Two green and sensitive spectrofluorimetric approaches for determination of Ambroxol and guaifenesin in their single and combined pharmaceutical formulations.

Ambroxol hydrochloride (AMX) and guaifenesin (GFN) are approved drugs utilized to treat coughs through their potent mucolytic and expectorant properties. Due to their massive, combined administration in many illnesses, there is a persistent need for their concurrent estimation in different pharmaceutical formulations. Two sensitive, environmentally friendly spectrofluorimetric methods were developed. AMX was determined using the first method (I) without interference from GFN. This method depends on the quenching of Erythrosine B (EB) native fluorescence at 552 nm after excitation at 527 nm due to the formation of a non-fluorescent AMX-EB ion-pair complex in Britton-Robinson buffer (BRB) solution pH (3.5). The concentration plot is linear over the 0.25-5.0 µg/mL range, with a mean percent found value of 99.74%. Method (II) depends on measuring the native fluorescence of aqueous GFN solution at two analytical wavelengths, either 300 or 600 nm, after excitation at 274 nm. Relative fluorescence intensity (RFI)-concentration plots are linear over the ranges of 0.02-0.5 and 0.1-2.0 µg/ml, with mean percent found at 99.96% and 99.91% at dual wavelengths, respectively. The proposed methods were successfully applied to assay both drugs in raw materials and different single and combined pharmaceutical formulations. These methods have been thoroughly validated following International Committee on Harmonisation (ICH) guidelines. National Environmental Methods Index, Analytical Eco-Scale, and Green Analytical Procedure Index were used to prove greenness, thereby enhancing their applicability. The proposed techniques provide straightforward, precise, and cost-effective solutions for routine formulation analysis in quality control laboratories.

Femoral vein stenting versus endovenectomy as adjuncts to iliofemoral venous stenting in extensive chronic iliofemoral venous obstruction.

PURPOSE: To compare femoral endovenectomy with the creation of an arteriovenous fistula (FE + AVF), versus iliofemoral endovenous stenting with the concurrent extended femoral vein (FV-S) stenting in patients with chronic iliofemoral venous obstruction (IFVO). MATERIALS AND METHODS: In a randomized prospective single-center study, 48 received (FV-S), while the other 54 had (FE + AVF). RESULTS: There were no statistically significant differences in the primary outcomes between the two groups (FV-S) and (FE + AVF) (59% vs 56.8%, 75% vs 79.1%, respectively). At a median of 13 months after the treatment. However, the FV-S group's patients experienced fewer postoperative problems (p = .012), shorter procedures (p = .001), and shorter stays in the hospital (p = .025). CONCLUSION: There is no difference between the efficacy and symptomatic resolution of the FV-S group and the FE + AVF group at the same time, FV-S has lower postoperative complications and a shorter procedure duration and hospital stay.

Exploring fluorescence of metal nanoparticles for effective utility in drug sensing: A Promising ''on-off'' fluorescence probe for analysis of cephalosporins is fabricated.

A promising fluorescent nano sensor was fabricated exploiting the unique optical and physicochemical properties of silver nanoparticles (AgNPs). AgNPs were prepared following a chemical reduction technique to get a highly water-soluble nano sensor, stable for at least 1 month without the need of organic stabilizers. Full characterization of AgNPs was done using different spectroscopic and microscopic techniques. They exhibit excellent water solubility, physicochemical and optical properties, enabling them to be successfully applied in chemical sensing of drugs. The prepared AgNPs could be conceived as a fluorescent probe for the fluorimetric determination of two commonly administered cephalosporins ceftriaxone (CTX) and cefepime (CFP) based on the quenching behavior of the fluorescence omitting the need for pre-derivatization or chromogenic reagents. The fluorescence intensity of AgNPs at 485 nm after excitation at 242 nm was quantitively quenched upon increasingly adding the studied drugs over the concentration ranges of 1-10 µg/mL and 0.9-9 µg/mL with detection limits of 0.178 µg/mL and 0.145 µg/mL for CTX and CFP, respectively. The quenching mechanisms were investigated and illustrated. The influence of different experimental parameters was studied and optimized. The suggested sensor provides an innovative, sensitive, and eco-friendly approach for the assay of the drugs in their pharmaceutical vials and quality control laboratories with excellent % recoveries of 99.88 ± 1.15, 99.95 ± 1.15 for CTX and CFP, respectively. The method was validated in accordance with ICH Q2 R1 recommendations. The greenness evaluation was performed through both Eco-Scale and GAPI revealing the green criteria of the developed method.

Three techniques for the determination of perindopril through derivatization with 4-chloro-7-nitrobenzo-2-oxa-1,3-diazole.

In addition to its pure form, three accurate, rapid, and simple methods have been established for determining perindopril (PRD) in its tablet form. At pH 9.0 using a borate buffer, developing the three designated methods was successful according to the reaction between PRD and 4-chloro-7-nitrobenzo-2-oxa-1,3-diazole (NBD-Cl) and the formation of a chromogen (with a yellow color) measurable at 460 nm using the spectrophotometric method (Method I). In addition, the produced chromogen was assessed using the spectrofluorimetric method (Method II) at 535 nm following excitation at 461 nm. Afterward, the same reaction product was separated and determined using the HPLC method with fluorescence detection (Method III). A Promosil C18 stainless steel column (Q7 5 mm particle size, 250-4.6 mm) has proven suitable for separation. The mobile phase adjustment was made at pH 3.0, with a 1.0 mL min -1 flow rate; its composition was methanol-sodium dihydrogen phosphate, 0.02 M (60: 40, v/v). Through concentration ranges of 5.0-60.0, 0.5-6.0, and 1.0-10.0 µg mL-1, the calibration curves were rectilinear for Methods I, II, and III, respectively, with limits of quantification (LOQ) of 1.08, 0.16 and 0.19 µg mL-1 as well as limits of detection (LOD) of 0.36, 0.05 and 0.06 µg mL-1. The developed methods were implemented to estimate PRD in tablets, and a comparison between the obtained outcomes utilizing the developed methods as well as obtained from the official method revealed that they were comparable. The official BP method was based on dissolving PRD in anhydrous acetic acid and titrating with 0.1 M perchloric acid, then the potentiometric determination of the end-point. The designated methods were also implemented in content uniformity testing with satisfying results. The reaction pathway proposal was speculated, and according to ICH Guidelines, the statistical evaluation of the data was performed. The three proposed methods were confirmed to be green, eco-friendly and safe to environment using Green Analytical procedure index (GAPI) method.

Satellite-based estimates of groundwater storage depletion over Egypt.

An arid climate accompanied by a freshwater shortage plagued Egypt. It has resorted to groundwater reserves to meet the increasing water demands. Fossil aquifers were lately adopted as the sole water source to provide the irrigation water requirements of the ongoing reclamation activities in barren areas. Yet, the scarcity of measurements regarding the changes in the aquifers' storage poses a great challenge to such sustainable resource management. In this context, the Gravity Recovery and Climate Experiment (GRACE) mission enables a novel consistent approach to deriving aquifers' storage changes. In this study, the GRACE monthly solutions during the period 2003-2021 were utilized to estimate alterations in terrestrial water storage (TWS) throughout Egypt. Changes in groundwater storage (GWS) were inferred by subtracting soil water content, derived from the GLDAS-NOAH hydrological model, from the retrieved TWS. The secular trends in TWS and GWS were obtained using the linear least square method, while the non-parametric technique (Mann-Kendall's tau) was applied to check the trend significance. The derived changes in GWS showed that all aquifers are undergoing a significant loss rate in their storage. The average depletion rate over the Sinai Peninsula was estimated at 0.64 ± 0.03 cm/year, while the depletion rate over the Nile delta aquifer was 0.32 ± 0.03 cm/year. During the investigated period (2003-2021), the extracted groundwater quantity from the Nubian aquifer in the Western Desert is estimated at nearly 7.25 km3. The storage loss from the Moghra aquifer has significantly increased from 32 Mm3/year (2003-2009) to 262 Mm3/year (2015-2021). This reflects the aquifer exposure for extensive water pumping to irrigate newly cultivated lands. The derived findings on the aquifers' storage losses provide a vital source of information for the decision-makers to be employed for short- and long-term groundwater management.

Novel approaches of erythrosine B as a food dye-derived spectroscopic probe for assessing trospium chloride in raw material and dosage form.

Two facile spectroscopic methodologies were designed for estimating trospium chloride (TPM) in raw material and tablets with high operational reliability and selectivity. The methods were based on using erythrosine B (EB) as a spectroscopic tool for ion-pair complex formation with the drug. In a mild acidic medium of Britton Robinson buffer (pH 4.0), the ionized hydroxyl group in the reagent interacted with the ionized amine in the studied drug. Method I was based on the spectrophotometric measuring of the absorbance of the reaction product at 557 nm. Method II was based on spectrofluorimetric measurement of the quenching effect of TPM on the inherent fluorescence of EB at 550 nm (λex. = 528 nm). The two methods showed linearity through ranges 1.0-10.0 and 0.5-10.0 µg/ml for Methods I and II, respectively. The suggested methods were exploited for analyzing TPM in Trospamexin® tablets and showed good applicability. The designed systems were validated as per International Conference on Harmonization guidelines. Experimental conditions were modulated to obtain the best sensitivities. The quenching mechanism was investigated and the quenching constant was computed relying on the Stern-Volmer equation. Environmental impact was appraised using novel metric green tools, GABI, and AGREE. The suggested systems excelled over other reported methods in terms of greenness, sensitivity, and cost-effectiveness.

Implementation of HILIC-UV technique for the determination of moxifloxacin and fluconazole in raw materials and pharmaceutical eye gel.

Hydrophilic interaction liquid chromatography (HILIC) has inherent merits over RP-HPLC in the analyzing of hydrophilic substances. Accordingly, an innovative HILIC-UV methodology is proposed for the simultaneous estimation of ethyl paraben (PRN), fluconazole (FLZ) and moxifloxacin hydrochloride (MOX) in raw materials and pharmaceutical eye gel. The separation process was conducted using Waters XBridge™ HILIC column (100 mm × 4.6 mm, 3.5 µm particle size) at room temperature. Isocratic mobile phase containing acetonitrile: 0.1% triethylamine buffer (90:10, v/v, pH 5.0), was pumped at flow rate 1.0 mL/min and detected at 260 nm. Under these optimized conditions, PRN, FLZ and MOX showed rectilinear relationships with the concentration ranges (0.5-6.0), (5.0-50.0) and (5.0-60.0) µg/mL, respectively. The developed method offered at least fivefold increase in sensitivity within shorter time than the reported methods. Three greenness assessment tools namely: Analytical eco-scale, GAPI and AGREE were exploited to investigate the method's impact on the environment and conduct a comparative study with the reported methods. International council of Harmonization (ICH) guidelines have been followed to calculate validation parameters. The statistical comparison between results of the suggested method and the comparison method showed no discrepancy confirming accuracy of the method.

Validation of a COVID-19 self-assessment tool for the prediction of COVID-19 in a primary health care setting in Egypt.

BACKGROUND: As SARS-CoV-2 infection is sweeping the globe, early identification and timely management of infected patients will alleviate unmet health care demands and ultimately control of the disease. Remote COVID-19 self-assessment tools will offer a potential strategy for patient guidance on medical consultation versus home care without requiring direct attention from healthcare professionals. OBJECTIVE(S): This study aimed to assess the validity and interrater reliability of the initial and modified versions of a COVID-19 self-assessment prediction tool introduced by the Egyptian Ministry of Health and Population (MoHP) early in the epidemic. The scoring tool was released for the public through media outlets for remote self-assessment of SARS-CoV-2 infection connecting patients with the appropriate level of care. METHODS: We evaluated the initial score in the analysis of 818 consecutive cases presenting with symptoms suggesting COVID-19 in a single-primary health care clinic in Alexandria during the epidemic in Egypt (mid-February through July). Validity parameters, interrater agreement and accuracy of the score as a triage tool were calculated versus the COVID-19 polymerase chain reaction (PCR) test. RESULTS: A total of 818 patients reporting symptoms potentially attributable to COVID-19 were enrolled. The initial tool correctly identified 296 of 390 COVID-19 PCR +ve cases (sensitivity = 75.9%, specificity = 42.3%, positive predictive value = 54.5%, negative predictive value = 65.8%). The modified versions of the MoHP triage score yielded comparable results albeit with a better accuracy during the late epidemic phase. Recent history of travel [OR (95% CI) = 12.1 (5.0-29.4)] and being a health care worker [OR (95% CI) = 5.8 (2.8-11.9)] were major predictors of SARS-CoV-2 infection in early and late epidemic phases, respectively. On the other hand, direct contact with a respiratory infection case increased the risk of infection by three folds throughout the epidemic period. CONCLUSION: The tested score has a sufficient predictive value and potential as a triage tool in primary health care settings. Updated implementation of this home-grown tool will improve COVID-19 response at the primary health care level.

Effectiveness of hepatitis B vaccination in chronic HCV patients after successful generic direct acting antiviral therapy: significance of isolated hepatitis B core antibodies.

OBJECTIVE: Previous reports show conflicting results regarding hepatitis B virus (HBV) vaccine efficacy in Hepatitis C virus (HCV) infected individuals and in those with isolated hepatitis B core antibodies (HBcAb). We aimed to evaluate the effectiveness of HBV vaccine and identify possible factors that may contribute to hyporesponsivness in HCV-treated patients, including those with isolated HBcAb. METHODS: We conducted a prospective study with 118 enrolled chronic HCV patients who followed a 12-week regimen of direct acting antivirals (DAAs) and were evaluated for HBV serological markers. Eventually, 98 received appropriate HBV vaccination and were assessed for response. RESULTS: A total of 57.1% were vaccine responders although only 5.1% achieved a seroprotective level of HBsAb titre. The response rate was significantly lower among treated HCV patients with isolated HBcAb [2 (5.6%) vs. 40 (64.5%) respectively]. On multivariate analysis, advanced age [OR (95% CI) = 1.09 (1.02-1.17)] and presence of isolated HbcAb [OR (95% CI) = 39.59 (7.98-196.63)] were predictors of vaccine non-response. In our cost-effectiveness models, the cost of HBV serological screening was less than the nationally adopted non-screening approach. A model ratifying reinforced vaccination in non-responder HBcAb seropositive HCV patients would incur extra cost. CONCLUSION: Hyporesponsiveness to the HBV vaccination is frequent in chronic HCV patients even after achieving SVR following DAAs. Although there is no consensus on the clinical management of patients with isolated HBcAb, our cost-effectiveness options may support decision-making for better clinical benefit and proper health investments.

Hepatoprotective effect of Thymus vulgaris extract on sodium nitrite-induced changes in oxidative stress, antioxidant and inflammatory marker expression.

The herb thyme (Thymus vulgaris) has multiple therapeutic uses. In this study, we explored how T. vulgaris leaf extract protects liver cells against sodium nitrite-(NaNO2) induced oxidative stress. Mice were divided into four groups; each group received one of the following treatments orally: saline; T. vulgaris extract alone; NaNO2 alone; or T. vulgaris extract + NaNO2. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), reduced glutathione (GSH), superoxide dismutase (SOD), malondialdehyde (MDA), IL-1ß, IL-6, TNF-α, and total proteins were measured in serum using standard methods. TNF-α, hemooxygenase-1 (HO-1), thioredoxin, SOD, and GSH synthase, all of which are linked to oxidative stress, were measured using quantitative real-time PCR (qRT-PCR). In mice treated with T. vulgaris extract, the effect of NaNO2 on ALT and AST levels and total proteins was reduced, and its effect on antioxidant levels was reversed. Normally, NaNO2 causes hepatocyte congestion and severe hepatic central vein congestion. Tissues in the mice treated with T. vulgaris were restored to normal conditions. Our results demonstrate that NaNO2-induced hepatic injury is significantly reduced by pretreatment with T. vulgaris extract, which protects against hepatic oxidative stress and its associated genes at the biochemical, molecular, and cellular levels.

SARS-CoV-2 Transmission Channels: A Review of the Literature.

BACKGROUND The novel coronavirus SARS-CoV-2 is responsible for the current global pandemic. There is a concerted effort within the global scientifi c community to identify (and thereby potentially mitigate) the possible modes of transmission through which the virus spreads throughout populations. OBJECTIVE Summarize the ways in which SARS-CoV-2 is transmitted and provide scientifi c support for the prevention and control of COVID-19. EVIDENCE AQUISITION We conducted an extensive literature search using electronic databases for scientifi c articles addressing SARSCoV-2 transmission published from December 28, 2019 through July 31, 2020. We retrieved 805 articles, but only 302 were included and discussed in this review. The report captured relevant studies investigating three main areas: 1) viral survival, 2) transmission period and transmissibility, and 3) routes of viral spread. DEVELOPMENT Currently available evidence indicates that SARSCoV-2 seems to have variable stability in different environments and is very sensitive to oxidants, such as chlorine. Temperature and humidity are important factors infl uencing viral survival and transmission. SARSCoV-2 may be transmitted from person to person through several different routes. The basic mechanisms of SARS-CoV-2 transmission person-to-person contact through respiratory droplets, or via indirect contact. Aerosolized transmission is likely the dominant route for the spread of SARS-CoV-2, particularly in healthcare facilities. Although SARS-CoV-2 has been detected in non-respiratory specimens, including stool, blood and breast milk, their role in transmission remains uncertain. A complicating factor in disease control is viral transmission by asymptomatic individuals and through what would otherwise be understood as innocuous human activities. CONCLUSIONS This article provides a review of the published research regarding human-to-human transmission of SARS-CoV-2 and insights into developing effective control strategies to stop viral propagation. KEYWORDS COVID-19, SARS-CoV-2, transmission, pandemics, microbial viability.

Spatio-temporal Distribution of Meningitis in HIV Patients in Northern Egypt (2000-2018).

BACKGROUND: Meningitis is a leading cause of death among patients living with HIV. There is no adequate tracking of the disease occurrence, distribution and etiologic agents among this risk group in Egypt, although the pattern could differ from that of the general population. OBJECTIVES: We aimed to describe the spatio-temporal distribution of meningitis in HIV patients in a region of Northern Egypt over 18 years (2000-2018). METHODS: We conducted a retrospective study of 352 adult HIV patients admitted to a tertiary care fever hospital with neurological manifestations suggesting meningitis. We retrieved from inpatient records all data relevant to patient demographics, clinical presentation, diagnostic work-up, results of laboratory investigations (CSF, blood, imaging), definitive diagnosis, and in-hospital mortality. RESULTS: The overall trend of over 2 decades showed fluctuating incidence of meningitis in HIV infected patients and increasing spread into rural areas, with a uniform circulation among adult males. Cryptococcal meningitis was the most common etiologic agent (26.9%) and was associated with worse outcomes. Focal neurological deficit (38.5%), cranial nerve involvement (48.1%) were common features in TB Meningitis. The mortality was high (56.8%) and was significantly associated with low CD4+ count, advanced AIDs clinical stage and the presence of co-morbidities. CONCLUSION: Despite the availability of cART, meningitis, particularly cryptococcal, is common in HIV/AIDS population in Egypt. Continued efforts are desperately needed to improve the outcomes of HIV-infected patients.

A clinical rule for the prediction of meningitis in HIV patients in the era of combination antiretroviral therapy.

BACKGROUND: The diagnosis of meningitis in HIV patients is challenging due to altered immune responses. Diagnostic scoring systems were recently proposed for use in research settings to help prompt and easy differential diagnosis. The objective of this study was to create a clinical prediction rule (CPR) for meningitis in HIV-infected patients and to address the enigma of differentiating bacterial (BM), TB (TBM) and cryptococcal (CCM) meningitis based on clinical features alone, which may be enhanced by easy-to-obtain laboratory testing. METHODS: We retrospectively enrolled 352 HIV patients presenting with neurological manifestations suggesting meningitis over the last 18 y (2000-2018). Relevant clinical and laboratory information were retrieved from inpatient records. The features independently predicting meningitis or its different types in microbiologically proven meningitis cases were modelled by multivariate logistic regression to create a CPR in an exploratory data set. The performance of the meningitis diagnostic score was assessed and validated in a subset of retrospective data. RESULTS: AIDS clinical stage, injecting drug use, jaundice and cryptococcal antigen seropositivity were equally important as classic meningitic symptoms in predicting meningitis. Arthralgia and elevated cerebrospinal fluid Lactate dehydrogenase (LDH) were strong predictors of BM. Patients with cryptococcal antigenemia had 25 times the probability of having CCM, whereas neurological deficits were highly suggestive of TBM. CONCLUSION: The proposed CPRs have good diagnostic potential and would support decision-making in resource-poor settings.

Evaluation of efficiency of insulin suppository formulations containing sodium salicylate or sodium cholate in insulin dependent diabetic patients.

Two formulations of insulin suppositories were prepared to contain different amounts of sodium salicylate and sodium cholate as absorption promoters and also of insulin with the purpose of obtaining the most effective formulation in reducing plasma glucose levels after rectal administration to diabetic patients. The results show that insulin suppositories containing 100 mg sodium salicylate and 100 or 200 U of crystalline insulin showed no significant difference in AUC, Cmax and Tmax and both formulations showed significant reduction in plasma glucose level compared to initial values within 1.5-2 h. The results from experiments carried out in health volunteers showed that 100 mg sodium salicylate is the optimum amount to be included in insulin suppositories producing significantly higher Cmax and AUC compared to those produced after rectal administration of insulin suppositories containing 50 or 200 mg sodium salicylate. The results also show that using sodium cholate in 50 mg amount did not produce any significant reduction in plasma glucose levels of insulin dependent diabetic patients given suppositories containing 100 U of insulin, but this amount in suppositories containing 200 U of insulin was able to produce significant (p < 0.05) reduction in plasma glucose level within 1 h which lasted till end of experiment producing Cmax of 29.7 +/- 6.61% at Tmax of 1.5 +/- 0.61 h. On increasing the amount of sodium cholate to 100 mg in the suppositories, a marked (p < 0.01) reduction in plasma glucose level took place and the Cmax increased to 47.7 +/- 12.24% at Tmax of 1.5 +/- 0.63 h. This resulted in AUC of 86.7 +/- 22.4 mg%h which was non significantly higher from that produced after administration of suppositories containing 50 mg sodium cholate and 200 U insulin (62.5 +/- 17.6 mg%h). The results also show that insulin suppositories containing 100 mg sodium cholate and 200 U insulin resulted in a non significant differences in Cmax and AUC from those produced by S.C. injection of insulin (20 U) but significantly (p < 0.001) shorter Tmax. This formulation also shows non significant differences in Tmax and AUC and significantly (p < 0.05) higher Cmax than from those produced after rectal administration of suppositories containing 100 mg of sodium salicylate and same amount of insulin. Further more this formulation produced severe hypoglycemia in control healthy volunteers within 1 h of administration producing Cmax of 57.0 +/- 18.8% at Tmax of 0.75 +/- 0.35 h. The results of this study showed that the formulation containing 100 mg of sodium cholate and 200 U of insulin tested in fasted insulin dependent diabetic patients produced a maximum % reduction in plasma glucose levels (Cmax) of 47.7 +/- 12.24% at tmax of 1.5 +/- 0.63 h compared to Cmax of 50.56 +/- 6.8% at tmax of 2.93 +/- 0.19 h resulted after subcutaneous injection of 20 U insulin. These suppositories produced an area under the curve (AUC) of 87 +/- 22.4 mg%h compared to an AUC of 81 +/- 13.4 mg%h obtained after subcutaneous injection. This formulation of suppositories studied in 7 insulin dependent diabetic patients was found to abolish the 2-h post-prandial significant rise in plasma glucose levels after meal. These results show that these insulin suppositories containing 100 mg of sodium cholate and 200 U of insulin can serve as effective buffer against meal related hyperglycemia. The suppositories were safe, effective, accepted and well tolerated by the tested individuals.