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1.
J Assoc Physicians India ; 72(1): 88-95, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38736080

RESUMEN

The rapidly increasing burden of hypertension is responsible for premature deaths from cardiovascular disease (CVD), renal disease, and stroke, with a tremendous public health and financial burden. Hypertension detection, treatment, and control vary worldwide; it is still low, particularly in low- and middle-income countries (LMICs). High blood pressure (BP) and CVD risk have a strong, linear, and independent association. They contribute to alarming numbers of all-cause and CVD deaths. A major culprit for increased hypertension is sympathetic activity, and further complications of hypertension are heart failure, ischemic heart disease (IHD), stroke, and renal failure. Now, antihypertensive interventions have emerged as a global public health priority to reduce BP-related morbidity and mortality. Calcium channel blockers (CCB) are highly effective vasodilators. and the most common drugs used for managing hypertension and CVD. Cilnidipine, with both L- and N-type calcium channel blocking activity, is a promising 4th generation CCB. It causes vasodilation via L-type calcium channel blockade and inhibits the sympathetic nervous system (SNS) via N-type calcium channel blockade. Cilnidipine, which acts as a dual L/N-type CCB, is linked to a reduced occurrence of pedal edema compared to amlodipine, which solely blocks L-type calcium channels. The antihypertensive properties of cilnidipine are very substantial, with low BP variability and long-acting properties. It is beneficial for hypertensive patients to deal with morning hypertension and for patients with abnormal nocturnal BP due to exaggerated sympathetic nerve activation. Besides its BP-lowering effect, it also exhibits organ protection via sympathetic nerve inhibition and renin-angiotensin-aldosterone system inhibition; it controls heart rate and proteinuria. Reno-protective, neuroprotective, and cardioprotective effects of cilnidipine have been well-documented and demonstrated.


Asunto(s)
Bloqueadores de los Canales de Calcio , Dihidropiridinas , Hipertensión , Humanos , Hipertensión/tratamiento farmacológico , Bloqueadores de los Canales de Calcio/uso terapéutico , Dihidropiridinas/uso terapéutico , India/epidemiología , Antihipertensivos/uso terapéutico , Consenso , Comorbilidad
2.
Mol Pharm ; 20(10): 4922-4941, 2023 Oct 02.
Artículo en Inglés | MEDLINE | ID: mdl-37699355

RESUMEN

Cardiovascular diseases (CVDs) refer to a collection of conditions characterized by abnormalities in the cardiovascular system. They are a global problem and one of the leading causes of mortality and disability. Nanotheranostics implies to the combination of diagnostic and therapeutic capabilities inside a single nanoscale platform that has allowed for significant advancement in cardiovascular diagnosis and therapy. These advancements are being developed to improve imaging capabilities, introduce personalized therapies, and boost cardiovascular disease patient treatment outcomes. Significant progress has been achieved in the integration of imaging and therapeutic capabilities within nanocarriers. In the case of cardiovascular disease, nanoparticles provide targeted delivery of therapeutics, genetic material, photothermal, and imaging agents. Directing and monitoring the movement of these therapeutic nanoparticles may be done with pinpoint accuracy by using imaging modalities such as cardiovascular magnetic resonance (CMR), computed tomography (CT), positron emission tomography (PET), photoacoustic/ultrasound, and fluorescence imaging. Recently, there has been an increasing demand of noninvasive for multimodal nanotheranostic platforms. In these platforms, various imaging technologies such as optical and magnetic resonance are integrated into a single nanoparticle. This platform helps in acquiring more accurate descriptions of cardiovascular diseases and provides clues for accurate diagnosis. Advances in surface functionalization methods have strengthened the potential application of nanotheranostics in cardiovascular diagnosis and therapy. In this Review, we have covered the potential impact of nanomedicine on CVDs. Additionally, we have discussed the recently developed various nanoparticles for CVDs imaging. Moreover, advancements in the CMR, CT, PET, ultrasound, and photoacoustic imaging for the CVDs have been discussed. We have limited our discussion to nanomaterials based clinical trials for CVDs and their patents.

3.
Mol Biol Rep ; 50(5): 4105-4117, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-36877346

RESUMEN

BACKGROUND: Synonymous variations have always been ignored while studying the underlying genetic mechanisms for most of the human diseases. However, recent studies have suggested that these silent changes in the genome can alter the protein expression and folding. METHODS AND RESULTS: CSRP3, which is a well-known candidate gene associated with dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM), was screened for 100 idiopathic DCM cases and 100 controls. Three synonymous variations were identified viz., c.96G > A, p.K32=; c.336G > A, p.A112=; c.354G > A, p.E118=. A comprehensive in silico analysis was performed using various web based widely accepted tools, Mfold, Codon Usage, HSF3.1 and RNA22. Mfold predicted structural changes in all the variants except c.96 G > A (p.K32=), however it predicted changes in the stability of mRNA due to all the synonymous variants. Codon bias was observed as evident by the Relative Synonymous Codon Usage and Log Ratio of Codon Usage Frequencies. The Human Splicing Finder also predicted remarkable changes in the regulatory elements in the variants c.336G > A and c.354 G > A. The miRNA target prediction using varied modes available in RNA22 revealed that 70.6% of the target sites of miRNAs in CSRP3 were altered due to variant c.336G > A while 29.41% sites were completely lost. CONCLUSION: Findings of the present study suggest that synonymous variants revealed striking deviations in the structural conformation of mRNA, stability of mRNA, relative synonymous codon usage, splicing and miRNA binding sites from the wild type suggesting their possible role in the pathogenesis of DCM, either by destabilizing the mRNA structure, or codon usage bias or else altering the cis-acting regulatory elements during splicing.


Asunto(s)
Cardiomiopatía Dilatada , Proteínas con Dominio LIM , Humanos , Cardiomiopatía Dilatada/genética , Codón , Uso de Codones , MicroARNs/genética , ARN Mensajero/genética , ARN Mensajero/metabolismo , Proteínas con Dominio LIM/genética
4.
J Assoc Physicians India ; 71(2): 11-12, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37354473

RESUMEN

;Heart failure (HF) is a huge global public health task due to morbidity, mortality, disturbed quality of life, and major economic burden. It is an area of active research and newer treatment strategies are evolving. Recently angiotensin receptor-neprilysin inhibitor (ARNI), a class of drugs (the first agent in this class, Sacubitril-Valsartan), reduces cardiovascular mortality and morbidity in chronic HF patients with reduced left ventricular ejection fraction (LVEF). Positive therapeutic effects have led to a decrease in cardiovascular mortality and HF hospitalizations (HFH), with a favorable safety profile, and have been documented in several clinical studies with an unquestionable survival benefit with ARNI, Sacubitril-Valsartan. This consensus statement of the Indian group of experts in cardiology, nephrology, and diabetes provides a comprehensive review of the power and promise of ARNI in HF management and an evidence-based appraisal of the use of ARNI as an essential treatment strategy for HF patients in clinical practice. Consensus in this review favors an early utility of Sacubitril-Valsartan in patients with HF with reduced EF (HFrEF), regardless of the previous therapy being given. A lower rate of hospitalizations for HF with Sacubitril-Valsartan in HF patients with preserved EF who are phenotypically heterogeneous suggests possible benefits of ARNI in patients having 40-50% of LVEF, frequent subtle systolic dysfunction, and higher hospitalization risk.


Asunto(s)
Insuficiencia Cardíaca , Humanos , Insuficiencia Cardíaca/tratamiento farmacológico , Neprilisina/farmacología , Volumen Sistólico/fisiología , Tetrazoles/uso terapéutico , Tetrazoles/farmacología , Calidad de Vida , Función Ventricular Izquierda , Antagonistas de Receptores de Angiotensina/uso terapéutico , Antagonistas de Receptores de Angiotensina/farmacología , Resultado del Tratamiento , Antihipertensivos/uso terapéutico , Combinación de Medicamentos
5.
Exp Cell Res ; 409(1): 112869, 2021 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-34666056

RESUMEN

NODAL signaling plays an essential role in vertebrate embryonic patterning and heart development. Accumulating evidences suggest that genetic mutations in TGF-ß/NODAL signaling pathway can cause congenital heart disease in humans. To investigate the implication of NODAL signaling in isolated cardiovascular malformation, we have screened 300 non-syndromic CHD cases and 200 controls for NODAL and ACVR1B by Sanger sequencing and identified two rare missense (c.152C > T; p.P51L and c.981 T > A; p.D327E) variants in NODAL and a novel missense variant c.1035G > A; p.M345I in ACVR1B. All these variants are absent in 200 controls. Three-dimensional protein-modelling demonstrates that both p.P51L and p.D327E variations of NODAL and p.M345I mutation of ACVR1B, affect the tertiary structure of respective proteins. Variants of NODAL (p.P51L and p.D327E) and ACVR1B (p.M345I), significantly reduce the transactivation of AR3-Luc, (CAGA)12-Luc and (SBE)4-Luc promoters. Moreover, qRT-PCR results have also deciphered a reduction in the expression of cardiac-enriched transcription factors namely Gata4, Nkx2-5, and Tbx5 in both the mutants of NODAL. Decreased expression of, Gata4, Nkx2-5, Tbx5, and lefty is observed in p.M345I mutant of ACVR1B as well. Additionally, reduced phosphorylation of SMAD2/3 in response to these variants, suggests impaired NODAL signaling and possibly responsible for defective cell fate decision and differentiation of cardiomyocytes leading to CHD phenotype.


Asunto(s)
Receptores de Activinas Tipo I/genética , Pueblo Asiatico/genética , Predisposición Genética a la Enfermedad/genética , Cardiopatías Congénitas/genética , Proteína Nodal/genética , Polimorfismo de Nucleótido Simple/genética , Adulto , Secuencia de Aminoácidos , Animales , Línea Celular , Femenino , Humanos , India , Masculino , Ratones
6.
World J Microbiol Biotechnol ; 38(7): 122, 2022 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-35637362

RESUMEN

Isoprene, a volatile C5 hydrocarbon, is a precursor of synthetic rubber and an important building block for a variety of natural products, solely being produced by petrochemical routes. To mitigate the ever-increasing contribution of petrochemical industry to global warming through significant carbon (CO2) evolution, bio-based process for isoprene production using microbial cell factories have been explored. Highly efficient fermentation-based processes have been studied for little over a decade now with extensive research on the rational strain development for creating robust strains for commercial isoprene production. Most of these studies involved sugars as feedstocks and using naturally occurring isoprene pathways viz., mevalonate and methyl erythritol pathway in E. coli. Recent advances, driven by efforts in reducing environmental pollution, have focused on utilization of inorganic CO2 by cyanobacteria or syngas from waste gases by acetogens for isoprene production. This review endeavors to capture the latest relevant progress made in rational strain development, metabolic engineering and synthetic biology strategies used, challenges in fermentation process development at lab and commercial scale production of isoprene along with a future perspective pertaining to this area of research.


Asunto(s)
Dióxido de Carbono , Escherichia coli , Butadienos/metabolismo , Dióxido de Carbono/metabolismo , Escherichia coli/metabolismo , Hemiterpenos/metabolismo
7.
Am J Transplant ; 20(10): 2675-2685, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32243663

RESUMEN

Active antibody-mediated rejection (AMR) is a potentially devastating complication and consistently effective treatment remains elusive. We hypothesized that the reversal of acute AMR requires rapid elimination of antibody-secreting plasma cells (PC) with a proteasome inhibitor, bortezomib, followed by the sustained inhibition of PC generation with CTLA4-Ig or belatacept (B/B). We show in mice that B/B therapy selectively depleted mature PC producing donor-specific antibodies (DSA) and reduced DSA, when administered after primary and secondary DSA responses had been established. A pilot investigation was initiated to treat six consecutive patients with active AMR with B/B. Compassionate use of this regimen was initiated for the first patient who developed early, severe acute AMR that did not respond to steroids, plasmapheresis, and intravenous immunoglobulin after his third kidney transplant. B/B treatment resulted in a rapid reversal of AMR, leading us to treat five additional patients who also resolved their acute AMR episode and had sustained disappearance of circulating DSA for ≤30 months. This study provides a proof-of-principle demonstration that mouse models can identify mechanistically rational therapies for the clinic. Follow-up investigations with a more stringent clinical design are warranted to test whether B/B improves on the standard of care for the treatment of acute AMR.


Asunto(s)
Trasplante de Riñón , Abatacept/uso terapéutico , Animales , Formación de Anticuerpos , Bortezomib/uso terapéutico , Rechazo de Injerto/tratamiento farmacológico , Rechazo de Injerto/prevención & control , Humanos , Isoanticuerpos , Ratones
8.
J Clin Lab Anal ; 32(2)2018 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-28444979

RESUMEN

BACKGROUND: Bead based flow cytometry and Luminex play a major role in identification of alloantibodies in renal transplant work-up. Strong sensitization events may lead to prozone phenomenon that can affect single antigen bead (SAB) assay and result in false negativity. However, this can also be due to high titer of other blocking antibodies. While methods like, heat inactivation, C1 inhibitor, Ethylene diamine tetra-acetic-acid and Dithio threitol treatment can remove interfering antibodies of complement and IgM, these methods are not optimal if false negativity is due to prozone effect, which is high titer of antibodies alone. METHODS: We hereby present a case of a highly sensitized renal transplant recipient with 64% panel reactive antibody positivity (PRA) and a subsequent negative SAB assay. This paradoxical finding hinted at SAB being a false negative result and serial dilutions were used to perform further tests. RESULTS: Serum dilutions lead to positive flow based panel reactive antibody (PRA) and flow cytometry crossmatch (FCXM), with an increasing trend in FCXM. CONCLUSIONS: In highly sensitized patients serial dilution should be considered during a transplant work-up to avoid missing any underlying antibodies. Serum dilution can be used as first option to circumvent prozone. Also, interference of other antibodies should not be labeled as prozone effect.


Asunto(s)
Antígenos HLA , Prueba de Histocompatibilidad , Adulto , Reacciones Falso Negativas , Citometría de Flujo , Antígenos HLA/sangre , Antígenos HLA/clasificación , Antígenos HLA/inmunología , Prueba de Histocompatibilidad/métodos , Prueba de Histocompatibilidad/normas , Humanos , Isoanticuerpos/sangre , Trasplante de Riñón , Masculino
9.
J Med Syst ; 40(1): 14, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26573651

RESUMEN

The revolution of internet and specifically mobile internet has occurred at a blinding pace over the last decade. With the advent of smart phones, the hand held device has become much more than a medium of voice calling. Healthcare has been catching up with the digital revolution in the form of Hospital Information System and Laboratory Information System. However, the advent of instant messaging services, which are abundantly used by the youth, can be used to improve communication and coordination among the various stake holders in the healthcare sector. We have tried to look at the impact of using the WhatsApp messenger service in the laboratory management system, by forming multiple groups of the various subsections of the laboratory. A total of 35 members used this service for a period of 3 months and their response was taken on a scale of 1 to 10. There was significant improvement in the communication in the form of sharing photographic evidence, information about accidents, critical alerts, duty rosters, academic activities and getting directives from seniors. There was also some increase in the load of adding information to the application and disturbance in the routine activities; but the benefits far outweighed the minor hassles. We thereby suggest and foresee another communication revolution which will change the way information is shared in a healthcare sector, with hospital specific dedicated apps.


Asunto(s)
Comunicación , Laboratorios de Hospital/organización & administración , Aplicaciones Móviles , Teléfono Inteligente , Envío de Mensajes de Texto , Confidencialidad , Humanos , Internet , Relaciones Interpersonales , Carga de Trabajo
10.
Acta Cytol ; 58(3): 309-17, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24685599

RESUMEN

BACKGROUND: Plasmablastic lymphoma (PL) is a relatively new category of lymphoma, which has been considered to be found predominantly in the oral cavity and has a strong association with HIV. CASE: We report a case of extraoral/mesenteric PL detected using cytological examination of ascitic fluid assisted by flow cytometric (FC) analysis. The cells were positive for CD38, CD138, CD10, CD45 and CD56 and negative for CD3, CD19, CD20 and CD79a, with cytoplasmic lambda light-chain restriction. We also reviewed 67 cases of extraoral PL from the available literature and found them to be less often associated with HIV (than oral PL), occurring mostly in males aged 30-60 years, with the most common extraoral site being the anorectal region. CONCLUSION: A high index of suspicion at the level of the cytopathologist is imperative for identifying lymphoma cells in a body fluid. A rare entity like PL can also be diagnosed on cytology assisted by ancillary techniques (like FC), without the need for a biopsy. We also suggest that the minimum panel to diagnose PLs should include CD138, MUM-1, Ki-67, ALK-1, CD3, immunoglobulin light-chains, CD20 and PAX5.


Asunto(s)
Líquido Ascítico/patología , Citodiagnóstico/métodos , Citometría de Flujo/métodos , Linfoma Inmunoblástico de Células Grandes/diagnóstico , Anciano , Humanos , Masculino
11.
Drug Dev Ind Pharm ; 40(12): 1576-84, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-25109399

RESUMEN

Alginates are natural polymers widely used in the food industry because of their biocompatible, biodegradable character, nontoxicity and easy availability. The bioadhesive character of alginates makes them useful in the pharmaceutical industry as well. The application areas of sodium alginate-based drug delivery systems are many and these systems can be formulated as gels, matrices, membranes, nanospheres, microspheres, etc. Worldwide researchers are exploring possible applications of alginates as coating material, preparation of controlled-release drug delivery systems such as microspheres, beads, pellets, gels, fibers, membranes, etc. In the present review, such applications of alginates are discussed.


Asunto(s)
Alginatos/química , Investigación Biomédica/métodos , Química Farmacéutica/métodos , Sistemas de Liberación de Medicamentos/métodos , Alginatos/administración & dosificación , Animales , Investigación Biomédica/tendencias , Química Farmacéutica/tendencias , Portadores de Fármacos/administración & dosificación , Portadores de Fármacos/química , Sistemas de Liberación de Medicamentos/tendencias , Ácido Glucurónico/administración & dosificación , Ácido Glucurónico/química , Ácidos Hexurónicos/administración & dosificación , Ácidos Hexurónicos/química , Humanos , Microesferas
12.
Angiology ; : 33197231225286, 2024 Jan 02.
Artículo en Inglés | MEDLINE | ID: mdl-38166442

RESUMEN

To evaluate deep learning-based calcium segmentation and quantification on ECG-gated cardiac CT scans compared with manual evaluation. Automated calcium quantification was performed using a neural network based on mask regions with convolutional neural networks (R-CNNs) for multi-organ segmentation. Manual evaluation of calcium was carried out using proprietary software. This is a retrospective study of archived data. This study used 40 patients to train the segmentation model and 110 patients were used for the validation of the algorithm. The Pearson correlation coefficient between the reference actual and the computed predictive scores shows high level of correlation (0.84; P < .001) and high limits of agreement (±1.96 SD; -2000, 2000) in Bland-Altman plot analysis. The proposed method correctly classifies the risk group in 75.2% and classifies the subjects in the same group. In total, 81% of the predictive scores lie in the same categories and only seven patients out of 110 were more than one category off. For the presence/absence of coronary artery calcifications, the deep learning model achieved a sensitivity of 90% and a specificity of 94%. Fully automated model shows good correlation compared with reference standards. Automating process reduces evaluation time and optimizes clinical calcium scoring without additional resources.

13.
Indian Heart J ; 65(1): 84-7, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23438619

RESUMEN

A 35-year-old man presented with dilated cardiomyopathy, an unusual association with tuberous sclerosis. Clinical history and examination were consistent with tuberous sclerosis including major features of tuberous sclerosis complex (TSC) like facial angiofibroma, shagreen patch, subependymal nodules, and angiomyolipoma of kidney. The clinical manifestations, pathogenesis and evaluation of tuberous sclerosis are discussed.


Asunto(s)
Cardiomiopatía Dilatada/complicaciones , Cardiomiopatía Dilatada/diagnóstico , Esclerosis Tuberosa/complicaciones , Esclerosis Tuberosa/diagnóstico , Adulto , Diagnóstico Diferencial , Ecocardiografía , Humanos , Imagen por Resonancia Magnética , Masculino , Radiografía Torácica
14.
J Appl Lab Med ; 8(6): 1054-1064, 2023 11 02.
Artículo en Inglés | MEDLINE | ID: mdl-37658801

RESUMEN

BACKGROUND: Adalimumab is a fully human monoclonal antibody developed against tumor necrosis factor (TNF), used for the treatment of autoimmune and chronic inflammatory diseases. Immunogenicity to this drug may lead to therapeutic failure. Various laboratory assays are used for measuring serum adalimumab and anti-drug antibodies (ADA) to adalimumab, for therapeutic monitoring and evaluation of clinical non-responsiveness. This study compared the performance of 2 clinical assays used by different reference laboratories. METHODS: In total, 120 residual clinical samples were tested at both laboratories. A sandwich ELISA for adalimumab detecting free drug and a bridging ELISA capable of detecting both free and bound ADA were performed at the Mayo Clinic. A functional cell-based reporter gene assay (RGA) was used at ARUP Laboratories for measuring bioactive serum drug concentrations, and neutralizing ADA. RESULTS: Seventy-eight samples had measurable concentrations of adalimumab by both methods and yielded a correlation coefficient r = 0.93, slope = 0.886, and intercept = 0.950. Overall agreement of 92.5% was observed between the assays, with most discrepant drug results being attributed to a higher positivity rate with ELISA (8/9). One outlier positive with RGA and negative with ELISA was confirmed by LC-MS/MS to be attributed to infliximab. Overall agreement of 79.2% was observed between the ADA assays. Differences in ADA results may be due to the bridging ELISA detecting total ADA (free, drug-bound, neutralizing, and non-neutralizing), while RGA detects free, neutralizing ADA only. CONCLUSIONS: Although the assays are fundamentally different, the results show significant concordance between the clinically validated tests performed in different laboratories.


Asunto(s)
Laboratorios Clínicos , Espectrometría de Masas en Tándem , Humanos , Adalimumab/uso terapéutico , Cromatografía Liquida , Anticuerpos Monoclonales
15.
Mini Rev Med Chem ; 23(21): 2053-2072, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36809967

RESUMEN

Nanogels have gotten much attention as nanoscopic drug carriers, especially for delivering bioactive mediators to specific sites or at certain times. The versatility of polymer systems and the ease with which their physicochemical properties can be changed have resulted in versatile nano gel formulations. Nanogels offer exceptional stability, drug-loading capacity, biological consistency, strong penetration ability, and the ability to respond to environmental stimuli. Nanogels have shown great promise in various sectors, including gene delivery, chemotherapeutic medication delivery, diagnostics, organ targeting, and many more. This review focuses on various types of nanogels, preparation methods, including drug loading methods, various modes of biodegradation mechanisms, and primary mechanisms of drug release from nanogels. The article also focuses on the historical data for herb-related nanogels that are used to treat various disorders with great patient compliance, delivery rate, and efficacy.

16.
Transplantation ; 107(12): 2526-2532, 2023 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-37493609

RESUMEN

BACKGROUND: Although donor-specific antibody pre- and posttransplantation is routinely assessed, accurate quantification of memory alloreactive B cells that mediate recall antibody response remains challenging. Major histocompatibility complex (MHC) tetramers have been used to identify alloreactive B cells in mice and humans, but the specificity of this approach has not been rigorously assessed. METHODS: B-cell receptors from MHC tetramer-binding single B cells were expressed as mouse recombinant immunoglobulin G1 (rIgG1) monoclonal antibodies, and the specificity was assessed with a multiplex bead assay. Relative binding avidity of rIgG1 was measured by modified dilution series technique and surface plasmon resonance. Additionally, immunoglobulin heavy chain variable regions of 50 individual B-cell receptors were sequenced to analyze the rate of somatic hypermutation. RESULTS: The multiplex bead assay confirmed that expressed rIgG1 monoclonal antibodies were preferentially bound to bait MHC class II I-E d over control I-A d and I-A b tetramers. Furthermore, the dissociation constant 50 binding avidities of the rIgG1 ranged from 10 mM to 7 nM. The majority of tetramer-binding B cells were low avidity, and ~12.8% to 15.2% from naive and tolerant mice and 30.9% from acute rejecting mice were higher avidity (dissociation constant 50 <1 mM). CONCLUSIONS: Collectively, these studies demonstrate that donor MHC tetramers, under stringent binding conditions with decoy self-MHC tetramers, can specifically identify a broad repertoire of donor-specific B cells under conditions of rejection and tolerance.


Asunto(s)
Complejo Mayor de Histocompatibilidad , Tolerancia al Trasplante , Humanos , Ratones , Animales , Antígenos de Histocompatibilidad Clase II , Inmunoglobulina G , Anticuerpos Monoclonales , Receptores de Antígenos de Linfocitos B
17.
J Clin Lab Anal ; 26(6): 452-8, 2012 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-23143628

RESUMEN

BACKGROUND: Management of aplastic anemia is etiology driven, whether constitutional or acquired. Age, gender, and severity of disease also play crucial role in the survival of aplastic anemia. Since, inadequate data are available from India, the present study was conducted with the aim to evaluate the etiology and survival of aplastic anemia. METHODS: Three hundred patients were enrolled between May 2007 and April 2010. Severity analysis and chromosomal breakage study was performed and patients were followed up to calculate the survival rate. RESULTS: Only 9.4% of the cases demonstrated the evidence of constitutional disease. Patients with acquired disease showed a significantly higher odd ratio for hepatitis. Overall survival was found to be independent of the gender and inherited etiology. Phenotype resembling to constitutional disease was present in only 22.22% (6/27) of patients. Similar ratio of the constitutional and acquired disease in both the age groups was observed. CONCLUSION: Irrespective of the age and phenotype, chromosomal breakage study should be mandatory for all patients with aplastic anemia. Hepatitis as a preceding event may be associated with the cause of aplastic anemia. Young age and less severe disease were strongly associated with better survival. Lack of tertiary care facility in the country, time lag between diagnosis and treatment, and unaffordability to abide the treatment cost could be the major contributory factors for poorer survival.


Asunto(s)
Anemia Aplásica/etiología , Adolescente , Adulto , Anemia Aplásica/genética , Anemia Aplásica/microbiología , Anemia Aplásica/terapia , Niño , Preescolar , Rotura Cromosómica , Enfermedades Transmisibles/sangre , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Fenotipo , Análisis de Supervivencia
18.
Indian Heart J ; 64(1): 95-8, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22572437

RESUMEN

Holt-Oram syndrome (HOS) is characterised by mild to severe congenital cardiac defects and skeletal abnormalities of the upper limb. This syndrome is also referred to as Hand-Heart syndrome. The most common cardiac disorder is an ostium secundum detected an atrial septal defect (ASD), followed by ventricular septal defect (VSD) and ostium primum ASD. We report a case of HOS with tetralogy of Fallot (TOF). This association is very rare and is hardly reported in the literature.


Asunto(s)
Cardiopatías Congénitas/complicaciones , Defectos del Tabique Interatrial/complicaciones , Deformidades Congénitas de las Extremidades Inferiores/complicaciones , Tetralogía de Fallot/complicaciones , Deformidades Congénitas de las Extremidades Superiores/complicaciones , Anomalías Múltiples/diagnóstico , Preescolar , Ecocardiografía Doppler , Electrocardiografía , Femenino , Cardiopatías Congénitas/diagnóstico , Defectos del Tabique Interatrial/diagnóstico , Humanos , Deformidades Congénitas de las Extremidades Inferiores/diagnóstico , Tetralogía de Fallot/diagnóstico , Deformidades Congénitas de las Extremidades Superiores/diagnóstico
19.
Reumatol Clin (Engl Ed) ; 18(1): 15-19, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-35090607

RESUMEN

INTRODUCTION: Anti-neutrophil cytoplasmic autoantibodies (ANCA) associated vasculitis (AAV) is a small vessel vasculitis with insufficient epidemiological estimates in India. We aimed to determine demographic, clinical features, and laboratory diagnosis of AAV patients presenting to a large tertiary care centre in India. MATERIAL AND METHODS: 1289 patient samples were screened for ANCA by indirect immunofluorescence test (IIFT) and confirmation of ANCA target antigens was done by line immunoassay. Association between IIFT and LIA was determined in AAV. RESULTS: By IIFT, ANCA was detected in 13.0% (168 out of 1289), of which 23.8% (40/168) were positive with P-ANCA pattern, 25.0% (42/168) were positive with C-ANCA and 47.6% (80/168) showed an atypical pattern. On evaluation with a line immunoassay, 6.7% (86/1289) were positive out of which 52.3% (45/86), 41.9% (36/86), 8.8% (6/86) were positive for anti-MPO, anti-PR3, and anti-GBM respectively. In eosinophilic granulomatosis with polyangiitis (EGPA) 87.5% (7/8), and microscopic polyangiitis (MPA/RLV) 91.3% (21/23), anti-MPO was the predominantly observed antibody. In granulomatosis with polyangiitis (GPA) anti-PR3 antibody was predominant in 87.5% (28/32) cases. Out of 168 IIF positive samples 8, 32, and 23 cases of EGPA, GPA, and MPA/RLV were observed respectively. CONCLUSIONS: The primary aim of the study was to provide single-centre data to determine the laboratory diagnosis of AAV. A combination of IIFT and LIA was found to be an optimum testing strategy for the laboratory diagnosis of AAV.


Asunto(s)
Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos , Síndrome de Churg-Strauss , Granulomatosis con Poliangitis , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/diagnóstico , Técnicas de Laboratorio Clínico , Técnica del Anticuerpo Fluorescente , Granulomatosis con Poliangitis/diagnóstico , Humanos , Inmunoensayo
20.
Colloids Surf B Biointerfaces ; 218: 112697, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35917688

RESUMEN

Abciximab (ABX) is a chimeric monoclonal antibody reported for antithrombotic activity but their delivery remains challenging due to its poor stability in a biological system. The purpose of this research was to deliver ABX on the target efficiently using mesoporous silica nanoparticles (MSN). ABX coated mesoporous silica nanoparticles (MSN-ABX) were formulated and analyzed for particle size, shape, zeta-potential, surface morphology and surface chemistry. XPS analysis confirmed the presence of ABX on the surface of amino functionalized mesoporous silica nanoparticles (MSN-NH2). The degree of ABX attachment was 67.53 ± 5.81 % which was demonstrated by the Bradford assay. Furthermore, the targeting efficiency of the targeted nanoparticles has been evaluated by capturing the fluorescent images in-vitro which showed the significant accumulation of the ABX coated nanoparticles towards activated platelets. The significant (P < 0.05) increase in affinity of DiD dye loaded nanoparticles towards the activated platelets was confirmed by using an in-vitro imaging through photon imager optima. The hemolysis study of the nanoparticle formulations revealed that they were non-hemolytic for healthy human blood. The in-vitro antithrombotic effects of MSN-ABX were observed by blood clot assay which revealed its superior antithrombotic activity over clinical injection of ABX and could be a promising carrier for improved ABX targeted delivery.


Asunto(s)
Nanopartículas , Dióxido de Silicio , Abciximab , Doxorrubicina/farmacología , Portadores de Fármacos , Sistemas de Liberación de Medicamentos/métodos , Fibrinolíticos/farmacología , Humanos , Porosidad
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