Asmaa Fathi Galal

Olmesartan medoxomil (OLM), a widely prescribed antihypertensive agent, suffers from poor solubility and first pass metabolism, which lowers its bioavailability. This work aimed to develop novel cationic nanocarriers (LeciPlex) for OLM to enhance its dissolution and oral bioavailability. A central composite design (CCD) was employed to optimize OLM-loaded LeciPlex (OLM-LPX) formulations. The independent variables included lecithin amount, surfactant amount, and surfactant type. The influence of these factors on particle size (PS), entrapment efficiency (EE), surface charge (ZP), and cumulative in vitro drug release (CR) was thoroughly evaluated and examined. The optimized formulation underwent additional evaluation for ex vivo permeation, morphology, stability, in vivo histopathology, and pharmacokinetic studies. The optimized OLM-LPX exhibited desirable PS (149.23 ± 2.02 nm), ZP (+ 62.03 ± 2.45 mV), EE (82.25 ± 4.63%), and CR (88.87 ± 1.97% after 8 h), aligning well with the predicted CCD values. Ex vivo permeation of optimized OLM-LPX across rabbit intestine showed a cumulative OLM transport of 1973.1 ± 207.9 µg versus 909.9 ± 217.8 µg for OLM suspension, with a permeability coefficient 3.4-fold higher and a 2.17-fold increase in intestinal permeability. Transmission electron microscope images showed spherical-shaped and smooth particles. It also exhibited accepted stability over the predetermined storage period (90 days), showing neither sedimentation nor particle coalescence. The orally administered optimized OLM-LPX showed no evidence for inflammatory signs or mucosal damage within intestinal gut segments under histopathological examination. Pharmacokinetic evaluation in rats demonstrated that OLM-LPX achieved a C _max of 3.48 ± 0.25 µg/mL versus 1.32 ± 0.21 µg/mL for suspension, extended t _max (2 h vs. 1 h), and a markedly enhanced AUC _₀–∞ of 41.17 ± 3.41 µg·mL⁻¹·h compared to 11.48 ± 1.69 µg·mL⁻¹·h, corresponding to a relative bioavailability of 358.62%. Collectively, LPX may serve as an effective nanocarrier for effective oral administration of poorly soluble OLM, contributing to its enhanced bioavailability. Graphical Abstract

The current study investigated the pharmacokinetic profile of a newly developed biodegradable subcutaneous tramadol implant and shed some light on neurochemical changes. Ribbons of polycaprolactone polymer were loaded with tramadol HCl in two quantities (T350, T650) and implanted in back skin of rats. Plasma tramadol levels were monitored for 45 days and pharmacokinetic parameters were evaluated in addition to analgesic activity. Cortical oxidative stress indicators, orexin, and serotonin levels were determined. The CB-1 receptor and PPAR-α receptor protein levels were assayed. Both T350 and T650 loaded ribbons attained a sustained release profile for 45 days. T650 implants achieved higher bioavailability than T350. However, the analgesic efficacy of tramadol started once it was implanted and decreased along time indicating accelerated tolerance. Oxidative biomarkers were of normal range. The ventrolateral periaqueductal gray (vlPAG) analgesic pathway involving orexin, endocannabinoid, and serotonin was found to be affected in relation to developing tolerance. Induced cortical 5-HT and orexin-A and decreased level of DA after implanting T350 and T650 were observed. PPAR-α and CB-1R were of elevated abundance in cortex after T650 implants. However, pharmacodynamics reported a sensitizing effect related to vlPAG pathway. The implant achieved long stable release profile but of diminished analgesic activity.

Background: The elderly population is suffering from many mental health problems that are aggravated as a matter of age and cognitive decline is a serious one of them. The aim of the present work is to screen the cognitive performance among a sample of Egyptian elderly volunteers and to investigate the associated risk factors. Results: A sample of 88 elderly volunteers from both genders was enrolled in the study according to the specified eligibility criteria after signing the approval consent. Medical history and socio-demographic data were collected from all participants in addition to basic clinical examination. Cognitive performance was assessed using the 6-Item Cognitive Impairment Test (6-CIT) while the endogenous event-related potentials (ERP) was measured using P300. The inflammatory biomarkers; TNF-α and COX-2 levels were assessed in serum using ELISA technique in addition to gene expression of TNF-α, PPAR-γ and CD-36 exploration using qRT-PCR. About half (51%) of the sample under investigation showed cognitive problems with scores on the 6-CIT exceeding the normal level. TNF-α serum levels showed positive correlation with P300 latency and correlated negatively with P300 reaction time. Furthermore, serum COX-2 levels correlated positively with P300 reaction time and negatively with P300 amplitude. Conclusion: The study population is showing early signs of cognitive decline that invites attention to the importance of spreading preventive measures against further deterioration. Inflammatory biomarkers under investigation and 6-CIT are suggested to be used in prediction of early stages of cognitive decline among the elderly population.

Background The elderly population is suffering from many mental health problems that are aggravated as a matter of age and cognitive decline is a serious one of which. Objectives The aim of the present work is to screen the cognitive performance among a sample of Egyptian elderly volunteers and to investigate the associated risk factors. Methods A sample of 88 elderly volunteers from both genders was enrolled to the study according to the specified eligibility criteria after signing the approval consent.Medical history and socio-demographic data were collected from all participants in addition to basic clinical examination. Cognitive performance was assessed using the 6-item Cognitive Impairment Test (6-CIT) whilethe endogenous event related potentials (ERP) was measured using P300. The inflammatory biomarkers; TNF-αand COX-2 levels were assessed in serum using ELISA technique in addition togene expression of TNF-α, PPAR-γ and CD-36 exploration using qRT-PCR. Results About half (51%) of the sample under investigation showed cognitive problems with scores on the 6-CIT exceeding the normal level. TNF-α serum levels showed positive correlation with P300 latency and correlated negatively with P300 reaction time. Furthermore, serum COX-2 levels correlatedpositively with P300 reaction time and negatively with P300 amplitude. Conclusion The study population is showing early signs of cognitive decline that invites attention to the importance of spreading preventive measures against further deterioration. Inflammatory biomarkers under investigation and 6-CIT aresuggested to be used in prediction of early stages of cognitive decline among the elderly population.

This study investigated the impact of Wi-Fi signals exposure on cognitive function and its relevant brain biomarkers and the possible role of designed Bio-Geometrical forms in restoring the neurobehavioral alterations resulting from the exposure to the emerging radiation.Rats were assigned into 3 groups; Gp I control group (away from exposure to radiation); Gp II, III were exposed to wireless router signals for 24 h for 6 months and Gp III was protected by a set of designed BioGeometrical shapes. Animals were tested for spatial memory, anxiety and emotionality in addition to the related neurotransmitters (dopamine, serotonin and acetylcholine) in different brain areas. Melatonin, Heat Shock Protein (HSP-70) and acetylcholine esterase (AchE) were also measured in various brain regions and histopathological examination was carried out as well. Wi-Fi radiation exposed group showed elevated anxiety level and impaired spatial memory. Moreover, significant decline in dopamine, serotonin and acetylcholine levels in the investigated brain areas has been recorded. Melatonin levels were decreased in the cortex, striatum and hippocampus while HSP-70 was depleted in the cortex only. Using Bio-Geometrical forms along with Wi-Fi exposure could combat the burden of Wi-Fi radiation. This was evidenced by the recovery of the anxiety level and the improvement of memory task. In addition, the presence of Bio-Geometrical shapes could retrieve dopamine, serotonin and acetylcholine as well as melatonin and HSP-70 levels This study provides solid foundation for the potential use of Bio-Geometrical shapes to modify the insult of Wi-Fi radiation on brain function and structure.

Objective: The causal effect relationship between smoking and stress is a subject that invites continuous research. Hypothetically, investigation of stress biomarkers that are reported to be affected by tobacco intake may give us some explanation of the association between stress and smoking as a habit. Consequently, the present study aimed to assess the serum level of some stress biomarkers and compare them among smokers and non-smokers in a sample of Egyptian male healthy volunteers. Methods: Fifty-nine subjects were enrolled in the study (29 smokers and 30 non-smokers of matched age and gender). We measured serum levels of cortisol and interleukin-6 (IL-6) using the ELISA technique, and serum levels of α-amylase, triglycerides (TG), and total cholesterol (TC) using colorimetric methods. Results: Serum cortisol levels were decreased in smokers, and IL-6, TG, and TC were significantly higher in smokers than non-smokers, whereas, serum α-amylase did not show a significant difference. Serum cortisol showed to be negatively correlated with serum IL-6 in smokers. Conclusions: The present study assumes that smokers suffer from a state of chronic stress as evidenced by the observed decrease in serum cortisol due to negative feedback effects and increase in levels of serum IL-6, TG, and TC. This in turn enhances the craving to smoke to face stressors and leads to a vicious circuit that smokers fail to quit smoking.