Can Intranasal Administration of Adipose-Derived Stem Cells Reach and Affect the Histological Structure of Distant Organs of Aged Wistar Rat?

Introduction: Stem cell therapy is a highly promising strategy in various degenerative diseases. Intranasal administration of stem cells could be considered as a non-invasive treatment option. However, there is great debate concerning the ability of stem cells to reach distant organs. It is also unclear in such a case if they can alleviate age-related structural changes in these organs. Aim: The aim of this study is to evaluate the ability of intranasal administration of adipose-derived stem cells (ADSCs) to reach distant organs of rats at different time intervals and to investigate their effects on age-related structural changes in these organs. Materials and Methods: Forty-nine female Wistar rats were used in this study, seven of which were adults (6-month-old) and 42 were aged (2-year-old). Rats were divided into three-groups: Group-I (adult control), Group-II (aged), and Group-III (aged ADSCs treated). Rats of Groups I and II were sacrificed after 15 days from the beginning of the experiment. Rats of Group III were treated with intranasal ADSCs and were sacrificed after 2-h, 1-day, 3-day, 5-day, and 15-day. Heart, liver, kidney, and spleen specimens were collected and processed for H and E, CD105 immunohistochemistry, and immunofluorescent techniques. Morphometric study and statistical analysis were performed. Results: ADSCs appeared in all organs examined after 2-h of intranasal administration. Their maximum presence was detected after 3-day of administration, after which their immunofluorescence gradually decreased and nearly disappeared from these organs by the 15th day. Improvement of some age-related deterioration in the structure of the kidney and liver occurred at day 5 after intranasal administration. Conclusions: ADSCs effectively reached the heart, liver, kidney, and spleen after intranasal administration. ADSCs ameliorated some age-related changes in these organs.

A Histological Study on the Acute Effect of Zinc Oxide Nanoparticles Administered by Different Routes on Albino Rat Lung.

Introduction and Aim of the Work: Zinc oxide nanoparticles (ZnO NPs) are considered the most frequently utilized NPs, so the potential for human exposure has increased tremendously. Hence, the study is aimed to compare the histopathological effects of high and low doses of ZnO NPs administered intranasally or intravenously on lung tissue of adult rat's male albino. Materials and Methods: Thirty-five male Wistar rats were divided into Group I; control group, Group II (intranasal administered group) was subdivided into Subgroup IIA and IIB, in which the animals were injected with 4 and 30 mg/kg of ZnO NPs, respectively. Group III (intravenous administered group) was subdivided into two subgroups with the same doses as Group II. Blood samples were collected after 24 h for estimating serum level of lactate dehydrogenase. Rat lungs were processed for histological, immunohistochemical, and ultrastructural analysis. Results: ZnO NPs caused thickening of interalveolar septa. Extravasated red blood cells were noticed in the alveolar lumen and in some bronchioles. Many dilated blood vessels exhibited focal disruption and focal thickening of their wall. Collagenous fibers were deposited in the interalveolar septa and the walls of bronchi. Tumor necrosis factor-alpha immune reactivity was significantly increased. These findings increased on dose increase, mainly in the intranasal administered group when compared with the intravenous group. Conclusion: ZnO NPs administration caused toxic effects on the histological structure of albino rat lung. These effects were route and dose-dependent, being more obvious after intranasal administration.

Novel role of peroxisome proliferator activated receptor-α in valproic acid rat model of autism: Mechanistic study of risperidone and metformin monotherapy versus combination.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder of heterogenous etiology exhibiting a challenge in understanding its exact neuro-pathophysiology. Recently, peroxisome proliferator activated receptor (PPAR)-α activation was found to play a fundamental role in neuroprotection and improving autistic-like-behaviors in experimental animal models of ASD through alleviating neuroinflammation, oxidative-stress, astrocyte reactivity, tauopathy in addition to its favorable role in metabolic regulation, thus attracting attention as a possible target in treatment of ASD. This study aimed to investigate the role of PPAR-α, astrocytic dysfunction and tauopathy in ASD and detect the possible neuroprotective effects of metformin (MET), through PPAR-α activation, and risperidone (RIS) either monotherapy or in combination in alleviating autistic-like-changes at behavioral and neurobiological levels in male Wistar rats. Pregnant female Wistar rats received valproic-acid (VPA) to induce autistic-like-behavioral and neurobiological alterations in their offspring. Chronic intra-peritoneal MET (100 mg/kg/day) and RIS (1 mg/kg/day) either monotherapy or in combination started from postnatal day (PND) 24 till PND61 (38 days). Prenatal VPA exposure simulated the autistic core behaviors associated with neurochemical and histopathological neurodevelopmental degenerative changes. Both MET and RIS either monotherapy or in combination were able to reverse these changes. The effect of MET was comparable to RIS. Moreover, MET was able to alleviate the RIS induced weight gain and improve cognitive functions highlighting its promising adjunctive role in alleviating ASD pathophysiology. Our study highlighted the favorable effects of MET and RIS both in monotherapy and in combination in alleviating the autistic-like-changes and proposed PPAR-α activation along with restoring astrocytes homeostasis as promising targets in novel therapeutic strategies in ASD.

EE-6S: an integrated approach for introducing early clinical exposure in the new Egyptian medical curriculum.

The electrocardiogram (ECG) is the primary diagnostic tool in cardiovascular diseases. Hence its interpretation is a core competency in medicine, where obvious deficiencies have been reported among learners. The aim of this study was to introduce the fundamentals of ECG knowledge and interpretation through early clinical exposure (ECE) based on a six-step approach for preclinical students (n = 110) and to study its influence on their knowledge and interpretation skills thereafter. The first step employed a blended learning format using didactic lectures on normal and pathological ECGs, each preceded by preinstructional videos. The second step focused on psychomotor skills and utilized laboratory exercises for ECG recording and interpretation. The third step focused on vertical integration, where the clinical relevance of the procedure was established with integrated lectures. The fourth step used the Moodle platform, where opportunities for peer interactions and clarifications by clinical faculty were made available. The fifth step incorporated clinical and diagnostic reasoning through cardiology ward visits and interpretation of patient ECGs. The sixth step was designed for critical thinking and problem solving through case-based discussions with peers and faculty. Students were assessed with multiple-choice questions and objective structured practical examination. Learner perceptions of the approach were evaluated with a feedback questionnaire and focus group discussion. Statistical analysis showed that ECE through a six-step approach significantly enhanced knowledge and interpretation of ECG as evidenced by the pre- and posttest scores. Analysis of the focus group data revealed that learner engagement and skills of critical thinking were enhanced along with diagnostic and clinical reasoning.

Validation of prenatal versus postnatal valproic acid rat models of autism: A behavioral and neurobiological study.

Despite the increasing prevalence of autism spectrum disorder (ASD), there is still a deficiency in understanding its exact pathophysiology and treatment, therefore validation of translational ASD animal model is warranted. Although strong evidences support the valproic acid (VPA) model of autism, yet a controversy exists regarding the best timing of exposure whether prenatal or postnatal. Accordingly, this study was designed to compare the time dependent effects of VPA exposure as regard its ability to induce autistic like changes in male Wistar rats. In this study, two different protocols of VPA exposure (prenatal and postnatal) were compared at different levels (behavioral, neurochemical and histopathological). Results of this study revealed that both prenatal and postnatal VPA exposures induced autistic-like behaviors manifested by reduced social interaction, increased repetitive stereotyped behavior and anxiety, cognitive dysfunction, lowered sensitivity to pain, and neurodevelopmental delay. Furthermore, inflammatory cytokines and oxidative/nitrosative stress markers were elevated in prefrontal cortex and hippocampal homogenates. Likewise, histopathological and immunohistochemical assessment confirmed the neurodegenerative and the apoptotic changes in prefrontal cortex, hippocampus and cerebellum exhibited by decreased viable cells number and Nissl's granules optical density, and increased caspase-3 immunoreactivity respectively. Interestingly, ASD core symptoms and histopathological changes were significantly (P < 0.05) altered in prenatal VPA model compared to postnatal VPA model. Additionally, postnatal mortality in prenatal model (4.3%) was much lower compared to the postnatal model (22.7%). In conclusion, our study overweighs the ability of prenatal VPA model over postnatal VPA model to induce behavioral and neuropathological alterations that simulate those observed in autistic individuals with a lower postnatal animal mortality, highlighting the privilege of prenatal over postnatal VPA exposure as a translational model for understanding pathophysiology and developing novel targets for management of ASD.

Potential neuroprotective effect of androst-5-ene-3ß, 17ß-diol (ADIOL) on the striatum, and substantia nigra in Parkinson's disease rat model.

Parkinson's disease (PD) is a progressive neurodegenerative disorder with behavioral and motor abnormalities. Androst-5-ene-3ß, 17ß-diol (ADIOL), an estrogen receptor (ER) ß agonist, was found to mediate a transrepressive mechanism that selectively modulates the extent of neuroinflammation and, in turn, neurodegeneration. In consensus, ERß polymorphism was more frequently detected in early-onset PD patients. Thus, in an approach to elucidate the role of ERß agonists on PD, our study was designed to investigate the possible neuroprotective effect of ADIOL, in three dose levels (0.35, 3.5, 35 mg/kg/day), against rotenone (ROT)-induced PD rat model. Amelioration in striatal dopamine (DA), nuclear factor-kappa B (NF-κB), and the expression of down-stream inflammatory mediators, as well as apoptotic markers were observed in the striatum and substantia nigra (SN) upon pre-treatment with the three doses of ADIOL. Similarly, light microscopy (LM) examination revealed declined degeneration of neurons upon pretreatment with ADIOL. Significant improvement in nigral tyrosine hydroxylase (TH) and reduction of nigral α-synuclein densities were also detected after ADIOL pre-treatment with better results frequently achieved with the middle dose (3.5 mg/kg/day). The middle dose of ADIOL showed behavioral improvement, with elevation in the ATP level, which was emphasized by the improvement in mitochondrial integrity observed upon electron microscopy (EM) examination. In conclusion, the present study confirmed for the first time the ability of ADIOL to protect against neuroinflammation and, in turn, neurodegeneration process and motor dysfunction in PD animal model, which was more obviously observed with the middle dose.

Animal model for training and improvement of the surgical skills in endolaryngeal microsurgery.

Animal models for training of surgical skills were widely used for a long time in the education of medical practitioners. It is recognized, however, that endolaryngeal microsurgery requires highly refined skills to handle the delicate structures of the vocal folds under the microscope. The availability of fresh human laryngeal specimens is markedly restricted by legal and hygienic issues. The aim of this work was to report on the design of a feasible and effective model to provide the much needed skills in an animal laryngeal model that is as close as possible to the human vocal fold structure. In the initial phase of the research, three animal larynges were studied: porcine/pig, bovine/calf, and ovine/sheep larynges. The pig/porcine larynx was chosen for this experimental training model because it closely resembled the human laryngeal/glottal configurations. A study was carried out on 10 porcine/pig larynges to assess the dimensions of the glottis and study the histology of the layered structure of the vocal fold. The study was pursued to confirm the resemblance of this animal specimen to the human vocal fold. A wooden box with a black finished interior was prepared with an acrylic bed at its floor. This bed allows placement of the porcine/pig larynx. The design of the box allows the endoscopic exposure of the porcine/pig larynx through a rubber diaphragm. The darkness and confinement of the box, apart from the light of the endoscope, approximates the situation in live endoscopy. The operating microscope is then used to expose the glottis. Routine fine microlaryngeal instruments were used for training in the prescribed skills.

Noninvasive assessment of hepatic fibrosis and necroinflammatory activity in Egyptian children with chronic hepatitis C virus infection using FibroTest and ActiTest.

BACKGROUND: Hepatitis C virus (HCV) is a major cause of chronic hepatitis and hepatic fibrosis. Liver biopsy, because of its limitations and risks, might be considered an imperfect gold standard for assessing the severity of chronic liver diseases. In this study, we aimed to prospectively validate FibroTest (FT) and ActiTest (AT) as noninvasive serum biochemical markers for assessment of the degree of hepatic fibrosis and necroinflammatory activity respectively, in pediatric patients with chronic HCV infection and compare them to liver biopsy. METHODS: Fifty patients, aged 2 to 18 years, with chronic HCV infection were prospectively enrolled. Two assessments were carried out, within 24-h duration, one of a liver biopsy specimen and the other FT and AT measured in serum sample. FINDINGS: A highly significant linear trend and correlation were found between FT-related fibrosis and fibrosis stage by METAVIR scoring on histopathological examination. A highly significant correlation was also found between AT and necroinflammatory histological activity using METAVIR as well. The FT area under the receiver operating characteristic curve (AUROC) is 0.97, SE=0.02 which can diagnose patients with mild stage of fibrosis, thus discriminating them from those with no (or minimal) fibrosis. The AT can successfully discriminate between patients with moderate activity and those with mild activity with AUROC=0.93, SE=0.06. CONCLUSION: FT and AT are potential noninvasive methods for assessment of hepatic fibrosis and necroinflammatory activity in pediatric patients with chronic HCV infection in comparison with liver biopsy.