Highly sensitive spectrofluorimetric method for the determination of the genotoxic methylglyoxal in glycerol-containing pharmaceuticals and dietary supplements.

Methylglyoxal (MGO) is a genotoxic α-dicarbonyl compound. Recently, it was found to be formed in glycerol preparations during storage through auto-oxidation. A simple fluorimetric determination of the carcinogenic degradation product of glycerol, MGO, was developed and validated. The proposed method is based on the derivatization of MGO with 4-carbomethoxybenzaldehyde (CMBA) and ammonium acetate to yield a fluorescent imidazole derivative that can be measured at 415 nm after excitation at 322 nm. The optimized conditions were determined to be 0.2 M CMBA, 1.0 M ammonium acetate and a reaction time of 40 min at 90°C using ethanol as diluting solvent. The linear range was 10.0-200.0 ng/ml. Detection and quantification limits were 2.22 and 6.72 ng/ml, respectively. The proposed method was validated according to International Council for Harmonisation (ICH) guidelines and compared with the reported method and no significant difference was found. It was successfully applied for the determination of MGO in six different glycerol-containing pharmaceutical preparations and dietary supplements.

Better outcome of COVID-19 positive kidney transplant recipients during the unremitting stage with optimized anticoagulation and immunosuppression.

INTRODUCTION: COVID-19 is an ongoing pandemic with high morbidity and mortality and with a reported high risk of severe disease in kidney transplant recipients (KTR). AIM: We aimed to report the largest number of COVID-19-positive cases in KTR in a single center and to discuss their demographics, management, and evolution. METHODS: We enrolled all the two thousand KTR followed up in our center in Kuwait and collected the data of all COVID-19-positive KTR (104) from the start of the outbreak till the end of July 2020 and have reported the clinical features, management details, and both patient and graft outcomes. RESULTS: Out of the one hundred and four cases reported, most of them were males aged 49.3 ± 14.7 years. Eighty-two of them needed hospitalization, of which thirty-one were managed in the intensive care unit (ICU). Main comorbidities among these patients were hypertension in 64.4%, diabetes in 51%, and ischemic heart disease in 20.2%. Management strategies included anticoagulation in 56.7%, withdrawal of antimetabolites in 54.8%, calcineurin inhibitor (CNI) withdrawal in 33.7%, the addition of antibiotics in 57.7%, Tocilizumab in 8.7%, and antivirals in 16.3%. During a follow-up of 30 days, the reported number of acute kidney injury (AKI) was 28.7%, respiratory failure requiring oxygen therapy 46.2%, and overall mortality rate was 10.6% with hospital mortality of 13.4% including an ICU mortality rate of 35.5%. CONCLUSION: Better outcome of COVID-19-positive KTR in our cohort during this unremitting stage could be due to the younger age of patients and early optimized management of anticoagulation, modification of immunosuppression, and prompt treatment of secondary bacterial infections. Mild cases can successfully be managed at home without any change in immunosuppression.

Micellar enhanced spectrofluorimetric approach for nanogram detection of certain α1 -blocker drugs: Application in pharmaceutical preparations and human plasma.

Alpha1-adrenergic-blocking drugs, namely; alfuzosin hydrochloride (ALF), doxazosin mesylate (DOX) and terazosin hydrochloride (TER) are effective as antihypertensive agents as well as in management of benign prostatic hypertrophy. In this study, a simple, very fast, highly sensitive and cheap technique was optimized for assay of these drugs in pure states and pharmaceutical tablets. The proposed method is dependent on enhancement of the native fluorescence of investigated drugs using the polyoxyethylene 50 stearate (POE50S) micellar system. The method showed excitation at 325, 340 and 250 nm for ALF, DOX and TER, respectively and an emission maxima at 382 nm. The fluorescence intensity-concentration charts of studied drugs were attained utilizing concentration ranges (2.0-60.0 ng mL-1 ) for DOX and (4.0-100.0 ng mL-1 ) for ALF and TER with quantitation limits 2.9, 1.6 and 2.5 ng mL-1 for ALF, DOX and TER, respectively. The suggested technique was approved according to International Council for Harmonisation (ICH) standards and the United States Food and Drug Administration (US FDA) bioanalytical method validation and has been effectively applied for assay of these medications in their dosage forms as well as for content uniformity test. The developed procedure was also efficiently applied for determination of these drugs in real human plasma with high accuracy.

Utility of Von Pechman synthesis of coumarin reaction for development of spectrofluorimetric method for quantitation of salmeterol xinafoate in pharmaceutical preparations and human plasma.

Simple, precise and selective spectrofluorimetric technique was evolved for quantitation of selective ß2 agonist drug namely salmeterol xinafoate (SAL). Utilizing its phenolic nature, a method was described based on the reaction of the studied drug with ethyl acetoacetate (EAA) to yield extremely fluorescent coumarin product which can be detected at 480 nm (λex  = 420 nm). The procedure obeys Beer's law with a correlation coefficient of r = 0.9999 in the concentration range between 500 and 5000 ng ml-1 with and 177 ng ml-1 for limit of detection (LOD) and limit of quantification (LOQ), respectively. Diverse reaction variables influencing the firmness and formation of the coumarin product were accurately examined and modified to ensure greatest sensitivity of the procedure. The proposed technique was performed and examined according to the US Food and Drug Administration (FDA) guidelines for bio-analytical methods and was efficiently applied for quantitation of SAL in both pharmaceutical preparations (% recovery = 100.06 ± 1.07) and spiked human plasma (% recovery = 96.64-97.14 ± 1.01-1.52).

Selective Spectrofluorimetric Method with Enhanced Sensitivity for Determination of Silodosine in Dosage Form and Human Plasma. Application to Stability Studies and Content Uniformity Testing.

A novel, sensitive and selective spectrofluorimetric method has been developed and validated for determination of silodosine (SLD) in its dosage form and human plasma. The method is based on nucleophilic substitution reaction of SLD with 5-(dimethylamino) naphthalene-1-sulfonyl chloride (dansyl chloride) in presence of 5.0 × 10-4 M sodium carbonate (pH 10.50) to yield a highly fluorescent derivative that was measured at 435 nm after excitation at 347 nm. The different experimental parameters affecting the development and stability of the reaction product were carefully studied and optimized. The fluorescence-concentration plot was rectilinear over the range 30.0-200.0 ng ml-1, with a correlation coefficient of 0.9979. The limits of detection (LOD) and quantification (LOQ) were found to be 5.44 and 16.47 ng ml-1, respectively. The proposed method was validated according to ICH guidelines, and successfully applied to the assay of commercial capsules as well as content uniformity testing. The high sensitivity of the proposed method allowed its successful application to the analysis of SLD in spiked human plasma with % recovery of 92.88 ± 1.05-100.73 ± 0.75%, (n = 6). The application of the proposed method was further extended to stability studies of SLD after exposure to different forced degradation conditions, such as acidic, alkaline and oxidative conditions, according to ICH guidelines, where this work describe the first attempt for selective spectrofluorimetric determination of silodosine in plasma and in the presence of its oxidative degradation.

Utility of Hantzsch reaction for development of highly sensitive spectrofluorimetric method for determination of alfuzosin and terazosin in bulk, dosage forms and human plasma.

A highly sensitive, cheap, simple and accurate spectrofluorimetric method has been developed and validated for the determination of alfuzosin hydrochloride and terazosin hydrochloride in their pharmaceutical dosage forms and in human plasma. The developed method is based on the reaction of the primary amine moiety in the studied drugs with acetylacetone and formaldehyde according to the Hantzsch reaction, producing yellow fluorescent products that can be measured spectrofluorimetrically at 480 nm after excitation at 415 nm. Different experimental parameters affecting the development and stability of the reaction products were carefully studied and optimized. The fluorescence-concentration plots of alfuzosin and terazosin were rectilinear over a concentration range of 70-900 ng ml-1 , with quantitation limits 27.1 and 32.2 ng ml-1 for alfuzosin and terazosin, respectively. The proposed method was validated according to ICH guidelines and successfully applied to the analysis of the investigated drugs in dosage forms, content uniformity test and spiked human plasma with high accuracy.

Development and Validation of highly Sensitive Stability Indicating Spectrofluorimetric Method for Determination of Amlodipine in Pharmaceutical Preparations and Human Plasma.

A highly sensitive and simple spectrofluorimetric method was developed for the determination of Amlodipine besylate (AML) in its pharmaceutical formulations and spiked human plasma. The proposed method is based on the investigation of the fluorescence spectral behaviour of AML in Tween-80 micellar system. In aqueous solution, the fluorescence intensity of AML was greatly enhanced (160 %) in the presence of Tween-80. The fluorescence intensity was measured at 427 nm after excitation at 385 nm. The fluorescence-concentration plot was rectilinear over the concentration range 0.1-4.0 µg/ml, with lower detection limit of 0.03 µg/ml. The suggested method was successfully applied for the analysis of AML in its commercial tablets alone or in combination with either Atorvastatin or Valsartan. The application of the proposed method was extended to the assay of AML in spiked human plasma and stability studies of AML after exposure to different forced degradation conditions, such as acidic, alkaline, photo- and oxidative conditions, according to ICH guidelines. The results were statistically compared to those obtained by comparison methods and were found to be in good agreement.

Development and validation of TLC-densitometric method for simultaneous determination of two binary antihypertensive mixtures containing felodipine in fixed dose combinations.

A new densitometric thin-layer chromatographic method has been developed for simultaneous determination of two binary mixtures containing felodipine in combination with either metoprolol (mixture I) or ramipril (mixture II). The two mixtures were quantitatively separated on 60 F254 silica gel plates using toluene-ethyl acetate-methanol-ammonia as mobile phase with UV detection at 233 and 229 nm for mixtures I and II, respectively. The studied drugs were satisfactorily resolved with retention factor (Rf ) values of 0.34 ± 0.03 and 0.65 ± 0.03 for metoprolol and felodipine, respectively, in mixture I and 0.35 ± 0.03 and 0.74 ± 0.03 for ramipril and felodipine, respectively, in mixture II. Linearity ranges were 2000-7000 and 200-700 ng/band for metoprolol and felodipine, respectively, in mixture I and 1500-4000 ng/band for both ramipril and felodipine in mixture II. Correlation coefficient (r) values were 0.9968 for both metoprolol and felodipine in mixture I and 0.9993 for ramipril and 0.9989 for felodipine in mixture II. The method has been validated according to International Conference on Harmonization guidelines and has been successfully applied for determination of the studied drugs in their dosage forms without interference from commonly encountered excipients.

Homology modeling and explicit membrane molecular dynamics simulation to delineate the mode of binding of thiazolidinediones into FFAR1 and the mechanism of receptor activation.

Free fatty acid receptor 1 (FFAR1) is a member of a previously characterized cluster of orphan G protein-coupled receptors (GPCRs). Later, this orphan receptor was identified as a target of medium- to long-chain free fatty acids in ß-cells of the pancreas. Administration of FFAR1 agonists has been proved to potentiate glucose-stimulated insulin secretion from pancreatic ß-cells. It was reported that some thiazolidinediones (TZDs), the best studied PPARγ agonists, are also able to stimulate FFAR1 in a dose-dependent manner. In the present study, a homology model of the human FFAR1 was constructed and inserted into a pre-equilibrated DPPC/TIP3P membrane system. This system was then simulated for 20 ns in complex with the FFAR1 agonist GW9085, as well as rosiglitazone and pioglitazone. We noticed that the salt bridge between Glu172 and Arg258 and the H bond between Glu145 and His153 could be responsible for the stabilization of the receptor in the inactive state. Moreover, we described for the first time the binding mode of TZDs in the binding site of FFAR1. The thiazolidinedione head forms a hydrogen bonding network with the critical polar residues in the binding site, Arg258 and Asn244, while the rest of the molecule is embedded into the receptor hydrophobic pocket. Based on this modeling study, we arrived at a proposal of the pharmacophore required for binding to both PPARγ and FFAR1. Insights gained from this investigation should provide future directions for the design of novel dual acting antidiabetic agents.

Design, synthesis, and enzyme kinetics of novel benzimidazole and quinoxaline derivatives as methionine synthase inhibitors.

Methionine synthase catalyzes the transfer of a methyl group from 5-methyltetrahydrofolate to homocysteine, producing methionine and tetrahydrofolate. Benzimidazole and deazatetrahydrofolates derivatives have been shown to inhibit methionine synthase by competing with the substrate 5-methyltetrahydrofolate. In this study, a novel series of substituted benzimidazoles and quinoxalines were designed and assessed for inhibitory activity against purified rat liver methionine synthase using a radiometric enzyme assay. Compounds 3g, 3j, and 5c showed the highest activity against methionine synthase (IC50: 20 µM, 18 µM, 9 µM, respectively). Kinetic analysis of these compounds using Lineweaver-Burk plots revealed characteristics of mixed inhibition for 3g and 5c; and uncompetitive inhibition for 3j. Docking study into a homology model of the rat methionine synthase gave insights into the molecular determinants of the activity of this class of compounds. The identification of these drug-like inhibitors could lead the design of the next generation modulators of methionine synthase.

Barriers to Mental Illness Treatment in Saudi Arabia: A Population-Based Cross-Sectional Study.

BACKGROUND: Mental illness is a disorder that can cause impairment and disability, affecting mood, thinking, and behavior; therefore, early intervention will reduce morbidity. This study aims to evaluate all the personal, family, societal, and medical barriers that prevent mental health patients from seeking consultation and treatment. METHODS: In Saudi Arabia, a cross-sectional study was conducted on 463 individuals aged 18 and above. Data were collected by face-to-face interviews using a validated questionnaire, which consisted of two parts. The first part included sociodemographic data, while the second part contained subsections of society/family, personal, and medical barriers. RESULTS: The results showed that 379 (81.9%) indicated that society and family barriers impacted them, whereas 325 (70.3%) believed that personal barriers hindered seeking help. However, 294 (63.5%) opted for medical barriers as a hindrance. Regarding the highest barriers, 120 of the total respondents (25.9%) saw psychiatric illness as a source of shame and stigma, 166 respondents (35.9%) said that the psychiatric patient is seen as crazy, 159 of them (34.3%) believed it is tough for anyone to talk about their feelings and emotions and 183 respondent (39.5%) feared that psychiatric illness would decrease the chance of marriage to the appropriate person. Our findings also indicated a low trust in hospital treatment, hence a loss of confidence in using medications. CONCLUSION: The findings of this study indicate that societal stigma is the most common barrier preventing people from seeking mental health consultation. Many barriers differ significantly between males and females.

Acute Kidney Injury Among COVID-19-Positive Patients Is Associated With Higher Mortality: A Single-Center Experience.

OBJECTIVES: Renal complications of COVID-19 are not yet well studied. We aimed to evaluate acute kidney injury prevalence among hospitalized patients with COVID-19 infection and explore its effect on patient outcomes. MATERIALS AND METHODS: We retrospectively evaluated 586 hospitalized patients with COVID-19. Of these patients, 267 (45.5%) developed acute kidney injury, as classified according to the Kidney Disease Improving Global Outcomes guidelines. We compared this group with 319 patients (54.5%) without acute kidney injury. RESULTS: Most patients in both study groups were men; mean age was 60.8 ± 14 versus 51.7 ± 16 years. Comorbid conditions that were substantially predominant among patients with acute kidney injury were diabetes mellitus (64% vs 42.9%), hypertension (72.6% vs 43.5%), and ischemic heart disease (25% vs 14.7%). Fever, cough, shortness of breath, and dehydration were the main presentations among patients with acute kidney injury, and patients in this group had greater prevalence of radiological findings concordant with COVID-19 (86.8% vs 59.8%). Sepsis, volume depletion, shock, arrhythmias, and acute respiratory distress syndrome were higher in patients with acute kidney injury. Anticoagulation (85% vs 59.2%), vasopressors, plasma infusions, antimicrobials, and steroids were more frequently used in patients with acute kidney injury. More patients with acute kidney injury had acute respiratory failure requiring mechanical ventilation (62.3% vs 32.9%), with higher overall mortality rate (63.2% vs 31.1%). CONCLUSIONS: We found more frequent prevalence of acute kidney injury associated with severe COVID-19 than shown in reports from Chinese, European, and North American cohorts. Patients with COVID-19 who developed acute kidney injury had risk factors such as hypertension and diabetes, greater need for mechanical ventilation, were males, and were older age. Mortality was high in this population, especially among older patients and those who developed Kidney Disease Improving Global Outcomes stage 3 disease.

Tissue factor antisense deoxyoligonucleotide prevents monocrotaline/LPS hepatotoxicity in mice.

Tissue factor (TF) is a membranous glycoprotein that functions as a receptor for coagulation factor VII/VIIa and activates the coagulation system when blood vessels or tissues are damaged. TF was upregulated in our monocrotaline (MCT)/lipopolysaccharide (LPS) hepatotoxicity model. We tested the hypothesis that TF-dependent fibrin deposition and lipid peroxidation in the form of oxidized low-density-lipoprotein (ox-LDL) accumulation contribute to liver inflammation induced by MCT/LPS in mice. In the present study, we blocked TF using antisense oligodeoxynucleotides against mouse TF (TF-ASO). TF-ASO (5.6 mg kg(-1) ) was given i.v. to ND4 male mice 30 min after administration of MCT (200 mg kg(-1) ) p.o. followed after 3.5 h by LPS i.p. (6 mg kg(-1) ). Blood alanine aminotransferase (ALT), TF, ox-LDL, platelets, hematocrit and keratinocyte-derived chemokine (KC) levels were evaluated in different treatment groups. Fibrin deposition and ox-LDL accumulation were also analyzed in the liver sections using immunofluorescent staining. The results showed that TF-ASO significantly restored blood ALT, hematocrit and KC levels, distorted after MCT/LPS co-treatment, as well as preventing the accumulation of ox-LDL and the deposition of fibrin in the liver tissues, and thereby inhibited liver injury caused by MCT/LPS. In a separate experiment, TF-ASO administration significantly prolonged animal survival. The current study demonstrates that TF is associated with MCT/LPS-induced liver injury. Administration of TF-ASO successfully prevented this type of liver injury.

Highly sensitive spectrofluorimetric method for determination of certain aminoglycosides in pharmaceutical formulations and human plasma.

A simple, reliable, highly sensitive and selective spectrofluorimetric method has been developed for determination of certain aminoglycosides namely amikacin sulfate, tobramycin, neomycin sulfate, gentamicin sulfate, kanamycin sulfate and streptomycin sulfate. The method is based on the formation of a charge transfer complexes between these drugs and safranin in buffer solution of pH 8. The formed complexes were quantitatively extracted with chloroform under the optimized experimental conditions. These complexes showed an excitation maxima at 519-524 nm and emission maxima at 545-570 nm. The calibration plots were constructed over the range of 4-60 pg mL(-1) for amikacin, 4-50 pg mL(-1) for gentamicin, neomycin and kanamycin, 4-40 pg mL(-1) for streptomycin and 5-50 pg mL(-1) for tobramycin. The proposed method was successfully applied to the analysis of the cited drugs in dosage forms. The proposed method was validated according to ICH and USP guidelines with respect to specificity, linearity, accuracy, precision and robustness. The high sensitivity of the proposed method allowed determination of amikacin and gentamicin in spiked and real human plasma.

SARS-CoV-2 Papain-like Protease Responsive ZnO/Daclatasvir-Loaded Chitosan/Gelatin Nanofibers as Smart Antimicrobial Medical Textiles: In Silico, In Vitro and Cell Studies.

A significant number of deaths are reported annually worldwide due to microbial and viral infections. The development of protective medical textiles for patients and healthcare professionals has attracted many researchers' attention. Therefore, this study aims to develop smart drug-eluting nanofibrous matrices to be used as a basic material for medical textile fabrication. First, chitosan/gelatin nanofibers were selected as the basic material owing to the wide antimicrobial activity of chitosan and the capability of gelatin to be hydrolyzed in the abundance of the papain-like protease (PLpro) enzyme secreted by SARS-CoV-2. Daclatasvir (DAC), an NS5A inhibitor, was selected as the model drug based on in silico studies where it showed high anti-SARS-CoV-2 potential compared to FDA-approved references. Due to their reported antimicrobial and antiviral activities, ZnO NPs were successfully prepared and incorporated with daclatasvir in chitosan/gelatin nanofibrous matrices through electrospinning. Afterward, an in vitro release study in a simulated buffer revealed the controlled release of DAC over 21 days from the nanofibers compared to only 6 h for free DAC. On the other hand, the abundance of PLpro induced the complete release of DAC from the nanofibers in only 4-8 h. Finally, the nanofibers demonstrated a wide antimicrobial activity against S. aureus, E. coli, and C. albicans.

Antimicrobial and anti-SARS-CoV-2 activities of smart daclatasvir-chitosan/gelatin nanoparticles-in-PLLA nanofibrous medical textiles; in vitro, and in vivo study.

This study aims at the development of electrospun polylactic acid nanofibers (PLLA NFs) incorporating smart daclatasvir-loaded chitosan gelatin nanoparticles to be used as medical textiles. First, smart nanoparticles were prepared through ionic gelation and optimized using Design Expert® software where daclatasvir (DAC), chitosan (CS), and gelatin (GL) amounts were selected to be the independent variables. DAC was used owing to its reported Anti-SARS-CoV-2 activity, CS was chosen due to its antimicrobial activity and GL was used owing to its sensitivity to be hydrolyzed upon exposure to Papain-like protease enzyme (PLpro). The optimum DAC-CS/TAN NPs possessed 109 nm size and 94.44 % entrapment efficiency in addition to sustained drug release for 14 days. Furthermore, upon exposure to PLpro, smart DAC-CS/GL NPs released the whole DAC amount within 3 h. Then, DAC-CS/GL NPs were incorporated within PLLA NFs through electrospinning. Swellability was found to increase gradually reflecting the controlled release of DAC from nanofibers within 3 weeks. Cell viability assessments using human fibroblasts showed that the developed nanofibers possess high biocompatibility. An in-vivo animal model for skin irritation was carried out for two weeks where visual inspection and histopathological investigations showed that neither edema nor erythema were observed.

Rapid microwave synthesis of N and S dual-doped carbon quantum dots for natamycin determination based on fluorescence switch-off assay.

Green, one-pot, quick, and easily synthesized nitrogen and sulfur co-doped carbon quantum dots (N,S-CDs) were obtained from cheap and readily available chemicals (sucrose, urea, and thiourea) using a microwave-assisted approach in about 4 min and utilized as a turn-off fluorescent sensor for estimation of natamycin (NAT). First, the effect of N and S doping on the microwave-synthesized CDs' quantum yield was carefully studied. CDs derived from sucrose alone failed to produce a high quantum yield; then, to increase the quantum yield, doping with heteroatoms was carried out using either urea or thiourea. A slight increase in quantum yield was observed upon using thiourea with sucrose, while an obvious enhancement of quantum yield was obtained when urea was used instead of thiourea. Surprisingly, using a combination of urea and thiourea together results in N,S-CDs with the highest quantum yield (53.5%), uniform and small particle size distribution, and extended stability. The fluorescent signal of N,S-CDs was quenched upon addition of NAT due to inner filter effect and static quenching in a manner that allowed for quantitative determination of NAT over a range of 0.5-10.0µg ml-1(LOD = 0.10µg ml-1). The N,S-CDs were applicable for determination of NAT in aqueous humor, eye drops, different environmental water samples, and bread with excellent performance. The selectivity study indicated excellent selectivity of the prepared N,S-CDs toward NAT with little interference from possibly interfering substances. In-silico toxicological evaluation of NAT was conducted to estimate its long-term toxicity and drug-drug interactions. Finally, the preparation of N,S-CDs, and analytical procedure compliance with the green chemistry principles were confirmed by two greenness assessment tools.

The Role of Oral Ascorbic Acid Administration in Combination With IV N-acetylcysteine in Delaying Inflammatory Cascade in Sepsis: A Case Report.

Sepsis is a life-threatening emergency that arises owing to a dysregulated host response to infection, leading to existence organ dysfunction. Vitamin C administration has led to a lower mortality rate in sepsis. N-acetylcysteine (NAC) treatment during sepsis improves hepatic function and enhances tissue oxygenation. The objective of this case report is to investigate the synergistic effect of the combination of vitamin C, thiamine, and NAC in delaying sepsis cascade and prolongation of survival time. In this case report, an oral dose of vitamin C 500 mg three times daily in combination with IV thiamine 100 mg three times daily, IV NAC, and hydrocortisone stress dose resulted in 12 days of survival of an immunocompromised patient with ventilator-associated pneumonia on single anti-pseudomonas beta-lactam antibiotic. The patient was a 60-year-old Malay female with previous bone marrow transplantation surgery and a medical history of ischemic stroke on phenytoin and valproate therapy. The patient was transferred to a medical ward in Penang General Hospital, Malaysia, due to community-acquired pneumonia. She was on ceftriaxone for five days, then sedated and ventilated in the ICU, with a shift to cefepime for three days, which was then changed to meropenem for nine days until the last day of life. Total anti-pseudomonas coverage was 12 days. The patient had multiple comorbidities from phenytoin-induced hepatic encephalopathy, acute kidney injury, and three sessions of hemodialysis. IV vitamin C was not available, so an oral dose was administered with potential efficacy in delaying the sepsis inflammatory cascade, leading to the use of a single (not double) anti-pseudomonas antibiotic for 12 days. Prolonged survival duration may be expected in the case of normal bone marrow patients with ventilator-associated pneumonia sepsis. In conclusion, Vitamin C, thiamine, and NAC combination resulted in delayed sepsis progression for 12 days and the survival of the immunocompromised patient on a single anti-pseudomonas beta-lactam antibiotic.

Feasible spectrofluorimetric approach for the ultrasensitive determination of lomefloxacin based on synergistic effects of micellization and metal complexation.

The purpose of the present work was to establish a fast and convenient strategy for lomefloxacin analysis using a fluorimetric approach. The methodology was based on the complex formation of the drug with aluminum ion to give a product having high fluorescence. Adding sodium dodecyl sulfate led to further boosting the intensity of fluorescence which was recorded at 429 nm after excitation at 332 nm. The relationship of emission intensity with lomefloxacin concentration was linear at 10-130 ng mL-1 with a correlation coefficient of 0.9996. The quantitation limit was 11.4 ng mL-1 and detection limit was 3.8 ng mL-1. The reaction conditions were carefully studied which included the pH, buffer type, its concentration, the type and concentration of surfactant and the diluting solvent. The method was utilized to quantify the aforementioned drug in tablet formulations and in real human plasma with high accuracy and reliability.

Response surface optimization of a vortex-assisted dispersive liquid-liquid microextraction method for highly sensitive determination of repaglinide in environmental water by HPLC/UV.

A vortex-assisted dispersive liquid-liquid microextraction (DLLME) method, mated to chemometrics and combined with HPLC/UV detection was optimized and validated for enrichment and determination of repaglinide in environmental samples using nateglinide as an internal standard (IS). A phosphate buffer (10 mM, pH 2.5): acetonitrile (45:55, v/v) was used as a mobile phase with a flow rate of 1 mL/min in an isocratic elution mode. Chemometrics-assisted optimization was performed using a quadratic integrated D-optimal design. The developed model assessed the statistical significance of the independent variables and their interactions to attain the optimum conditions revealing that extractant type, extractant volume and pH are the most influential factors. Optimization of the extraction procedures was performed with the aid of Design Expert 8® software, which suggested 58 different experiments. The optimal conditions were 30 µL of 1-octanol as extractant, 100 µL of acetonitrile as a disperser at pH 8. Under the optimized conditions, the method showed linearity over the range of 1-100 ng/mL with a limit of detection of 0.4 ng/mL. The accuracy, the intra- and inter-day precision were assessed, the %recoveries were found to be between 98.48 and 100.81% with %RSD lower than 1.3. Using chemometrics in method optimization helped achieve the maximum possible enrichment with the least effort, time, and reagents while considering all possible interactions between variables.