Evaluation of prescribing patterns using WHO core drug use indicators in a pediatric hospital of Kabul Afghanistan: A prospective cross-sectional study.

Background: The global issue of irrational drug use, particularly concerning pediatric patients, is a significant concern. Notably, there has been a lack of studies assessing rational drug prescribing for pediatric patients within Afghanistan's healthcare system. This investigation aimed to address this gap by examining drug prescribing patterns at the Indira Gandhi Pediatric Health Institute (IPHI) in Kabul, Afghanistan. Methods: A prospective cross-sectional analysis was conducted to evaluate the prevailing drug prescribing practices at the outpatient department of IPHI in Kabul, Afghanistan. A systematic random sampling method was employed to select 600 outpatient prescriptions from the institute, following the World Health Organization (WHO) guidelines for investigating drug utilization in healthcare facilities. Results: The average age of patients was 4 years, and the average number of drugs per prescription was 2.9. Notably, 84% of prescriptions included one or more antibiotics, surpassing the WHO standard of <30%. Furthermore, 67% of the prescribed drugs were listed on Afghanistan's national essential drugs list (EDL), falling below the standard value of 100%. Only 35.1% of the prescribed drugs were in generic form, also lower than the recommended 100%. Moreover, 5.7% of all prescriptions included injections, the ideal value is <20%. The most frequently prescribed drug groups were anti-microbials (25.7%), followed by non-steroidal anti-inflammatory drugs (NSAIDs), (21.4%), gastrointestinal drugs (17.3%), and vitamins (7.8%). Conclusion: The study's findings indicate that, on average, a higher number of drugs were prescribed per patient visit at IPHI compared to recommended standards. Additionally, there was a lower utilization of generic drugs and drugs from Afghanistan's national essential drugs list (EDL), with an over-prescription of antibiotics.

Molecular characterization and antimicrobial resistance of nasal Staphylococcus aureus in the community of Kabul.

OBJECTIVES: This study aimed to investigate the prevalence and molecular characteristics of community methicillin-resistant Staphylococcus aureus (MRSA) nasal carriage among students at Kabul University. METHODS: Nasal swabs were collected from anterior nares of 150 healthy non-medical students at Kabul University. Antimicrobial susceptibility testing was performed on all S. aureus isolates, and all detected MRSA isolates were then confirmed by mecA/mecC polymerase chain reaction and characterized using DNA microarray. RESULTS: A total of 50 S. aureus strains were isolated from the anterior nares of the 150 participants. The prevalence of S. aureus and MRSA nasal carriage among Kabul students was 33.3% and 12.7%, respectively. Seven (36.8%) MRSA isolates and 8 (25.8%) methicillin-susceptible S. aureus (MSSA) isolates were multidrug-resistant (i.e. resistant to at least three different antimicrobials tested). All MRSA isolates (n = 19) were susceptible to linezolid, rifampicin, and fusidic acid. Seven MRSA clones, belonging to four clonal complexes (CCs), were identified. The most commonly identified clone was CC22-MRSA-IV TSST-1-positive, which accounted for 63.2% (12/19) of MRSA isolates. SCCmec typing showed that most MRSA strains harboured SCCmec type IV (94.7%). Thirteen (68.4%) MRSA isolates carried the TSST-1 and 5 (26.3%) PVL genes. CONCLUSION: Our findings revealed the relatively high prevalence of MRSA nasal carriers in the community in Kabul, with the predominance of the CC22-MRSA-IV TSST-1-positive clone and frequent multidrug resistance among these isolates.

Comparative study between direct analysis in whole blood, oral fluid, and declaration of consumption for the prevalence of nonsteroidal anti-inflammatory drugs and acetaminophen in ultratrail runners.

Ultratrail running is a sport with growing number of adherents. To complete ultratrail despite physical issues such as joint and muscle pain, many runners use nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen. Studies asking participants about their consumption of drugs during ultratrail revealed a prevalence of NSAIDs and acetaminophen up to 70% and 25%, respectively. The aims of the present study were to determine the prevalence of NSAIDs and acetaminophen for 81 runners during the 2021 Ultratrail du Mont Blanc® (UTMB®) using direct analysis of dried blood spots (DBS) and oral fluid (OF) and to compare results with the declaration of consumption by runners; this is to identify the most relevant method to study the prevalence of drugs. Our results show a prevalence of NSAIDs of 46.6% using DBS, 18.5% using OF, and 13.8% based on a questionnaire. Prevalence of acetaminophen were 30.1%, 30.9%, and 22.5% using DBS, OF, and questionnaire, respectively. From this study, we conclude that the analysis of drugs directly in DBS is the most relevant tool to determine the prevalence in ultratrail events.

Antibiotic resistance profile and molecular characterization of Staphylococcus aureus strains isolated in hospitals in Kabul, Afghanistan.

The aim of this study was to investigate the molecular features and the antibiotic resistance profile of 98 clinical Staphylococcus aureus isolates collected during 6 months in two hospitals of Kabul, Afghanistan. For all isolates, antimicrobial resistance patterns were determined by the disc diffusion method (including methicillin resistance which was detected using cefoxitin). The presence of the mecA/mecC genes was detected by PCR. Strains were then extensively characterized using microarray analysis. Of the 98 S. aureus isolates, methicillin-resistant S. aureus (MRSA) prevalence was high at 66.3%. Antibiotic susceptibility testing also revealed a high resistance rate to penicillin (100%), erythromycin (66.3%), ciprofloxacin (55.1%), and cotrimoxazole (40.8%). Resistance to tobramycin was detected in 25.5%, to gentamicin in 16.3%, to chloramphenicol in 34.7%, and to doxycycline in 23.5% of the isolates. All the MRSA isolates were mecA-positive and none of them harbored mecC. Isolates were grouped into twelve clonal complexes and twenty-seven distinct clones. The most frequently detected clones were the Southwest Pacific clone (CC30-MRSA-IV PVL+) (21/65 MRSA, 32.3%), the CC22-MRSA-IV TSST-1+ clone (11/65 MRSA, 16.9%), and the Bengal Bay clone (ST772-MRSA-V PVL+) (11/65 MRSA, 16.9%). The PVL genes were found in 59.2% (46/65 MRSA and 12/33 methicillin-susceptible S. aureus, MSSA) and tst1 gene in 16.3% of isolates. This molecular study highlights the high prevalence of MRSA and the large genetic diversity of the S. aureus isolates circulating and detected in two hospitals of Kabul, with the presence of multiple virulence and antibiotic resistance genes.

Muscular and mitochondrial effects of long-term fluoxetine treatment in mice, combined with physical endurance exercise on treadmill.

AIM: Fluoxetine, one of the first newer SSRI antidepressant, is an extremely popular treatment for depression that could improve mental health problems. Many recent studies have suggested that SSRI have potential beneficial effects on skeletal muscle tissue. MAIN METHOD: We evaluated the potential beneficial effects of oral fluoxetine (18 mg/kg/day for 6 weeks) on muscle performance, after 6 weeks of physical exercise on treadmill. Male mice were randomly assigned to four groups (n = 12 per group) for treatment. Each group received treatment with following specifications: 1) no exercise with vehicle treatment (SED-S); 2) no exercise with fluoxetine treatment (SED-F); 3) exercise with vehicle treatment (EX-S); and 4) exercise with fluoxetine treatment (EX-F). Exercise performances were assessed based on the exhaustive running time and forelimb grip strength, anxious behavior by elevated plus-maze and open-field tests. Mitochondrial enzymes activity and ROS production were measured in the gastrocnemius and soleus muscles. KEY FINDING: Fluoxetine treatment had a significant effect on maximal aerobic capacity in mice without exercise, but more significant effects on gripping strength and anxiety when combined with exercise training, e.g. increased strength and decreased anxiety. SIGNIFICANCE: Fluoxetine treatment and exercise stimulation also had synergistic effects on strength and increased mitochondrial activity, cellular oxidative and antioxidant capacity in two different muscles.

Nanoprecipitation process: From encapsulation to drug delivery.

Drugs encapsulation is a suitable strategy in order to cope with the limitations of conventional dosage forms such as unsuitable bioavailability, stability, taste, and odor. Nanoprecipitation technique has been used in the pharmaceutical and agricultural research as clean alternative for other drug carrier formulations. This technique is based on precipitation mechanism. Polymer precipitation occurs after the addition of a non-solvent to a polymer solution in four steps mechanism: supersaturation, nucleation, growth by condensation, and growth by coagulation that leads to the formation of polymer nanoparticles or aggregates. The scale-up of laboratory-based nanoprecipitation method shows a good reproducibility. In addition, flash nanoprecipitation is a good strategy for industrial scale production of nanoparticles. Nanoprecipitation is usually used for encapsulation of hydrophobic or hydrophilic compounds. Nanoprecipitation was also shown to be a good alternative for the encapsulation of natural compounds. As a whole, process and formulation related parameters in nanoprecipitation technique have critical effect on nanoparticles characteristics. Biodegradable or non-biodegradable polymers have been used for the preparation of nanoparticles intended to in vivo studies. Literature studies have demonstrated the biodistribution of the active loaded nanoparticles in different organs after administration via various routes. In general, in vitro drug release from nanoparticles prepared by nanoprecipitation includes two phases: a first phase of "burst release" which is followed by a second phase of prolonged release. Moreover, many encapsulated active molecules have been commercialized in the pharmaceutical market.

Polycaprolactone Based Nanoparticles Loaded with Indomethacin for Anti-Inflammatory Therapy: From Preparation to Ex Vivo Study.

PURPOSE: This work focused on the preparation of polycaprolactone based nanoparticles containing indomethacin to provide topical analgesic and anti-inflammatory effect for symptomatic treatment of inflammatory diseases. Indomethacin loaded nanoparticles are prepared for topical application to decrease indomethacin side effects and administration frequency. Oppositely to already reported works, in this research non-invasive method has been used for the enhancement of indomethacin dermal drug penetration. Ex-vivo skin penetration study was carried out on fresh human skin. METHODS: Nanoprecipitation was used to prepare nanoparticles. Nanoparticles were characterized using numerous techniques; dynamic light scattering, SEM, TEM, DSC and FTIR. Regarding ex-vivo skin penetration of nanoparticles, confocal laser scanning microscopy has been used. RESULTS: The results showed that NPs hydrodynamic size was between 220 to 245 nm and the zeta potential value ranges from -19 to -13 mV at pH 5 and 1 mM NaCl. The encapsulation efficiency was around 70% and the drug loading was about 14 to 17%. SEM and TEM images confirmed that the obtained nanoparticles were spherical with smooth surface. The prepared nanoparticles dispersions were stable for a period of 30 days under three temperatures of 4°C, 25°C and 40°C. In addition, CLSM images proved that obtained NPs can penetrate the skin as well. CONCLUSION: The prepared nanoparticles are submicron in nature, with good colloidal stability and penetrate the stratum corneum layer of the skin. This formulation potentiates IND skin penetration and as a promising strategy would be able to decline the side effects of IND.

Encapsulation of NSAIDs for inflammation management: Overview, progress, challenges and prospects.

Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most widely prescribed drugs. Debilitating diseases such as rheumatoid arthritis and osteoarthritis are commonly managed by NSAIDs. However, NSAIDs pharmacological mechanism is often associated with the presence of gastrointestinal side effects. NSAIDs encapsulation is performed in order to overcome some of the drawbacks linked to their clinical use. To fulfill this purpose, various vectors like polymer-based nanoparticles, liposomes and solid lipid nanoparticles have been proposed. Such vehicles could have advantages but some limitations as well. This manuscript highlights current NSAIDs encapsulation approaches based on either preformed polymers or lipids. Moreover, properties of the prepared carriers and their applications are also discussed. Many factors are taken into account for selecting carrier type and encapsulation method. It was concluded that different vehicles and preparation methods have been employed for NSAIDs encapsulation. Mostly, vehicles sizes ranged within the nanoscale. Main advantages that have been confirmed by in vitro and in vivo studies include promoted stability, sustained release and bioavailability enhancement.

Potential protective effect of highly bioavailable curcumin on an oxidative stress model induced by microinjection of sodium nitroprusside in mice brain.

Curcumin, a polyphenolic compound has several pharmacological activities, such as anticancer, anti-inflammatory and antioxidant effects. However, curcumin shows poor oral bioavailability. The purpose of this study was to investigate the protective effects of highly bioavailable curcumin, Theracurmin(®), and curcumin, against sodium nitroprusside (SNP)-induced oxidative damage in mice brain. Intrastriatal microinjection of Theracurmin(®) or curcumin with SNP significantly protected against SNP-induced brain damage and motor dysfunction. Oral administration of Theracurmin(®) (1 and 3 g kg(-1), containing 100 and 300 mg kg(-1) curcumin, respectively) significantly protected against SNP-induced brain damage and motor dysfunction. However, oral administration of 300 mg kg(-1) curcumin did not protect against motor dysfunction induced by SNP. These results suggest that curcumin and Theracurmin(®) have protective effects against SNP-induced oxidative damage. Moreover, oral administration of Theracurmin(®), had more potency in protecting against brain damage, suggesting a higher bioavailability of Theracurmin(®) following oral administration.

Neuroprotective effects of curcumin and highly bioavailable curcumin on oxidative stress induced by sodium nitroprusside in rat striatal cell culture.

Curcumin, a polyphenolic compound extracted from Curcuma longa, has several pharmacological activities such as anticancer, anti-inflammatory, and antioxidant effects. The purpose of this study was to investigate the protective effects of curcumin and THERACURMIN, a highly bioavailable curcumin, against sodium nitroprusside (SNP)-induced oxidative damage in primary striatal cell culture. THERACURMIN as well as curcumin significantly prevented SNP-induced cytotoxicity. To elucidate the cytoprotective effects of curcumin and THERACURMIN, we measured the intracellular glutathione level in striatal cells. Curcumin and THERACURMIN significantly elevated the glutathione level, which was decreased by treatment with SNP. Moreover, curcumin showed potent 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging ability. Finally, a ferrozine assay showed that curcumin (10-100 µg/mL) has potent Fe(2+)-chelating ability. These results suggest that curcumin and THERACURMIN exert potent protective effects against SNP-induced cytotoxicity by free radical-scavenging and iron-chelating activities.

Protective effect of luteolin on an oxidative-stress model induced by microinjection of sodium nitroprusside in mice.

Accumulating lines of evidence showed that luteolin, a polyphenolic compound, has potent neuroprotective effects. The purpose of this study was to examine whether luteolin can protect against sodium nitroprusside (SNP)-induced oxidative damage in mouse brain. Intrastriatal co-injection of luteolin (3 - 30 nmol) with SNP (10 nmol) dose-dependently protected against brain damage and motor dysfunction. Oral administrations of luteolin (600 - 1200 mg/kg) dose-dependently protected against brain damage and motor dysfunction induced by striatal injection of SNP. Furthermore, luteolin (30 - 100 µM) concentration dependently protected against Fe(2+)-induced lipid peroxidation in mouse brain homogenate. Luteolin (1 - 100 µg/ml) showed potent DPPH radical scavenging ability, when compared with ascorbic acid and glutathione. Finally, a ferrozine assay showed that luteolin (30 - 100 µg/ml) has Fe(2+)-chelating ability, but this was weaker than that of ethylenediaminetetraacetic acid. These results suggest that intrastriatal or oral administration of luteolin protected mice brain from SNP-induced oxidative damage by scavenging and chelating effects.

In vivo brain oxidative stress model induced by microinjection of sodium nitroprusside in mice.

Sodium nitroprusside (SNP) is widely used as a potent vasodilator and a nitric oxide (NO) donor, whereas the cytotoxicity of SNP has been well documented. SNP releases several potentially toxic products such as cyanide anion, NO, and iron. We investigated the mechanisms of cell death and motor dysfunction induced by microinjection of SNP in mice to establish a brain oxidative stress model and then examined the anti-oxidant activity of glutathione. Intrastriatal microinjection of SNP (1 - 10 nmol) induced brain damage and motor dysfunction in a dose-dependent manner when the effects were evaluated with behavioral tests and TTC staining. NOC-18 (10 nmol), another NO donor, and KCN (10 nmol) did not cause motor dysfunction. However, FeCl(2) (10 nmol) caused motor dysfunction. In addition, simultaneous injection of SNP and deferoxamine (10 nmol), an iron-chelating agent, prevented SNP-induced brain damage and motor dysfunction, suggesting a role of iron-related radicals in SNP-toxicity. Moreover, reduced glutathione (1 - 10 nmol), a natural anti-oxidant substance, dose-dependently prevented motor dysfunction induced by SNP-toxicity. Finally, deferoxamine and glutathione (10 nmol) significantly protected against brain damage and motor dysfunction induced by FeCl(2) toxicity. These results suggest that cell death induced by injection of SNP is caused by iron-related radical reactions, but not by NO and cyanide anion.