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People living with HIV (PLWH) are susceptible to severe COVID-19 infection and hence this fragile population has prioritised vaccination. This systematic review and meta-analysis aimed to assess the humoral immune response after receiving two doses schedule of COVID-19 mRNA vaccinations in this high-risk population. A systematic electronic search on the PubMed database and manual searches were performed for relevant articles until 30 Sep 2022. Two outcomes of interest were seroconversion rates and anti-spike receptor binding domain (anti-S-RBD) antibody titres at the median time of 14-35 days following two-dose vaccination among PLWH. Nineteen cohorts and one cross-sectional study were eligible for inclusion in this study. The pooled estimate of seroconversion rate after receiving two doses of mRNA vaccination schedule were 98.4% and 75.2% among PLWH with CD4>500 cells/mm3 and CD4<200 cells/mm3 , respectively. Compared with controls, PLWH with CD4>500 cells/mm3 had a 51% likelihood of having positive anti-Spike-RBD immunoglobulin G (IgG) (OR: 0.509, 95% CI: 0.228, 1.133, p = 0.098) post-vaccination and this value was only 1.4% (OR: 0.014, 95% CI: 0.002, 0.078, p = 0.000) for PLWH with CD4<200 cells/mm3 . There was no significant difference in titres of antibodies on 14-35 days post-vaccination between PLWH with CD4>500 cells/mm3 and healthy controls (p = 0.06). The pooled median of anti-S-RBD IgG values were 1461.93 binding antibody units (BAU)/ml and 457.41 BAU/ml in PLWH with CD4>500 cells/mm3 and CD4<200 cells/mm3 , respectively. According to these findings, vaccination with both Pfizer-BioNTech and Moderna vaccines induced a robust humoral response in ART-treated HIV patients with preserved CD4 cell count. A diminished humoral immune response to vaccination against COVID-19 in PLWH with unrestored CD4 count implied the need of specific vaccination schemes.
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COVID-19 , Infecções por HIV , Humanos , Imunidade Humoral , COVID-19/prevenção & controle , Estudos Transversais , Imunoglobulina G , Vacinação , Anticorpos AntiviraisRESUMO
Purpose: Solid organ transplant recipients (SOTR) have a high risk for severe COVID-19 infection; hence it is necessary to find alternative treatment strategies to protect these patients from the complications caused by the severe progression of the disease. This study aimed to determine the effectiveness of sotrovimab among SOTR with COVID-19.Materials and methods: A systematic literature search was conducted with relevant keywords to find studies that reported clinical outcomes regarding sotrovimab administration in SOTR outpatients with confirmed COVID-19 infection, who had mild-to-moderate symptoms.Results: Of 796 records found by a systematic search, only 14 met the inclusion criteria for reporting in a systematic review and only 6 enrolled in a meta-analysis. This meta-analysis indicated that SOTR outpatients with mild to moderate COVID-19 who received sotrovimab had lower likelihood of all-cause hospitalization (OR: 0.29, CI: 0.16, 0.52, p < 0.001), ICU admission (OR: 0.17, CI: 0.05, 0.64, p = 0.009) and mortality (OR: 0.15, CI: 0.03, 0.64, p = 0.010) within 30 days of drug infusion compared to controls.Conclusions: Our findings confirm that monoclonal antibody therapy with sotrovimab in SOTR is associated with better outcomes and consequently a reduced risk of disease progression in this high-risk population.
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COVID-19 , Transplante de Órgãos , Humanos , Anticorpos Monoclonais Humanizados/efeitos adversos , Imunoterapia , Transplante de Órgãos/efeitos adversosRESUMO
Neurodegenerative diseases are questions that modern therapeutics can still not answer. Great milestones have been achieved regarding liver, heart, skin, kidney and other types of organ transplantations but the greatest drawback is the adequate supply of these organs. Furthermore, there are still a few options available in the treatment of neurodegenerative diseases. With great advances in medical science, many health problems faced by humans have been solved, and their quality of life is improving. Moreover, diseases that were incurable in the past have now been fully cured. Still, the area of regenerative medicine, especially concerning neuronal regeneration, is in its infancy. Presently allopathic drugs, surgical procedures, organ transplantation, stem cell therapy forms the core of regenerative therapy. However, many times, the currently used therapies cannot completely cure damaged organs and neurodegenerative diseases. The current review focuses on the concepts of regeneration, hurdles faced in the path of regenerative therapy, neurodegenerative diseases and the idea of using peptides, cytokines, tissue engineering, genetic engineering, advanced stem cell therapy, and polyphenolic phytochemicals to cure damaged tissues and neurodegenerative diseases.
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Doenças Neurodegenerativas , Polifenóis , Humanos , Doenças Neurodegenerativas/terapia , Polifenóis/farmacologia , Qualidade de Vida , Medicina Regenerativa/métodos , Transplante de Células-Tronco/métodos , Engenharia TecidualRESUMO
This study evaluates the ability of heterogeneous Fenton-like reaction (nano zero-valent iron (NZVI)/H2O2) in combination with weak magnetic field (WMF) under continuous oxygen supply by air bubbling for pollutant abatement (using ciprofloxacin as a model pollutant). The considered operating variables were initial pH, catalyst dosage, reaction time and different intensities of magnetic field. Results indicated that NZVI/H2O2/aeration/weak magnetic field could effectively decompose ciprofloxacin at neutral condition and higher removal rates are observed at higher pH and NZVI concentrations. Superimposing a weak magnetic field leads to 20% enhancement in ciprofloxacin removal by catalytic Fenton under aeration condition. Employing simultaneously magnetic field induction and aeration exhibit excellent capability to the NZVI oxidation and significantly increased the dissolution rate of iron. Based on Fourier transform infrared spectroscopy, transformation products of NZVI are Fe3O4 and FeO(OH). The faster mass transport due to Lorentz and field gradient force, more oxygen diffusion to the iron surface and promoted electrochemical reactions results in more OH° production. Generation of weak magnetic field by permanent magnets and using aeration for both mixing and in situ oxygen supply significantly enhanced the Fenton reaction performance. This combination technology doesn't need any energy input and costly chemicals hence can be used easily for wastewater treatment applications.
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Ciprofloxacina , Poluentes Químicos da Água , Peróxido de Hidrogênio , Ferro , Campos MagnéticosRESUMO
Despite all efforts, tuberculosis (TB) remains one of the 10 leading causes of death worldwide. The hematopoietic system is seriously affected by TB and there is little information about the hematological profile of patients with TB. In this regard, this systematic review and meta-analysis aimed to assess hematological parameters among newly diagnosed TB patients. Relevant papers were found by searching in the PubMed database until April 2023. Fifteen papers involving 3354 patients were included. One-sample meta-analysis revealed the low pooled mean values for Hgb of 11.679 g/dl (95 % CI: 10.982-12.377) and the increased pooled ESR of 63.569 mm/h (95 % CI: 57.834-69.304) among newly diagnosed TB patients. The pooled prevalence of anemia, leukocytosis, thrombocytosis, and lymphopenia was 61.6 % (95 % CI: 45.4-75.6 %), 45.9 % (95 % CI: 39.1-52.9 %), 31.9 % (95%CI: 15-55.3 %) and 23.1 % (95%CI: 5.4-61.5 %) between TB patients, respectively. From a two-sample meta-analysis, the RBC and HgB values for TB patients were significantly lower than that of healthy controls (p < 0.05). Awareness of common blood abnormalities like elevated ESR, leukocytosis, and anemia in newly diagnosed TB patients helps physicians in early diagnosis and better management of disease.
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Anemia , Mycobacterium tuberculosis , Tuberculose , Humanos , Leucocitose/diagnóstico , Leucocitose/epidemiologia , Leucocitose/complicações , Tuberculose/diagnóstico , Tuberculose/epidemiologia , Tuberculose/etiologia , Anemia/diagnóstico , Anemia/epidemiologia , Anemia/complicações , Diagnóstico PrecoceRESUMO
Corneal diseases are among the most common causes of blindness worldwide. Regardless of the etiology, corneal opacity- or globe integrity-threatening conditions may necessitate corneal replacement procedures. Several procedure types are currently available to address these issues, based on the complexity and extent of injury. Corneal allograft or keratoplasty is considered to be first-line treatment in many cases. However, a significant proportion of the world's population are reported to have no access to this option due to limitations in donor preparation. Thus, providing an appropriate, safe, and efficient synthetic implant (e.g., artificial cornea) may revolutionize this field. Nanotechnology, with its potential applications, has garnered a lot of recent attention in this area, however, there is seemingly a long way to go. This narrative review provides a brief overview of the therapeutic interventions for corneal pathologies, followed by a summary of current biomaterials used in corneal regeneration and a discussion of the nanotechnologies that can aid in the production of superior implants.
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Doenças da Córnea , Engenharia Tecidual , Humanos , Engenharia Tecidual/métodos , Materiais Biocompatíveis/uso terapêutico , Córnea/cirurgia , Doenças da Córnea/cirurgia , NanotecnologiaRESUMO
Today the nano drug delivery systems are among the hot topics in drug design and pharmacy studies. Extensive researches are conducted worldwide for obtaining more effective therapeutics and screen the best drug carrier in-vivo and in-vitro. Considering the high cost of such experiments and the ethical issues linked with in-vivo studies, the in-silico analysis provides the time and cost-effective opportunity to evaluation of physiochemical properties and the interactions between drugs and their carriers. In this study using molecular dynamics (MD) simulation, five commonly used biodegradable biopolymers in pharmaceutical formulations including Chitosan, Alginate, Cyclodextrin, Hyaluronic Acid, and Pectin were investigated as proper carriers for the erythropoietin (EPO) in heat stress. The EPO was simulated in different temperatures of 298 and 343 K and the ability of polymers for temperature stabilization of the protein was evaluated comparatively. Overall, the results obtained in this study suggest that the pectin polysaccharide is the preferable carrier than others in term of protein stability in high temperatures and using for the delivery of erythropoietin.Communicated by Ramaswamy H. Sarma.
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Quitosana , Polímeros , Polímeros/química , Simulação de Dinâmica Molecular , Portadores de Fármacos/química , Quitosana/química , Alginatos/química , Pectinas/químicaRESUMO
BACKGROUND: One of the most important routes of HIV transmission is through injections of drugs, and this group, due to unawareness of their infection, causes the spread of HIV. The coexistence of other opportunistic infections and diseases with HIV among people who inject drugs (PWID) imposes healthcare costs and is associated with high morbidity/mortality rates. Early detection of HIV among PWID is essential to prevent and control the spread of the disease. OBJECTIVES: This study aimed to determine the prevalence of PWID among those with late presentation (LP). METHODS: Three electronic databases of PubMed, Scopus, and Web of science were searched using appropriate keywords. Besides the prevalence data reported for PWID among LP, the other outcomes of interest were LP defined as having CD4 count < 350 cells/µL or HIV or advanced disease defined with CD4 count < 200 cells/µL or HIV at the time of diagnosis. RESULTS: Of the 160 studies found, only eight met the inclusion criteria. Among those presented late, 36.5% were PWID (95% CI = 24.88-48.17). Compared with men who have sex with men (MSM), HIV-infected PWID had a higher risk of LP [OR = 1.51; 95% CI = 0.96-2.06]. CONCLUSION: The results of this study show that HIV is diagnosed late in the majority of PWID when CD4 is less than 350 cells/µL. Targeted interventions/strategies are highly required to reduce LP among HIV-infected PWID.
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Usuários de Drogas , Infecções por HIV , Minorias Sexuais e de Gênero , Abuso de Substâncias por Via Intravenosa , Infecções por HIV/diagnóstico , Homossexualidade Masculina , Humanos , Masculino , Prevalência , Abuso de Substâncias por Via Intravenosa/complicações , Abuso de Substâncias por Via Intravenosa/epidemiologiaRESUMO
Objectives: Military personnel are unique occupational groups who happen to frequently experience sleep insuffciencies. Since sleep disorders are known to be linked to many psychiatric symptoms, sleep disturbance is a salient concern among active duty service members and veterans. Existing evidence indicates that although sleep disturbances co-occur with mental illnesses, there is a tendency to particularly label them as consequences of certain mental health issues. Material and Methods: This review focuses on the emerging evidence which identifies sleep disturbances as a precursor for mental illnesses. In this regard, the impact of sleep disturbance on the development of mental health outcomes including post-traumatic stress disorder (PTSD), depression, and anxiety has been thoroughly scrutinized. A systematic search was conducted using PubMed, Scopus, and Web of Science academic databases using appropriate keywords. Results: Reviewed evidence substantiates the predicting role of sleep complaints and disorders to herald PTSD, depression, and anxiety among military staff. Conclusion: Early diagnosis of sleep disturbances and properly addressing them in active-duty service members and veterans should be then sought to prevent the development and progression of consequent mental health- related comorbidities in this study group.
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Sleep plays an important role in stabilizing and reinforcing memory of newly acquired information. Like nocturnal sleep, a daytime nap is shown to effectively contribute to memory processing. However, studies are often focused on nocturnal sleep. This review has aimed at systematically compiling the results of studies which have examined the effects of napping on declarative memory performance in healthy adults. Such studies have focused on different aspects of memory reinforcement following a diurnal nap including the involved mechanisms in memory reconsolidation, type of declarative tasks, cross-gender differences, the role of age, duration of nap and its delayed onset. One of the reviewed studies reported that even as short as 6 min of napping exerts a positive effect on memory function. Evidence from these studies indicates hippocampal-dependent enhancement of the learned information. Diurnal naps predominantly include non-rapid eye movement sleep with slow waves yielding potential effects on declarative memory. Evidence has shown that the empowered learning and retrieval depends upon spindle density during the nap. Moreover, the role of coordinated autonomic and central events in enhancing declarative memory has also been reported. Slow waves and sleep spindles are known to fuel declarative memory function during the NREM-2 (N2) stage of sleep.
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Memória , Sono , Cognição , Hipocampo , Humanos , AprendizagemRESUMO
BACKGROUND: Total knee arthroplasty (TKA) is an accepted, effective treatment to restore function, relieve pain, and improve the quality of life in patients with advanced osteoarthritis. One complication of this major surgery is impaired sleep quality. This study examines the quality of sleep in patients undergoing TKA before and after their operation. METHODS: All relevant records were obtained using a systematic search in three online databases: PubMed, Scopus, and Cochrane library. Out of the 177 records retrieved, only eight matched the inclusion criteria. Due to the lack of sufficient data, only four studies entered the meta-analysis. Values reported for sleep quality based on the Pittsburgh Sleep Quality Index (PSQI) were extracted from patient records before and after surgery. A random-effect model was used to analyze the data. RESULTS: The results of the meta-analysis show a significant difference in the improvement of sleep quality after surgery at two time points of 4-6 weeks after surgery from the preoperative baseline (SMD - 0.16; 95% CI - 1.05 to 0.74; P = 0.0) and 3-6 months after surgery from the preoperative baseline (SMD - 0.92; 95% CI - 1.61 to - 0.24; P = 0.0). CONCLUSIONS: The results show that TKA generally improves the patients' sleep quality. Although some studies reported disrupted sleep quality in periods close to the surgery (especially in the early days after surgery), all studies have reported improved sleep quality in the late postoperative intervals.
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Artroplastia do Joelho , Qualidade de Vida , Sono , Humanos , Período Pós-Operatório , Inquéritos e QuestionáriosRESUMO
BACKGROUND AND PURPOSE: Today, color additives such as Allura red (AR) are widely used in different kinds of food products. Pepsin is a globular protein that is secreted as a digestive protease from the main cells in the stomach. Because of the important role of pepsin in protein digestion and because of its importance in digestive diseases the study of the interactions of pepsin with chemical food additives is important. EXPERIMENTAL APPROACH: In this study, the interactions between AR and pepsin were investigated by different computational and experimental approaches such as ultraviolet and fluorescence spectroscopy along with computational molecular modeling. FINDINGS/RESULTS: The experimental results of fluorescence indicated that AR can strongly quench the fluorescence of pepsin through a static quenching. Thermodynamic analysis of the binding phenomena suggests that van der Waals forces and hydrogen bonding played a major role in the complex formation. The results of synchronous fluorescence spectra and furrier transformed infra-red (FTIR) experiments showed that there are no significant structural changes in the protein conformation. Also, examined pepsin protease activity revealed that the activity of pepsin was increased upon ligand binding. In agreement with the experimental results, the computational results showed that hydrogen bonding and van der Waals interactions occurred between AR and binding sites. CONCLUSION AND IMPLICATIONS: From the pharmaceutical point of view, this interaction can help us to get a deeper understanding of the effect of this synthetic dye on food digestion.
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Finding a facile and practical method to produce black TiO2 remains a challenge. Bismuth-vanadium co-doped black TiO2 (BVBT) was synthesized as a visible light driven photocatalyst by a simple one-pot hydrothermal method. The synthesized BVBT was characterized using scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray powder diffraction (XRD), UV-vis diffuse reflectance spectroscopy (UV-Vis DRS). The light absorption of the synthesized Bi-V co-coped black TiO2 nanoparticles was significantly improved in the visible and infrared regions. The XRD patterns indicated that the black TiO2 contained mixed phases of brookite, anatase, and rutile of TiO2. This was further confirmed by Raman spectroscopy. The photocatalytic activity of the sample was evaluated by reduction of hexavalent chromium (Cr(VI)) under visible light irradiation. Among investigated hole (h+) scavengers, ethylenediaminetetraacetic acid (EDTA) led to the highest reduction of Cr(VI) with a molar ratio of 1:5 (EDTA:Cr(VI)). The results indicated that the Bi-V co-coped black TiO2 nanocomposite can reduce 94% of 1 mg/L of Cr(VI) within 20 min irradiation time (pH 3 and catalyst dose of 1 g/L). Introducing a simple method to synthesize black TiO2 which has absorption in the visible and infrared region can open up new applications.
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Titânio , Cromo , LuzRESUMO
Pepsin is an aspartic protease that is involved in the digestion of food in the stomach of mammals. Continuous and long-term use of therapeutic agents will cause chronic contact of the drug with pepsin, and as a result, the structure and function of enzyme may change. In this regard the interactions of isoniazid and rifampin as the first line treatments of tuberculosis with pepsin were investigated by various methods such as fluorescence spectroscopy, FTIR, molecular docking and molecular dynamics simulation. Based on the results obtained in this study, the mentioned drugs can form stable complexes with pepsin and the structure of protein changes slightly. According to the results, the major forces in the formation of the protein-drug complex are electrostatic and hydrophobic forces for isoniazid and rifampin respectively and isoniazid shows to form a stronger binding with protein. The FTIR spectrum of the protein shows that little change was occurred in the structure of pepsin in the presence of the drugs. Molecular modeling results of the binding of isoniazid and rifampin to the pepsin confirm laboratory results and show that the binding site of drugs is close to the active site of the enzyme. Also, the activity of pepsin in the presence of both drugs has significantly increased.
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Isoniazida , Pepsina A , Animais , Simulação de Acoplamento Molecular , Pepsina A/metabolismo , Ligação Proteica , RifampinaRESUMO
Application of proteinous drugs can be associated with difficulties during both in storage/transportation and in the body when they are used. However, using pharmaceutical carbohydrates that are widely employed in drug delivery systems, besides the drug can be protected, these systems leading to gradually release the drug over time, or deliver it to the target cell. Using a combination of molecular modeling and simulation techniques, in this study the effects of five carbohydrate polymers of Chitosan, Alginate, Cyclodextrin, Hyaluronic acid and Pectin on structure and dynamics of interleukin2 protein at 298 K and 343 K, are investigated. Data achieved using molecular modeling methods showed that when the temperature rises, the protein stability decreases. Among different polymers, Chitosan and Cyclodextrin have shown to be able to protect protein against the negative effects of high temperatures in comparison with other polymers which suggests that the use of Cyclodextrin biopolymer for the preparation of pharmaceutical formulations of interleukin2 can be the best possible choice among other polymers investigated in this research.Communicated by Ramaswamy H. Sarma.
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Quitosana , Preparações Farmacêuticas , Alginatos , Sistemas de Liberação de Medicamentos , Resposta ao Choque Térmico , PolímerosRESUMO
In this study, the effect of long-term use drugs of cholesterol-lowering atorvastatin and simvastatin on the activity and molecular structure of pepsin as important gastric enzyme was investigated by various experimental and computational methods. Based on the results obtained from fluorescence experiments, both drugs can bond to pepsin and quench the fluorescence intensity of protein through the static quenching mechanism. Also analysis of the thermodynamic parameters of binding the drugs to pepsin showed that the main forces in the complex formation for both are hydrophobic interactions and van der Waals forces. The effects of the drugs on the enzymatic activity of pepsin were then investigated and results showed that in the presence of both drugs the catalytic activity of the enzyme was significantly increased in lower (0.3-0.6 mM) concentrations however about the atorvastatin, increasing the concentration (0.9 mM) decreased the protease activity of pepsin. Also as a result of the FTIR studies, it was found that binding of the drugs to protein did not significant alteration in the structure of the protein. In order to obtain the atomic details of drug-protein interactions, the computational calculations were performed. The results in good agreement with those obtained from the experimental for interaction; confirm that the drugs both are bind to a cleft near the active site of the protein without any change in the structure of pepsin. Overall from the results obtained in this study, it can be concluded that both simvastatin and atorvastatin can strongly bond to a location close to the active site of pepsin and the binding change the enzymatic activity of protein.
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Anticolesterolemiantes/química , Atorvastatina/química , Pepsina A/química , Sinvastatina/química , Sítios de Ligação , Catálise , Domínio Catalítico , Fluorescência , Ligação de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Modelos Moleculares , Simulação de Acoplamento Molecular , Estrutura Molecular , Preparações Farmacêuticas/química , Ligação Proteica , Proteólise , Espectrometria de Fluorescência , Espectrofotometria , Espectroscopia de Infravermelho com Transformada de Fourier , TermodinâmicaRESUMO
Although Isoniazid (INH) is one of the drugs used as the first line treatment of tuberculosis, its high concentrations in the human body can cause severe complications such as; recurrent seizures, profound metabolic acidosis, coma and even death. Hence it is necessary to designing the sensors capable of detecting very low amounts of drug. A Cu doped Tragacanth/Chitosan carbon dot (CD) with excellent optical properties and photo-thermal stability was synthesized, characterized and used for sensing Isoniazid by a fluorescence Off-ON mechanism based on redox reaction between INH and Fe3+ as quencher. During the first step of reaction, Fe3+ bind to the CDs and due to an electron transfer process the fluorescence intensity of CDs is quenched. There after by introduction of Isoniazid to the CDs-Fe3+ system, Fe3+ converts to Fe2+ and the fluorescence was recovered. Experiments confirm that new method has high ability to detect low concentration of Isoniazid even in the presence of other drugs and interfering materials. In conclusion, this innovative strategy for developing a low cost and sensitive sensor can be used in future health-related programs.
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Antituberculosos/química , Técnicas Biossensoriais , Quitosana/química , Química Verde/métodos , Isoniazida/análise , Pontos Quânticos/química , Biopolímeros/química , Calibragem , Carbono/química , Cobre/química , Elétrons , Humanos , Ferro/química , Isoniazida/química , Microscopia Eletrônica de Varredura , Nanotecnologia/métodos , Oxirredução , Soro/química , Espectrometria de Fluorescência , Temperatura , Tragacanto/química , Difração de Raios XRESUMO
This study evaluates the biochemical interactions between two widely used anticoagulants agents, Aspirin and Warfarin, with the Pepsin as the main stomach protease. These two drugs usually prescribe orally for long period daily use to reduce cardiovascular and thrombi death which leads to being in close contact with Pepsin. This interaction could induce related gastrointestinal problems such as peptic ulcer. In this regard, the conformational changes and enzymatic activity of the Pepsin induced by Aspirin and Warfarin were studied by using several spectroscopic methods along with molecular modeling approaches. Results confirm the formation of stable complexes between protein and drugs which leads to slight subsequent conformational changes of protein structure. The quenching mechanisms for both drug-Pepsin interactions are static. In the case of Warfarin, the hydrophobic interactions are the most important interactions. Also for Aspirin, hydrogen bond and van der Waals forces are mainly involved in the binding process. The Warfarin shows the induction of some conformational changes resulted in suppressing the protease activity and the Aspirin reversely enhanced the enzyme activity function. This study provides useful information regarding the effects of Warfarin and Aspirin on Pepsin which are helpful for the choosing of therapeutics depending on the patients' condition.
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Aspirina/farmacologia , Interações Medicamentosas , Pepsina A/química , Varfarina/farmacologia , Sítios de Ligação , Dicroísmo Circular , Simulação por Computador , Humanos , Ligação de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Simulação de Dinâmica Molecular , Ligação Proteica , Conformação Proteica , Espectrometria de Fluorescência , Espectrofotometria , Espectrofotometria Ultravioleta , Espectroscopia de Infravermelho com Transformada de Fourier , TermodinâmicaRESUMO
Calcium Hydroxide (CH) is commonly employed as intracanal medicament in endodontics. In order to maximize its therapeutic effects, it is essential to develop new approaches for preparing the controlled drug release systems which, in turn, facilities the dissociation of CH into calcium and hydroxyl ions. This work studies the sustained-controlled release of calcium ions and the effect of pH changes on the different formulation of CH with hydrophilic natural polymers over a period of 30 days. Various formulations were prepared by combining CH with gelatin, aloe vera and gum tragacanth. Root canals of 60 human teeth were instrumented and filled with a different formulation of CH and suspended in plastic tubes containing distilled water. Three formulas of polymer/CH were evaluated, and pure CH powder was used as a control. At specific time intervals, the calcium ions release and the pH changes of the medium in different formulations were analyzed. The main interactions between the studied polymers and CH were investigated using FTIR spectra. The antibacterial activity of formulations against Enterococcus faecalis was also studied. Faster release of CH was observed for aloe vera/CH. Gum tragacanth/CH showed a slow-release during the first 15 days. In contrast, only Gelatin/CH formulation showed a prolonged release with statistically significant differences (P < 0.05). The pure CH showed significantly higher pH values than the other formulations. The Gelatin/CH formulation was a better sustained-release system than the pure CH, and it can be used as a promising vehicle for CH in the root canal treatment.
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Pepsin, as the main protease of the stomach, plays an important role in the digestion of food proteins into smaller peptides and performs about 20% of the digestive function. The role of pepsin in the development of gastrointestinal ulcers has also been studied for many years. Edible drugs that enter the body through the gastrointestinal tract will interact with this enzyme as one of the first targets. Continuous and long-term usage of some drugs will cause chronic contact of the drug with this protein, and as a result, the structure and function of pepsin may be affected. Therefore, the possible effect of atenolol and diltiazem on the structure and activity of pepsin was studied. The interaction of drugs with pepsin was evaluated using various experimental methods including UV-Visible spectroscopy, fluorescence spectroscopy, FTIR and enzymatic activity along with computational approaches. It was showed that after binding of atenolol and diltiazem to pepsin, the inherent fluorescence of the protein is quenched. Determination of the thermodynamic parameters of interactions between atenolol and diltiazem with pepsin indicates that the major forces in the formation of the protein-drug complexes are hydrophobic forces and also atenolol has a stronger protein bonding than diltiazem. Additional tests also show that the protease activity of pepsin, decreases and increases in the presence of atenolol and diltiazem, respectively. Investigation of the FTIR spectrum of the protein in the presence and absence of atenolol and diltiazem show that in the presence of atenolol the structure of protein has slightly changed. Molecular modeling studies, in agreement with the experimental results, confirm the binding of atenolol and diltiazem to the enzyme pepsin and show that the drugs are bind close to the active site of the enzyme. Finally, from experimental and computational results, it can be concluded that atenolol and diltiazem interact with the pepsin and change its structure and protease activity.