Efficacy of stem cells versus microvesicles in ameliorating chronic renal injury in rats (histological and biochemical study).

Chronic exposure to heavy metals as aluminum chloride (AlCl3) could result in severe health hazards such as chronic renal injury. The present study aimed to evaluate the therapeutic potential of adipose tissue-derived stem cells (ASCs) in comparison to their microvesicles (MV) in AlCl3-induced chronic renal injury. Forty-eight adult male Wistar rats were divided into four groups: Control group, AlCl3-treated group, AlCl3/ASC-treated group, and AlCl3/MV-treated group. Biochemical studies included estimation of serum urea and creatinine levels, oxidative biomarkers assay, antioxidant biomarkers, serum cytokines (IL-1ß, IL-8, IL-10, and IL-33), real time-PCR analysis of renal tissue MALT1, TNF-α, IL-6, and serum miR-150-5p expression levels. Histopathological studies included light and electron microscopes examination of renal tissue, Mallory trichrome stain for fibrosis, Periodic acid Schiff (PAS) stain for histochemical detection of carbohydrates, and immunohistochemical detection of Caspase-3 as apoptosis marker, IL-1B as a proinflammatory cytokine and CD40 as a marker of MVs. AlCl3 significantly deteriorated kidney function, enhanced renal MDA and TOS, and serum cytokines concentrations while decreased the antioxidant parameters (SOD, GSH, and TAC). Moreover, serum IL-10, TNF-α, miR-150-5p, and renal MALT1 expression values were significantly higher than other groups. Kidney sections showed marked histopathological damage in both renal cortex and medulla in addition to enhanced apoptosis and increased inflammatory cytokines immunoexpression than other groups. Both ASCs and MVs administration ameliorated the previous parameters levels with more improvement was detected in MVs-treated group. In conclusion: ASCs-derived MVs have a promising ameliorating effect on chronic kidney disease.

Intranasal Versus Buccal Versus Intramuscular Midazolam for the Home and Emergency Treatment of Acute Seizures in Pediatric Patients: A Randomized Controlled Trial.

BACKGROUND: Benzodiazepines are the recommended first-line treatment of acute seizures. We wished to compare the efficacy, side effects, and satisfaction after midazolam administration by the buccal, intranasal, or intramuscular route in the treatment of acute seizures in children at homes and in emergency room (ER). METHODS: A prospective, randomized, controlled trial was performed in children aged one month to 17 years with acute seizures lasting longer than five minutes. The primary end point was seizure cessation within 10 minutes of drug administration and no seizure recurrence within 30 minutes. RESULTS: In the home group, 67 patients received midazolam via buccal route, 60 via intranasal route, and 69 via intramuscular route, whereas in the ER group, 37 patients received buccal, 34 received intranasal, and 34 received intramuscular midazolam. The primary end point was achieved in 94.2% and 85.3% after intramuscular midazolam in the home and ER groups, respectively. The intranasal midazolam was successful in stopping seizures in 93.3% in the home group and 88.2% in the ER group. The buccal route was effective in 91% in the home group and 78.4% in the ER group. There were no significant differences in efficacy between all groups (P = 0.763 and P = 0.509) among the home and ER groups, respectively. There were no significant cardiorespiratory events in all groups. CONCLUSIONS: Intramuscular, intranasal, and buccal doses of midazolam resolved most seizures in prehospital and emergency settings. Our results indicate that there is no statistically significant difference detected between different routes of midazolam. Intranasal route showed the highest satisfaction rate among caregivers.

Histological and biochemical evaluation of the effects of silver nanoparticles (AgNps) versus titanium dioxide nanoparticles (TiO2NPs) on rat parotid gland.

The unlimited use of nanoparticles (NPs) results in toxic impacts on different tissues. The current study aimed to compare the adverse effects of AgNPs and TiO2NPs on the parotid gland of adult male albino rats as regards the histopathological, immunohistochemical, and biochemical changes, exploring the possible underlying mechanisms and the degree of improvement after cessation of administration. Fifty-four adult male albino rats were divided into control group (I), AgNPs-injected group (II), and TiO2NPs-injected group (III). We measured the levels of tumor necrosis factor-alpha (TNF-α) and interleukin (IL-6) in the serum, and levels of MDA and GSH in parotid tissue homogenate. Quantitative real-time polymerase-chain reaction (qRT-PCR) was used to measure the expression levels of peroxisome proliferator-activated receptor-gamma coactivator 1-alpha (PGC1-α), nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4), mouse double minute 2 (MDM2), Caspase-3 Col1a1, and Occludin. Parotid tissue sections were examined by light microscope (Hematoxylin & Eosin and Mallory trichrome stains), electron microscope, and immunohistochemical examination of CD68 and anti-caspase-3 antibodies. Both NPs severely affected the acinar cells and damaged the tight junction between them by enhancing expression of the inflammatory cytokines, inducing oxidative stress, and disturbing the expression levels of the studied genes. They also stimulated fibrosis, acinar cell apoptosis, and inflammatory cells infiltration in parotid tissue. TiO2NPs effects were less severe than AgNPs. Cessation of exposure to both NPs, ameliorated the biochemical and structural findings with more improvement in TiO2NPs withdrawal. In conclusion: AgNPs and TiO2NPs adversely affected the parotid gland, but TiO2NPs were less toxic than AgNPs.

Pediatric vs. adult stroke: comparative study in a tertiary referral hospital, Cairo, Egypt.

Background: Even though stroke is rare in children, it is associated with serious or life-threatening consequences. Despite its rarity, the occurrence of stroke in children has age-related differences in risk factors, etiopathogenesis, and clinical presentations. Unlike adults, who have arteriosclerosis as the major cause of stroke, risk factors for pediatric strokes are multiple, including cardiac disorders, infection, prothrombotic disorders, moyamoya disease, moyamoya syndrome, and others. The goal of the current study was to compare the characteristics, clinical features, etiology, subtypes, and workup of pediatric and adult strokes. Methods: This was a hospital-based observational study conducted on 222 participants. All patients underwent a full clinical and neurological examination, full laboratory study, cardiac evaluation, and neuroimaging; CT scan, MRI, MRA, MRV, carotid duplex, and transcranial Doppler (TCD). Ischemic stroke (IS) etiology was classified according to the Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria, the "proposed classification for subtypes of arterial ischemic stroke in children," and the Oxfordshire Community Stroke Project (OCSP). Stroke severity was determined by the National Institutes of Health Stroke Scale (NIHSS) and PedNIHSS on admission. Results: The proportion of pediatric ischemic strokes in the current study was 63.4 percent, while hemorrhagic strokes were 36.5%. The majority of the adult patients had ischemic strokes (84.1%), while hemorrhagic strokes were noted in 15.8% of the patients. According to the original TOAST classification, in the current study, the etiology of pediatric IS was other determined causes in 63.6%, undetermined etiology in 27.2%, and cardioembolic in 9.0%. For the adult group, the major stroke subtypes were large artery disease, small vessel disease, cardioembolic, other determined causes, and undetermined etiology at 49.6%, 28.6%, 6.9%, 0.6%, and 12.5%, respectively. Conclusions: There is a greater etiological role for non-atherosclerotic arteriopathies, coagulopathies, and hematological disorders in pediatric stroke, while adults have more atherothrombotic causes. The co-existence of multiple risk factors in pediatric ischemic stroke is noticed. Thrombophilia evaluation is helpful in every case of childhood stroke. Children who have had a stroke should undergo vascular imaging as soon as possible. Imaging modalities include TCD and Doppler ultrasound, CT, MRI, MRA, and MRV, and cerebral angiography.

Electron microscopic study on the effect of chronic fluoxetine treatment on pituitary gland and the possible therapeutic effect of adipose-derived mesenchymal stem cells in adult male albino rats.

BACKGROUND: Adipose-derived mesenchymal stem cells (ADSCs) have therapeutic potential for the treatment of a variety of disorders due to their self-renewal and multipotential differentiation capabilities. AIM OF THE WORK: This study was planned to demonstrate the electron microscopic structure of the pituitary gland after chronic fluoxetine treatment and the possible therapeutic effect of ADSCs. MATERIALS AND METHODS: Thirty healthy male adult albino rats were classified into Control group (Group I). Fluoxetine treated (Group II) received 24 mg/kg/day of fluoxetine dissolved in 1.0 mL of tap water once a day. Fluoxetine group treated with ADSCs (Group III) received fluoxetine as group (II) for 30 days and then was injected once by ADSCs at a dose of 1 × 106 cells/rat in the tail vein suspended in 0.5 ml of phosphate-buffered saline (PBS). Recovery group (Group IV) received fluoxetine for 30 days and then received no treatment till the end of the experiment. RESULTS: The ultrastructural observations of the fluoxetine-treated group revealed major histological changes in both the pars distalis and nervosa. Pars distalis revealed cells with different shapes, sizes, nuclei, and variable profiles of the cytoplasm. Pars nervosa, on the other hand, revealed pituicytes with electron-lucent cytoplasm and small apoptotic nuclei. Administration of ADSCs greatly improved the microscopic appearance of cells, while the recovery group showed similar histological changes as the fluoxetine group. CONCLUSION: Fluoxetine caused various deleterious changes in the pituitary gland of albino rats, as evidenced by electron microscopy. These changes were almost corrected by the ADSCs treatment.    .

Therapeutic efficacy of adipose-derived mesenchymal stem cells after chronic fluoxetine treatment on pars distalis in adult male albino rats.

BACKGROUND: Fluoxetine hydrochloride is one of the most commonly used antidepressants in the selective serotonin reuptake inhibitor class. THE AIM OF WORK: The study was conducted to detect the effect of chronic fluoxetine treatment on pars distalis and the possible therapeutic effect of adipose-derived mesenchymal stem cells (ADSCs). MATERIAL AND METHOD: Thirty healthy male adult albino rats were classified into four groups. Control group (Group I) included fifteen rats. Fluoxetine treated (Group II) included five rats that received 24 mg/kg/day of fluoxetine dissolved in 1.0 ml of tap water once a day for 30 days. Fluoxetine group treated with ADSCs (Group III) included five rats that received fluoxetine as group (II) for 30 days, then supplied once by ADSCs at a dose of 1 × 106 cells/rat in the tail vein suspended in 0.5 ml of phosphate-buffered saline (PBS). Recovery group (Group IV) included five rats that received fluoxetine as the group (II) then received no treatment till the end of the experiment. Samples from pars distalis were processed for light, electron microscopic examination, morphometrical and statistical analyses. RESULTS: In the fluoxetine-treated group, there was a disruption in cellular architecture, size, shape, and staining characteristics of pars distalis cells. The administration of ADSCs significantly improved the microscopic appearance of cells, while the recovery group showed some histological changes similar to the fluoxetine group. CONCLUSION: Fluoxetine induced various deleterious changes in the pars distalis of albino rats. These changes were almost corrected by the ADSCs treatment.

Neurological complications in Egyptian children with nephrotic syndrome.

AIM: This study aimed at describing the incidence, risk factors and outcomes for neurological manifestations in Egyptian children with nephrotic syndrome (NS) and determining correctable factors that could lower the risk for these complications. METHODS: The medical records of all children with NS who presented to Nephrology clinic, Ain Shams University Children hospital (a tertiary hospital) from April 2018 to April 2020 were reviewed retrospectively for the clinical progression of NS with special emphasis on neurological manifestations, contributory risk factors and outcomes. RESULTS: Among 67 children with NS, 13 children had neurological events. Seven patients had posterior reversible encephalopathy syndrome (PRES), four patients suffered from cerebral sinovenous thrombosis (CSVT) and two patients presented with arterial strokes. Hypertension was significantly higher in patients with NS and neurological manifestations (NS/N+) when compared to patients with NS without neurological manifestations (NS/N-) (76.9% vs. 40.7%; P = 0.019). NS/N+ group had significantly higher levels of triglycerides and cholesterol (209.7 ± 41.4 and 323.6 ± 40.7 in NS/N+ vs. 181.96 ± 31.8 and 243.8 ± 38.8 in NS/N-). Prothrombotic tendency was significantly higher in NS/N+ group as compared to NS/N- group. All patients recovered totally except patients with arterial strokes who had residual hemiparesis. CONCLUSION: Neurological complications in form of PRES, CSVT and arterial strokes were detected in children with NS. The outcome was favourable in most of the cases. Investment in parental education about the importance of follow up of blood pressure, dietary modification and good hydration could help in minimising the risk of patients with NS to develop neurological complications.