Flumazenil Pretreatment Reduces Mefenamic Acid-Induced Central Nervous System Toxicity in Mice.

BACKGROUND: Mefenamic acid (MFA), a common analgesic, causes central nervous system (CNS) toxicity at high doses with a proposed activity on the Gamma-aminobutyric acid (GABA) system. However, it remains unknown whether flumazenil (FMZ), a GABA type A receptor (GABAAR) antagonist, can reverse MFA toxicity. METHODS: The behavioral and neurophysiological effects of MFA were investigated in mice with and without FMZ pre-treatment. The elevated zero maze (EZM) and marble burying tests were used to assess anxiety-like behaviors and burying activities, respectively. The standard bar test was used to evaluate catalepsy, while the actophotometer test was used to measure locomotor activity. Seizure intensity was scored, and fatalities were counted. RESULTS: Without FMZ pre-treatment, MFA induced behavioral and neurophysiological effects in a dose-dependent manner as follows: At a dose of 20 mg/kg, i.p, MFA-treated mice exhibited anxiety-like behaviors, which was determined by a significant increase in the time spent in the closed areas and a significant decrease in the number of entries to the open areas of the EZM apparatus. These mice also showed a significant decrease in the burying activity, manifested as a significant decrease in the number of buried marbles. At 40 mg/kg, i.p., MFA-treated mice showed catalepsy that was associated with a significant decrease in locomotor activity. At a dose of 80 mg/kg, i.p., mice developed fatal tonic-clonic seizures (seizure score = 4). Pre-treatment with FMZ (5 mg/kg, i.p.) significantly reversed the anxiety-like behaviors and restored marble-burying activity. Additionally, FMZ prevented catalepsy, significantly restored locomotor activity, reduced seizure intensity (seizure score = 0.3) and significantly reduced mortalities. CONCLUSIONS: The present study's findings indicate that activation of the GABAAR is involved in the CNS toxicity of MFA, and FMZ reverses MFA toxicity by interfering with this receptor.

Hepatic ultrastructural alterations induced by copper oxide nanoparticles: In vivo electron microscopy study.

Copper oxide nanomaterials (CuO NPs) have been widely utilized in many fields, including antibacterial materials, anti-tumor, osteoporosis treatments, imaging, drug delivery, cosmetics, lubricants for metallic coating, the food industry, and electronics. Little is known about the potential risk to human health and ecosystems. The present work was conducted to investigate the ultrastructural changes induced by 20 ± 5 nm CuO NPs in hepatic tissues. Adult healthy male Wister albino rats were exposed to 36 intraperitoneal (ip) injections of 25 nm CuO NPs (2 mg/kg bw). Liver biopsies from all rats under study were processed for transmission electron microscopy (TEM) processing and examination for hepatic ultrastructural alterations. The hepatic tissue of rats exposed to repeated administrations of CuO NPs exhibited the following ultrastructural alterations: extensive mitochondrial damage in the form of swelling, crystolysis and matrix lysis, formation of phagocytized bodies and myelin multilayer figures, lysosomal hyperplasia, cytoplasmic degeneration and vacuolation, fat globules precipitation, chromatin clumping, and nuclear envelope irregularity. The findings indicated that CuO NPs interact with the hepatic tissue components and could induce alterations in the hepatocytes with the mitochondria as the main target organelles of copper nanomaterials. More work is recommended for better understanding the pathogenesis of CuO NPs.

Taste Masking of Promethazine Hydrochloride Using l-Arginine Polyamide-Based Nanocapsules.

Promethazine hydrochloride (PMZ), a potent H1-histamine blocker widely used to prevent motion sickness, dizziness, nausea, and vomiting, has a bitter taste. In the present study, taste masked PMZ nanocapsules (NCs) were prepared using an interfacial polycondensation technique. A one-step approach was used to expedite the synthesis of NCs made from a biocompatible and biodegradable polyamide based on l-arginine. The produced NCs had an average particle size of 193.63 ± 39.1 nm and a zeta potential of −31.7 ± 1.25 mV, indicating their stability. The NCs were characterized using differential scanning calorimetric analysis and X-ray diffraction, as well as transmission electron microscopy that demonstrated the formation of the NCs and the incorporation of PMZ within the polymer. The in vitro release study of the PMZ-loaded NCs displayed a 0.91 ± 0.02% release of PMZ after 10 min using artificial saliva as the dissolution media, indicating excellent taste masked particles. The in vivo study using mice revealed that the amount of fluid consumed by the PMZ-NCs group was significantly higher than that consumed by the free PMZ group (p < 0.05). This study confirmed that NCs using polyamides based on l-arginine and interfacial polycondensation can serve as a good platform for the effective taste masking of bitter actives.

On the toxicity of gold nanoparticles: Histological, histochemical and ultrastructural alterations.

Gold nanoparticles (Au NPs) are used in diagnostic and therapeutic applications together with a variety of industrial purposes and in many biomedical sectors with potential risks to human health. The present study aimed to the histological, histochemical, and ultrastructural alterations induced by Au NPS in vital organs. Healthy male Wistar Albino rats (Rattus norvegicus) were subjected to 20 injections of 10-nm Au NPs at a daily dose of 2 mg/kg. Liver, kidney, heart, and lung biopsies from control and Au NPs-treated rats under study were subjected to histological and histochemical examinations. In comparison with the control rats, the renal tissue of Au NPs-treated rats demonstrated glomerular congestion, interstitial inflammatory cell infiltration, renal tubular hydropic degeneration, cloudy swelling, necrosis, and hyaline cast precipitation. In addition, Au NPs induced the following hepatic alterations: hepatocyte cytolysis, cytoplasmic vacuolation, hydropic degeneration, and nuclear alterations together with sinusoidal dilatation. Moreover, the hearts of the treated rats demonstrated myocarditis, cardiac congestion, hyalinosis, cardiomyocyte hydropic degeneration, myofiber disarray and cardiac congestion. The lungs of Au NPs-treated rats also exhibited the following pulmonary alterations: alectasis, emphysema, inflammatory cell inflammation, thickened alveolar walls, pulmonary interstitial edema, congestion, hypersensitivity, fibrocyte proliferation, and honeycombing. In conclusion, exposure to Au NPs induced histological, histochemical and ultrastructural alterations in the vital organs that may alter the function of these organs. Additional efforts are needed for better understanding the potential risks of Au NPs to human health.

Renal ultrastructural damage induced by chronic exposure to copper oxide nanomaterials: Electron microscopy study.

Copper oxide nanomaterials are used in many biomedical, agricultural, environmental, and industrial sectors with potential risk to human health and the environment. The present study was conducted to determine the renal ultrastructural damage caused by 25 nm CuO nanoparticles in renal tissues. Adult healthy male Wister Albino rats (Rattus norvegicus) were administered 35 intraperitoneal injections of CuO nanoparticles (2 mg/kg). Ultrastructural changes were evaluated using transmission electron microscopy techniques. The renal tissues of rats with subchronic exposure to CuO nanoparticles demonstrated glomerular alterations that included hypertrophic endothelial cells, dilated capillaries and occlusions, podocyte hypertrophy, pedicle disorganization, mesangial cell hyperplasia, and crystalloid precipitation. Moreover, the treated renal cells exhibited mitochondrial swelling and crystolysis, cytoplasmic vacoulization, lysosomal hypertrophy, apoptotic activity, endoplasmic reticulum dilatation, nuclear deformity, chromatin dissolution, and basement membrane thickening. In addition, disruption and disorganization of the renal cells microvilli together with cystolic inclusions were also detected. It was concluded from the present findings that CuO nanoparticles could interact with the components of the renal tissues in ways that could cause ultrastructural injury, suggesting renal tissue pathophysiology. Additional studies are suggested for a better understanding the nanotoxicity of CuO nanomaterials.

Synthesis and In-Vivo Evaluation of Benzoxazole Derivatives as Promising Anti-Psoriatic Drugs for Clinical Use.

2-(4-Chlorophenyl)-5-benzoxazoleacetic acid (CBA) and its ester, methyl-2-(4-chloro-phenyl)-5-benzoxazoleacetate (MCBA), were synthesized, and their structures were confirmed by 1HNMR, IR, and mass spectrophotometry. The anti-psoriatic activities of CBA and MCBA were tested using an imiquimod (IMQ)-induced psoriatic mouse model, in which mice were treated both topically (1% w/w) and orally (125 mg/kg) for 14 days. The erythema intensity, thickness, and desquamation of psoriasis were scored by calculating the psoriasis area severity index (PASI). The study also included the determination of histopathological alterations in the skin tissues of treated mice. Topical and oral administration of CBA and MCBA led to a reduction in erythema intensity, thickness, and desquamation, which was demonstrated by a significant decrease in the PASI value. In addition, skin tissues of mice treated with CBA and MCBA showed less evidence of psoriatic alterations, such as hyperkeratosis, parakeratosis, scale crust, edema, psoriasiform, and hyperplasia. After administration of either topical or oral dosing, the anti-psoriatic effects were found to be stronger in MCBA-treated than in CBA-treated mice. These effects were comparable to those produced by Clobetasol propionate, the reference drug. This drug discovery could be translated into a potential new drug for future clinical use in psoriasis treatment.

Assessment of the need for pharmacogenomics education among pharmacists in the West Bank of Palestine.

BACKGROUND: Pharmacogenomics testing aims to optimise therapy and reduce the inter-individual variation in drug response. One of the major barriers against the implementation of pharmacogenomics testing is the low level of knowledge on the topic. AIMS: This study aimed to evaluate the need for pharmacogenomics education among pharmacists in the West Bank of Palestine. METHODS: This study was cross-sectional and included 370 pharmacists, among different cities in the West Bank of Palestine between October and December 2020. The questionnaire consisted of 25 close-ended questions that evaluated the exposure to pharmacogenomics education, attitude toward the role of pharmacogenomics testing in clinical practice and self-capability of pharmacists in pharmacogenomics testing. RESULTS: It was found that 60% of the respondents disagreed that pharmacogenomics was an integral part of the pharmacy school curriculum and/or experiential education. The vast majority of the respondents (94%) agreed that pharmacists should be required to have some knowledge of pharmacogenomics. The majority of the respondents (88.6%) believe that pharmacogenomics testing will improve pharmacists' ability to more effectively control drug therapy expenditures. However, only 38% of the respondents could identify medications that require pharmacogenomics testing, and only 35.1% could identify reliable sources of information regarding pharmacogenomics for healthcare providers and patients. CONCLUSION: It is seen from the results of this study that there is a high need to learn about pharmacogenomics testing, which can help the pharmacists make pharmacotherapy decisions. Additionally, current pharmacists have low self-confidence in making decisions depending on the results of pharmacogenomics testing. It is recommended to increase the exposure of pharmacogenomics knowledge by including the subject in courses and workshops in pharmacy school curricula in the West Bank of Palestine.

Renal ultrastructural alterations induced by various preparations of mefenamic acid.

Mefenamic acid (MFA) treatment is associated with a number of cellular effects that potentiate the incidence of renal toxicity. The aim of this study is to investigate the potential ultrastructural alterations induced by various preparations of MFA (free MFA, MFA-Tween 80 liposomes, and MFA-DDC liposomes) on the renal tissues. Sprague-Dawley rats were subjected to a daily dose of MFA preparations for 28 days. Renal biopsies from all groups of rats under study were processed for transmission electron microscopic examination. The findings revealed that MFA preparations induced various ultrastructural alterations including mitochondrial injury, nuclear and lysosomal alterations, tubular cells steatosis, apoptotic activity, autophagy, and nucleophagy. These alterations were more clear in rats received free MFA, and MFA-Tween 80 liposomes than those received MFA-DDC liposomes. It is concluded that MFA-DDC liposomes are less potential to induce renal damage than free MFA and MFA-Tween 80 liposomes. Thus, MFA-DDC liposomes may offer an advantage of safe drug delivery.

In vivo study of silver nanomaterials' toxicity with respect to size.

Silver nanoparticles (Ag NPs) are widely used in nanomedicine, pharmaceutical products, industry and other consumer products owing to their unique physiochemical properties with probable potential risk to human health and the ecosystems. The aim of this work was to investigate the in-life morphological effects, biochemical, histological and histochemical alterations that might be induced by variable sizes of Ag NPs in hepatic, renal and testicular tissues with the hypothesis that variable sizes of nano-Ag could induce variable effects in the vital organs. Five groups of adult healthy male mice (BALB/C) were exposed to 35 intraperitoneal injections of Ag NPs (1 mg/kg bw) using five different particle sizes (10, 20, 40, 60 and 100 nm). All mice were subjected to in-life morphometric, biochemical, histological and histochemical analysis. The findings demonstrated that Ag NPs could induce alterations in the average body weight gain, food consumption, water intake and organ indices. In addition, these NPs significantly altered hepatic and renal biomarkers. Moreover, Ag NPs produced ground glass hepatocyte cytoplasm, with mitotic activity, nuclear alterations, degeneration, glycogen depletion and inflammatory cells infiltration in the liver. The kidneys of treated mice exhibited proximal renal tubules degeneration, distal renal tubules regeneration, glomerular shrinkage, Bowman's capsule thickening and interstitial inflammation. The testicular tissues demonstrated spermatocyte sloughing and spermatid giant cell formation. The findings together indicated that Ag NPs could interact with the anatomical structures of the liver, kidney and testis in ways that could induce injury. In addition, the results indicated that smaller Ag NPs posed a greater potential risk than the larger ones, which might be associated with their behaviour, dissolution rate, bioavailability and their probable variable toxicokinetics.

Pharmacokinetics and Metabolism of Liposome-Encapsulated 2,4,6-Trihydroxygeranylacetophenone in Rats Using High-Resolution Orbitrap Liquid Chromatography Mass Spectrometry.

2,4,6-trihydroxy-3-geranylacetophenone (tHGA) is a bioactive compound that shows excellent anti-inflammatory properties. However, its pharmacokinetics and metabolism have yet to be evaluated. In this study, a sensitive LC-HRMS method was developed and validated to quantify tHGA in rat plasma. The method showed good linearity (0.5-80 ng/mL). The accuracy and precision were within 10%. Pharmacokinetic investigations were performed on three groups of six rats. The first two groups were given oral administrations of unformulated and liposome-encapsulated tHGA, respectively, while the third group received intraperitoneal administration of liposome-encapsulated tHGA. The maximum concentration (Cmax), the time required to reach Cmax (tmax), elimination half-life (t1/2) and area under curve (AUC0-24) values for intraperitoneal administration were 54.6 ng/mL, 1.5 h, 6.7 h, and 193.9 ng/mL·h, respectively. For the oral administration of unformulated and formulated tHGA, Cmax values were 5.4 and 14.5 ng/mL, tmax values were 0.25 h for both, t1/2 values were 6.9 and 6.6 h, and AUC0-24 values were 17.6 and 40.7 ng/mL·h, respectively. The liposomal formulation improved the relative oral bioavailability of tHGA from 9.1% to 21.0% which was a 2.3-fold increment. Further, a total of 12 metabolites were detected and structurally characterized. The metabolites were mainly products of oxidation and glucuronide conjugation.

Effects of nonsteroidal anti-inflammatory drugs on the expression of arachidonic acid-metabolizing Cyp450 genes in mouse hearts, kidneys and livers.

Arachidonic acid (ARA) metabolites are involved in cardiovascular diseases and drug-induced cardiotoxicity. The present study aimed to investigate the effects of nonsteroidal anti-inflammatory drugs (NSAIDs) on the gene expression of ARA-metabolizing cyp450 genes in the hearts, kidneys and livers of experimental mice. Thirty five Balb/c mice were divided into 5 groups, and each group contained 7 mice. Then, the groups were administered different NSAIDs, diclofenac mefenamic acid, ibuprofen, or meloxicam, for 14 days in doses equivalent to those used in human treatment. Subsequently, liver, kidney and heart samples were isolated for analysis of the expression of ARA-metabolizing cyp450 genes using real-time polymerase chain reaction. In addition, the histological alterations induced by mefenamic acid were examined. It was found that 20-HETE synthesizing gene cyp4a12 was upregulated (> 2.2 fold) in the hearts of NSAID-treated mice, which was associated with the 2-fold downregulation of the cardio-protective biomarker GATA4 gene and the induction of cox2 expression (p value < 0.05). In the kidneys, the expression of cyp4a12 was significantly reduced (p value <0.05) while cyp2c29 expression was upregulated by more than 2 fold. In the liver, all NSAIDs except diclofenac significantly decreased the expression of all genes tested (p value <0.05) and were associated with abnormal accumulation of fat in the liver. Furthermore, these molecular findings were in parallel to histological alterations induced in the liver, kidney, and heart after mefenamic acid administration. This study concluded that NSAIDs altered the expression of ARA-metabolizing cyp450 genes and induced histological alterations that may influence the function of the vital organs.

Histomorphometric Alterations Induced in the Testicular Tissues by Variable Sizes of Silver Nanoparticles.

OBJECTIVE: To investigate the histomorphometric alterations induced in testicular tissues by variable sizes of silver nanoparticles (SNPs). STUDY DESIGN: Male mice (BALB/C) were treated with SNPs (1 mg/kg) using 5 different sizes (10, 20, 40, 60, and 100 nm) for 35 days. Testicular biopsies from all mice under study were examined histomorphologically. RESULTS: SNPs sized 10 and 20 nm had provoked morphometric changes in the testes of the subjected mice together with the following histological alterations: seminiferous tubules, degeneration, spermatocyte cytoplasmic vacuolation, spermatocyte sloughing, and spermatid giant cell formation. Larger SNPs (40, 60, and 100 nm) induced little or no testicular histomorphometric alterations. CONCLUSION: The findings of the present work may indicate that subchronic exposure to SNPs could have a deleterious impact on the testicular tissues and spermatogenic process that could affect fertility and reproduction, with smaller SNPs being more toxic than larger ones.

Comparative ultrastructural hepatic alterations induced by free and liposome-encapsulated mefenamic acid.

Mefenamic acid (MFA) is used as an anti-inflammatory, antinociceptive, and antipyretic agent for treatment of a wide range of pathological disorders. While the uncertainty of its safety and the poor oral bioavailability constitute the major limiting factors of its medical use, considerable efforts including liposomal encapsulation are needed to achieve maximum therapeutic advantages. The current work was conducted to investigate the ultrastructural alterations in the liver induced by free MFA and its liposomal preparation. Female Sprague-Dawley rats were treated with daily oral doses of either free MFA or MFA entrapped in Tween 80 inoculated liposomes at the concentration of 80 mg/kg for 28 days. Ultrathin sections were prepared from biopsies taken from the liver of each member of all animals under study and subjected to examination by transmission electron microscopy. The liver of rats that were exposed to liposomal MFA showed more ultrastructural alterations than the rats treated with the free drug. While both groups of rats demonstrated sinusoidal dilatation, Kupffer cell hyperplasia, mitochondrial damage, and nuclear alterations, rats treated with liposome-encapsulated MFA induced an increase in the multiple lysosomes formation, hepatocytic steatosis, and apoptotic activity than free MFA-treated rats. The ultrastructural findings of the present study indicate that the use of liposomal MFA induces more hepatic damage than the use of free MFA.

Evaluating NSAIDs in SARS-CoV-2: Immunomodulatory mechanisms and future therapeutic strategies.

Non-steroidal anti-inflammatory drugs (NSAIDs) are widely recognized for their analgesic and anti-inflammatory properties. Amidst the SARS-CoV-2 pandemic, the role of NSAIDs in modulating viral and bacterial infections has become a critical area of research, sparking debates and necessitating a thorough review. This review examines the multifaceted interactions between NSAIDs, immune responses, and infections. Focusing on the immunomodulatory mechanisms of NSAIDs in SARS-CoV-2 and their implications for other viral and bacterial infections, we aim to provide clarity and direction for future therapeutic strategies. NSAIDs demonstrate a dual role in infectious diseases. They reduce inflammation by decreasing neutrophil recruitment and cytokine release, yet potentially compromise antiviral defense mechanisms. They also modulate cytokine storms in SARS-CoV-2 and exhibit the potential to enhance anti-tumor immunity by inhibiting tumor-induced COX-2/PGE2 signaling. Specific NSAIDs have shown efficacy in inhibiting viral replication. The review highlights NSAIDs' synergy with other medications, like COX inhibitors and immunotherapy agents, in augmenting therapeutic effects. Notably, the World Health Organization's analysis found no substantial link between NSAIDs and the worsening of viral respiratory infections. The findings underscore NSAIDs' complex role in infection management. Understanding these interactions is crucial for optimizing therapeutic approaches in current and future pandemics. However, their dual nature warrants cautious application, particularly in vulnerable populations. NSAIDs present a paradoxical impact on immune responses in viral and bacterial infections. While offering potential benefits, their usage in infectious diseases, especially SARS-CoV-2, demands a nuanced understanding to balance therapeutic advantages against possible adverse effects.

Effects of Calamintha incana (Sm.) Helder Ethanolic Extract on the mRNA Expression of Drug-metabolizing cyp450s in the Mouse Livers.

BACKGROUND: Alteration in the expression and activity of drug-metabolizing enzymes (DMEs) can alter the pharmacokinetics and hence the response of the drug. Some chemicals found in herbs and fruits affect the expression of DMEs. Calamintha incana is commonly used in Middle Eastern Arabic countries. There is no report regarding the influence of Calamintha incana on the hepatic expression of DMEs. AIMS: The current investigation aimed to investigate the effect of Calamintha incana consumption on the mRNA expression of major hepatic drug-metabolizing cytochrome (cyp) P450 genes in mice. METHODS: The chemical composition of the ethanoic extract was analyzed using liquid chromatography/ mass spectrometry. Then, 21 BALB/c mice were used for the in vivo experiment. The mice were divided into three groups, each consisting of seven mice. The first group (low-dose group) was treated with 41.6 mg/kg of Calamintha incana extract and the second group was administered the high-dose (125 mg/kg) of the extract for one month. The mice in the third "control" group administrated the vehicle 20% polyethylene glycol 200. Then, the expression of cyp3a11, cyp2c29, cyp2d9, and cyp1a1 was analyzed using the real-time polymerase chain reaction. The relative liver weights of the mice and the hepatic pathohistological alterations were assessed. RESULTS: The ethanolic extract of Calamintha incana contained 27 phytochemical compounds. The most abundant compounds were linolenic acid, myristic acid, and p-cymene. It was found that the low dose of Calamintha incana extract upregulated significantly (P < 0.05) the expression of cyp3a11 by more than ten folds in the liver of treated mice. Furthermore, the histological analysis showed that low- and high-dose administration of the C. incana did not cause pathological alterations. CONCLUSION: It can be concluded from these findings that consumption of low doses of Calamintha incana upregulated the mRNA expression of mouse cyp3a11 without causing histopathological alterations in the livers. Further studies are needed to determine the influence of Calamintha incana on the pharmacokinetics and response of drugs metabolized by cyp3a11.

Preclinical evaluation of novel synthesised nanoparticles based on tyrosine poly(ester amide) for improved targeted pulmonary delivery.

Fixed dose combinations (FDCs) incorporating two or three medicines in a single inhaler have been created to enhance patient compliance and hence clinical outcomes. However, the development of dry powder inhalers (DPIs), particularly for FDCs, faces challenges pertinent to formulation uniformity and reproducibility. Therefore, this project aimed to employ nanotechnology to develop a FDC of DPIs for market-leading medicines-fluticasone propionate (FP) and salmeterol xinafoate (SAL)-for asthma management. Nanoaggregates were prepared using a novel biocompatible and biodegradable poly(ester amide) based on the amino acid tyrosine, utilising a one-step interfacial polymerisation process. The produced tyrosine poly (ester amide) drug-loaded nanoparticles were evaluated for content uniformity, PSA, FTIR, TEM, DSC, XRD and aerodynamic performance (in vitro and in vivo). The optimised formulation demonstrated high entrapment efficiency- > 90%. The aerodynamic performance in terms of the emitted dose, fine particle fraction and respirable dose was superior to the carrier-based marketed product. In-vivo studies showed that FP (above the marketed formulation) and SAL reached the lungs of mice in a reproducible manner. These results highlight the superiority of novel FDC FP/SAL nanoparticles prepared via a one-step process, which can be used as a cost-effective and efficient method to alleviate the burden of asthma.

Maternal separation influences hepatic drug-metabolizing CYP450 gene expression without pathological changes in adult mice.

OBJECTIVES: The principal motive of this study is to explore the influence maternal separation (MS) exhibits on the mRNA expression of major drug metabolizing-cyp450s in parallel with the assessment of pathological changes that can be induced by MS in the livers of experimental mice. METHODS: Eighteen Balb/c mouse pups, comprising of both males and females, were separated from their mothers after birth. Following a six-week period during when the pups became adults, the mice were sacrificed and their livers were isolated for analysis of weight, pathohistological alterations, and the mRNA expression of drug metabolizing cyp450 genes: cyp1a1, cyp3a11, cyp2d9, and cyp2c29. RESULTS: The study demonstrated that MS markedly downregulated (p<0.05) the mRNA expression of all tested drug-metabolizing cyp450s in livers of female and male mice. Furthermore, the mRNA levels of major drug-metabolizing cyp450s were notably lower (p<0.05) in livers of female MS mice as compared with male MS mice. It was found that values of the total body weight and liver weight of MS mice did not vary significantly (p>0.05) from those of the control groups. Additionally, histological examination revealed that the hepatic tissue of MS mice was normal, similar to that of the control mice. CONCLUSIONS: In summary, MS downregulates the gene expression of major hepatic drug-metabolizing cyp450s without inducing pathological alterations in the livers of mice. These findings provide an explanation for the heterogeneity in pharmacokinetics and drug response of patients with early life stress.

Medicine and Pharmacy Students' Knowledge, Attitudes, and Practice regarding Artificial Intelligence Programs: Jordan and West Bank of Palestine.

Background: Artificial intelligence (AI) programs generate responses to input text, showcasing their innovative capabilities in education and demonstrating various potential benefits, particularly in the field of medical education. The current knowledge of health profession students about AI programs has still not been assessed in Jordan and the West Bank of Palestine (WBP). Aim: This study aimed to assess students' awareness and practice of AI programs in medicine and pharmacy in Jordan and the WBP. Methods: This study was in the form of an observational, cross-sectional survey. A questionnaire was electronically distributed among students of medicine and pharmacy at An-Najah National University (WBP), Al-Isra University (Jordan), and Al-Balqa Applied University (Jordan). The questionnaire consisted of three main categories: sociodemographic characteristics of the participants, practice of AI programs, and perceptions of AI programs, including ChatGPT. Results: A total of 321 students responded to the distributed questionnaire, and 261 participants (81.3%) stated that they had heard about AI programs. In addition, 135 participants had used AI programs before (42.1%), while less than half the participants used them in their university studies (44.2%): for drug information (44.5%), homework (38.9%), and writing research articles (39.3%). There was significantly (48.3%, P<0.005) more conviction in the use of AI programs for writing research articles among pharmacy students from Palestine compared to Jordan. Lastly, there was significantly more (53.8%, P<0.05) AI program use among medicine students than pharmacy students. Conclusion: While most medicine and pharmacy students had heard about AI programs, only a small proportion of the participants had used them in their medical study. In addition, attitudes and practice related to AI programs in their education differs between medicine and pharmacy students and between WBP and Jordan.

Hydroxychloroquine Toxicity in the Vital Organs of the Body: In Vivo Study.

BACKGROUND: Hydroxychloroquine (HCQ) toxicity can adversely affect vital organs, cause pathologic ocular damage, and can have direct cardiovascular effects. This study aims to identify the biochemical, hematological, and histological alterations of the vital organs associated with the effects of HCQ. METHODS: Male albino rats were exposed to the equivalent of HCQ therapeutic doses given to human patients being affected by malaria, lupus erythematosus, and COVID-19. The animal blood samples were subjected to hematological analysis, biochemical analysis, liver function tests, kidney function tests, and cardiac biomarkers. Liver, kidney, heart, spleen, and testis biopsies were subjected to histological examination. RESULTS: HCQ significantly lowered the values of erythrocytes, hemoglobin, hematocrit, platelets, leucocytes, and lymphocytes but significantly increased the values of aspartate aminotransferase (AST), alanine aminotransferase (ALT), amylase, alkaline phosphatase, lactate dehydrogenase, cholesterol, and chlorine ions. The renal tissues of HCQ-treated animals demonstrated glomerular fragmentation, partial atrophy degeneration, renal tubules hydropic degeneration, hyaline cast formation, and interstitial edema formation. Additionally, the heart exhibited myofiber necrosis, myolysis, wavy appearance, disorganization, and disarray. The testicular tissues also demonstrated spermatocyte degeneration, spermatogenic cell sloughing, testicular interstitial edema, and occasional spermatogenic arrest. Additionally, the spleen showed a decrease in the number and size of the white pulp follicles, a decrease in the number of apoptotic activity, and a decline in the number of T-rich cells. However, the red pulp demonstrated a diffuse decline in B rich-lymphocytes and macrophages. The liver was also the least affected but showed Kupffer cell hyperplasia and occasional hepatocyte dysplasia. CONCLUSIONS: The results indicate that chronic exposure to HCQ could alter the structures and functions of the vital organs.

Quantification of Ochratoxin A in 90 spice and herb samples using the ELISA method.

This study addressed the challenge of accurately detecting mycotoxins in herbs and spices, which have gained popularity as alternative medicines but pose health risks due to potential contamination. We used a competitive direct ELISA kit (Art No. 8610), Veratox for Ochratoxin, to quantify Ochratoxin A in the herb and spice samples. The samples were first prepared using solid-liquid extraction with 70% methanol. The resulting filtrate was then subjected to ELISA analysis. The results of the analysis were then further analyzed using principal component analysis (PCA). In this study, PCA was used to classify the concentration levels of Ochratoxin A based on various factors, such as the packaging type, country of origin, shelf life, and sample weight. The limits of detection (LOD) and quantification (LOQ) values indicate the lowest amount of Ochratoxin A that can be detected and quantified, respectively, with high accuracy and precision. The range of the LOD and LOQ values (0.43-0.58 µg/kg and 1.45-1.95 µg/kg, respectively) suggests that the method used was capable of detecting and quantifying Ochratoxin A in the herb and spice samples at different concentrations with a high degree of accuracy and precision. These results suggest that while most of the samples (73.33%) were below the maximum residue limit (MRL) for Ochratoxin A, a significant number of samples (26.67%) had concentrations of Ochratoxin A that were higher than the MRL. This highlights the importance of monitoring Ochratoxin A in herb and spice samples and ensuring the products are safe for consumption.