Investigation of 5-fluorouracil cardiotoxicity in combinational therapy: Influence of risk factors and demographics in a Pakistani population.

INTRODUCTION: 5-Fluorouracil (5-FU) is a chemotherapeutic agent used to treat various types of cancers. Although widely used, it has consistently been attributed to cardiotoxicities after administration. The purpose of this study was to assess the parameters and predictors of cardiotoxicities associated with various 5-FU-based chemotherapeutic protocols in patients with GI/colorectal cancer, as well as the correlation of these cardiotoxic events with age, sex, cumulative dose, and risk factors such as obesity, hypertension, and family history of cardiac diseases. METHODS: A prospective study consisting of 396 patients of both sexes was conducted in the oncology ward of Nishtar Hospital in Multan, Pakistan. Patients were grouped according to the therapeutic protocol they received (5-FU monotherapy or in combination, with different dosing regimens). Electrocardiography and serum troponin levels were used to assess 5-FU-induced cardiotoxicity. In cases where cardiotoxicity was detected, 5-FU treatment was interrupted; nitroglycerin, nitrates, and calcium channel blockers were administered; and cardiac monitoring was initiated. 5-FU was discontinued in all cases of acute myocardial infarction. RESULTS: Of the 396 patients, 28.5% reported different cardiotoxic symptoms after receiving various 5-FU-containing protocols. 35% had anginal pain, 13% suffered a myocardial infarction, 11% developed hypertension, and 10% presented heart failure. Patients receiving 5-FU combination therapy showed cardiotoxic events that were significantly different from those on 5-FU monotherapy. Based on the ECG results, only the QTc-d interval increased significantly (p < 0.001) after therapy. 68% of the patients had troponin levels > 2 ng/mL at the end of treatment. CONCLUSIONS: Pre-existing cardiac diseases, treatment duration, smoking, and obesity were found to be influential components in the development of cardiotoxicity, and patients with cancer should be closely monitored during 5-FU chemotherapy.

Somatic Problems in Children Disclosing Sexual Abuse: The Mediating Role of Alexithymia and Dissociation.

Child sexual abuse (CSA) is linked to heightened levels of medically unexplained symptoms. Research indicates that victims of CSA display alexithymia and dissociation symptoms. Alexithymia and dissociation may potentially contribute to developing somatic complaints in CSA victims. They represent mechanisms through which psychological distress is avoided and could then manifest as physical symptoms like somatic problems (e.g. headaches, nausea, stomachache, etc.). This study aimed to investigate if alexithymia and dissociation are mechanisms explaining the link between CSA and somatic complaints. The sample included 245 children who had disclosed child sexual abuse and 100 non-abused children aged 6-12 years old. Results of a sequential mediation model revealed that the CSA-somatic complaints relationship was mediated by alexithymia and dissociation. This study suggests that intense negative emotion leads children to focus on external stimuli to reduce psychological suffering. To mitigate somatic problems in victims of CSA, treatment should target overregulation of affect, namely alexithymia, and dissociation. In the long term, this could prevent unnecessary diagnostic testing and delay in appropriate interventions.

Traumatic head injury due to child maltreatment: epidemiology, cost analysis, and impact of prevention.

BACKGROUND: Traumatic head injury due to child maltreatment (THI-CM), also known as abusive head trauma (AHT), is a significant public health problem due to the wide array of consequences affecting multiple domains of a child's health and development. Several studies have evaluated its cost on healthcare systems, families, and societies. Many jurisdictions have implemented caregiver education programs to prevent THI-CM. OBJECTIVES: This paper aims to provide a brief overview of the epidemiology and cost analysis of THI-CM and discuss its prevention and the intergenerational transmission of child maltreatment. METHODS: Although not systematic, a literature search of original articles published from 2000 to 2022 in English and French was undertaken using the following databases: PubMed, EMBASE (Ovid), and PsycINFO (OVID). The search combined terms related to traumatic head injury and child maltreatment, with terms related to its cost and prevention. Studies of children aged 0-5 years old were included. The authors completed a screen of the titles and abstracts to determine relevance with respect to this article. RESULTS: Globally, although THI-CM accounts for a small proportion of cases of child maltreatment, there is a high incidence of death and neurological sequelae compared to other causes of head trauma.The incidence of THI-CM is likely underestimated due to the lack of standardized definitions, differences in reporting, and challenges in identifying less severe cases. Cost analysis studies reveal the significant short- and long-term costs associated with THI-CM. Caregiver education programs have been studied and implemented in many centers and have shown varying but promising results. CONCLUSION: A multi-pronged approach to prevention efforts should be considered to support families and help to prevent THI-CM and maltreatment throughout childhood.

DEVELOPMENT AND VALIDATION OF FAST REVERSED-PHASE HPLC METHOD FOR ANALYSIS OF ESOMEPRAZOLE IN RABBIT PLASMA.

The present study focused to develop rapid, accurate and sensitive reversed-phase high pressure liquid chromatography method for the quantification of esomeprazole (ESO) magnesium in rabbit plasma. Chromatographic separation was achieved isocratically on a reversed-phase C,, column using simple mobile phase consisting of of methanol : acetonitrile: 0.05 M phosphate buffer, pH 7 adjusted with potassium hydroxide (45 : 10 : 45, v/v/v) at a flow rate of 1.0 mL/min and UV detection at 302 nm. The method was validated for system suitability, linearity, precision, accuracy, stability, robustness, LOD and LOQ. The described method stated good linearity over the range of 0.01 to 2.5 pg/mL (r = 0.999). The extraction recovery of esomeprazole was more than 95.3%. The method was precise with relative standard deviation < 1% with more than 90% accuracy and limit of quantification 0.0309 µg/mL. The freeze thaw stability studies indicated that the rabbit plasma samples containing esomeprazole could be stored in freezer at -20°C and handled under normal laboratory conditions without significant loss of drug. In conclusion, the developed method is simple, cost effective and reproducible, with improved sensitivity and running time of analysis.

APPLICATION OF VARIOUS POLYMERS AND POLYMERS BASED TECHNIQUES USED TO IMPROVE SOLUBILITY OF POORLY WATER SOLUBLE DRUGS: A REVIEW.

Solubility is concerned with solute and solvent to form a homogenous mixture. If solubility of a drug is low, then usually it is difficult to achieve desired therapeutic level of drug. Most of the newly developed entities have solubility problems and encounter difficulty in dissolution. Basic aim of solubility enhancement is to achieve desired therapeutic'level of drug to produce required pharmacological response. Different techniques are being used to enhance the solubility of water insoluble drugs. These techniques include particle size reduction, spray drying, kneading method, solvent evaporation method, salt formation, microemulsions, co-solven- cy, hydrosols, prodrug approach, supercritical fluid process, hydrogel micro particles etc. Selection of solubility improving method depends on drug properties, site of absorption, and required dosage form characteristics. Variety of polymers are also used to enhance solubility of these drugs like polyethylene glycol 300, polyvinyl pyrrolidone, chitosan, ß-cyclodextrins etc.

FABRICATION AND IN VITRO EVALUATION OF 5-FLOROURACIL LOADED CHONDROITIN SULFATE-SODIUM ALGINATE MICROSPHERES FOR COLON SPECIFIC DELIVERY.

Chondroitin sulfate and sodium alginate were incorporated in different ratios to prepare glutaraldehyde (GA) crosslinked microspheres by water-in-oil emulsion crosslinking method for delivery of 5-flurouracil (5-FU) to colon. Chemical interaction, surface morphology, thermal degradability, crystallinity evaluation, elemental analysis and drug release results were computed by using FTIR, SEM, DSC and TGA, PXRD, EXD and dissolution studies at pH 1.2, pH 6.8 and pH 7.4, respectively. Results revealed an acetal ring formation, non-porous surfaces, stability up to 450 degrees C with mass loss of 84.31%, variation in carbon and oxygen contents and targeted release at pH 7.4. Different kinetic models were applied on release studies i.e., zero order, first order, Higuchi and Korsmeyer-Peppas. Higuchi model was declared as best fit model based on r2 value (0.99) and mechanism of release was non-Fickian diffusion. A potential approach for colonic delivery of 5-FU was successfully developed.

PREPARATION AND EVALUATION OF pH RESPONSIVE POLY(2-HYDROXYETHYL METHACRYLATE-CO-ITACONIC ACID) MICROGELS FOR CONTROLLED DRUG DELIVERY.

In this study, a series of pH sensitive microgels (MGs) were prepared by modified free radical suspension polymerization of 2-hydroxyethyl methacrylate (HEMA) and itaconic acid (IA), using ethylene glycol dimethacrylate (EGDMA) as crosslinker. Equilibrium swelling technique was employed for esomeprazole magnesium trihydrate (EMT) loading. Prepared microgels were characterized through Fourier transforms infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), dynamic light scattering technique (DLS), scanning electron microscopy (SEM), equilibrium swelling and in vitro drug release kinetics. FTIR and TGA confirmed the formation of copolymeric p(HEMA-co-IA) network. SEM and DLS revealed smooth, round and uniformly distributed microspheres with particle size up to 10 µm. Developed microgels found to be pH responsive in nature. All the formulations (HIDI - HID5) followed Higuchi model with non-Fickian diffusion mechanism of drug release. It was concluded that p(HEMA-co-IA) microgels have potential to be used as drug carriers for site specific and controlled drug delivery.

Design, Synthesis, Evaluation, and Molecular Docking Study of Ascorbic Acid Dual-Coated Omeprazole Pellets and the Antioxidative Effect of Ascorbic Acid on Omeprazole-Induced Renal Injury in an Animal Model.

The present study was carried out to investigate the antioxidant effect of ascorbic acid on omeprazole (O.P.)-induced acute kidney infection (AKI). Design of experiment (DoE) was employed to fabricate formulations (P1-P8) by the extrusion spheronization technique, and they were evaluated using various analytical techniques. P1-P8 formulations have % drug loading ranging from 56.34 ± 1.10 to 98.67 ± 1.05%, encapsulation efficiency from 70.98 ± 0.96 to 98.67 ± 1.05%, percentage drug release varying from 36.56 ± 1.34 to 93.45 ± 1.45%, Hausner's ratio ranging from 1.026 ± 0.05 to 1.065 ± 0.02%, and Carr's index varying from 2.3 ± 0.07 to 6.1 ± 0.06 g/mL. The optimized formulation (P6) was dual-coated with Eudragit L-100 (5% w/v) and ascorbic acid (2% w/v). A smooth uniform morphology was found after coating, and particle size nonsignificantly changed from 85.31 ± 77.43 to 101.99 ± 65.56 µm. IR spectra showed omeprazole characteristic peaks confirming drug loading, and peaks at 1747.40 and 1611.51 cm-1 confirmed ascorbic acid and Eudragit L-100 coating. X-ray diffraction (XRD) analysis confirmed the crystalline nature, and thermal degradation studies until 500 °C demonstrated increased stability after coating. Cytotoxicity analysis with 97% cell viability revealed the nontoxic behavior of pellets. In vitro dissolution studies of coated pellets showed <20% drug release at pH 1.2 and 99.54% at pH 6.8. Animal studies showed that pure omeprazole showed a nonsignificant decrease in weight, urine output, and fecal output compared to rodents on ascorbic acid pellets. Increased uric acid and creatinine levels in the group on pure omeprazole indicated AKI. Histopathological studies of renal cells also supported these results. The integration of experimental pellet formulation with molecular docking simulations has unveiled the potential of ascorbic acid and omeprazole as highly promising therapeutic agents for addressing oxidative stress and inflammation.

Unintentional Cannabis Ingestions and Supervisory Neglect.

Unintentional pediatric ingestions of substances can lead to serious and even fatal consequences in children1 and raises concern for supervisory neglect. Supervisory neglect occurs when a caregiver's supervisory decisions or behaviors place a child in their care at significant risk for physical, emotional or psychological harm.2 A caregiver who is taking prescription medication or who uses recreational or therapeutic substances, such as cannabis, must protect children in their care from accessing these potentially harmful drugs. Studies have demonstrated that unintentional cannabis ingestions by children has increased in states that have legalized medical and recreational cannabis.3 Given the changing laws surrounding cannabis in Rhode Island, this study aims to provide a conceptual framework to diagnose, manage and understand supervisory neglect when children present to care with a cannabis ingestion. Additionally, this paper provides guidance for providers to help prevent unintentional cannabis ingestions.

Green Synthesis and Evaluation of Lepidium didymum-mediated Silver Nanoparticles for in vitro Antibacterial Activity and Wound Healing in the Animal Model.

Wounds serve as an appropriate medium for the growth of pathogenic bacteria, and bacterial resistance to already available antibiotics demands new and safe approaches in the field of medicine. Silver nanoparticles (AgNPs) exhibited a wide range of applications in biomedicine and emerged as promising nano-antibiotics. The biological preparation of AgNPs by utilizing aqueous plant extract has become an encouraging alternative to traditional chemical methodologies, owing to a viable eco-friendly approach. In the present study, Lepidium didymum leaves extract was used for the biosynthesis of AgNPs-LD. The nanoparticles were characterized through UV-Vis spectroscopy, Fourier transforms infrared spectrometry (FTIR), Scanning electron microscopy (SEM), and X-ray diffraction (XRD). The antibacterial activity of AgNPs-LD was evaluated against Staphylococcus aureus, Escherichia coli, Klebsiella pneumonia, and Pseudomonas aeruginosa. Further, AgNPs-LD nanoparticles were incorporated into topical gels to evaluate their effectiveness for wound healing in the rat model. UV-visible spectra showed a surface resonance peak around 400 nm correlated with the synthesis of AgNPs; FTIR spectra verified the participation of phytochemicals present in L. didymum leaves extract in AgNPs-LD synthesis; and SEM revealed dispersed spherical nanoparticles as well as aggregated clusters. XRD analysis confirmed the crystalline nature, face-centered cubic lattice, and average crystallite size of 21.42 nm. The AgNPs-LD showed promising antibacterial activity against tested strains with a maximum zone of inhibition against P. aeruginosa and showed accelerated wound healing capacity comparable to control and standard treatments over the time course of wound healing. The current study concluded that biosynthesized AgNPs-LD nanoparticles are effective as antibacterial agents and are promising novel wound healing products for clinical applications.

Molecularly imprinted ormosil as a sorbent for targeted dispersive solid phase micro extraction of pyriproxyfen from strawberry samples.

Novel molecularly imprinted organically modified silica was prepared by reacting acrylamide and 3-(tri-methoxysilyl) propyl methacrylate followed by condensation and hydrolysis with tetraethyl ortho-silicate for the determination of pyriproxyfen. The sorbent proved to be highly selective for the template molecule, pyriproxyfen. The characterization of sorbent was carried out using SEM, BET and TGA. The prominent peaks in FTIR at 3700 cm-1 and 1071 cm-1 confirmed the stretching of amide group's N-H and Si-O-Si bond linkage of MIOrmosil. The pseudo-first-order model (R2 0.99) described the adsorption kinetics of the MIOrmosil, whereas among adsorption isotherms, Freundlich model showed the best fit (R2 0.99). The molecularly imprinted silica was applied for the determination of target analytes from strawberries sample using dispersive solid-phase micro extraction (DSPME) followed by high-performance liquid chromatography (HPLC). The LOD (4.93 x10-5 µg mL-1) and LOQ (1.49 x10-4 µg m-1) values were calculated by signal to noise ratio through HPLC. Results show that the maximum binding capacity and percentage recovery values of MIOrmosil were 13 mg g-1 (n = 5) and 97.3% respectively.

Experimental design by response surface methodology for efficient cefixime uptake from hospital effluents using anion exchange membrane.

The excessive use of antibiotics and their ultimate routes to the environment have prompted the drug resistance, which is becoming a major ecological issue. In this work, we have evaluated the performance of quaternary ammonium poly (2, 6-dimethyl-1,4-phenylene oxide) and polyvinyl alcohol (QPPO/PVA) based anion exchange membrane against cefixime (a third generation cephalosporin antibiotic) present in hospital effluents. The membrane's surface morphology was studied through scanning electron microscopy. The optimization of experimental parameters through Response Surface Methodology helped to evaluate the inter parameter dependence and predict maximum uptake capacity (qe). The speculated value of qe (6.72 mg g-1) obtained through central composite design was close to the experimental value of 7.01 mg g-1 with percent relative error of 4.31%. Further, the evaluation of experimental data using isotherms (Langmuir and Freundlich) and kinetic models (pseudo-first-order and second-order) proposed that the interactions between cefixime and the membrane were physisorptive in nature. The intra-day and inter-day assays exhibited lower %RSD values of 0.4% (n = 5) and 0.3% (n = 5). Furthermore, a percentage recovery of 98.2% (n = 9) and limit of detection 1 × 10-5 µg mL-1 was observed. The chromatogram of the treated water samples presented only negligible amount of cefixime indicating a great potential of QPPO/PVA membrane for the removal of cefixime from real water samples. The membrane could be regenerated for three consecutive cycles without any prominent loss in efficiency.

Tailoring Vanadium-Based Magnetic Catalyst by In Situ Encapsulation of Tungsten Disulfide and Applications in Abatement of Multiple Pollutants.

A magnetic nanocomposite of tungsten and vanadium was employed as a catalyst for the mitigation of water contaminants, including a carcinogenic dye (Congo red, CR), a widely used pesticide (glyphosate), and the bacterial strain Escherichia coli. Additionally, it was subjected to several characterization techniques. X-ray diffraction spectroscopy examination validated the synthesized nanoparticles' crystalline nature, and scanning electron microscopy and energy-dispersive X-ray analysis were employed to examine the morphology and elemental composition of the catalyst. The use of thermogravimetric analysis enabled the elaboration of the thermal behavior of tungsten sulfide-vanadium decorated with Fe2O3 nanoparticles. The experiments were conducted under visible light conditions. The highest levels of photodegradation of 96.24 ± 2.5% for CR and 98 ± 1.8% for glyphosate were observed following a 180 min exposure to visible light at pH values of 6 and 8, respectively. The quantum yields for CR and Gly were calculated to be 9.2 × 10-3 and 4.9 × 10-4 molecules photon-1, respectively. The findings from the scavenger analysis suggest the involvement of hydroxyl radicals in the degradation mechanism. The study evaluated the inhibition of E. coli growth when exposed to a concentration of 0.1 g/10 mL of the photocatalyst, utilizing a 1 mL sample of the bacterial strain. The successful elimination of CR and glyphosate from water-based solutions, along with the subsequent antibacterial experiments, has substantiated the efficacy of the photocatalyst in the field of environmental remediation.

Synthesis and characterization of Hyaluronic Acid (HA) modified polymeric composite for effective treatment of wound healing by transdermal drug delivery system (TDDS).

The present study aimed to fabricate a novel polymeric spongy composite to enhance skin regeneration composed of Nystatin (antifungal agent) and Silver Nanoparticles (AgNps). Different formulations (F1-F8) were developed & characterized by using various analytical techniques. AgNps synthesized by chemical reduction method showed spherical morphology 2 µm in size showed by SEM and XRD. A fine porous structure of gel embedded with AgNps having an amorphous structure with 10 % crystallinity due to AgNps was found. IR spectra revealed no chemical interaction between polymers and Nystatin. An increase in thermal stability of formulation was observed till 700 â„ƒ analyzed by Differential Scanning Calorimetry. Cytotoxic analysis on L929 mouse skin fibroblast cells showed a decrease in cell viability as Ag concentration increased (inactivating Fibroblast and keratinocytes) while 10 mg composition was found safest concentration (94%). Optimized formulation (F2) presented in-vitro drug release up to 90.59% ± 0.76 at pH 7.4, swelling studies (87.5% ± 0.57), water retention (26.60 ± 0.34), pH (5.31 ± 0.03). In the animal burn model, the group that received CHG/Ag/Nystatin healed the wound significantly (p < 0.05). These results suggested that optimized carrier can be used for other anti-fungal drugs facilitating the early healing of the wound.

Polyaniline-coated nanoparticles of zinc oxide and copper oxide as antifungal agents against Aspergillus parasiticus.

Aspergillus parasiticus (A. parasiticus) is known for producing aflatoxins and is a major threat to the food industry. Green synthesis of nanoparticles (NPs) is a cost-effective and environment-friendly approach. A variety of NPs have been explored as antifungal agents; however, their antifungal characteristics need to be further enhanced to compete with traditional fungicides. The present work describes the green synthesis of ZnO and CuO NPs by precipitation method using aqueous leaf extract of Manilkara zapota and their surface modification through polyaniline (PANI). Still, there is no published study on the application of PANI-coated particles as antifungal agents against A. parasiticus and hence was the focus of this work. The polymer-coated NPs were synthesized, characterized, and investigated for their antifungal properties against A. parasiticus. Textural and structural characterization of PANI-coated and non-coated ZnO and CuO NPs were confirmed through FT-IR, SEM, and XRD techniques. The PANI-coated NPs presented higher fungal growth inhibition (%) as compared to the non-coated ones. The maximum inhibition of 77 ± 2% (n = 3) was shown by PANI/ZnO NPs at a concentration of 12 mmol L-1 and 72 h of incubation. The non-coated NPs presented a lower inhibition rate with respect to their coated NPs, thus justifying the role of polymeric coating in improving antifungal efficiency.