- An Unusual Presentation of Nocardiosis in an Allogeneic Transplant Recipient. [Journal Article]
- CCureus 2016 Oct 17; 8(10):e834
- Nocardiosis is a rare cause of opportunistic infection post hematopoietic stem cell transplant (HSCT) occurring in about 0.3% of patients. The risk factors include delayed immune reconstitution, prol...
Nocardiosis is a rare cause of opportunistic infection post hematopoietic stem cell transplant (HSCT) occurring in about 0.3% of patients. The risk factors include delayed immune reconstitution, prolonged neutropenia, and graft-versus-host disease. The most common site of infection is the lung, followed by the brain and the skin. Concomitant pulmonary and central nervous system (CNS) nocardiosis is an extremely rare entity as presented in our case. We present the case of a 72-year-old male at 137 days post transplant presenting with complaints of headache and slurred speech. A magnetic resonance imaging (MRI) brain scan revealed two ring-enhancing lesions: 1.6 cm in the right frontal lobe and 1 cm in the left parietal lobe. The patient had an outpatient computed tomography (CT) chest scan a month prior showing a 1.4 cm solid right upper lobe nodule prompting bronchoalveolar lavage (BAL) that was nondiagnostic. On repeat inpatient CT chest scan, the nodule had increased in size to 3.3 x 2.5 x 2.1 cm, prompting a percutaneous fine-needle aspiration biopsy. He was started on empiric trimethoprim-sulfamethoxazole (TMP-SMX) and liposomal amphotericin B. The tissue mycology and acid-fast cultures were reported positive for nocardia species. The patient was discharged on intravenous TMP-SMX. A follow-up CT chest scan and MRI brain scan four months later showed resolution of the right upper lobe nodule and significant decrease in size of the brain lesions. The patient will continue TMP-SMX for a total of nine to 12 months. Given the increase in transplant recipients and the ongoing risk of developing nocardiosis several months post transplant, there is a need for standardized diagnostic and treatment guidelines. Meanwhile, our case highlights the importance of aggressiveness in pursuing a prompt diagnosis including invasive procedures, if required, in order to begin specific treatment.
- Arene guest selectivity and pore flexibility in a metal-organic framework with semi-fluorinated channel walls. [Journal Article]
- PTPhilos Trans A Math Phys Eng Sci 2017 Jan 13; 375(2084)
- A metal-organic framework (MOF) with one-dimensional channels of approximately hexagonal cross-section [Ag2(O2CCF2CF2CO2)(TMP)] 1: (TMP =2,3,5,6-tetramethylpyrazine) has been synthesized with MeOH fi...
A metal-organic framework (MOF) with one-dimensional channels of approximately hexagonal cross-section [Ag2(O2CCF2CF2CO2)(TMP)] 1: (TMP =2,3,5,6-tetramethylpyrazine) has been synthesized with MeOH filling the channels in its as-synthesized form as [Ag2(O2CCF2CF2CO2)(TMP)]·n(MeOH) 1-MEOH: (n = 1.625 by X-ray crystallography). The two types of ligand connect columns of Ag(I) centres in an alternating manner, both around the channels and along their length, leading to an alternating arrangement of hydrocarbon (C-H) and fluorocarbon (C-F) groups lining the channel walls, with the former groups projecting further into the channel than the latter. MeOH solvent in the channels can be exchanged for a variety of arene guests, ranging from xylenes to tetrafluorobenzene, as confirmed by gas chromatography, (1)H nuclear magnetic resonance (NMR) spectroscopy, thermogravimetric analysis and (13)C cross-polarization magic angle spinning NMR spectroscopy. Alkane and perfluoroalkane guests, however, do not enter the channels. Although exhibiting some stability under a nitrogen atmosphere, sufficient to enable crystal structure determination, the evacuated MOF 1: is unstable for periods of more than minutes under ambient conditions or upon heating, whereupon it undergoes an irreversible solid-state transformation to a non-porous polymorph 2: , which comprises Ag2(O2CCF2CF2CO2) coordination layers that are pillared by TMP ligands. This transformation has been followed in situ by powder X-ray diffraction and shown to proceed via a crystalline intermediate.This article is part of the themed issue 'Coordination polymers and metal-organic frameworks: materials by design'.
- Ligustrazine-Oleanolic Acid Glycine Derivative, G-TOA, Selectively Inhibited the Proliferation and Induced Apoptosis of Activated HSC-T6 Cells. [Journal Article]
- MMolecules 2016 Nov 23; 21(11)
- Hepatic fibrosis is a naturally occurring wound-healing reaction, with an imbalance of extracellular matrix (ECM) during tissue repair response, which can further deteriorate to hepatocellular carcin...
Hepatic fibrosis is a naturally occurring wound-healing reaction, with an imbalance of extracellular matrix (ECM) during tissue repair response, which can further deteriorate to hepatocellular carcinoma without timely treatment. Inhibiting activated hepatic stellate cell (HSC) proliferation and inducing apoptosis are the main methods for the treatment of liver fibrosis. In our previous study, we found that the TOA-glycine derivative (G-TOA) had exhibited more significant inhibitory activity against HepG2 cells and better hydrophilicity than TOA, ligustrazine (TMP), and oleanolic acid (OA). However, inhibiting activated HSC proliferation and inducing apoptosis by G-TOA had not been reported. In this paper, the selective cytotoxicity of G-TOA was evaluated on HSC-T6 cells and L02 cells, and apoptosis mechanisms were explored. It was found that G-TOA could selectively inhibit the proliferation of activated HSC-T6 cells, induce morphological changes, early apoptosis, and mitochondrial membrane potential depolarization, increase intracellular free calcium levels, downregulate the expression of NF-κB/p65 and COX-2 protein, and decrease the ratio of Bcl-2/Bax, thereby inducing HSC-T6 cell apoptosis. Thence, G-TOA might be a potential antifibrosis agent for the therapy of hepatic fibrosis, provided that it exerts anti-fibrosis effects on activated HSC-T6 cells.
- Disseminated nocardiosis caused by Nocardia otitidiscaviarum in an immunocompetent host: A case report and literature review. [Journal Article]
- ETExp Ther Med 2016; 12(5):3339-3346
- The aim of the present study was to summarize the clinical characteristics of nocardiosis caused by Nocardia otitidiscaviarum in order to improve the knowledge of nocardiosis. A case of dissemination...
The aim of the present study was to summarize the clinical characteristics of nocardiosis caused by Nocardia otitidiscaviarum in order to improve the knowledge of nocardiosis. A case of dissemination nocardiosis caused by N. otitidiscaviarum in an immunocompetent host is reported and the associated literature reviewed. Informed consent for publication of this case report was provided by the patient. The present patient was a young immunocompetent man suffering from disseminated nocardiosis induced by infection with N. otitidiscaviarum. Following a poor response to β-lactam antibiotic, a combination of sulfonamide with minocycline was administered, which successfully ameliorated the symptoms. Previous studies published in English were retrieved from PubMed with 'Nocardia otitidiscaviarum' used as the search keyword. A total of 23 articles were retrieved from the PubMed database, supporting the assertion that N. otitidiscaviarum is a rare Nocardia species. Among these 23 cases, there were 11 cases of lymphocutaneous (48%), 5 of pulmonary (22%), 2 of brain (9%) and 1 of pyothorax (4%) infection, and 4 cases of disseminated infections (17%). Analysis of the immune state of these patients demonstrated that 9 were immunocompetent (39%), 7 of whom had cutaneous infections (30%) with a predominant history of trauma (6/7), and 14 were immunosuppressed, 9 of whom were treated with prednisolone. Microbiology and histopathology were necessary in all cases for definite diagnosis. Among the 13 cases who underwent drug susceptibility testing, 10 cases were sensitive to trimethoprim-sulfamethoxazole (TMP-SMX) and 12 cases were sensitive to aminoglycoside. In conclusion, although N. otitidiscaviarum is one of the less commonly isolated species of Nocardia, it is capable of inducing localized or disseminated infection, even in an immunocompetent host. The majority of cases respond well to TMP-SMX and aminoglycoside, but the therapeutic action of cephalosporin is weak. Identification of bacteria and drug sensitivity tests for Nocardia is critical for guiding clinical treatment.
- Understanding the role of hydrogen bonding in Brønsted acidic ionic liquid-catalyzed transesterification: a combined theoretical and experimental investigation. [Journal Article]
- PCPhys Chem Chem Phys 2016 Nov 23
- Brønsted acidic ionic liquids (BAILs) can play a dual role, as a solvent and as a catalyst, in many reactions. However, molecular details of the catalytic mechanism are poorly understood. We present ...
Brønsted acidic ionic liquids (BAILs) can play a dual role, as a solvent and as a catalyst, in many reactions. However, molecular details of the catalytic mechanism are poorly understood. We present here a density functional theory (DFT) study for the catalytic mechanism of the transesterification of methyl ester (ME) with trimethylolpropane (TMP), in the presence of three representative BAILs, namely, N-methylimidazole-IL, pyridinium-IL, and triethylamine-IL. The deprotonation of the BAIL cation and the transesterification step are investigated. Key inter- and intra-molecular hydrogen bonds (HBs) that govern the catalytic performance of BAILs were identified and analyzed using natural bond orbital (NBO) and atoms in molecule (AIM) methods. For the deprotonation of BAILs, it was found that the intermolecular O-HO HB between the hydroxyl group of TMP and the oxygen of the sulfonic group of BAIL was indispensable for proton transfer. DFT computed free energy barriers for the transesterification step are in excellent agreement with the experimental results only after taking into account the BAIL cation-anion interaction in terms of HBs in which the O-HO between the hydroxyl group of the anion and the oxygen of the sulfonic group of the cation was the strongest HB, suggesting the role of the anion in governing the catalytic activity of BAILs. The existence of the HBs suggested by DFT calculations was further validated using in situ FTIR experiments/ATR-FTIR.
- Study of local intracellular signals regulating axonal morphogenesis using a microfluidic device. [Journal Article]
- STSci Technol Adv Mater 2016; 17(1):691-697
- The establishment and maintenance of axonal patterning is crucial for neuronal function. To identify the molecular systems that operate locally to control axonal structure, it is important to manipul...
The establishment and maintenance of axonal patterning is crucial for neuronal function. To identify the molecular systems that operate locally to control axonal structure, it is important to manipulate molecular functions in restricted subcellular areas for a long period of time. Microfluidic devices can be powerful tools for such purposes. In this study, we demonstrate the application of a microfluidic device to clarify the function of local Ca(2+) signals in axons. Membrane depolarization significantly induced axonal branch-extension in cultured cerebellar granule neurons (CGNs). Local application of nifedipine using a polydimethylsiloxane (PDMS)-based microfluidic device demonstrated that Ca(2+) entry from the axonal region via L-type voltage-dependent calcium channels (L-VDCC) is required for branch extension. Furthermore, we developed a method for locally controlling protein levels by combining genetic techniques and use of a microfluidic culture system. A vector for enhanced green fluorescent protein (EGFP) fused to a destabilizing domain derived from E. coli dihydrofolate reductase (ecDHFR) is introduced in neurons by electroporation. By local application of the DHFR ligand, trimethoprim (TMP) using a microfluidic device, we were able to manipulate differentially the level of fusion protein between axons and somatodendrites. The present study revealed the effectiveness of microfluidic devices to address fundamental biological issues at subcellular levels, and the possibility of their development in combination with molecular techniques.
- Fractal Geometry-Based Decrease in Trimethoprim-Sulfamethoxazole Concentrations in Overweight and Obese People. [Journal Article]
- CPCPT Pharmacometrics Syst Pharmacol 2016 Nov 21
- Trimethoprim-sulfamethoxazole (TMP-SMX) is one of the most widely drugs on earth. The World Health Organization recommends it as an essential basic drug for all healthcare systems. Dosing is inconsis...
Trimethoprim-sulfamethoxazole (TMP-SMX) is one of the most widely drugs on earth. The World Health Organization recommends it as an essential basic drug for all healthcare systems. Dosing is inconsistently based on weight, assuming linear relationships. Given that obesity is now a global "pandemic" it is vital that we evaluate the effect of obesity on trimethoprim-sulfamethoxazole concentrations. We conducted a prospective clinical experiment based on optimized design strategies and artificial intelligence algorithms and found that weight and body mass index (BMI) had a profound effect on drug clearance and volume of distribution, and followed nonlinear fractal geometry-based relationships. The findings were confirmed by demonstrating decreased TMP-SMX peak and area under the concentration-time curves in overweight patients based on standard regression statistics. The nonlinear relationships can now be used to identify new TMP-SMX doses in overweight and obese patients for each of the infections caused by the >60 pathogens for which the drug is indicated.
- Long-term wastewater irrigation of vegetables in real agricultural systems: Concentration of pharmaceuticals in soil, uptake and bioaccumulation in tomato fruits and human health risk assessment. [Journal Article]
- WRWater Res 2016 Nov 10; 109:24-34
- Wastewater (WW) reuse for vegetable crops irrigation is regularly applied worldwide. Such a practice has been found to allow the uptake of pharmaceutical active compounds (PhACs) by plants and their ...
Wastewater (WW) reuse for vegetable crops irrigation is regularly applied worldwide. Such a practice has been found to allow the uptake of pharmaceutical active compounds (PhACs) by plants and their subsequent entrance to the food web, representing an important alternative pathway for the exposure of humans to PhACs, with potential health implications. Herein we report the impacts of the long-term (three consecutive years) WW irrigation of a tomato crop with two differently treated effluents under real agricultural conditions, on (1) the soil concentration of selected PhACs (i.e. diclofenac, DCF; sulfamethoxazole, SMX; trimethoprim, TMP), (2) the bioaccumulation of these PhACs in tomato fruits, and (3) the human risks associated with the consumption of WW-irrigated fruits. Results revealed that the concentration of the studied PhACs in both the soil and tomato fruits varied depending on the qualitative characteristics of the treated effluent applied and the duration of WW irrigation. The PhAC with the highest soil concentration throughout the studied period was SMX (0.98 μg kg(-1)), followed by TMP (0.62 μg kg(-1)) and DCF (0.35 μg kg(-1)). DCF was not found in tomato fruits harvested from WW-irrigated plants during the first year of the study. However, DCF displayed the highest fruit concentration (11.63 μg kg(-1)) throughout the study (as a result of prolonged WW irrigation), followed by SMX (5.26 μg kg(-1)) and TMP (3.40 μg kg(-1)). The calculated fruit bioconcentration factors (BCFF) were extremely high for DCF in the 2nd (108) and 3rd year (132) of the experimental period, with the respective values for SMX (0.5-5.4) and TMP (0.2-6.4) being significantly lower. The estimated threshold of toxicity concern (TTC) and hazard quotients (HQ) values revealed that the consumption of fruits harvested from tomato plants irrigated for long period with the WW applied for irrigation under field conditions in this study represent a de minimis risk to human health. However, more studies need to be performed in order to obtain more solid information on the safety of WW reuse for irrigation.
- Six-membered cyclic carbonates from trimethylolpropane: Lipase-mediated synthesis in a flow reactor and in silico evaluation of the reaction. [Journal Article]
- BPBiotechnol Prog 2016 Nov 14
- Six-membered cyclic carbonates with hydroxyl and methoxycarbonyloxy functional groups were prepared by transesterification of trimethylolpropane (TMP) with dimethylcarbonate (DMC) by solvent-free lip...
Six-membered cyclic carbonates with hydroxyl and methoxycarbonyloxy functional groups were prepared by transesterification of trimethylolpropane (TMP) with dimethylcarbonate (DMC) by solvent-free lipase-mediated flow reaction followed by thermal cyclization. The flow reaction efficiency was evaluated using different configurations of reactor consisting of packed beds of Novozym®435 (immobilized Candida antarctica lipase B-CalB-a.k.a. N435) and molecular sieves, flowrate, and biocatalyst loads. The mixed column of the biocatalyst and molecular sieves, allowing rapid and efficient removal of the by-product-methanol-was the most efficient setup. Higher conversion (81.6%) in the flow reaction compared to batch process (72%) was obtained using same amount of N435 (20% (w/w) N435:TMP) at 12 h, and the undesirable dimer and oligomer formation were suppressed. Moreover, the product was recovered easily without extra separation steps, and the biocatalyst and the molecular sieves remained intact for subsequent regeneration and recycling. The reaction of CalB with DMC and the primary transesterification product, monocarbonated TMP, respectively, as acyl donors was evaluated by in silico modeling and empirically to determine the role of the enzyme in the formation of cyclic carbonates and other side products. DMC was shown to be the preferred acyl donor, suggesting that TMP and its carbonated derivatives serve only as acyl acceptors in the lipase-catalyzed reaction. Subsequent cyclization to cyclic carbonate is catalyzed at increased temperature and not by the enzyme. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 2016.
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- Metal-free Synthesis of Aryl Amines: Beyond Nucleophilic Aromatic Substitution. [Journal Article]
- ACAngew Chem Int Ed Engl 2016 Nov 16
- A mild and metal-free approach to C-N coupling is described that employs diaryliodonium salt electrophiles and secondary aliphatic amine nucleophiles. This reaction results in direct ipso-substitutio...
A mild and metal-free approach to C-N coupling is described that employs diaryliodonium salt electrophiles and secondary aliphatic amine nucleophiles. This reaction results in direct ipso-substitution of the iodonium moiety and unsymmetrical aryl(TMP)iodonium salts are primarily employed. Moreover, arene substituents and substitution patterns that currently pose a challenge to classical metal-free methods are accommodated and the alicyclic amine nucleophiles used here are unprecedented in other contemporary metal-free C-N coupling reactions.