Search

Introduction The integration of Point of Care Ultrasound (POCUS) into the care of trauma patients, specifically the E-FAST, has improved the accuracy of initial diagnoses and improved time to surgical intervention in critically ill patients. Physician assistants (PAs) are critically important members of any military trauma resuscitation team and are often team leaders in a pre-hospital setting. They may receive training in ultrasound but there are little data to support their use or evaluate their effectiveness in using POCUS. We designed a study to evaluate the image quality of an E-FAST Exam performed by Emergency Medicine Physician Assistant (EMPA) Fellows and Emergency Medicine (EM) Interns following identical training. Our hypothesis is that image quality obtained by EMPAs will be non-inferior to those images obtained by EM Interns. Materials and Methods This is a prospective single-blinded study comparing the image quality of E-FAST exams performed by first year EM interns and first year EMPA fellows. All participants completed standard POCUS training prior to enrollment in the study. A total of 8 EMPAs and 8 EM first year residents completed 10 recorded E-FAST exams to be used as study images. Participants also viewed a 15-question slide show containing images of positive (6) and negative (9) E-FAST exams and recorded their interpretations. Images were reviewed by expert reviewers who were blinded to which images were collected by which group. An image quality score was recorded for each view as well as an overall image quality score. Image quality was rated on a 1 to 5 image quality scale. Results For overall image quality, the mean score for EMPAs was 3.6 ± 0.5 and for EM residents was 3.2 ± 0.5 with statistical significance favoring better image quality from the EMPAs. The time to completion for the EFAST exam for EMPAs was 4.8 ± 1.3 minutes and for interns it was 3.4 ± 1.4 minutes (P value = 0.02). There was no difference in image interpretation quiz scores between the groups (mean score 92% among interns and 95% among PAs). Conclusions POCUS is an imaging modality which is very portable and relatively inexpensive which makes it ideal for military medicine. PAs are essential members of military trauma teams, and often run an initial trauma resuscitation. Being able to correctly identify patients who have free fluid early in the course of treatment allows for more correct evacuation criteria to ensure the sickest patients get to care the fastest. Although there are limited data to support POCUS use by non-physicians, our data support a growing body of evidence that it is not the profession or baseline medical education that determines an individual's ability to use and incorporate ultrasound into bedside and clinical practice. Our study shows that with training and experience PAs or other members of the military health care team can use the EFAST to better care for trauma patients. [ABSTRACT FROM AUTHOR]

Objectives Neoadjuvant chemotherapy (NACT) is recommended for muscle-invasive bladder cancer, and robust treatment response may result in lack of grossly identifiable tumor in the cystectomy specimen. Current gross examination and reporting protocols, however, do not include specific guidance on the approach to these specimens. Methods A Qualtrics survey was disseminated by email and X (formerly Twitter). Responses from pathologists and pathologists' assistants (PAs) were included. The survey interrogated demographics, practice settings, prevalence of NACT use, approach to gross examination, and reporting practices in the setting of both grossly visible tumor or ulcer bed and the complete absence of a gross lesion. Results Based on 55 respondents' experience, identifying gross tumor occurred less frequently than tumor or ulcer bed (40% vs 71%). Lack of identification of any gross lesions was estimated to occur in 29% of cases. Gross examination practices were relatively consistent in cases with residual gross tumor or gross tumor bed, with agreement that gross tumor should be submitted as 1 block per centimeter (66%), and tumor or ulcer bed should be submitted in its entirety (97%). Gross examination practices appeared more varied when no gross lesions were identified. Overall, most responders stated they "definitely" or "maybe" support a standardized gross examination (89%) and reporting (96%) protocol. Conclusions With the increased use of NACT, lack of any gross lesion leads to inconsistent gross examination techniques. This study provides insight into the current approach to examination of post-NACT cystectomies and suggests that a desire exists among pathologists and pathologists' assistants for more standardized practice. [ABSTRACT FROM AUTHOR]

Tuberculosis treatment with the first-line agents becomes ineffective due to multidrug resistance. Therefore, the importance of the second-line drugs, including p-amino-salicylic acid, is steadily increasing. The parenteral administration of p-aminosalicylic acid in the form of a sodium salt is compromised due to its partial decomposition by gastric juice and liver. The inhalation delivery, which provides rapid administration of both topical and systemic drugs, is a promising alternative approach. At the same time, creating an amorphous form of the active pharmaceutical ingredient by forming solid dispersions makes it possible to further increase the rate of its dissolution. In the present work, microspherical particles of solid dispersions of p-aminosalicylic acid with polyvinylpyrrolidone of various molecular weights were prepared. For all formulations, physicochemical characteristics and dissolution profiles were obtained. The results of this study enable development of a technique for creating microspherical particles of solid dispersions of drugs suitable for inhalation administration. [ABSTRACT FROM AUTHOR]

The bone impaction grafting through femoral head–neck fenestration was a favorable hip preservation procedure but without prognosis estimation. This study retrospectively reviewed 79 patients' clinical data (114 hips) with osteonecrosis of the femoral head (ONFH) who underwent this procedure from June 2009 to June 2019. By the end of June 2022, the median survival time of the hip was (74.13 ± 44.88) months, and the success rate of hip preservation was 68.42%. Lateral reserved angle (LPA) and combined reserved angle (CPA) had statistically significant differences (P  < 0.001) both in univariate analysis and a multivariate logistic regression model. The multivariate logistic regression model of area under curve (AUC) area of the receiver operating characteristic (ROC) curve was 0.931(sensitivity = 95.00%, specificity = 88.40%, log-rank test: P  < 0.01), and the calibration curve indicated good prediction accuracy. The ROC analysis and Cox proportional hazards regression model revealed that the cutoff point of LPA was 50.95° (sensitivity = 95.00%, specificity = 72.09%, log-rank test: P  < 0.05) and the cutoff point of CPA was 90.51° (sensitivity = 90.00%, specificity = 90.70%, log-rank test: P  < 0.05). A nomogram plot to predict the risk of failure (C-index = 0.873, 95% CI: 0.785 to 0.961) and nomograms for predicting the survival probability at 1, 2 or 3 years whose calibration curves showed excellent prediction accuracy were available for the clinician. Preserved angles (PAs) are valuable in the prediction of prognosis in surgical treatment. The bone impaction grafting through femoral head–neck fenestration can achieve better clinical efficacy, especially for patients with LPA >50.95° and CPA >90.51°. [ABSTRACT FROM AUTHOR]

Starting from a new organic sunscreen synthesized in our laboratory by the condensation of sodium salt of the p-aminosalicylic acid with 2,6 – dichloroacetanilide, efficient cosmetic formulation with broad photoprotective properties was obtained by using the new compound as organic UV filter, metal oxides as inorganic filters, and vegetable extracts, oils and other ingredients with emollient, protective, and moisturizing effect. After showing the lack of toxicity of the new compound, in order to reduce the amount of UV filter used, it was encapsulated into nanostructured lipid carriers (NLCs). The final cream has demonstrated good qualities for skin application, possessing suitable physicochemical characteristics (pH, viscosity) and spreadability. The SPF value of the product is 16, a value considered to be satisfactory.

In this work, we determined the influenced of the reaction time at the synthesis of gold nanoparticles (AuNPs) by p-aminosalicylic acid and p-aminobenzoic acid as reducing agent. Besides working as a reducing agent, the p-aminobenzoic acid and p-aminosalicylic acid also simultaneously played a role as a capping agent/stabilizing agent. Gold ion was first mixed with the pH adjusted p-aminobenzoic acid and p-aminosalicylic acid. The mixture then heated in boiling water at 86 °C. The formation of AuNPs was indicated by the appearance of red color and analyzed with UV/Vis spectrophotometry to evaluate their surface plasmon resonance (SPR) absorption in the wavelength range 400–800 nm. The reducing ability of the reducing agents was affected by its structure. Gold nanoparticles that were synthesized with p-aminosalicylic acid were more stable, faster and had a smaller size than its counterpart that is synthesized with p-aminobenzoic acid. The stability test over a periods 5 months showed that AuNPs were relatively stable.

ABSTRACTp-Aminosalicylic acid (PAS) is an important second-line antibiotic for treating multidrug-resistant tuberculosis (MDR-TB). Due to gastrointestinal disturbance and intolerance, its potent and efficacy in the treatment of extensively drug-resistant (XDR)-TB commonly are poor. Thus, it is important to reveal the mechanism of susceptibility and resistance of Mycobacterium tuberculosis (Mtb) to this drug. Herein, we screened and established PAS-resistant (PASr) folC mutated and un-mutated Mtb strains, then utilized a multi-omics (genome, proteome, and metabolome) analysis to better characterize the mechanisms of PAS resistance in Mtb. Interestingly, we found that promotion of SAM-dependent methyltransferases and suppression of PAS uptake via inhibiting some drug transport associated membrane proteins were two key pathways for the folC mutated strain evolving into the PASr Mtb strain. However, the folC un-mutated strain was resistant to PAS via uptake of exogenous methionine, mitigating the role of inhibitors, and promoting DfrA, ThyA and FolC expression. Beyond these findings, we also found PAS resistance in Mtb might be associated with the increasing phenylalanine metabolism pathway. Collectively, our findings uncovered the differences of resistant mechanism between folC mutated and un-mutated Mtb strains resistant to PAS using multi-omics analysis and targeting modulators to these pathways may be effective for treatment of PASr Mtb strains.

Synthesis of gold nanoparticles (AuNPs) by reduction of HAuCl4 with p-aminobenzoic acid and p-aminosalicylic acid as a reducing agent was investigated. This work was conducted in order to determine the optimum condition of AuNPs synthesis and examine the effect of the hydroxyl group in p-aminosalicylic acid towards the size, shape, and stability of the synthesized gold nanoparticles (AuNPs). The optimum condition of the gold nanoparticles synthesis was determined by UV/Vis spectrophotometer, the shape and size of gold nanoparticles were measured by Transmission Electron Microscope (TEM). The synthesis process was started by reacting HAuCl4 and the reducing agents in an aqueous solution at 86 ºC. The initial gold concentration, reducing agents concentration and pH were varied in order to obtain the optimum condition. In the optimum condition, the results showed that p-aminosalicylic acid containing both hydroxyl and amino groups performed higher reduction ability compared to p-aminobenzoic acid that only containing an amino group. Reducing agents which have a hydroxyl group (p-aminosalicylic acid) could produce AuNPs with a smaller concentration of HAuCl4 than p-aminobenzoic acid. Gold nanoparticles that were synthesized with p-aminosalicylic acid were more stable and had a smaller particle size compared to its counterpart that is synthesized with p-aminobenzoic acid.

An improved synthesis of p-aminosalicylic acid (PASA) via hydrogenation of p-nitrosalicylic acid in the presence of organometallic palladium and nickel catalysts under mild conditions is proposed. The catalyst properties are compared to those of classical heterogeneous analogs used in modern pharmaceutical production. The organometallic catalysts are found to exceed significantly their heterogeneous analogs in stability, selectivity, and activity. The developed catalytic synthesis of PASA can be considered an alternative to the existing method and an environmentally efficient method for obtaining PASA that meets the main criteria of green chemistry. [ABSTRACT FROM AUTHOR]

Starting from a new organic sunscreen synthesized in our laboratory by the condensation of sodium salt of the p-aminosalicylic acid with 2,6 - dichloroacetanilide, efficient cosmetic formulation with broad photoprotective properties was obtained by using the new compound as organic UV filter, metal oxides as inorganic filters, and vegetable extracts, oils and other ingredients with emollient, protective, and moisturizing effect. After showing the lack of toxicity of the new compound, in order to reduce the amount of UV filter used, it was encapsulated into nanostructured lipid carriers (NLCs). The final cream has demonstrated good qualities for skin application, possessing suitable physicochemical characteristics (pH, viscosity) and spreadability. The SPF value of the product is 16, a value considered to be satisfactory. [ABSTRACT FROM AUTHOR]

To evaluate the acetabular morphology in healed Legg–Calvé–Perthes disease after skeletal maturity using computed tomography (CT) scan and to compare with matched controls. We identified 33 (37 hips) patients with healed Legg–Calvé–Perthes disease and closed triradiate cartilage who underwent pelvic CT scan. Each patient was matched based on sex, age and side to a subject with no history of hip disease who had undergone pelvic CT evaluation because of abdominal pain. Both cohorts had 23 (70%) males and mean age of 16.4–16.5 ± 3.6 years. Two independent readers assessed lateral center-edge angle (LCEA), acetabular inclination angle (IA), acetabular depth-width ratio (ADR), acetabular version 10 mm below the dome (cranial) and at the acetabular center and anterior (AASA) and posterior acetabular sector angles (PASA). All measurements had good to excellent interobserver agreement (intraclass coefficients ≥ 0.87). The hips in the Legg–Calvé–Perthes disease cohort had a smaller mean ± standard deviation (SD) superior, anterior and posterior acetabular coverage as assessed by LCEA (13.2° ± 10.7° versus 28.2° ± 3.4°; P  < 0.0001), IA (11.6° ± 6.7° versus 3.5° ± 2.8°; P  < 0.0001), AASA (52.4° ± 9.5° versus 59.3° ± 5.0°; P  = 0.001) and PASA (79.3° ± 5.9° versus 92.3° ± 5.5°; P  < 0.0001) compared with controls. The acetabulum was shallower (ADR 287 ± 45 versus 323 ± 28; P  = 0.0002) and the acetabular version was decreased cranially (0.4°±9.2° versus 8.2°±6.8°; P  = 0.0002) and at the acetabular center (13.7°±5.1° versus 17.2° ±3.8°; P  = 0.004) in Legg–Calvé–Perthes disease hips. After skeletal maturity, hips with healed Legg–Calvé–Perthes disease have shallower and more cranially retroverted acetabula, with globally reduced coverage of the femoral head compared with age-, sex- and side-matched control hips. [ABSTRACT FROM AUTHOR]

The selective recognition of drugs and its metabolism or decomposition products is significant to drug development and drug resistance research. Fluorescence-based techniques provide satisfying sensitivity by target-triggered chemical reaction. However, the interference from the matrix or additives usually restricts the specific detection. It is highly desirable to explore specific chemical reactions for achieving selective perception of these species. We report a specific m -aminophenol (MAP)-dopamine (DA) reaction, which generates highly fluorescent azamonardine-like products. Based on this reaction, fluorometric and indirect detection of p -aminosalicylic acid (typical antituberculosis drug, PAS) can be realized using the DA-based probe with high sensitivity. The acid induces the decarboxylation of PAS and produces MAP, which reacts with DA and generates fluorescent azamonardine-like products. The practical application of the proposed method is validated by the accurate PAS analysis in urine samples and Pasinazid tablets. Interestingly, none of additives in the Pasinazid tablets contribute comparable fluorescence variation. This work discovers a new MAP-DA reaction for the first time, it not only explores sensitive PAS drug detection probe, but also demonstrates the feasibility of the development of novel drug analysis platform by recognizing decomposition product with specific reaction. Thus, new avenues for the exploration of simple and rapid spectrophotometric probes toward various drug analytes with high specify and sensitivity based on this tactic might be possible in analytical and drug-related fields. [Display omitted] • A novel m -aminophenol-dopamine chemical reaction with high specificity was reported. • Acid-induced hydrolysis of p -aminosalicylic acid and generation of m -aminophenol was demonstrated. • Indirect and fluorometric p -aminosalicylic acid assay was proposed based on dopamine probe. • Quantification of p -aminosalicylic acid in Pasiniazid tablet was achieved. [ABSTRACT FROM AUTHOR]

Objectives: A validated and objective method to quantify the gross dissection time of pathologists' assistants (PAs) does not exist. We propose a method to calculate standardized work units (dissection time values [DTVs]) to monitor PA productivity.Methods: The Current Procedural Terminology system specifies six levels of specimen complexity encompassing 176 unique specimen types. Using our institutional dictionary, we designated all specimen types into a priori five levels of complexity based on expected dissection time. We hypothesized that expected time could be matched prospectively with the actual measured dissection time for all specimens. Dissection time data were collected prospectively for 12,775 specimens at two tertiary academic medical centers, and work effort was converted to a numeric DTV equivalent (number of minutes to dissect single specimen/420 minutes in a working day).Results: For 44 of 155 specimen types, measured dissection time for the five "levels" was lower than expected dissection (P < .0001). Accordingly, those 44 specimen types were reclassified to a lower level.Conclusions: A numeric standard of the work effort for dissection time for 155 specimen types was developed, validated, and then used prospectively to monitor grossing efficiency of PA workforce. [ABSTRACT FROM AUTHOR]

In this study, silver nanoparticles (AgNPs) were successfully synthesized using p-aminosalicylic acid as a reducing and stabilizing agent simultaneously. The AgNPs were synthesized by mixing silver nitrate solution as a precursor with the pH adjusted by p-aminosalicylic acid solution and heating it in a boiling water bath. The formed AgNPs were analyzed using UV-Vis spectrophotometry to evaluate their SPR absorbance in the wavelength range of 400-500 nm. The optimum reaction time is 10 min and the optimum pH is 11. The AgNPs resulted in the optimum synthesis condition have average size of 32.3 nm, spherical morphology, and face-centered cubic crystal characterized by using PSA, TEM, and XRD, respectively. The formed AgNPs had good stability for more than 2 months. The mechanism of silver ion reduction and AgNPs stabilization by p-aminosalicylic acid were also proposed in the paper based on the FTIR analysis result. [ABSTRACT FROM AUTHOR]

Polyfluorinated analogues of salicylamide and p -aminosalicylic acid have been synthesized based on methyl polyfluorosalicylates. Polyfluorosalicylamides were obtained by the reaction with aqueous ammonia, while 4-aminopolyfluorosalicylic acids were prepared in two steps via regio-oriented nucleophilic replacement of para-positioned fluorine atom with azido group followed by its reduction. 3,4,5-Trifluorosalicylamide showed pronounced analgesic in vivo activity in hot plate test while 4-amino-3,5-difluorosalicylic acid revealed high tuberculostatic activity. [ABSTRACT FROM AUTHOR]

The present work concerns an efficient strategy to obtain novel medical devices materials able to inhibit biofilm formation. The new materials were achieved by covalent grafting of p-aminocinnamic or p-aminosalicylic acids on low density polyethylene coupons. The polyethylene surface, previously activated by oxygen plasma treatment, was functionalized using 2-hydroxymethylmetacrylate as linker. The latter was reacted with succinic anhydride affording the carboxylic end useful for the immobilization of the antibiofilm molecules. The modified surface was characterized by scanning electron microscope, X-ray photoelectron spectroscopy, attenuated total reflectance Fourier transform infrared and fluorescence analyses. The antibiofilm activity of the modified materials were tested against Escherichia coli biofilm grown in the Center of Disease Control biofilm reactor. The results revealed that the grafted cinnamic and salicylic acid derivatives reduced biofilm biomass, in comparison with the control, by 73.7 ± 10.7% and 63.4 ± 7.1%, respectively. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 3251-3261, 2017. [ABSTRACT FROM AUTHOR]

Approaches to creating complexes based on branched oligohexamethyleneguanidine hydrochloride are addressed. Novel combinations of bactericidal agents were obtained, methods for the synthesis of a series of p-aminosalicylic acid derivatives were selected, the solubilities of their complexes with oligohexamethyleneguanidine were determined, and the bactericidal activities of the resulting complexes against Mycobacterium smegmatis were assessed. The minimum inhibitory concentrations of all complexes were in the range 0.1 - 1 μg/ml of culture medium. Thus, these complexes may be useful for creating a bactericidal formulation with powerful and long-lasting biocidal action, highly reproducible properties, and low toxicity. [ABSTRACT FROM AUTHOR]

[Display omitted] • A NF membrane with positively and negatively charged groups was prepared. • Positively charged regions were created on the polyamide layer through a chelation. • The NF membrane had high rejection for Mg2+ and high permeance for Li+. • The NF membrane exhibited a high S Li , Mg of 81.5 with a high flux. High-performance nanofiltration (NF) membrane plays a key role in Li+/Mg2+ separation process. In this work, a new NF membrane with positively and negatively charged groups was prepared by grafting p-aminosalicylic acid (AS) onto the surface of polyamide (PA) membrane followed by chelation with Fe3+ ions for Li+/Mg2+ separation. The AS grafting (PA-g-AS) and Fe3+ chelating (PA-g-AS-Fe) NF membranes had almost same surface and section structure and surface pore size as the PA membrane. But Zeta potential (about −8 mV at pH 7) of the obtained PA-g-AS-Fe membrane was improved in comparison with the PA and PA-g-AS NF (about −20 mV at pH 7) membranes due to Fe3+ addition, suggesting that there were positively and negatively charged groups on the membrane surface. The PA-g-AS-Fe membrane showed a high Mg2+ rejection of 97.7% and high Li+ permeation (negative rejection of −87.6%); while a high Li+/Mg2+ separation factor (S Li , Mg) of about 81.5 was achieved, which is much higher than those for PA and PA-g-AS NF membranes and surpassed those of the results reported in literature. The fluxes of three membranes were about the same. The results demonstrated the NF membrane with positively and negatively charged groups was suitable for efficient separation of Li+/Mg2+ and would have promising applications in recovery of lithium from brine. [ABSTRACT FROM AUTHOR]

Unlike conventional polymeric drug delivery systems, where drugs are entrapped in polymers, this study focuses on the incorporation of the drug into the polymer backbone to achieve higher loading and sustained release. Crosslinked, biodegradable, xylitol based polyesters have been synthesized in this study. The bioactive drug moiety, p-aminosalicylic acid (PAS), was incorporated in xylitol based polyesters to impart its anti-mycobacterial activity. To understand the influence of the monomer chemistry on the incorporation of PAS and its subsequent release from the polymer, different diacids have been used. Controlled release profiles of the drug from these polyesters were studied under normal physiological conditions. The degradation of the polyesters varied from 48% to 76% and the release of PAS ranged from 54% to 65% of its initial loading in 7 days. A new model was developed to explain the release kinetics of PAS from the polymer that accounted for the polymer degradation and drug concentration. The thermal, mechanical, drug release and cytocompatibility properties of the polymers indicate their suitability in biomedical applications. The released products from these polymers were observed to be pharmacologically active against Mycobacteria. The high drug loading and sustained release also ensured enhanced efficacy. These polymers form biocompatible, biodegradable polyesters where the sustained release of PAS may be tailored for potential treatment of mycobacterial infections. Statement of significance In the present work, we report on novel polyesters with p-aminosalicylic acid (PAS) incorporated in the polymer backbone. The current work aims to achieve controlled release of PAS and ensures the delivered PAS is stable and pharmacologically active. The novelty of this work primarily involves the synthetic chemistry of polymerization and detailed analysis and efficacy of active PAS delivery. A new kinetic model has been developed to explain the PAS release profiles. These polymers are biodegradable, cytocompatible and anti-mycobacterial in nature. [ABSTRACT FROM AUTHOR]

The present study reports the preparation and preliminary biological activity results of co-conjugates of platinum ferrocene based drugs by using a novel synthetic route for the incorporation of ferrocene into the carrier. The Fe content obtained by ICP-AES was found in the range of 1.8-2.3 % by mass for the conjugates and 1.4-2.0 % by mass for the co-conjugates. The Pt content obtained by ICP-OES was in the range of 5.6-7.2 % by mass for the co-conjugates. The preliminary pharmacological evaluation performed on the MCF-7 human breast cancer cell line for conjugate 1 and 4, and corresponding co-conjugate 6 and 9 revealed that the conjugates were 5 and 2 times more active than the free drug, while the corresponding co-conjugates were 16 and 6 times more active than the free drug. [ABSTRACT FROM AUTHOR]

Purpose: To develop a new spectrophotometric method with improved sensitivity and at higher wavelength for the determination of p-aminosalicylic acid in tablets. Methods: Two simple and sensitive spectrophotometric methods (methods A and B) were developed using p-dimethylaminobenzaldehyde (DAB), and p-dimethylaminocinnamaldehyde (DAC) as derivatizing reagents for the determination of p-aminosalicylic acid (PAS) in tablets. The derivatization was carried out using 3M HCl-KCl buffer for DAB and 5M HCl-KCl buffer solutions. Result: The new derivatives of PAS absorbed maximally with bathochromic shift to 460 and 555 nm in the linear concentration range of 0.4 - 2.0 μg/mL with molar absorptivities of 2.4 x 104 and 3.8 x 104 L/mole/cm, respectively, compared to pure PAS which absorbed at λmax of 264 nm with molar absorptivity 7.65 x 103 L/mole/cm in the linear concentration range of 2 - 10 μg/mL. The developed methods were successfully applied to assay PAS in tablets with % recovery of 97.6 ± 1.71 and 98.4 ± 1.45 for methods A and B, respectively. Conclusion: Both PAS derivatives absorb in the visible spectral region. The presence of excipients in pharmaceutical preparations did not interfere in the determination of PAS as PAS-DAB and PAS-DAC derivatives. Both methods can be applied to determine PAS from bulk and various pharmaceutical dosage forms. [ABSTRACT FROM AUTHOR]

Objectives The objective of this work was to spray dry p-aminosalicylic acid (PAS) and its ammonium salt and to investigate the impact of the pore-forming agent, ammonium carbonate (AC), on the morphological, aerodynamic and physicochemical properties of the resulting powders. Methods Microparticles were prepared by spray drying from ethanol/water solvent systems. Their solid-state properties were evaluated by scanning electron microscopy, powder X-ray diffraction, differential scanning calorimetry, thermogravimetric analysis and in-vitro deposition, using the twin impinger. Key Findings The physicochemical properties of PAS were altered on spray drying with AC and a new solid state was produced. The solution composition impacted on the morphology of the resulting powders, which ranged from irregular crystal agglomerates to spherical crystal clusters and porous microparticles. The chemical composition, structure and morphology were dependent on process inlet temperature, low inlet temperatures resulting in a novel solid of stoichiometry; PAS : ammonia : water, 2 : 1 : 0.5. At higher temperatures pure PAS was obtained. In-vitro deposition studies showed an increase in emitted dose from spray dried drug, relative to the micronised PAS. Conclusions Under appropriate process conditions AC interacts with the acidic PAS, resulting in the formation of a novel solid-state drug phase. Spray-dried PAS powders have potential for pulmonary delivery. [ABSTRACT FROM AUTHOR]

Neuraminidase (NA) is a major glycoprotein of influenza virus which is essential for viral infection. It offers a potential target for antiviral drug design and discovery. To develop novel potent neuraminidase inhibitors (NAI), Surflex-Dock was employed to dock 40 hydrophobic p-aminosalicylic acid derivatives into the active site of NA. The 3D-quantitative structure-activity relationship studies involving comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were carried out on 40 molecules. Both CoMFA ( q2 = 0.628, r2 = 0.697) and CoMSIA ( q2 = 0.746, r2 = 0.816) gave reasonable results. A preliminary pharmacokinetic profile of these NAI was also performed on the basis of Volsurf predictions. The results obtained from this study will be useful in the design of novel potent NAI. [ABSTRACT FROM AUTHOR]

The complexes were synthesized by the reaction between sodium salt of p-aminosalicylic acid (PAS) and Cu(II) for 1 and corresponding ethylenediamine (en) or its derivatives for 2- 6. The complexes were characterized by using elemental analyses, FT-IR, UV-Vis, magnetic moment measurements, and thermal analyses techniques. In complex 1[Cu(PA)(HO)], two Cu(II) ions were found as bridged by four μ-O:O′ p-aminosalicylato (PA) ligands, forming a cage structure, and two aqua ligands to form dinuclear square-pyramidal geometry around Cu(II) ions. In the complexes 2- 6, the PA (anionic form of p-aminosalicylic acid) coordinated to Cu(II) ions as monodentate manner by using its oxygen atom of deprotonated carboxylic acid and ethylenediamine derivatives coordinated to the Cu(II) ions in bidentate manner to form mononuclear octahedral complexes [Cu(PA)(L)] (L = ethylendiamine, N, N-dimethylethylendiamine, N, N′-dimethylethylendiamine, N, N, N′, N′-tetramethylethylendiamine, and 1,3-propanediamine, for complexes 2, 3, 4, 5, and 6, respectively). In all the complexes OH and NH groups of PA ligands were not coordinated to metals. [ABSTRACT FROM AUTHOR]

Abstract: The lateral cilia of the gill of Crassostrea virginica are controlled by a dopaminergic–serotonergic innervation. Dopamine is the neurotransmitter causing cilio-inhibition. High levels of manganese are neurotoxic to people, causing Manganism, a Parkinson-like disease. Clinical interventions for Manganism have not been very successful. Recently, p-Aminosalicylic acid (PAS) was reported as an effective treatment of severe Manganism in humans; however, its mechanism of action is unknown. Previously, we reported that manganese treatments caused disruption of the dopaminergic innervation of gill of C. virginica. Here we compared the effects of manganese on gill innervation in the presence of PAS, EDTA or Acetylsalicylic acid (ASA), and examined whether co-treating animals with PAS could block the deleterious effects of manganese on the oyster''s dopaminergic innervation of the gill. Beating rates of the lateral cilia of the gill were measured by stroboscopic microscopy. Pre-treating gill preparations with PAS or EDTA blocked the neurotoxic effects of manganese, while ASA did not. In other experiments, animals exposed to three day treatments with manganese produced a dose dependent impairment of the dopaminergic, cilio-inhibitory system, which was decreased by co-treatment with PAS. The study shows that PAS protects the animal against neurotoxic effects of manganese and the mechanism of action of PAS in alleviating Manganism is more likely related to its chelating abilities than its anti-inflammatory actions. [Copyright &y& Elsevier]

The Topliss method was used to guide a synthetic path in support of drug discovery efforts toward the identification of potent antimycobacterial agents. Salicylic acid and its derivatives, p-chloro, p-methoxy, and m-chlorosalicylic acid, exemplify a series of synthetic compounds whose minimum inhibitory concentrations for a strain of Mycobacterium were determined and compared to those of the reference drug, p-aminosalicylic acid. Several physicochemical descriptors (including Hammett’s sigma constant, ionization constant, dipole moment, Hansch constant, calculated partition coefficient, Sterimol-L and -B4 and molecular volume) were considered to elucidate structure–activity relationships. Molecular electrostatic potential and molecular dipole moment maps were also calculated using the AM1 semi-empirical method. Among the new derivatives, m-chlorosalicylic acid showed the lowest minimum inhibitory concentration. The overall results suggest that both physicochemical properties and electronic features may influence the biological activity of this series of antimycobacterial agents and thus should be considered in designing new p-aminosalicylic acid analogs. [ABSTRACT FROM AUTHOR]

Abstract: The aim of the current research project was to explore the possibilities of combining pressurized carbon dioxide with hot stage extrusion during manufacturing of solid dispersions of the thermally labile p-aminosalicylic acid (p-ASA) and ethylcellulose 20cps (EC 20cps) and to evaluate the ability of the pressurized gas to act as a temporary plasticizer. The thermal stability of the p-ASA was investigated using DSC, TGA and HPLC. The compound decomposes completely upon melting. Below 110°C and under atmospheric conditions, the compound is thermally stabile for 10min. Pressurized carbon dioxide was injected into a Leistritz Micro 18 intermeshing co-rotating twin-screw melt extruder using an ISCO 260D syringe pump. Carbon dioxide acted as plasticizer for p-ASA/EC 20cps, reducing the processing temperature during the hot stage extrusion process. HPLC showed that without carbon dioxide injection, approximately 17% of p-ASA degraded, while less than 5% degraded with CO2 injection. The experiments clearly showed that injecting pressurized carbon dioxide broadens the application of hot stage extrusion to thermally labile compounds in a one step process. [Copyright &y& Elsevier]

A multiwavelength spectrophotometric method, called Dip-Probe Absorption Spectroscopy (D-PAS), developed previously for pKa determination was applied for the determination of the molar absorption coefficients of ionizable compounds. Specifically, the spectral data obtained from a spectrophotometric titration are resolved using Target Factor Analysis (TFA) to generate the molar absorption coefficients of each ionizing species. The D-PAS method has been exemplified by the spectral data of p-aminosalicylic acid and nicotinic acid. It has been shown that the molar absorption coefficients as determined by the D-PAS method are comparable to those deduced by manual titration experiment. [ABSTRACT FROM AUTHOR]

The bioavailability (plasma concentrations, AUC and urinary excretion) of an oral solution of rifampicin was investigated in six healthy volunteers. Simultaneous administration of PAS granules produced a significant decrease in the absorption of RMP, whereas Na-PAS tablets had no effect. This indicated that the dosage form of the granules and not PAS itself was responsible for the interaction, and that the dissolution of RMP was not involved. The interaction could be reproduced by giving dummy granules that contained the same excipients but no PAS. The disintegration and dissolution of PAS granules in vitro correlated well with the disappearance of RMP from the solution. The major excipient of the granules, bentonite (a mineral closely related to kaolin), was found to adsorb rifampicin rapidly and strongly. [ABSTRACT FROM AUTHOR]

The binding of rifampicin to human plasma proteins has been investigated by equilibrium dialysis. Plasma from eleven healthy subjects not taking drugs bound 87-91% of added rifampicin. Binding was lower (84-88%) in plasma from ten tuberculous patients on long-term treatment with rifampicin. Physiological concentrations of human albumin, gamma globulin and fibrinogen bound 41, 10 and 8%, respectively, of added rifampicin. Isoniazid, p-aminosalicylic acid, streptomycin and ethambutol did not significantly affect rifampicin binding to plasma proteins. [ABSTRACT FROM AUTHOR]

Single oral doses of rifampicin (10 mg/kg body weight), p-aminosalicylic acid (0.2 g/kg), isoniazid (10 mg/kg), or rifampicin and either p-aminosalicylic acid or isoniazid, were given to 69 tuberculous patients with normal renal and hepatic function. Ten-fold interindividual differences were observed in the peak serum concentrations and half-lives of rifampicin; its half-life was reduced from 4.3 h after the first dose to 3.1 h after the third dose, possibly due to self-induction of its own metabolism. No effect on its serum concentration or half-life, nor on those of isoniazid, were found after simultaneous oral administration of the two drugs. After treatment with rifampicin and p-aminosalicylic acid, the peak serum level of the former was delayed from 2 to 4 h, it was reduced from 8.0 to 3.8 µg/ml, and the mean area under the serum concentration curve throughout the entire 8 h study period was also lowered by about half. Individual patients did not attain therapeutically effective peak serum concentrations of rifampicin if also treated with p-aminosalicylic acid. The interaction observed between the two drugs is probably due to impaired gastrointestinal absorption of rifampicin, either by alteration of its physico-chemical properties or by a decrease in the gastric emptying rate combined with more rapid intestinal transit. The combination of these two drugs is unsuitable for the routine chemotherapy of tuberculosis. [ABSTRACT FROM AUTHOR]

Background Prostate abscess (PA) is uncommon and the diagnosis is often delayed or missed. Traditionally, PA has resulted from acute prostatitis or ascending genitourinary (GU) infection due to gram-negative bacilli but S. aureus is an emerging cause. Methods A retrospective review of all adult patients admitted with an ICD-9 or -10 diagnosis of PA between January 2013 and July 2018 was conducted. Inclusion criteria included age ≥18 years, a compatible GU infection syndrome, and imaging consistent with PA. Results Twenty-two patients with PA were identified. The median age was 57 years. Five patients (22.7%) were immunosuppressed and 11 (50%) had diabetes. The median Charlson Comorbidity Index was 2. No patient had a prior history of PA but 3 patients had a past diagnosis of prostatitis. Only 1 patient had GU instrumentation in the preceding 6 weeks and no patient had an indwelling urethral catheter. Fever (59%), dysuria (49%), and urinary retention (32%) were the most common presenting symptoms. Only 7/18 (39%) patients had a tender prostate on examination; fluctuance was not described. Pelvic CT revealed PAs in all patients; 14 (64%) were solitary and 16 (73%) were >2 cm in greatest diameter. The median abscess size was 3.2 cm. Urine cultures were positive in 11/18 (61%) patients with 6/11 (55%) growing S. aureus (MRSA 3); 9/16 (56%) patients had positive blood cultures (S. aureus 7 with MRSA 3) and 5/5 had positive PA cultures (S. aureus 1). Nine patients (41%) were managed with antibiotics alone whereas 13 (59%) underwent abscess drainage. The median duration of antibiotic therapy was 34.5 days. All-cause mortality at 4 weeks was 9.1%. No relapses were documented at 6 months. When comparing patients with S. aureus PA to those with other causes, S. aureus patients more often had diabetes (86% vs. 33%, P = 0.06) and a longer median duration of antibiotic therapy (35 days vs. 31 days, P = 0.04) but age, abscess size, and mortality did not differ between groups. Conclusion PA is relatively uncommon and may be difficult to distinguish clinically from acute prostatitis. CT is critical to an accurate diagnosis. Optimal management usually requires both antibiotics and drainage. Given the frequent occurrence of S. aureus as a cause, coverage for MRSA should be a component of empiric treatment for PA. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]