LB) pathology. In this study, we attempted to recapitulate both these features in a novel in vitro model for PD. To achieve this, we combined the αSyn pre-formed fibril (PFF)-seeded LB-like pathology with 6-hydroxydopamine (6-OHDA)-induced mitochondrial toxicity in mouse embryonic midbrain cultures. To pilot the model for therapeutics testing, we assessed the effects of cerebral dopamine neurotrophic factor (CDNF) on αSyn aggregation and neuron survival. PFF-seeded pathology did not lead to DA neuron loss even with the highest dose of PFFs. The combination of PFFs and 6-OHDA did not trigger additional neurodegeneration or LB-like pathology and instead presented DA neuron loss to a similar extent as with 6-OHDA only. CDNF did not affect the PFF-seeded αSyn pathology or the DA neuron survival in the combination model but showed a trend toward neuroprotection in the 6-OHDA-only cultures.
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Doença de Parkinson , Sinucleinopatias , Camundongos , Animais , alfa-Sinucleína/metabolismo , Oxidopamina/toxicidade , Dopamina , Estudos de Viabilidade , Doença de Parkinson/patologia , Sinucleinopatias/patologia , Degeneração Neural/patologia , Mesencéfalo/metabolismoRESUMO
PURPOSE: The purpose of this study was to study the outcome of single-staged entropion surgery along with lid margin mucous membrane grafting for cicatrizing ocular surface disease. METHODS: Retrospective review of medical records of patients who underwent single-staged surgical correction of cicatricial entropion along with lid margin mucous membrane grafting for lid margin keratinization. RESULTS: Twenty-six eyes of 19 patients were studied. The mean age of patients was 42.5 years (standard deviation, SD-17.67), of which 7 patients were male and 12 were female. The most common disorder was Stevens-Johnson syndrome (SJS) sequelae (83.33%, n = 20), followed by mucous membrane pemphigoid (n = 4, 16.67%). The most common eyelid changes observed were cicatricial entropion in all 26 eyes (100%, n = 26), followed by trichiasis in 13 eyes (50%, n = 13). Lid margin keratinization was noted in all eyes. Postoperative improvement in corneal surface staining was noted in 70% of the patients (n = 13), no change in 20% of the patients (n = 4), and worsening of corneal surface staining in 10% of the patients (n = 2). Postoperative visual acuity improvement was noted in 50% of the eyes (n = 13), no improvement in 39% of the eyes (n = 10), and vision worsened in 12% of the eyes (n = 3). An entropion recurrence rate of 25% (n = 6) was observed over an average 10-month follow-up, whereas 75% (n = 20) reported no recurrence. CONCLUSIONS: Single-staged correction of eyelid cicatricial entropion with a lid margin mucous membrane graft (MMG) has promising outcomes in ocular surface diseases. It can decrease the need for multiple surgeries and provide symptomatic relief in patients with chronic cicatricial surface changes.
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Entrópio , Oftalmopatias , Doenças Palpebrais , Penfigoide Mucomembranoso Benigno , Síndrome de Stevens-Johnson , Humanos , Masculino , Feminino , Adulto , Entrópio/cirurgia , Síndrome de Stevens-Johnson/cirurgia , Pálpebras/cirurgia , Mucosa/transplante , Doenças Palpebrais/cirurgiaRESUMO
The lacrimal gland undergoes significant structural and functional deterioration with aging. Marked with increased inflammation and fibrosis, the aged lacrimal gland is unable to perform its protective function. As a result, the ocular surface becomes highly susceptible to various ocular surface pathologies, including corneal epitheliopathy. We and others have previously shown that mast cells mediate tissue inflammation by recruiting other immune cells. However, despite their well-known characteristics of secreting various inflammatory mediators, whether mast cells contribute to the immune cell aggregation and activation, and acinar dystrophy of the aged lacrimal gland has not been investigated. Here, we demonstrate the role of mast cells in age-related lacrimal gland pathophysiology using mast cell-deficient (cKitw-sh) mice. Our data demonstrated a significant increase in mast cell frequencies and immune cell infiltration in the lacrimal gland of aged mice. Interestingly, mast cell deficiency resulted in a substantial reduction in inflammation and preservation of lacrimal gland structure, suggesting that mast cells mediate the aging process of the lacrimal gland.
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Purpose: Regulation of inflammation is critical for achieving favorable outcomes in wound healing. In this study, we determine the functional role and mechanism of action of IL-11, an immunomodulatory cytokine, in regulating inflammatory response at the ocular surface. Methods: Corneal injury was induced by mechanical removal of the epithelium and anterior stroma using an AlgerBrush II. Transcript and protein levels of IL-11 in injured cornea were quantified using real-time PCR and ELISA analysis. Corneal inflammation was assessed by measuring frequencies of total CD45+ inflammatory cells, CD11b+Ly6G+ polymorphonuclear cells (neutrophils), and CD11b+Ly6G- mononuclear cells (macrophages, monocytes) at the ocular surface using flow cytometry. To assess the effect of IL-11 on innate immune cell function, cell activation marker and inflammatory cytokines including major histocompatibility complex (MHC) class II, myeloperoxidase (MPO), TNFα, and inducible nitric oxide synthase (iNOS) were measured following recombinant IL-11 treatment (1 µg/mL). Injured corneas were topically treated with IL-11 (1 µg/mL), and wound healing was evaluated using corneal fluorescein staining. Results: Corneal injury resulted in increased levels of IL-11 in the cornea, particularly in the stroma. Neutrophils and CD11b+ mononuclear cells (macrophages, monocytes) substantially expressed IL-11 receptor. Interestingly, IL-11 significantly downregulated the activation of immune cells, as evidenced by the lower expression of MHC II and TNFα by CD11b+ mononuclear cells and lower levels of MPO by neutrophils. Topical administration of IL-11 to injured corneas led to faster wound healing and better retention of tissue architecture. Conclusions: Our findings demonstrate IL-11 is a key modulator of ocular surface inflammation and provide novel evidence of IL-11 as a potential therapeutic to control inflammatory damage and accelerate wound repair following injury.
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Lesões da Córnea , Interleucina-11 , Córnea , Lesões da Córnea/tratamento farmacológico , Citocinas , Inflamação , Fator de Necrose Tumoral alfa , Animais , CamundongosRESUMO
Progression of rheumatoid arthritis (RA) and osteoarthritis (OA) is associated with inflammation and oxidative stress. Previous studies have shown that there was no difference between RA and OA patients regarding the percentages of the different lymphocytes subsets reflecting the abnormalities in T cells and its subsets that may contribute to the pathogenesis of OA as in RA. Therefore, the present study was aimed to analyze that whether disease activity of OA is able to affect a few serological and biochemical parameters in the same way as RA does or differently. The study was done on 36 asymptomatic controls (25 women), 28 patients with OA (20 women), 36 patients with RA (22 women). Patients with OA were screened according to radiological and clinical finding of Kellgren and Lawrence grade and ACR criteria and assessed by VAS and WOMAC score. Patients with RA were selected who were fulfilling 4/5 symptoms of ACR criteria, and their DAS28-CRP, VAS score, and RF positivity were evaluated. Participants of the groups were matched for sex, age, weight, and height (body mass index). The BMI of all three groups was also found to be the same (P > 0.05). The mean level of LDL, cholesterol, MDA, CRP, and triglyceride was significantly (P < 0.05 or P < 0.01) higher in both OA and RA as compared to control. The mean level of total lipid, cholesterol, MDA, CRP, and triglyceride was found to be significantly (P < 0.05 or P < 0.01) higher in RA as compared to OA. The pre-treatment CRP level of both groups of patients showed significant and direct relation with total lipid (r = 0.27, P < 0.05) and cholesterol (r = 0.66, P < 0.01). Inverse relation was observed between uric acid and creatinine (r = -0.26, P < 0.05) and cholesterol and HDL (r = -0.34, P < 0.01). Our study shows the similar trend in lipid profile and other parameters studied in both patients with OA and patients with RA with more pronounced changes in RA.
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Artrite Reumatoide/sangue , Mediadores da Inflamação/sangue , Lipídeos/sangue , Osteoartrite/sangue , Estresse Oxidativo , Análise de Variância , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/imunologia , Biomarcadores/sangue , Proteína C-Reativa/análise , Distribuição de Qui-Quadrado , Creatinina/sangue , Feminino , Humanos , Índia , Masculino , Malondialdeído/sangue , Pessoa de Meia-Idade , Osteoartrite/diagnóstico , Osteoartrite/tratamento farmacológico , Osteoartrite/imunologia , Ácido Úrico/sangueRESUMO
INTRODUCTION: Dry eye is one of the frequently encountered ophthalmological disorders. Following the pandemic of Coronavirus disease 2019, use of masks and electronic devices has taken an upraise globally. These factors are one of the causes for dry eye disease. This study emphasises dry eye symptoms among lecturers working in medical colleges of Nepal. MATERIALS AND METHODS: This was a descriptive cross sectional study conducted among 217 lecturers working in various medical colleges in Nepal. Dry eye evaluation was done using the Ocular Surface Disease Index (OSDI) questionnaire. Analysis of data was using Microsoft Excel 2016 and IBM Statistical Package for Social Sciences (SPSS) version 26.0. RESULTS: One fourth (25.80%) of 217 participants experienced symptoms of dry eye disease. CONCLUSION: Increasing use of mask and laptop during this pandemic era has shown to cause mild dry eye symptoms in lecturers working in medical colleges of Nepal. Proper care and precaution needs to be practised in order to minimise dry eye symptoms and its consequences.
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COVID-19 , Síndromes do Olho Seco , Humanos , Estudos Transversais , SARS-CoV-2 , Nepal/epidemiologia , COVID-19/epidemiologia , Síndromes do Olho Seco/diagnóstico , Síndromes do Olho Seco/epidemiologia , Síndromes do Olho Seco/etiologia , Surtos de DoençasRESUMO
Regulation of mitochondrial calcium import is less understood in evolutionarily distinct protozoan parasites, such as Leishmania, as some of the mitochondrial calcium uniporter complex proteins are either missing or functionally diverged. Here, we show that Actin-related protein4 (ARP4), localizes exclusively into the Leishmania mitochondrion and depletion of this protein causes cells to accumulate calcium in the mitochondrion. The ARP4 depleted cells show increased activation of pyruvate dehydrogenase and production of ATP. Overall, our results indicate that ARP4 negatively regulates calcium uptake in the Leishmania mitochondrion.
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Actinas/metabolismo , Cálcio/metabolismo , Regulação da Expressão Gênica/fisiologia , Leishmania/metabolismo , Mitocôndrias/metabolismo , Actinas/genética , Animais , Anticorpos Antiprotozoários/imunologia , Mitocôndrias/genética , CoelhosRESUMO
AIMS: To report the global uptake of simple limbal epithelial transplantation (SLET) and compare the economic, clinical and social outcomes of SLET with those of cultured limbal epithelial transplantation (CLET). METHODS: A comprehensive literature review and an online survey of eye surgeons were conducted to understand the efficacy and current uptake of SLET surgery. A de novo economic model was developed to estimate the cost savings with SLET compared with CLET. Our economic analysis is conducted from an Indian perspective, as this is where the technique originated. A scenario analysis using the UK cost data and a user-friendly Excel model is included to allow users to input the costs from their setting to estimate the cost savings with using SLET compared with using CLET RESULTS: The anatomical success with SLET in adults (72.6% (range 62%-80%)) was the same as CLET (70.4% (range 68%-80.9%)). For children, the outcome for SLET (77.8% (range 73%-83%)) was better than with CLET (44.5% (range 43%-45%)). In response to our informal questionnaire, 99 surgeons reported to have performed SLET on 1174 patients in total. They appreciated that SLET negates the requirement for costly tissue engineering facilities. Results of economic analysis suggested that SLET provided an estimated cost-savings of US$6470.88 for adults and US$6673.10 for children. In broad terms, the cost of SLET is approximately 10% of the cost of CLET for adults and 8% for children. CONCLUSION: SLET offers a more accessible and financially attractive alternative to CLET to treat limbal stem cell deficiency.
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Doenças da Córnea , Epitélio Corneano , Limbo da Córnea , Doenças da Esclera , Adulto , Criança , Doenças da Córnea/cirurgia , Humanos , Limbo da Córnea/cirurgia , Mudança Social , Transplante de Células-Tronco/métodos , Transplante AutólogoRESUMO
OBJECTIVES: To explore trends in hospitalization rate, resource use, and outcomes of Kawasaki Disease (KD) in children in the United States from 2008 to 2017. METHODS: This was a retrospective, serial cross-sectional analysis of pediatric hospitalizations with International Classification of Disease diagnostic codes for KD in the National Inpatient Sample. Hospitalization rates per 100 000 populations were calculated and stratified by age group, gender, race, and US census region. Prevalence of coronary artery aneurysms (CAA) were expressed as proportions of KD hospitalizations. Resource use was defined in terms of length of stay and hospital cost. Cochran-Armitage and Jonckheere-Terpstra trend tests were used for categorical and continuous variables, respectively. P <.05 was considered significant. RESULTS: A total of 43 028 pediatric hospitalizations identified with KD, yielding an overall hospitalization rate of 5.5 per 100 000 children. The overall KD hospitalization rate remained stable over the study period (P = .18). Although KD hospitalization rates differed by age group, gender, race, and census region, a significant increase was observed among Native Americans (P = .048). Rates of CAA among KD hospitalization increased from 2.4% to 6.8% (P = .04). Length of stay remained stable at 2 to 3 days, but inflation-adjusted hospital cost increased from $6819 in 2008 to $10 061 in 2017 (Ptrend < 0.001). CONCLUSIONS: Hospitalization-associated costs and rates of CAA diagnostic codes among KD hospitalizations increased, despite a stable KD hospitalization rate between 2008 and 2017. These findings warrant further investigation and confirmation with databases with granular clinical information.
Assuntos
Síndrome de Linfonodos Mucocutâneos , Criança , Estudos Transversais , Custos Hospitalares , Hospitalização , Humanos , Tempo de Internação , Síndrome de Linfonodos Mucocutâneos/epidemiologia , Síndrome de Linfonodos Mucocutâneos/terapia , Estudos Retrospectivos , Estados Unidos/epidemiologiaRESUMO
Optical coherence tomography (OCT) is analogous to ultrasound biometry in the cross sectional imaging of ocular tissues. Development of current devices with deeper penetration and higher resolution has made it popular tool in clinics for visualization of anterior segment structures. In this review, the authors discussed the application of AS-OCT for diagnosis and management of various corneal and ocular surface disorders. Further, recent developments in the application of the device for pediatric corneal disorders and extending the application of OCT angiography for anterior segment are introduced.