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The excessive production of IL-10, an anti-inflammatory cytokine, by Leishmania antigen-activated T cells is supposed to be a key player in the onset and progression of visceral leishmaniasis (VL). The IL-10-producing sources in VL remain unidentified and uncharacterized. In this study, we reveal that antigen-activated CD4+ T cells, i.e., CD44+CD4+ T cells expressing CD200R receptors, are the prime IL-10-producing phenotypes in Leishmania donovani infection-induced pathogenesis. These phenotypes are separate from CD25+Foxp3+CD4+ T regulatory cells, which are classical IL-10-producing phenotypes. In order to ascertain the role of CD200R and CD25 receptors in IL-10 overexpression-associated VL pathogenesis, we abrogated CD200R and CD25 receptor-mediated signaling in the infected mice. The splenic load of parasites and the size of the liver and spleen were significantly reduced in CD200-blocked mice as compared to CD25-blocked mice. Further, the CD200 blocking polarized CD4+ T cells to pro-inflammatory cytokines-producing phenotypes, as we observed a higher frequency of IFN-γ, TNF-α, and IL-12 positive cells as compared to controls including the CD25 blocking. Our findings suggest that in L. donovani infection-induced pathogenesis the expression of CD200R on antigen-activated T cells helps them to acquire IL-10-producing abilities as part of its one of the survival strategies. However, more studies would be warranted to better understand CD200R receptors role in VL pathogenesis and to develop the next generation of therapeutic and prophylactic control measures.
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Leishmania donovani , Leishmaniasis Visceral , Animales , Ratones , Interleucina-10/metabolismo , Citocinas/metabolismo , Linfocitos T Reguladores , FenotipoRESUMEN
Herein, we have developed a base mediated, transition metal-free intermolecular epoxide ring opening by the nucleophilic attack of ortho-halogenated NH-sulfoximine followed by intramolecular aromatic nucleophilic substitution (SNAr) for the synthesis of separable diastereomers of selected benzo[b][1,4,5]oxathiazepine 1-oxides. Both C-N and C-O bonds are formed simultaneously in a single step. This strategy has a good substrate scope and requires simple reaction conditions (room temperature) and cost-effective reagents, and shows good applicability for accessing sulfoximine analogues of benzoxathiazepine 1-oxide like bioactive skeletons. The absolute configurations of the separable major isomer 4z (R,R), minor isomer 4z' (R,S) and single isomer 4r (R,R,S) were confirmed by 2D NMR. On the other hand, the relative configuration of 4q (S,R) was assigned by 2D NMR along with X-ray crystal data analysis.
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Óxidos , Elementos de Transición , Compuestos Epoxi , Indicadores y ReactivosRESUMEN
The Stanford Integrated Psychosocial Assessment for Transplant (SIPAT) is a standardized psychosocial evaluation tool used in liver transplantation (LT) evaluation. We assessed the impact of the SIPAT score and subdomains on transplant waitlisting decisions and post-LT outcomes including immunosuppression (IS) nonadherence, biopsy-proven rejection, andmortality/graft failure. We conducted a single-center observational cohort study of 1430 patients evaluated for LT. Patients were divided in 2 groups based on a SIPAT cutoff score of <21 or ≥21 (higher SIPAT scores indicate higher psychosocial risk). Regression models assessed relationships between total SIPAT score and domain scores and waitlisting decisions, IS nonadherence, allograft rejection, and death/graft failure. Elevated total SIPAT and SIPAT domain scores were associated not being added to the waitlist (total SIPAT core ≥21 adjusted odds ratio [aOR], 1.78 [95% confidence interval, CI, 1.36-2.33]; readiness score ≥5 aOR, 2.01 [95% CI, 1.36-2.76]; social support score ≥4aOR, 1.50 [95% CI, 1.15-1.94]; psychopathology score ≥7 aOR, 1.45 [95% CI, 1.07-1.94]; lifestyle/substance abuse score ≥12 aOR, 1.72 [95%CI, 1.23-2.39]) and were more likely to experience IS nonadherence as measured by the tacrolimus coefficient of variation (CoV) (total SIPAT score ≥21 aOR, 2.92 [95% CI, 1.69-5.03]; readiness score ≥5 aOR, 3.26 [95% CI, 1.63-6.52]; psychopathology score ≥7 aOR, 1.88 [95% CI, 1.00-3.50]; lifestyle substance abuse score ≥12 aOR, 3.03 [95% CI, 1.56-5.86]). SIPAT readinessscore ≥5 was associated with biopsy-proven allograft rejection (aOR, 2.66; 95% CI, 1.20-5.91). The SIPAT score was independently associated with LT listing decisions and IS nonadherence, and the readiness domain was associated with the risk of allograft rejection. These findings offer insights into higher risk recipients who require additional support before and aftertransplantation.
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Trasplante de Corazón , Trasplante de Hígado , Rechazo de Injerto/diagnóstico , Rechazo de Injerto/epidemiología , Humanos , Trasplante de Hígado/efectos adversos , Estudios Retrospectivos , Apoyo SocialRESUMEN
The residing microbiome with its vast repertoire of genes provide distinctive properties to the host by which they can degrade and utilise nutrients that otherwise pass the gastro-intestinal tract unchanged. The polyphenols in our diet have selective growth promoting effects which is of utmost importance as the state of good health has been linked to dominance of particular microbial genera. The polyphenols in native form might more skilfully exert anti-oxidative and anti-inflammatory properties but in a living system it is the microbial derivatives of polyphenol that play a key role in determining health outcome. This two way interaction has invoked great interest among researchers who have commenced several clinical surveys and numerous studies in in-vitro, simulated environment and living systems to find out in detail about the biomolecules involved in such interaction along with their subsequent physiological benefits. In this review, we have thoroughly discussed these studies to develop a fair idea on how the amalgamation of probiotics and polyphenol has an immense potential as an adjuvant therapeutic for disease prevention as well as treatment.
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Nutrición, Alimentación y Dieta , Promoción de la Salud , Polifenoles , Probióticos , Microbioma Gastrointestinal , Tracto Gastrointestinal/microbiologíaRESUMEN
Antigenic inefficacy to induce robust immune responses and durable memory are major causes of constantly failing prophylactic approaches in leishmaniasis. Here, we determine the potential of a standardized whole-killed Leishmania vaccine (Leishvacc) adjuvanted with anti-CD200 and anti-CD300a antibodies, either alone or with monophosphoryl lipid A (MPL-SE) emulsified in squalene oil, in restoring the compromised antigen presenting abilities of dendritic cells (DCs), effector properties of CD4+T cells and providing protection against Leishmania donovani parasites. In animals vaccinated with antibodies adjuvanted vaccines, either alone or with MPL-SE, the antigen presenting abilities of CD11c+ DCs against Leishmania antigens, measured in terms of CD80, CD86, MHC-I, and MHC-II surface receptors and intracellular IL-12 were found enhanced than non-adjuvanted vaccine. We observed more proliferative and pro-inflammatory cytokines i.e. IL-2, IFN-γ, IL-23, and IL-12 producing CD4+T cells in antibodies/MPL-SE adjuvanted vaccinated animals further suggesting that this approach helps antigen activated CD4+T cells to acquire pro-inflammatory cytokines producing abilities. In antibodies, either alone or with MPL-SE, vaccinated animals, the number of CD4+ central memory T cells and their longevity were found significantly enhanced that further evidenced the impact of this vaccination approach in inducing long term protective immunity. The animals, receiving antibodies adjuvanted vaccines, either alone or with MPL-SE, exhibited excellent protection against virulent parasites by restricting their growth, which correlated with the significantly reduced parasitemia, splenomegaly, and hepatomegaly, along with fewer numbers of liver granulomas. Our findings provide an insight to a new immunoprophylactic approach against visceral leishmaniasis, which not only satisfies the safety criteria, but also provides a robust immunogenic response with remarkable potential for parasites control. However, further in-depth investigations are needed to ascertain its ability in inducing long-lasting immunity.
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INTRODUCTION: Intravesical drug delivery (IDD) has gained recognition as a viable approach for treating bladder-related diseases over the years. However, it comes with its set of challenges, including voiding difficulties and limitations in mucosal and epithelial penetration. These challenges lead to drug dilution and clearance, resulting in poor efficacy. Various strategies for drug delivery have been devised to overcome these issues, all aimed at optimizing drug delivery. Nevertheless, there has been minimal translation to clinical settings. AREAS COVERED: This review provides a detailed description of IDD, including its history, advantages, and challenges. It also explores the physical barriers encountered in IDD, such as voiding, mucosal penetration, and epithelial penetration, and discusses current strategies for overcoming these challenges. Additionally, it offers a comprehensive roadmap for advancing IDD into clinical trials. EXPERT OPINION: Physical bladder barriers and limitations of conventional treatments result in unsatisfactory efficacy against bladder diseases. Nevertheless, substantial recent efforts in this field have led to significant progress in overcoming these challenges and have raised important attributes for an optimal IDD system. However, there is still a lack of well-defined steps in the workflow to optimize the IDD system for clinical settings, and further research is required to establish more comprehensive in vitro and in vivo models to expedite clinical translation.
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Sistemas de Liberación de Medicamentos , Vejiga Urinaria , Administración Intravesical , Preparaciones FarmacéuticasRESUMEN
A young male presented with clinical and radiological features of right apical lung mass and Horner's syndrome. Subsequently the patient was diagnosed as a case of malignant peripheral nerve sheath tumour (MPNST) at the apex of right lung originating from an intercostal nerve and compressing ipsilateral cervical sympathetic plexus and lower cord of brachial plexus, in a case of neurofibromatosis type 1.
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Neuropatías del Plexo Braquial/diagnóstico , Neuropatías del Plexo Braquial/etiología , Síndrome de Horner/complicaciones , Síndrome de Horner/diagnóstico , Neoplasias de la Vaina del Nervio/complicaciones , Neoplasias de la Vaina del Nervio/diagnóstico , Neoplasias del Sistema Nervioso Periférico/complicaciones , Neoplasias del Sistema Nervioso Periférico/diagnóstico , Adulto , Neuropatías del Plexo Braquial/terapia , Terapia Combinada , Diagnóstico Diferencial , Síndrome de Horner/terapia , Humanos , Masculino , Neoplasias de la Vaina del Nervio/terapia , Neoplasias del Sistema Nervioso Periférico/terapiaRESUMEN
BACKGROUND AND AIMS: Liver transplantation is a life-saving procedure for end-stage liver disease. However, post-transplant medication regimens are complex and non-adherence is common. Post-transplant medication non-adherence is associated with graft rejection, which can have long-term adverse consequences. Transplant centres are equipped with clinical staff that monitor patients post-transplant; however, digital health tools and proactive immunosuppression adherence monitoring has potential to improve outcomes. METHODS AND ANALYSIS: This is a patient-randomised prospective clinical trial at three transplant centres in the Northeast, Midwest and South to investigate the effects of a remotely administered adherence programme compared with usual care. The programme monitors potential non-adherence largely levering text message prompts and phenotypes the nature of the non-adhere as cognitive, psychological, medical, social or economic. Additional reminders for medications, clinical appointments and routine self-management support are incorporated to promote adherence to the entire medical regimen. The primary study outcome is medication adherence via 24-hour recall; secondary outcomes include additional medication adherence (ASK-12 self-reported scale, regimen knowledge scales, tacrolimus values), quality of life, functional health status and clinical outcomes (eg, days hospitalised). Study implementation, acceptability, feasibility, costs and potential cost-effectiveness will also be evaluated. ETHICS AND DISSEMINATION: The University of Pennsylvania Review Board has approved the study as the single IRB of record (protocol # 849575, V.1.4). Results will be published in peer-reviewed journals and summaries will be provided to study funders. TRIAL REGISTRATION NUMBER: NCT05260268.
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Enfermedad Hepática en Estado Terminal , Trasplante de Hígado , Humanos , Estudios Prospectivos , Calidad de Vida , Cumplimiento y Adherencia al TratamientoRESUMEN
Content available: Audio Recording.
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Cannabinoid use in patients seeking solid organ transplantation (SOT) is an important and unsettled matter which all transplantation clinicians regularly encounter. It is also a multifaceted, interprofessional issue, difficult for any specialty alone to adequately address in a research article or during clinical care. Such uncertainty lends itself to bias for or against cannabinoid use accompanied by inconsistent policies and procedures. Scientific literature in SOT regarding cannabinoids often narrowly examines the issue and exists mostly in liver and kidney transplantation. Published recommendations from professional societies are mosaics of vagueness and specificity mirroring the ongoing dilemma. The cannabinoid information SOT clinicians need for clinical care may require data and perspectives from diverse medical literature which are rarely synthesized. SOT teams may not be adequately staffed or trained to address various neuropsychiatric cannabinoid effects and risks in patients. In this article, authors from US transplantation centers conduct a systematized review of the few existing studies regarding clinician perceptions, use rates, and clinical impact of cannabinoid use in SOT patients; collate representative professional society guidance on the topic; draw from diverse medical literature bases to detail facets of cannabinoid use in psychiatry and addiction pertinent to all transplantation clinicians; provide basic clinical and policy recommendations; and indicate areas of future study.
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Cannabinoides , Trasplante de Riñón , Trasplante de Órganos , Humanos , Cannabinoides/uso terapéuticoRESUMEN
In continuing efforts of improving benzoxazepine derivatives as an anti-breast cancer agent, a new chemical entity, benzoxazine, was designed from scaffold morphing. Structure-activity relationship studies revealed that H, -OMe, -CF3, and -F were well tolerated on R1 and R2 positions of ring A, and R2 as -CH2CH2N(CH2)4 (N-ethyl pyrrolidine) and -CH2CH2N(CH2)5 (N-ethyl piperidine) chains on ring D increased activities (Series B, Figure 3). 13d selected as a lead compound (IC50: 0.20 to 0.65 µM) induces apoptosis, cell cycle arrest, and loss of mitochondrial membrane potential in breast cancer cells. Compound 13d was formulated into 13d-f using cyclodextrin to improve its solubility for a pharmacokinetic, in vivo efficacy study. Both 13d and 13d-f regressed tumor growth at concentrations of 5 and 20 mg/kg better than tamoxifen without any mortality in a rat syngenic mammary tumor model. Collectively, our data suggest that tyrosine-derived novel benzoxazine 13d could be a potential lead for the treatment of breast cancer and hence deserve further in-depth studies.
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Benzoxazinas/metabolismo , Neoplasias Mamarias Experimentales/metabolismo , Tirosina/metabolismo , Animales , Puntos de Control del Ciclo Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Femenino , Humanos , Neoplasias Mamarias Experimentales/patología , RatasRESUMEN
A new dinuclear nickel(II) complex, [Ni(2)(LH(2))(H(2)O)(2)(OH)(NO(3))](NO(3))(3) (1), of an "end-off" compartmental ligand 2,6-bis(N-ethylpiperazine-iminomethyl)-4-methyl-phenolato, has been synthesized and structurally characterized. The X-ray single crystal structure analysis shows that the piperazine moieties assume the expected chair conformation and are protonated. The complex 1 exhibits versatile catalytic activities of biological significance, viz. catecholase, phosphatase, and DNA cleavage activities, etc. The catecholase activity of the complex observed is very dependent on the nature of the solvent. In acetonitrile medium, the complex is inactive to exhibit catecholase activity. On the other hand, in methanol, it catalyzes not only the oxidation of 3,5-di-tert-butylcatechol (3,5-DTBC) but also tetrachlorocatechol (TCC), a catechol which is very difficult to oxidize, under aerobic conditions. UV-vis spectroscopic investigation shows that TCC oxidation proceeds through the formation of an intermediate. The intermediate has been characterized by an electron spray ionizaton-mass spectrometry study, which suggests a bidentate rather than a monodentate mode of TCC coordination in that intermediate, and this proposition have been verified by density functional theory calculation. The complex also exhibits phosphatase (with substrate p-nitrophenylphosphate) and DNA cleavage activities. The DNA cleavage activity exhibited by complex 1 most probably proceeds through a hydroxyl radical pathway. The bioactivity study suggests the possible applications of complex 1 as a site specific recognition of DNA and/or as an anticancer agent.
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Níquel/química , Piperazinas/química , Cristalografía por Rayos X , ADN/química , Modelos Moleculares , Oxidación-ReducciónAsunto(s)
Médicos/psicología , Relaciones Profesional-Paciente , Psicoterapia/métodos , Adulto , Atención Ambulatoria , Niño , HumanosRESUMEN
Three novel dinuclear Zn(II) complexes of phenol-based compartmental macrocyclic ligands have been synthesized and characterized by routine physicochemical techniques as well as by X-ray single-crystal structure analysis. The dinuclear macrocyclic complexes 1, 2, and 3 were obtained through a 1:2 condensation reaction of 2,6-diformyl-4-methylphenol and N-(hydroxyalkyl) ethylenediamine (L(1), L(2), and L(3), respectively) in the presence of zinc(II) acetate, followed by the addition of thiocyanate anion [L(1) = N-(2-hydroxyethyl)ethylenediamine, L(2) = N-(3-hydroxypropyl)ethylenediamine, and L(3) = N-(2-hydroxypropyl)ethylenediamine]. The synthesized 18-membered macrocycles are noted to be structurally unique, and their formation proceeds with the generation of two oxazolidine side rings in complexes 1 and 3 and two oxazine side rings in 2, along with the creation of four new chiral centers in each case. Complexes 1 and 2 are characterized by a butterfly-like arrangement with the SCN ligands situated on the same side with respect to the Zn(2)O(2) moiety, whereas the centrosymmetric complex 3 exhibits a stepped arrangement with parallel methyl-phenoxy fragments (spaced at ca. 1.5 A) and trans located SCN ligands with respect to the Zn(2)O(2) core. The formation of these unusual macrocycles is considered to be zinc-mediated. Preliminary studies with the complexes show that all of them exhibit an inhibitory effect, on the cell proliferation of human stomach cancer cell line AGS, though with different degrees, where complex 3 shows the highest efficiency.
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Compuestos Macrocíclicos/síntesis química , Compuestos Organometálicos/síntesis química , Oxazinas/química , Oxazoles/química , Zinc/química , Antineoplásicos/síntesis química , Antineoplásicos/farmacología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Cristalografía por Rayos X , Humanos , Compuestos Macrocíclicos/farmacología , Estructura Molecular , Compuestos Organometálicos/farmacologíaRESUMEN
A series of dinuclear copper(II) complexes has been synthesized with the aim to investigate their applicability as potential structure and function models for the active site of catechol oxidase enzyme. They have been characterized by routine physicochemical techniques as well as by X-ray single-crystal structure analysis: [Cu 2(H 2L2 (2))(OH)(H 2O)(NO 3)](NO 3) 3.2H 2O ( 1), [Cu(HL1 (4))(H 2O)(NO 3)] 2(NO 3) 2.2H 2O ( 2), [Cu(L1 (1))(H 2O)(NO 3)] 2 ( 3), [Cu 2(L2 (3))(OH)(H 2O) 2](NO 3) 2, ( 4) and [Cu 2(L2 (1))(N 3) 3] ( 5) [L1 = 2-formyl-4-methyl-6R-iminomethyl-phenolato and L2 = 2,6-bis(R-iminomethyl)-4-methyl-phenolato; for L1 (1) and L2 (1), R = N-propylmorpholine; for L2 (2), R = N-ethylpiperazine; for L2 (3), R = N-ethylpyrrolidine, and for L1 (4), R = N-ethylmorpholine]. Dinuclear 1 and 4 possess two "end-off" compartmental ligands with exogenous mu-hydroxido and endogenous mu-phenoxido groups leading to intermetallic distances of 2.9794(15) and 2.9435(9) A, respectively; 2 and 3 are formed by two tridentate compartmental ligands where the copper centers are connected by endogenous phenoxido bridges with Cu-Cu separations of 3.0213(13) and 3.0152(15) A, respectively; 5 is built by an end-off compartmental ligand having exogenous mu-azido and endogenous mu-phenoxido groups with a Cu-Cu distance of 3.133(2) A (mean of two independent molecules). The catecholase activity of all of the complexes has been investigated in acetonitrile and methanol medium by UV-vis spectrophotometric study using 3,5-di- tert-butylcatechol (3,5-DTBC) and tetrachlorocatechol (TCC) as substrates. In acetonitrile medium, the conversion of 3,5-DTBC to 3,5-di- tert-butylbenzoquinone (3,5-DTBQ) catalyzed by 1- 5 is observed to proceed via the formation of two enzyme-substrate adducts, ES1 and ES2, detected spectroscopically for the first time. In methanol medium no such enzyme-substrate adduct has been detected, and the 3,5-DTBC to 3,5-DTBQ conversion is observed to be catalyzed by 1- 5 very efficiently. The substrate TCC forms an adduct with 2- 5 without performing further oxidation to TCQ due to the high reduction potential of TCC (in comparison with 3,5-DTBC). But most interestingly, 1 is observed to be effective even in TCC oxidation, a process never reported earlier. Kinetic experiments have been performed to determine initial rate of reactions (3,5-DTBC as substrate, in methanol medium) and the activity sequence is 1 > 5 > 2 = 4 > 3. A treatment on the basis of Michaelis-Menten model has been applied for kinetic study, suggesting that all five complexes exhibit very high turnover number, especially 1, which exhibits turnover number or K cat of 3.24 x 10 (4) (h (-1)), which is approximately 3.5 times higher than the most efficient catalyst reported to date for catecholase activity in methanol medium.
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Catecol Oxidasa/metabolismo , Catecoles/metabolismo , Cobre/química , Compuestos Organometálicos/síntesis química , Compuestos Organometálicos/metabolismo , Acetonitrilos/química , Cristalografía por Rayos X , Electroquímica , Cinética , Metanol/química , Oxidación-Reducción , Espectrofotometría UltravioletaRESUMEN
Cancer chemotherapy suffers from selectivity and undesired toxicity of the drugs. Since zinc is a biocompatible tracer element and cysteine derivatives are used in cancer chemoprevention, we intend to develop a complex of zinc and cysteine-derivatives as potent, non-toxic anticancer agents. Herein, we synthesized and characterized cysteine based ligand, 2-[(2-Hydroxy-3-methoxy-benzylidene)-amino]-3-mercapto-propionic acid and its Zn-complex, which are found to be non-toxic towards normal human PBMC. Data also revealed that only Zn-complex exhibited remarkable apoptosis in drug-sensitive CCRF-CEM and multidrug-resistant CEM/ADR5000 cancer cells as assessed by MTT, Cell cycle and AnnexinV binding assay. Moreover, Zn-complex altered ROS and GSH level of the respective cell lines. Finally, treatment of Zn-complex in Swiss albino mice did not show any systemic toxicity in preliminary trials in normal mice and remarkably increased the life-span of EAC bearing mice. In conclusion, the synthesized Zn-complex may be developed for efficacious, multidrug resistance reversal, non-toxic chemotherapeutic agents in future.
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Carcinoma de Ehrlich/tratamiento farmacológico , Complejos de Coordinación/administración & dosificación , Cisteína/química , Zinc/química , Animales , Apoptosis , Carcinoma de Ehrlich/metabolismo , Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Complejos de Coordinación/síntesis química , Complejos de Coordinación/química , Complejos de Coordinación/farmacología , Progresión de la Enfermedad , Resistencia a Múltiples Medicamentos/efectos de los fármacos , Resistencia a Antineoplásicos/efectos de los fármacos , Humanos , Ratones , Especies Reactivas de Oxígeno/metabolismo , Bases de Schiff/química , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Vanadium compounds are well known for their therapeutic interventions against several diseases. Various biochemical attributes of vanadium complexes inspired us to evaluate the cancer cell killing efficacy of the vanadium complex, viz., vanadyl N-(2-hydroxyacetophenone) glycinate [VO(NG)2]. Previously we showed that VO(NG)2 is an effective anticancer agent in in vitro and in vivo cancer models and imposed miniscule side effects. Herein we report that VO(NG)2 is significantly cytotoxic to various cancer cell lines. Furthermore, this redox active vanadyl complex altered the redox homeostatsis of many human cancer cell lines significantly. VO(NG)2 actuates programmed cell death in human colorectal carcinoma cells(HCT-116) through mitochondrial outer membrane permeabilization but in caspase independent manner, possibly by altering cellular redox status and by inflicting DNA damage. Thus, the present work is an attempt to provide many evidences regarding the potent and selective chemotherapeutic efficacy of the novel VO(NG)2.
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Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Neoplasias Colorrectales/metabolismo , Vanadio/farmacología , Antineoplásicos/química , Antineoplásicos/uso terapéutico , Apoptosis/fisiología , Células Cultivadas , Neoplasias Colorrectales/tratamiento farmacológico , Células HCT116 , Humanos , Leucocitos Mononucleares/efectos de los fármacos , Leucocitos Mononucleares/metabolismo , Bases de Schiff/química , Bases de Schiff/farmacología , Bases de Schiff/uso terapéutico , Oligoelementos/química , Oligoelementos/farmacología , Oligoelementos/uso terapéutico , Vanadio/química , Vanadio/uso terapéuticoRESUMEN
Osteosarcoma is the most common primary bone tumor in children and young adults arising from primitive mesenchymal bone-forming cells. The lung is the most common site of metastasis of osteosarcoma. Here, we report a case of a 14-year-old male patient having osteosarcoma of tibia presenting to us for evaluation of left-sided pleural effusion after 4 years of mid-thigh amputation. Contrast-enhanced computed tomography thorax revealed a large, heterogeneous, calcified mass (+277 H.U) at left upper and middle lobe along with massive left-sided pleural effusion. Thoracoscopy revealed a lung metastasis in the right upper and middle lobe along with 2-cm diameter mass found on the surface of parietal pleura. Lung tumor was resected and biopsy of the pleural mass was carried out. Histopathological examination from both the masses was suggestive of metastatic osteosarcoma. The case underlines the importance of performing thoracoscopy in patients of osteosarcoma who recur with lung metastasis.
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The Chandipura virus (CHPV) belonging to the Vesiculovirus genus and Rhabdoviridae family, has recently been associated with a number of encephalitis epidemics, with high mortality in children, in different parts of India. No full length genome sequences of CHPV isolates were available in GenBank and little is known about the molecular markers for pathogenesis. In the present study, we provide the complete genomic sequences of four isolates from epidemics during 2003-2007. These sequences along with the deduced sequence of the prototype isolate of 1965 were analysed using phylogeny, motif search, homology modeling and epitope prediction methods. Comparison with other rhaboviruses was also done for functional extrapolations. All CHPV isolates clustered with the Isfahan virus and maintained several functional motifs of other rhabdoviruses. A notable difference with the prototype vesiculovirus, Vesicular Stomatitis Virus was in the L-domain flanking sequences of the M protein that are known to be crucial for interaction with host proteins. With respect to the prototype isolate, significant additional mutations were acquired in the 2003-2007 isolates. Several mutations in G mapped onto probable antigenic sites. A mutation in N mapped onto regions crucial for N-N interaction and a putative T-cell epitope. A mutation in the Casein kinase II phosphorylation site in P may attribute to increased rates of phosphorylation. Gene junction comparison revealed changes in the M-G junction of all the epidemic isolates that may have implications on read-through and gene transcription levels. The study can form the basis for further experimental verification and provide additional insights into the virulence determinants of the CHPV.
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Genoma Viral/genética , ARN Viral/genética , Rhabdoviridae/genética , Vesiculovirus/genética , Adolescente , Secuencia de Aminoácidos , Secuencia de Bases , Sitios de Unión/genética , Niño , Preescolar , Epidemias , Humanos , India/epidemiología , Modelos Moleculares , Datos de Secuencia Molecular , Filogenia , Estructura Terciaria de Proteína , ARN Viral/clasificación , ARN Viral/aislamiento & purificación , Rhabdoviridae/clasificación , Rhabdoviridae/aislamiento & purificación , Infecciones por Rhabdoviridae/epidemiología , Infecciones por Rhabdoviridae/virología , Homología de Secuencia de Aminoácido , Homología de Secuencia de Ácido Nucleico , Vesiculovirus/clasificación , Vesiculovirus/aislamiento & purificación , Proteínas Virales/química , Proteínas Virales/genéticaRESUMEN
OBJECTIVES: Our objectives were to describe the QOL and its determinants among software professionals of Kolkata, and to compare the same according to information technology (IT) and IT-enabled services (ITeS) sub-sectors. METHODS: An institution-based cross-sectional study was conducted among software professionals of Kolkata applying a two-stage stratified random sampling technique. The WHO QOL BREF questionnaire was administered along with a list of pertinent variables. RESULTS: Overall, the analysis for 338 software professionals (177 IT and 161 ITeS) clearly demonstrated significant differences between mean scores of these two sectors for each of the six outcome domains of WHO QOL BREF. Multilevel multivariate analysis outlined 13 significant predictors of QOL-four positive (age, regular fitness regimes, foreign placements and changing companies frequently) and the rest of the nine, negative (multiple sex partners, multiple addictions, extended working hours, night-shift duties, income, expenditure, carrying office work home, current illness and ITeS company type). CONCLUSIONS: Our study helps in obtaining a clear understanding of the multifaceted risk factors prevailing in this sector, the majority of which can be effectively addressed by specific health promotional interventions. A dedicated health policy is mandated at both government and company levels.