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Calcitriol, the bioactive form of vitamin D, exerts its biological functions by binding to its cognate receptor, the vitamin D receptor (VDR). The indicators of the severity of allergies and asthma have been linked to low vitamin D levels. However, the role of calcitriol in regulating IL-4 and IL-13, two cytokines pivotal to allergic inflammation, remained unclear. Our study observed diminished IL-4 and IL-13 secretion in murine and human Th2 cells treated with calcitriol. In murine Th2 cells, Gata3 expression was attenuated by calcitriol. However, the expression of the transcriptional repressor Gfi1, too, was attenuated in the presence of calcitriol. Ectopic expression of either Gfi1 or VDR impaired the secretion of IL-13 in Th2 cells. In murine Th2 cells, VDR interacted with Gata3 but not Gfi1. Gfi1 significantly impaired Il13 promoter activation, which calcitriol failed to restore. Conversely, calcitriol augmented Gfi1 recruitment to the Il13 promoter. Ecr, a conserved region between these two genes, which enhanced the transactivation of Il4 and Il13 promoters, is essential for calcitriol-mediated suppression of both the genes. Calcitriol augmented the recruitment of VDR to the Il13 promoter and Ecr regions. Gata3 recruitment was significantly impaired at the Il13 and Ecr loci in the presence of calcitriol but increased at the Il4 promoter. Furthermore, the recruitment of the histone deacetylase HDAC1 was universally increased at the promoters of Il4, Il13, and Ecr when calcitriol was present. Together, our data clearly elucidate that calcitriol modulates VDR, Gata3, and Gfi1 to suppress IL-4 and IL-13 production in Th2 cells.
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Left ventricular assist devices (LVAD) are increasingly used for management of heart failure; infection remains a frequent complication. Phage therapy has been successful in a variety of antibiotic refractory infections and is of interest in treating LVAD infections. We performed a retrospective review of four patients that underwent five separate courses of intravenous (IV) phage therapy with concomitant antibiotic for treatment of endovascular Pseudomonas aeruginosa LVAD infection. We assessed phage susceptibility, bacterial strain sequencing, serum neutralization, biofilm activity, and shelf-life of phage preparations. Five treatments of one to four wild-type virulent phage(s) were administered for 14-51 days after informed consent and regulatory approval. There was no successful outcome. Breakthrough bacteremia occurred in four of five treatments. Two patients died from the underlying infection. We noted a variable decline in phage susceptibility following three of five treatments, four of four tested developed serum neutralization, and prophage presence was confirmed in isolates of two tested patients. Two phage preparations showed an initial titer drop. Phage biofilm activity was confirmed in two. Phage susceptibility alone was not predictive of clinical efficacy in P. aeruginosa endovascular LVAD infection. IV phage was associated with serum neutralization in most cases though lack of clinical effect may be multifactorial including presence of multiple bacterial isolates with varying phage susceptibility, presence of prophages, decline in phage titers, and possible lack of biofilm activity. Breakthrough bacteremia occurred frequently (while the organism remained susceptible to administered phage) and is an important safety consideration.
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Bacteriemia , Bacteriófagos , Corazón Auxiliar , Terapia de Fagos , Infecciones por Pseudomonas , Humanos , Pseudomonas aeruginosa , Corazón Auxiliar/efectos adversos , Infecciones por Pseudomonas/terapia , Infecciones por Pseudomonas/microbiología , Antibacterianos/uso terapéutico , Profagos , Bacteriemia/tratamiento farmacológicoRESUMEN
17-ß Estradiol (E2) has long standing known functions in regulating human physiology as well as immune system. E2 is known to elicit a protective role against experimental autoimmune encephalomyelitis (EAE) and has been used as a drug for treatment against multiple sclerosis. Moreover, E2 regulates the adaptive immune system by directly affecting the T helper cell subsets differentiation and antibody secretion mediated by B cells. Reports have shown that E2 promotes Th1 and Treg cell differentiation; whereas it attenuated the Th17 and Tfh cell differentiation. Albeit multiple and contrasting studies, the mechanisms of behind E2 action on Th2 cells remained understudied. Hence, we sought to dissect the impact of E2 in Th2 cell differentiation. In this study, we elucidated the molecular mechanisms behind E2-mediated regulation of the differentiation of Th2 cells. We observed that E2 significantly attenuated the IL-4-secreting Th2 population in an ERα-dependent manner. We validated these findings using ICI 182, 780, an antagonist to ERα, not ERß and ectopically overexpressing ERα in Th2 cells. We further determined that ERα alters the recruitment of GATA3 and PU.1 to Il4 gene by directly interacting with them. This altered recruitment was observed to be stronger at Il4 than Il13 locus. Interestingly, we detected a distinct recruitment of GATA3 and PU.1 at Il13 gene; however, there was no E2-mediated broad alteration in the recruitment of histone-modifiers at Il13 locus. These findings suggest that E2 regulates Il4 in a distinctly separate mechanism as opposed to Il13 locus in Th2 cells.
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Encefalomielitis Autoinmune Experimental , Células Th2 , Animales , Humanos , Interleucina-13/metabolismo , Interleucina-4/metabolismo , Estradiol/farmacología , Receptor alfa de Estrógeno/genética , Receptor alfa de Estrógeno/metabolismo , Diferenciación Celular , Células TH1 , Células Th17/metabolismo , Factor de Transcripción GATA3/genética , Factor de Transcripción GATA3/metabolismoRESUMEN
The liquid structure of systems wherein water is limited in concentration or through geometry is of great interest in various fields such as biology, materials science, and electrochemistry. Here, we present a combined polarized Raman and molecular dynamics investigation of the structural changes that occur as water is added incrementally to propylene carbonate (PC), a polar, aprotic solvent that is important in lithium-ion batteries. Polarized Raman spectra of PC solutions were collected for water mole fractions 0.003 ≤ χwater ≤ 0.296, which encompasses the solubility range of water in PC. The novel approach taken herein provides additional hydrogen bond and solvation characterization of this system that has not been achievable in previous studies. Analysis of the polarized carbonyl Raman band in conjunction with simulations demonstrated that the bulk structure of the solvent remained unperturbed upon the addition of water. Experimental spectra in the O-H stretching region were decomposed through Gaussian fitting into sub-bands and comparison to studies of dilute HOD in D2O. With the aid of simulations, we identified these different bands as water arrangements having different degrees of hydrogen bonding. The observed water structure within PC indicates that water tends to self-aggregate, forming a hydrogen bond network that is distinctly different from the bulk and dependent on concentration. For example, at moderate concentrations, the most likely aggregate structures are chains of water molecules, each with two hydrogen bonds.
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Dopamine is an important amine-based chemical neurotransmitter whose protonated state plays a crucial role in the recognition process. Understanding the structure and protonated state of dopamine at the aqueous interface is desired as the diffusion as well as binding of dopamine with the receptors take place frequently in the aqueous interface region. Vibrational sum frequency generation (VSFG) study of the OH stretch of water at the air/water interface in the presence of dopamine is performed and compared with its analog, phenylethylamine, and catechol. The VSFG data suggest that, unlike the bulk case, the population of the deprotonated amine group of dopamine is higher at the aqueous interface. This study suggests that the structure of dopamine at the aqueous interface is different from the bulk which may be useful in understanding the recognition process of dopamine in the interfacial region.
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Dopamina , Agua , Neurotransmisores , Análisis Espectral/métodos , Propiedades de Superficie , Agua/químicaRESUMEN
BACKGROUND: The mayhem COVID-19 that was ushered by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) was declared pandemic by the World Health Organization in March 2020. Since its initial outbreak in late 2019, the virus has affected hundreds of million adults in the world and killing millions in the process. After the approval of newly developed vaccines, severe challenges remain to manufacture and administer them to the adult population globally in quick time. However, we have witnessed several mutations of the virus leading to 'waves' of viral spread and mortality. WHO has categorized these mutations as variants of concern (VOCs) and variants of interest (VOIs). The mortality due to COVID-19 has also been associated with various comorbidities and improper immune response. This has created further complications in understanding the nature of the SARS-CoV2-host interaction that has fuelled doubts in the efficacy of the approved vaccines. Whether there is requirement of booster dose and whether the impending wave could affect the children are some of the hotly debated topics. MATERIALS AND METHODS: A systematic literature review of PubMed, Medline, Scopus, Google Scholar was utilized to understand the nature of Delta variant and how it alters our T-cell responses and cytokine production and neutralizes vaccine-generated antibodies. CONCLUSION: In this review, we discuss the variants of SARS-CoV2 with specific focus on the Delta variant. We also specifically review the T-cell response against the virus and bring a narrative of various factors that may hold the key to fight against this marauding virus.
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COVID-19 , Vacunas , Adulto , Anticuerpos Antivirales , COVID-19/prevención & control , Vacunas contra la COVID-19 , Niño , Humanos , Pandemias , ARN Viral , SARS-CoV-2 , Linfocitos TRESUMEN
BACKGROUND: Acute diarrhea is an important contributor to under-5 mortality. Green banana is traditionally used as a home-based remedy for diarrhea. OBJECTIVES: To identify the effect of green banana on duration, recovery and prevention of severe dehydration in under-5 children with acute watery diarrhea with no/some dehydration. METHODS: This study was conducted in the rural field practice area of a tertiary care center between January 2020 and December 2021 in under-5 children presenting with acute diarrhea with no/some dehydration. One hundred fifty-three children were divided into group A (received cooked green banana supplementation along with standard management) and group B (received only standard management). Duration of diarrhea, proportion of children recovered, requirement of hospitalization, development of persistent diarrhea and number of diarrheal episodes in 1 year follow-up period were compared between two groups. RESULTS: Green banana supplementation was significantly associated with reduction in duration [median (interquartile range)-4 (1.5) day versus 5.5 (1) day, P < 0.001] of diarrhea, less hospitalization (9.2% versus 22.1%, P = 0.03) and early recovery, both at day 3 (17.1% versus 3.9%, P = 0.007) and day 7 (90.8% versus 77.9%, P = 0.03). Green banana also protected children from the development of persistent diarrhea (7.9% versus 19.5%, P = 0.04). It also reduced future episodes of diarrhea by 40.5%. CONCLUSION: Green banana supplementation could be a promising adjunct therapy in acute diarrhea and thereby it might reduce under-5 mortality.
Acute diarrhea is the second leading cause of under-5 mortality excluding neonatal causes in India where green banana has traditionally been used as a home-based remedy for diarrhea since ancient days. Some of the previous literatures have found promising results of green banana supplementation in prolonged diarrhea, dysentery and hospital management of acute diarrhea but none have considered it in the home management of diarrhea and have not reviewed its role on duration, recovery and prevention of severe dehydration in under-5 children with acute watery diarrhea with no/some dehydration. These issues along with the possible role of green banana in preventing future episodes of diarrhea have been addressed in our study. One hundred fifty-three under-5 children presenting with acute diarrhea with no/some dehydration were studied over 2 years dividing into group A (received cooked green banana supplementation along with standard management) and group B (received only standard management). Green banana supplementation was significantly associated with reduction in duration of diarrhea, less hospitalization and early recovery, lesser incidences of development of persistent diarrhea, and it also significantly reduced the future episodes of diarrhea. Hence, green banana could be a promising adjunct therapy in acute diarrhea and might reduce under-5 mortality.
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Deshidratación , Musa , Niño , Humanos , Lactante , Diarrea/tratamiento farmacológico , Diarrea/complicaciones , FluidoterapiaRESUMEN
Cancer is a disorder that rigorously affects the human population worldwide. There is a steady demand for new remedies to both treat and prevent this life-threatening sickness due to toxicities, drug resistance and therapeutic failures in current conventional therapies. Researchers around the world are drawing their attention towards compounds of natural origin. For decades, human beings have been using the flora of the world as a source of cancer chemotherapeutic agents. Currently, clinically approved anticancer compounds are vincristine, vinblastine, taxanes, and podophyllotoxin, all of which come from natural sources. With the triumph of these compounds that have been developed into staple drug products for most cancer therapies, new technologies are now appearing to search for novel biomolecules with anticancer activities. Ellipticine, camptothecin, combretastatin, curcumin, homoharringtonine and others are plant derived bioactive phytocompounds with potential anticancer properties. Researchers have improved the field further through the use of advanced analytical chemistry and computational tools of analysis. The investigation of new strategies for administration such as nanotechnology may enable the development of the phytocompounds as drug products. These technologies have enhanced the anticancer potential of plant-derived drugs with the aim of site-directed drug delivery, enhanced bioavailability, and reduced toxicity. This review discusses mechanistic insights into anticancer compounds of natural origins and their structural activity relationships that make them targets for anticancer treatments.
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Antineoplásicos , Neoplasias , Antineoplásicos/química , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Humanos , Neoplasias/tratamiento farmacológico , Plantas , Podofilotoxina/química , Relación Estructura-ActividadRESUMEN
BACKGROUND: Prosthetic joint infection (PJI) is a potentially limb-threatening complication of total knee arthroplasty. Phage therapy is a promising strategy to manage such infections including those involving antibiotic-resistant microbes, and to target microbial biofilms. Experience with phage therapy for infections associated with retained hardware is limited. A 62-year-old diabetic man with a history of right total knee arthroplasty 11 years prior who had suffered multiple episodes of prosthetic knee infection despite numerous surgeries and prolonged courses of antibiotics, with progressive clinical worsening and development of severe allergies to antibiotics, had been offered limb amputation for persistent right prosthetic knee infection due to Klebsiella pneumoniae complex. Intravenous phage therapy was initiated as a limb-salvaging intervention. METHODS: The patient received 40 intravenous doses of a single phage (KpJH46Φ2) targeting his bacterial isolate, alongside continued minocycline (which he had been receiving when he developed increasing pain, swelling, and erythema prior to initiation of phage therapy). Serial cytokine and biomarker measurements were performed before, during, and after treatment. The in vitro anti-biofilm activity of KpJH46Φ2, minocycline and the combination thereof was evaluated against a preformed biofilm of the patient's isolate and determined by safranin staining. RESULTS: Phage therapy resulted in resolution of local symptoms and signs of infection and recovery of function. The patient did not experience treatment-related adverse effects and remained asymptomatic 34 weeks after completing treatment while still receiving minocycline. A trend in biofilm biomass reduction was noted 22 hours after exposure to KpJH46Φ2 (Pâ =â .063). The addition of phage was associated with a satisfactory outcome in this case of intractable biofilm-associated prosthetic knee infection. Pending further studies to assess its efficacy and safety, phage therapy holds promise for treatment of device-associated infections.
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Artroplastia de Reemplazo de Rodilla , Terapia de Fagos , Infecciones Relacionadas con Prótesis , Antibacterianos/uso terapéutico , Artroplastia de Reemplazo de Rodilla/efectos adversos , Biopelículas , Humanos , Klebsiella pneumoniae , Masculino , Persona de Mediana Edad , Infecciones Relacionadas con Prótesis/tratamiento farmacológicoRESUMEN
Hydrated proton at membrane interfaces plays an important role in the bioenergetic process of almost all organisms. Herein, the signature of the hydrated proton at membrane interfaces has been investigated by measuring the vibrational sum frequency generated (VSFG) spectra of negatively charged and zwitterionic lipids in the presence of different concentrations of acids. The addition of acids decreases the intensity of the OH stretch of the VSFG signal of water present at the negatively charged and zwitterionic lipids along with the enhanced intensity of the broad VSFG signal in the range of 2500-2800 cm-1. The enhanced intensity of the broad continuum observed in the range of 2500-2800 cm-1 has been assigned to the signature of the hydrated proton at the lipid interfaces. The decrease in the VSFG signal of the OH stretch of water along with the appearance of the broad signal suggests that the hydrated proton exists in the vicinity of the lipid interfaces and restructures the interaction between the interfacial water molecules.
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Propofol, the most administered drug for general anesthesia, affects the acid-base equilibrium at the interfacial region of arterial blood. Hence, the structure of propofol at the water interface under different pH conditions has been measured using the surface-selective vibrational sum frequency generation (VSFG) technique to understand the hydration as well as the dissociation of propofol at the water interface. Propofol remains in its neutral form at pH ≤ 5.8 in which the OH group of propofol forms a hydrogen bond with interfacial water molecules, where a few interfacial water molecules also interact with the π electron density of propofol. By contrast, propofol prefers to be in the deprotonated state at pH ≥ 7, due to which the surface of water becomes negatively charged and hence the interfacial water becomes oriented and the intensity of the OH stretch of water is enhanced. The pKa of propofol at the water interface is â¼three units lower than in the bulk medium indicating that the dissociation of propofol is notably enhanced at the water interface. These VSFG studies suggest that, unlike the bulk, propofol prefers to be in the charged state at the water interface under physiological conditions, which may be important in understanding its diffusion and acid-base equilibrium in the interfacial arterial blood region.
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Propofol/química , Agua/química , Concentración de Iones de Hidrógeno , Estructura Molecular , Propiedades de Superficie , VibraciónRESUMEN
Cartilage is avascular with limited to no regenerative capacity, so its loss could be a challenge for reconstructive surgery. Current treatment options for damaged cartilage are also limited. In this aspect there is a tremendous need to develop an ideal cartilage-mimicking biomaterial that could repair maxillofacial defects. Considering this fact in this study we have prepared twelve silicone-based materials (using Silicone 40, 60, and 80) reinforced with hydroxyapatite, tri-calcium phosphate, and titanium dioxide which itself has proven their efficacy in several studies and able to complement the shortcomings of using silicones. Among the mechanical properties (Young's modulus, tensile strength, percent elongation, and hardness), hardness of Silicone-40 showed similarities with goat ear (P > .05). Silicone peaks have been detected in FTIR. Both AFM morphology and SEM images of the samples confirmed more roughed surfaces. All the materials were nonhemolytic in hemocompatibility tests, but among the twelve materials S2, S3, S5, and S6 showed the least hemolysis. For all tested bacterial strains, adherence was lower on each material than that grown on the plain industrial silicone material which was used as a positive control. S2, S3, S5, and S6 samples were selected as the best based on mechanical characterizations, surface characterizations, in vitro hemocompatibility tests and bacterial adherence activity. So, outcomes of this present study would be promising when developing ideal cartilage-mimicking biocomposites and their emerging applications to treat maxillofacial defects due to cartilage damage.
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Materiales Biocompatibles/química , Materiales Biomiméticos/química , Cartílago/química , Siliconas/química , Fosfatos de Calcio/química , Durapatita/química , Dureza , Humanos , Ensayo de Materiales , Resistencia a la Tracción , Titanio/químicaRESUMEN
Cancer or uncontrolled cell proliferation is a major health issue worldwide and is the second leading cause of deaths globally. The high mortality rate and toxicity associated with cancer chemotherapy or radiation therapy have encouraged the investigation of complementary and alternative treatment methods, such as plant-based drugs. Moreover, over 60% of the anti-cancer drugs are molecules derived from plants or their synthetic derivatives. Therefore, in the present review, an attempt has been made to summarize the cytotoxic plants available in the Indian subcontinent along with a description of their bio-active components. The review covers 99 plants of 57 families as well as over 110 isolated bioactive cytotoxic compounds, amongst which at least 20 are new compounds. Among the reported phytoconstituents, artemisinin, lupeol, curcumin, and quercetin are under clinical trials, while brazilin, catechin, ursolic acid, ß-sitosterol, and myricetin are under pharmacokinetic development. However, for the remaining compounds, there is little or no information available. Therefore, further investigations are warranted on these subcontinent medicinal plants as an important source of novel cytotoxic agents.
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Extractos Vegetales/química , Extractos Vegetales/farmacología , Plantas Medicinales/química , Antineoplásicos/química , Antineoplásicos/aislamiento & purificación , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Humanos , Estructura Molecular , Extractos Vegetales/aislamiento & purificación , Análisis EspectralRESUMEN
In the present study protein was isolated from tamarind seed powder and was subjected to ultrasonication by varying the time (15 and 30 min) and intensity (100 and 200 W) of treatment. The effect of the ultrasound treatment on the various properties like solubility, emulsifying property, foaming property, water holding capacity, oil holding capacity, particle density and molecular weight was investigated. The solubility, emulsifying property, foaming property, water holding capacity and oil holding capacity of the ultrasonically treated tamarind seed protein isolates improved after treatment and was found to increase with time or intensity of the treatment. The particle density slightly decreased after ultrasonication, but significant differences could not be observed for the different treatment conditions. The SDS-PAGE profiling did not reveal any differences in the molecular weights of the treated and untreated proteins, implying that ultrasonication did not affect the primary structure of the proteins. It can be concluded from the study that ultrasonication can be used to improve the functional properties of tamarind seed protein isolates and therefore has potential for use in various food and non-food applications.
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Interaction of α-Synuclein (αS) with biological lipids is crucial for the onset of its fibrillation at the cell membrane/water interface. Probed herein is the interaction of αS with membrane-mimicking lipid monolayer/water interfaces. The results depict that αS interacts negligibly with zwitterionic lipids, but strongly affects the pristine air/water and charged lipid/water interfaces by perturbing the structure and orientation of the interfacial water. The net negative αS (-9 in bulk water; pHâ 7.4) reorients the water as hydrogen-up (H-up) at the air/water interface, and electrostatically interacts with positively charged lipids, making the interface nearly net neutral. αS also interacts with negatively charged lipids: the net H-up orientation of the interfacial water decreases at the anionic lipid/water interface, revealing a domain-specific interaction of net negative αS with the negatively charged lipids at the membrane surface.
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Fosfolípidos/química , Agua/química , alfa-Sinucleína/química , Secuencia de Aminoácidos , Humanos , Estructura Molecular , Análisis Espectral , Propiedades de SuperficieRESUMEN
A patient with a trauma-related left tibial infection associated with extensively drug-resistant Acinetobacter baumannii and multidrug-resistant Klebsiella pneumoniae was treated with bacteriophages and antibiotics. There was rapid tissue healing and positive culture eradication. As a result, the patient's leg did not have to be amputated and he is undergoing rehabilitation.
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Antibacterianos/uso terapéutico , Bacteriófagos/fisiología , Infección de Heridas/tratamiento farmacológico , Infección de Heridas/terapia , Infecciones por Acinetobacter/tratamiento farmacológico , Infecciones por Acinetobacter/terapia , Acinetobacter baumannii/efectos de los fármacos , Acinetobacter baumannii/patogenicidad , Adulto , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Humanos , Klebsiella pneumoniae/patogenicidad , MasculinoRESUMEN
Bacteriophage therapy (BT) uses bacteriophages to treat pathogenic bacteria and is an emerging strategy against multidrug-resistant (MDR) infections. Experience in solid organ transplant is limited. We describe BT in 3 lung transplant recipients (LTR) with life-threatening MDR infections caused by Pseudomonas aeruginosa (n = 2) and Burkholderia dolosa (n = 1). For each patient, lytic bacteriophages were selected against their bacterial isolates. BT was administered for variable durations under emergency Investigational New Drug applications and with patient informed consent. Safety was assessed using clinical/laboratory parameters and observed clinical improvements described, as appropriate. All patients received concurrent antibiotics. Two ventilator-dependent LTR with large airway complications and refractory MDR P. aeruginosa pneumonia received BT. Both responded clinically and were discharged from the hospital off ventilator support. A third patient had recurrent B. dolosa infection following transplant. Following BT initiation, consolidative opacities improved and ventilator weaning was begun. However, infection relapsed on BT and the patient died. No BT-related adverse events were identified in the 3 cases. BT was well tolerated and associated with clinical improvement in LTRs with MDR bacterial infection not responsive to antibiotics alone. BT may be a viable adjunct to antibiotics for patients with MDR infections.
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Infecciones Bacterianas/prevención & control , Infecciones Bacterianas/terapia , Farmacorresistencia Bacteriana Múltiple , Enfermedades Pulmonares/cirugía , Trasplante de Pulmón , Terapia de Fagos/métodos , Adulto , Anciano , Antibacterianos/uso terapéutico , Burkholderia , Femenino , Humanos , Enfermedades Pulmonares/complicaciones , Enfermedades Pulmonares/microbiología , Trasplante de Pulmón/efectos adversos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias , Pseudomonas aeruginosa , Infecciones del Sistema Respiratorio/microbiología , Receptores de TrasplantesRESUMEN
Widespread antibiotic use in clinical medicine and the livestock industry has contributed to the global spread of multidrug-resistant (MDR) bacterial pathogens, including Acinetobacter baumannii We report on a method used to produce a personalized bacteriophage-based therapeutic treatment for a 68-year-old diabetic patient with necrotizing pancreatitis complicated by an MDR A. baumannii infection. Despite multiple antibiotic courses and efforts at percutaneous drainage of a pancreatic pseudocyst, the patient deteriorated over a 4-month period. In the absence of effective antibiotics, two laboratories identified nine different bacteriophages with lytic activity for an A. baumannii isolate from the patient. Administration of these bacteriophages intravenously and percutaneously into the abscess cavities was associated with reversal of the patient's downward clinical trajectory, clearance of the A. baumannii infection, and a return to health. The outcome of this case suggests that the methods described here for the production of bacteriophage therapeutics could be applied to similar cases and that more concerted efforts to investigate the use of therapeutic bacteriophages for MDR bacterial infections are warranted.
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Infecciones por Acinetobacter/terapia , Acinetobacter baumannii/efectos de los fármacos , Antibacterianos/uso terapéutico , Bacteriófagos/clasificación , Seudoquiste Pancreático/terapia , Pancreatitis Aguda Necrotizante/terapia , Terapia de Fagos/métodos , Infecciones por Acinetobacter/microbiología , Acinetobacter baumannii/aislamiento & purificación , Acinetobacter baumannii/virología , Anciano , Farmacorresistencia Bacteriana Múltiple , Cálculos Biliares/patología , Humanos , Masculino , Minociclina/uso terapéutico , Seudoquiste Pancreático/microbiología , Pancreatitis Aguda Necrotizante/microbiologíaRESUMEN
The local structures between water-water, alcohol-water and alcohol-alcohol have been investigated for aqueous mixtures of ethanol (ETH) and monofluoroethanol (MFE) by the deconvolution of IR bands in the OH stretching region, molecular dynamics simulation and quantum chemical calculations. It has been found that the addition of a small amount of ETH into the aqueous medium increases the strength of the hydrogen bonds between water molecules. In an aqueous mixture of MFE, the substitution of a single fluorine induces a change in the orientation as well as the hydrogen bonding site of water molecules from the oxygen to the fluorine terminal of MFE. The switching of the hydrogen bonding site of water in the aqueous mixture of MFE results in comparatively strong hydrogen bonds between MFE and water molecules as well as less clustering of water molecules, unlike the case of the aqueous mixture of ETH. These findings about the modification of a hydrogen bond network by the hydrophobic fluorine group probably make fluorinated molecules useful for pharmaceutical as well as biological applications.
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The presence of the fluorocarbon group in fluorinated alcohols makes them an important class of molecules that have diverse applications in the field of separation techniques, synthetic chemistry, polymer industry, and biology. In this paper, we have performed the density function theory calculation along with atom in molecule analysis, molecular dynamics simulation, and IR measurements of bulk monofluoroethanol (MFE) and compared them with the data for bulk ethanol (ETH) to understand the effect of the fluorocarbon group in the structure and the hydrogen bond network of bulk MFE. It has been found that the intramolecular O-H···F hydrogen bond is almost absent in bulk MFE. Molecular dynamics simulation and density function theory calculation along with atom in molecule analysis clearly depict that in the case of bulk MFE, a significant amount of intermolecular O-H···F and C-H···F hydrogen bonds are present along with the intermolecular O-H···O hydrogen bond. The presence of intermolecular O-H···F and C-H···F hydrogen bonds causes the difference in the IR spectrum of bulk MFE as compared to bulk ETH. This study clearly depicts that the organic fluorine (fluorocarbon) of MFE acts as a hydrogen bond acceptor and plays a significant role in the structure and hydrogen bond network of bulk MFE through the formation of weak O-H···F as well C-H···F hydrogen bonds, which may be one of the important reasons behind the unique behavior of the fluoroethanols.