Novel isoniazid-hydrazone derivatives induce cell growth inhibition, cell cycle arrest and apoptosis via mitochondria-dependent caspase activation and PI3K/AKT inhibition.

In this study, seven isoniazid-hydrazone derivatives (3a-g) were synthesized and their structures elucidated by chromatographic techniques, and then the antiproliferative effects of these compounds on various cancer cells were tested. The advanced anticancer mechanism of the most potent compound was then investigated. Antiproliferative activities of the synthesized compounds were evaluated on human breast cancer MCF-7, lung cancer A-549, colon cancer HT-29, and non-cancerous mouse fibroblast 3T3-L1 cell lines by XTT assay. Flow cytometry analysis were carried out to determine cell cycle distribution, apoptosis, mitochondrial membrane potential, multi-caspase activity, and expression of PI3K/AKT signaling pathway. The XTT results showed that all the title molecules displayed cytotoxic activity at varying strengths in different dose ranges, and among them, the strongest cytotoxic effect and high selectivity were exerted by 3d against MCF-7 cells with the IC50 value of 11.35 µM and selectivity index of 8.65. Flow cytometry results revealed that compound 3d induced apoptosis through mitochondrial membrane disruption and multi-caspase activation in MCF-7 cells. It also inhibited the cell proliferation via inhibition of expression of PI3K/AKT and arrested the cell cycle at G0/G1 phase. In conclusion, all these data disclosed that among the synthesized compounds, 3d is notable for in vivo anticancer studies.

Validation of an HPLC Method for the Determination of Diclofenac Diethylamine and Three of Its Impurities in a Gel Pharmaceutical Form.

BACKGROUND: Monitoring impurities in drug products is a principal requirement of pharmaceutical regulatory authorities all over the world to ensure drug safety. For this reason, there is a great need for analytical QC of dugs products. OBJECTIVE: In this study, a simple, efficient, and direct HPLC method was developed for the determination of three impurities of diclofenac. METHODS: The HPLC method was developed using a mobile phase which consisted of an HPLC grade mixture, acetonitrile-0.01M phosphoric acid adjusted to pH 2.3 (1 + 3, by volume). RESULTS: The separation was performed in 15 min. The calibration curves of the three impurities were linear; the correlation coefficients were 0.999 at concentrations of 0.00015-0.003 µg/mL. CONCLUSION: The validation of this method shows that it meets all validation criteria. This shows the reliability of this method for the routine control of diclofenac impurities. HIGHLIGHTS: The validation of a robust HPLC method for the determination of diclofenac impurities is of great importance for the pharmaceutical industry to control its products.

Synthesis, Spectroscopic Characterization, Antibacterial Activity, and Computational Studies of Novel Pyridazinone Derivatives.

In this work, a novel series of pyridazinone derivatives (3-17) were synthesized and characterized by NMR (1H and 13C), FT-IR spectroscopies, and ESI-MS methods. All synthesized compounds were screened for their antibacterial activities against Staphylococcus aureus (Methicillin-resistant), Escherichia coli, Salmonella typhimurium, Pseudomonas aeruginosa, and Acinetobacter baumannii. Among the series, compounds 7 and 13 were found to be active against S. aureus (MRSA), P. aeruginosa, and A. baumannii with the lowest MIC value range of 3.74-8.92 µM. Afterwards, DFT calculations of B3LYP/6-31++G(d,p) level were carried out to investigate geometry structures, frontier molecular orbital, molecular electrostatic potential maps, and gap energies of the synthesized compounds. In addition, the activities of these compounds against various bacterial proteins were compared with molecular-docking calculations. Finally, ADMET studies were performed to investigate the possibility of using of the target compounds as drugs.

A Novel Approach for Therapeutic Drug Monitoring of Valproic Acid Using FT-IR Spectroscopy and Nonlinear Support Vector Regression.

BACKGROUND: Recent technological progress has bolstered efforts to bring personalized medicine from theory into clinical practice. However, progress in areas such as therapeutic drug monitoring (TDM) has remained somewhat stagnant. In drugs with well-known dose-response relationships, TDM can enhance patient outcomes and reduce health care costs. Traditional monitoring methods such as chromatography-based or immunoassay techniques are limited by their higher costs and slow turnaround times, making them unsuitable for real-time or onsite analysis. OBJECTIVE: In this work, we propose the use of a fast, direct, and simple approach using Fourier transform infrared spectroscopy (FT-IR) combined with chemometric techniques for the therapeutic monitoring of valproic acid (VPA). METHOD: In this context, a database of FT-IR spectra was constructed from human plasma samples containing various concentrations of VPA; these samples were characterized by the reference method (immunoassay technique) to determine the VPA contents. The FT-IR spectra were processed by two chemometric regression methods: partial least-squares regression (PLS) and support vector regression (SVR). RESULTS: The results provide good evidence for the effectiveness of the combination of FT-IR spectroscopy and SVR modeling for estimating VPA in human plasma. SVR models showed better predictive abilities than PLS models in terms of root-mean-square error of calibration and prediction RMSEC, RMSEP, R2Cal, R2Pred, and residual predictive deviation (RPD). CONCLUSIONS: This analytical tool offers potential for real-time TDM in the clinical setting. HIGHLIGHTS: FTIR spectroscopy was evaluated for the first time to predict VPA in human plasma for TDM. Two regressions were evaluated to predict VPA in human plasma, and the best-performing model was obtained using nonlinear SVR.

A Preliminary Study on the Potential of FT-IR Spectroscopy and Chemometrics for Tracing the Geographical Origin of Moroccan Virgin Olive Oils.

BACKGROUND: The authentication of the geographical origin of virgin olive oils (VOO) generally requires the use of sophisticated and time-consuming analytical techniques. There is a need for quick and simple analytical techniques to predict the origin of olive oils. OBJECTIVE: This study aims to examine the physico-chemical data of olive oils collected in six regions of Morocco during two consecutive years 2020 and 2021, and also to evaluate the ability of FT-IR in combination with discrimination tools to study the geographical origin of Moroccan olive oils. METHOD: Fourier transform infrared spectroscopy (FTIR) was used in this study as an emerging analytical technique to express a unique "fingerprint." A preliminary processing of the ATR-FTIR spectral data was performed by preprocessing algorithm to reduce the noise and the effect of signal variation as well as to minimize the effects of light scattering to extract the maximum analytical information from the spectra. A multivariate statistical procedure based on principal component analysis (PCA) coupled with linear discriminant analysis (LDA) as well as partial least-squares discriminant analysis (PLS-DA) was developed to provide a powerful classification approach. RESULTS: Based on the PCA, six clusters were identified. The application of PCA-LDA and PLS-DA procedures demonstrate a powerful capacity in predicting the geographic origin of olive oils; this capacity is shown by the high value of correct classification rate (CCR), varying between 84.09 and 100%. CONCLUSIONS: The suggested procedure has given reliable results for the classification of olive oils according to their geographical origin, with advantages such as being fast, inexpensive, and not requiring any prior separation process. HIGHLIGHTS: The performance of this approach is significantly faster and possesses a higher degree of selectivity and sensitivity. The implementation of this technique for routine analysis of olive oil would save significant time, resources, and solvents.

Comparative study of three fingerprint analytical approaches based on spectroscopic sensors and chemometrics for the detection and quantification of argan oil adulteration.

BACKGROUND: Argan oil is one of the purest and rarest oils in the world, so that the addition of any further product is strictly prohibited by international regulations. Consequently, it is necessary to establish reliable analytical methods to ensure its authenticity. In this study, three multivariate approaches have been developed and validated using fluorescence, UV-visible, and attenuated total reflectance Fourier transform mid-infrared (FT-MIR) spectroscopies. RESULTS: The application of a partial least squares discriminant analysis model showed an accuracy of 100%. The quantification of adulteration have been evaluated using partial least squares (PLS) regression. The PLS model developed from fluorescence spectroscopy provided the best results for the calibration and cross-validation sets, as it showed the highest R2 (0.99) and the lowest root mean square error of calibration and cross-validation (0.55, 0.79). The external validation of the three multivariate approaches by the accuracy profile shows that these approaches guarantee reliable and valid results of 0.5-32%, 7-32%, and 10-32% using fluorescence, FT-MIR and UV-visible spectroscopies respectively. CONCLUSION: This study confirmed the feasibility of using spectroscopic sensors (routine technique) for rapid determination of argan oil falsification. © 2021 Society of Chemical Industry.

Anticancer drug waste minimization and cost-saving study by using a closed-system transfer device for chemotherapy compounding.

INTRODUCTION: There is a need for an economic evaluation of the use of closed system (CSTD) in chemotherapy compounding, especially in resource-constrained settings. OBJECTIVE: The objective of this study was to assess the cost saving of the management of cancer drug leftovers before and after introduction of CSTD associated with an extension of the beyond-use date (BUD) of cancer vials. A secondary objective was to estimate the level of minimization of drug wastage. MATERIALS AND METHODS: This was a prospective, single-center study with two periods of two months each. The cost of drugs saved by using conventional systems (syringe and needle) without a closed system in the first period was compared to the cost of drugs saved by using the CSTD Chemoclave® system in the second period. The drug waste minimization rate compared actual drug waste to potential waste in Period 2. RESULTS: In Period 1, the amount of drug saved accounted for an average of 10.3% of the amount used in milligrams and the amount of drug wasted accounted for an average of 18.7%. In period 2, these proportions were 15.2% and 6.4% respectively. The CSTD generated an extra cost of 11,962.5 USD compared to the conventional system. The drug saved cost related only to the CSTD and the acquisition cost of the CSTD was a deficit of -7,444.95 USD and the cost saved from the compounding (CSTD and syringes) was a gain of 1,722.01 USD. The waste minimization represented an average of 72.5% ± 24.4% of potential waste. CONCLUSION: The use of CSTD to extend the BUD allowed to reduce waste due to microbiological instability without adding an economic profit.

Patients' Perception of Morocco's Medicine Pricing Reform and Determinants of Their Access to Health Care and Medicine.

BACKGROUND: In 2014, the Ministry of Health of Morocco implemented a reform of medicine pricing that leads to lower prices. This reform has brought about a new method of pricing medicines and a reduction in the prices of more than 1,400 of the 5,000 medicines on the market. The objective of this study was to survey patients' perceptions of the impact of the reform on medicine prices and affordability of health care, including medicine. METHODS: Between September 2017 and September 2018, 360 patients that visited a community pharmacy in four selected areas of different socioeconomic levels were interviewed based on a questionnaire. Findings were studied through univariate and multivariate analyses. RESULTS: Three hundred patients (83%) were included given their completed questionnaire. The majority (89%) of respondents considered medicine prices as a potential barrier to access to health care. Lower medicine prices following the reform were not perceived to have actually impacted respondents' spending on health care. In some cases, care was delayed, in particular by lower-income respondents and people without insurance and health coverage. CONCLUSION: The majority of patients participating in the study did not perceive the decrease in medicine prices as sufficient. In addition, the study findings pointed to the relevance of further determinants of access to medicines, such as health insurance coverage. Patients think that the generalized third-party payment mode, which does not oblige patients to spend out of their pockets to have their treatment but rather their health insurance funds that will pay for them, provides optimal access to medicines.

Optimization of a Ligand Exchange Chromatography Method for the Enantioselective Separation of Levofloxacin and Its Chiral Impurity.

BACKGROUND: Levofloxacin is a third-generation fluoroquinolone that has several advantages over its (R) ofloxacin isomer. It is used to treat different types of infection, including urinary infection and prostatitis. OBJECTIVE: A new HPLC method for the enantioselective separation of levofloxacin and its chiral impurity was developed and validated to improve the separation of the enantiomers of levofloxacin [impurity(R) and active principle (S)] by increasing the value of the resolution between the eutomer and the distomer. METHOD: Chromatographic separation was performed on a Prodigy ODS -2, 5 µm 4.6 × 150 mm column, with a gradient of buffer solution and methanol (80:20, v/v). A Box-Behnken design was considered when optimizing the enantioseparation involving the effects of many factors such as the concentration of d-phenylalanine, the pH of the buffer, the percentage of organic modifier in the mobile phase, the flow rate, the temperature of the column, and the type of column. RESULTS: Chiral separation was achieved with an optimal resolution of 3.8. The method was successfully validated following the International Conference on Harmonization Q2 (R1) guideline, fulfilling the acceptance criteria for selectivity [no interference in the retention time of (S) levofloxacin and (R) levofloxacin], linearity (r ≥0.999 in the range 1.25-3.75 µg/mL for all enantiomers), and precision (RSD <2%). Accuracy was assessed by the application of the analytical method to an analyte of known purity, providing evidence for the usefulness of this monitoring system. CONCLUSIONS: The method was successfully used for the determination of levofloxacin impurity in raw material and pharmaceutical dosage forms. HIGHLIGHTS: The following method is accurate and robust to quantify and characterize the presence of levofloxacin impurity in raw material for pharmaceutical compounds.

Chemometric Analysis of UV-Visible Spectral Fingerprints for the Discrimination and Quantification of Clinical Anthracycline Drug Preparation Used in Oncology.

In clinical treatment, the analytical quality assessment of the delivery of chemotherapeutic preparations is required to guarantee the patient's safety regarding the dose and most importantly the appropriate anticancer drug. On its own, the development of rapid analytical methods allowing both qualitative and quantitative control of the formulation of prepared solutions could significantly enhance the hospital's workflow, reducing costs, and potentially providing optimal patient care. UV-visible spectroscopy is a nondestructive, fast, and economical technique for molecular characterization of samples. A discrimination and quantification study of three chemotherapeutic drugs doxorubicin, daunorubicin, and epirubicin was conducted, using clinically relevant concentration ranges prepared in 0.9% NaCl solutions. The application of the partial least square discriminant analysis PLS-DA method on the UV-visible spectral data shows a perfect discrimination of the three drugs with a sensitivity and specificity of 100%. The use of partial least square regression PLS shows high quantification performance of these molecules in solution represented by the low value of root mean square error of calibration (RMSEC) and root mean square error of cross validation (RMSCECV) on the one hand and the high value of R-square on the other hand. This study demonstrated the viability of UV-visible fingerprinting (routine approach) coupled with chemometric tools for the classification and quantification of chemotherapeutic drugs during clinical preparation.

Assessment of a Nondestructive Method for Rapid Discrimination of Moroccan Date Palm Varieties via Mid-Infrared Spectroscopy Combined with Chemometric Models.

BACKGROUND: Morocco is an important world producer and consumer of several varieties of date palm. In fact, the discrimination between varieties remains difficult and requires the use of complex and high-cost techniques. OBJECTIVE: We evaluated in this work the potential of mid-IR (MIR) spectroscopy and chemometric models to discriminate eight date palm varieties. METHOD: Four chemometric models were applied for the analysis of the spectral data, including principal-component analysis (PCA), support-vector machine discriminant analysis (SVM-DA), linear discriminant analysis (LDA), and partial-least-squares (PLS) analysis. MIR spectroscopic data were recorded from the wavenumber range 4000-600 cm-1, with a spectral resolution of 4 cm-1. RESULTS: The discriminant analysis was performed by LDA and SVM-DA with a 100% correct classification rate for the date mesocarp. PLS analysis was applied as a complementary chemometric tool aimed at quantifying moisture content; the validation of this model shows a good predictive capacity with a regression coefficient of 84% and a root-mean-square error of cross-validation of 0.50. CONCLUSIONS: The present study clearly demonstrates that MIR spectroscopy combined with chemometric approaches constitutes a promising analytical method to classify date palms according to their varietal origin and to establish a regression model for predicting moisture content. HIGHLIGHTS: An alternative analytical method to discriminate date palm cultivars by FTIR-attenuated total reflection spectroscopy coupled with chemometric approaches is described.

Development and Validation of a UPLC-DAD Method for the Simultaneous Quantification of Eight Antihypertensive Drugs in the Pharmaceutical Matrix.

BACKGROUND: Hypertension is a critical health problem; it is a prevalent risk factor for cardiovascular disease. Many treatments to combat hypertension are available, however many patients are resistant to the standard therapeutic approaches. The association of two or more substances in a fixed-dose combination is effective and tolerated as a substitute for the standard therapeutic approach. OBJECTIVE: The new ultra performance liquide chromatography method was developed and validated to assay a combination of eight antihypertensive drugs including a diuretic: hydrochlorothiazide, dihydropyridine calcium channel blocker: Amlodipine and angiotensin II type 1 receptor blockers (sartans): valsartan, candesartan, eprosartan, olmesartan, losartan, and irbesartan in the pharmaceutical matrix. METHODS: Chromatographic separation was performed on an Acquity® UPLC C18 1.7 µm 2.1 × 100 mm column, with a gradient of buffer solution and acetonitrile, in the proportion of (80:20 v/v). RESULTS: Good resolution was obtained, and an optimal analysis time of less than 5 min was achieved. The method was validated according to the International Conference on Harmonization guidelines following the classical approach and accuracy profile, and it is shown to be suitable for intended applications. The method was successfully used for quality control laboratories and the determination of these drugs combinations in pharmaceutical dosage forms.

Proposal of a simple and rapid method for the chemotherapy preparations analytical control by spectrophotometry UV-Vis method.

INTRODUCTION: The preparation of anticancer chemotherapy in a hospital must meet several objectives; the first main is the quality, which can be provided by setting up a surveillance system and a quality control of each preparations. The aim of this work is to present a simple, fast and accurate spectrophotometric method for the routine control of cytotoxic preparations. MATERIALS AND METHODS: This is a study carried out in the cytotoxic preparation unit of the university center of Rabat-Sale children's hospital in Morocco. All samples of preparations were collected and analyzed daily on the site. After validation of the analytical method with respect to many parameters such as: linearity, accuracy and precision according to ICH Q2 guidelines, samples of cytotoxic preparations collected were assayed. RESULTS: The results are satisfactory with good level of exactitude, and high precision. CONCLUSION: Compared to other techniques, this method can be considered as a useful alternative in the routine quality control of preparations. It can quickly obtain qualitative and quantitative information with instrumentation and inexpensive reagents.

Rapid Analytical Method to Characterize the Freshness of Olive Oils Using Fluorescence Spectroscopy and Chemometric Algorithms.

One of the most important issues in the field of quality assurance of olive oils is the detection of the freshness of olive oil. In this study, 400 nm laser-induced fluorescence spectroscopy was used with supervised and unsupervised multivariate analysis methods to develop a rapid method able to discriminate between freshly produced olive oils and oil that has been stored for a period of time ranging from 12 to 24 months. The fluorescence spectral data were firstly processed by the PCA. This method shows strong discrimination of the three oil classes using the first three components which present 96% of the total variability of the initial data, and then supervised classification models were constructed using the discriminant partial least square regression PLS-DA, support vector machine SVM, and linear discriminant analysis LDA. These methods show a high capacity in the classification of the three classes of olive oil. The validation of these classification models by external samples shows a high capacity of classification of the samples in their class with an accuracy of 100%. This study demonstrated the feasibility of the fluorescence spectroscopy fingerprint (routine technique) for the classification of olive oils according to their freshness and storage time.

E-Cigarette Quality Control: Impurity and Nicotine Level Analysis in Electronic Cigarette Refill Liquids.

This work targets mainly the quality control of electronic cigarette liquids. It relies on an analytical control of a "32-product" sample made of several types of e-cigarette liquids taken from various supermarkets and tobacconist's offices in Morocco. All along this study, we made sure to check both the conformity of the nicotine level indicated in the packaging of each product and the existence of any other components inside the product, especially toxic or unknown impurities. The method used for this study is known under the name of high-performance liquid chromatography. For statistical analysis, we used Student's t-test for a single sample in order to analyze the relative differences between nicotine quantity reported in the product and the one measured during our experiment. Finally, we used linear regression test to determine the relationship between the nicotine level accuracy on the packaging and the level of toxic impurities in the products. The differences between the nicotine concentrations reported in the packages and the measured ones varied from -100% to +3.3%. The study showed that 31% of analyzed products have an accurate indication of the level of nicotine on the packaging. However, 47% of the studied products showed more than 20% difference between measure and packaging indication. In all analyzed samples, the level of impurities altered from 0 to 32.6%. Furthermore, the level of the nicotine breakdown products did not exceed 2% of the nicotine content in pretty much all of the samples. The actual nicotine content of electronic cigarette refill liquids is not always as precise as what is stated on the packaging; in addition to the level of impurities detected in several brands and that exceeds the European Pharmacopoeia standards, some may even present a risk of causing toxicological damage.

Development of Fast Analytical Method for the Detection and Quantification of Honey Adulteration Using Vibrational Spectroscopy and Chemometrics Tools.

In this study, the Fourier transform mid-infrared (FT-MIR) spectroscopy technique combined with chemometrics methods was used to monitor adulteration of honey with sugar syrup. Spectral data were recorded from a wavenumber region of 4000-600 cm-1, with a spectral resolution of 4 cm-1. Principal component analysis (PCA) and hierarchical cluster analysis (HCA) were used for qualitative analysis to discriminate between adulterated and nonadulterated honey. For quantitative analysis, we used partial least-squares regression (PLS-R) and the support vector machine (SVM) to develop optimal calibration models. The use of PCA shows that the first two principal components account for 96% of the total variability. PCA and HCA allow classifying the dataset into two groups: adulterated and unadulterated honey. The use of the PLS-R and SVM-R calibration models for the quantification of adulteration shows high-performance capabilities represented by a high value of correlation coefficients R 2 greater than 98% and 95% with lower values of root mean square error (RMSE) less than 1.12 and 1.85 using PLS-R and SVM-R, respectively. Our results indicate that FT-MIR spectroscopy combined with chemometrics techniques can be used successfully as a simple, rapid, and nondestructive method for the quantification and discrimination of adulterated honey.

Impact of Disparities in Reimbursement Rules Between Public and Private Sectors on Accessibility to Care in Moroccan Mandatory Health Insurance: A Cross-Sectional Study.

BACKGROUND: Disparities in the reimbursement rules between the 2 funds that manage mandatory health insurance in Morocco could negatively affect the accessibility of insured persons to healthcare services and products. OBJECTIVE: The objective is to analyze the impact of these disparities on access to care and to assess the insured's copayment difference between the 2 funds. METHODS: Healthcare utilization rates of the insured population in the 2 funds were analyzed by sector, sex, and age groups for 2014. We also looked at the percentage of copayment paid by the insured depending on the fund, methods of reimbursement, type of care, and nature of diseases. The analysis was based on data retrieved and aggregated at the National Agency for Health Insurance. RESULTS: The healthcare utilization rate differs significantly between the 2 funds. It is higher for the insured in the public sector (45%) compared with those in the private sector (18.5%) (P < .001). The healthcare utilization rate differs significantly according to the age groups in the 2 sectors (P < .001, respectively), and according to the sex of the insured in the 2 sectors (the healthcare utilization rate is higher for women than for men [P < .001, respectively]). The copayment percentage incurred by insured persons was 32.1% for employees in the public sector and 36.4% for employees in the private sector. CONCLUSION: Differences in reimbursement rules between the 2 funds may be the cause of inequity in access to care between insured persons. This situation can jeopardize the objectives of a universal and equitable health insurance scheme.

Contribution of fibrin glue in the surgery of cyanogenic and non-cyanogenic congenital cardiopathies: retrospective cohort study.

BACKGROUND: Postoperative bleeding in cardiovascular surgery is a frequent and complicated situation for the surgical team, and may also be responsible for significant hospital expenditures. Fibrin glue are indicated in surgery to improve hemostasis when conventional techniques such as compression, sutures or electrocoagulation are insufficient. Through this study, we tried to study the contribution of fibrin glue to the improvement of the clinical parameters (volume of postoperative bleeding, length of stay in intensive care, volume of blood transfusion ...) in two populations having undergone cardiac surgery, one in which we used the fibrin glue and one without fibrin glue. METHODS: This was a retrospective cohort study conducted in the cardiovascular surgery department of our Hospital in Rabat between June 2012 and June 2015. Fibrin glue (Tissucol® of BAXTER) was used in one group with an haemostatic aim. The pre and post-operative clinical data of the patients were analyzed and compared with data from patients who were operated without the use of fibrin glue because it was not yet available in the hospital. The clinical parameters were collected analyzed using the SPSS 13.0 software. RESULTS: One hundred ten patients were included in this study. The fibrin glue was used intraoperatively in 55 patients and not used in 55 patients. 43 (39.1%) had cyanogenic diseases and 67 (60.9%) had non-cyanogenic pathologies. The volume of transfused red blood cells was lower in patients in whom we used biological glue (p = 0.005), as well as the number of days spent in intensive care (p = 0.02). However, the difference was not significant between the two groups for other parameters such as bleeding volume per kg, the number of units of fresh frozen plasma and the platelet units count transfused. CONCLUSIONS: The results we found show that fibrin glue reduces the duration of hospitalization in resuscitation and reduces the number of units of transfused red blood cells to patients after surgery. However, it does not reduce significantly the total postoperative bleeding volume per weight, the number of fresh frozen plasma units or platelets units transfused. The fibrin glue could therefore be of moderate benefit in pediatric cardiac surgery.

Interactions between injectable anticancer drugs and polyvinyl chloride bags: Evaluation of the adsorption phenomenon after reconstitution.

INTRODUCTION: During the reconstitution of a drug and during its storage, there are risks of interactions between the drug and the bag used for the preparation. Polyvinyl chloride is a material used in the manufacture of a large part of chemotherapy infusion bags. It is subject to many interactions like sorption of drugs and release of phthalate additives. MATERIAL AND METHODS: Seven anticancer drugs used in pediatric oncology were involved in our study. After reconstitution of the anticancer agents in polyvinyl chloride bags, the adsorption phenomenon between the container and the contents is evaluated by infrared spectroscopy by analyzing the inner surface of the polyvinyl chloride. Subsequently, for the anticancer agents which exhibited an adsorption-container-content, the analysis was carried out by ultraviolet-visible spectrophotometry in order to examine the kinetics of the concentration of reconstituted anticancer drugs. RESULTS: All the polyvinyl chloride bags gave a spectrum identical to the spectrum of the reference bag, except the bags used to reconstitute etoposide whose spectra showed 12 additional peaks. With the absorbances measured by ultraviolet-visible spectrophotometry at different times, the analysis of variance statistical analysis shows that there is a significant difference in absorbances between t0 and all the other measurement times. CONCLUSION: This study testifies to the existence of a container-content interaction between etoposide and polyvinyl chloride. Thus, reconstitution of etoposide for intravenous infusion into a polyvinyl chloride bag should be used immediately. For etoposide preparations intended for storage beyond 24 h, it is recommended to use a container other than the polyvinyl chloride bag.

Prevalence and management of coronary artery anomalies in tetralogy of Fallot at Cheikh Zaid Hospital's Pediatric Cardiac Surgery Department in Morocco: retrospective study.

INTRODUCTION: Tetralogy of Fallot (TOF) is one of the most common cyanogenic congenital heart defects. It represents 10% of congenital heart diseases in children. Coronary artery anomalies (CAA) have been reported in 2% to 14% of cases in patients with TOF, according to angiographic, surgical and autopsy series. Many of these anomalies are difficult to detect during surgery. The objective of this article is to study the prevalence of the coronary artery anomalies in patients with TOF as well as their surgical management in our hospital between 2007 and 2015. METHODS: A retrospective study was conducted on 90 patients with TOF aged 1 month to 10 years who were operated on in the Department of Paediatric Cardiac Surgery of Cheikh Zaid Hospital between 2007 and 2015. None of the patients had preoperative coronary angiography and all the anomalies were diagnosed during surgery. Patient clinical data were collected from patient records and from the hospital information system. The qualitative variables are expressed as mean and standard deviation and the quantitative variables are expressed as a percentage. Statistical analyses were performed using SPSS 13.0 software. RESULTS: Of the 90 patients with TOF followed in the study period, 9 (10%) patients had coronary artery anomalies. We found in 3 (33%) patients an anomalous origin of the left anterior descending coronary artery (LAD) from the right coronary artery (RCA), an anomalous origin of the RCA from the left coronary trunk (LCT) in 1 (11%) patient and a large infundibular branch blocking the pulmonary infundibulum in 5 (56%) patients. All the patients underwent a complete surgical treatment (closure of the ventricular septal defect (VSD) by patch plus stenosis resection plus infundibular enlargement by patch). Eight (89%) patients progressed well in postoperative care and 1 (11%) died immediately after surgery in intensive care. CONCLUSION: The coronary anomalies detected in patients with TOF are rare but represent a challenge for the surgical team because of the difficulty of diagnosing them pre-operatively. The management of these anomalies is mainly surgical and the technique used by our team is proved to be safe and effective.