Melatonin ameliorates amyloid beta‐induced memory deficits,tau hyperphosphorylation and neurodegeneration via PI3/Akt/GSk3β pathway in the mouse hippocampus

Alzheimer's disease (AD) is the most prevalent age‐related neurodegenerative disease, pathologically characterized by the accumulation of amyloid beta (Aβ) aggregation in the brain, and is considered to be the primary cause of cognitive dysfunction. Aβ aggregates lead to synaptic disorder, tau hyperphosphorylation, and neurodegeneration. In this study, the underlying neuroprotective mechanism of melatonin against Aβ_1‐42‐induced neurotoxicity was investigated in the mice hippocampus. Intracerebroventricular (i.c.v.) Aβ_1‐42‐injection triggered memory impairment, synaptic disorder, hyperphosphorylation of tau protein, and neurodegeneration in the mice hippocampus. After 24 hr of Aβ_1‐42 injection, the mice were treated with melatonin (10 mg/kg, intraperitonially) for 3 wks, reversed the Aβ_1‐42‐induced synaptic disorder via increasing the level of presyanptic (Synaptophysin and SNAP‐25) and postsynaptic protein [PSD95, p‐GluR1 (Ser845), SNAP23, and p‐CREB (Ser133)], respectively, and attenuated the Aβ_1‐42‐induced memory impairment. Chronic melatonin treatment attenuated the hyperphosphorylation of tau protein via PI3K/Akt/GSK3β signaling by activating the p‐PI3K, p‐Akt (Ser 473) and p‐GSK3β (Ser9) in the Aβ_1‐42‐treated mice. Furthermore, melatonin decreased Aβ_1‐42‐induced apoptosis through decreasing the overexpression of caspase‐9, caspase‐3, and PARP‐1 level. Additionally, the evaluation of immunohistochemical analysis of caspase‐3, Fluorojade‐B, and Nissl staining indicated that melatonin prevented neurodegeneration in Aβ_1‐42‐treated mice. Our results demonstrated that melatonin has neuroprotective effect against Aβ_1‐42‐induced neurotoxicity through decreasing memory impairment, synaptic disorder, tau hyperphosphorylation, and neurodegeneration via PI3K/Akt/GSK3β signaling in the Aβ_1‐42‐treated mouse model of AD. On the basis of these results, we suggest that melatonin could be an effective, promising, and safe neuroprotective candidate for the treatment of progressive neurodegenerative disorders, such as AD.     

Safety of pregabalin among hemodialysis patients suffering from uremic pruritus

Objectives: The aim of this study was to assess the safety and probability of adverse events associated with the use of 75 mg pregabalin post hemodialysis (pHD) among patients with UP. Methods: A cross-sectional study done among the hemodialysis patients suffering from uremic pruritus (UP) Aljaber Kidney Center (AJKC), Al-Ahsa, Eastern Province, Saudi Arabia. Assessment for the safety profile of pregabalin was done using Naranjo’s algorithm. A predictive model was developed using binary multiple logistic regression to explore association of patients’ demographics and risk factors with the occurrence of AEs. Throughout statistical significance level was considered significant at 0.05. Key findings: Assessment of safety of pregabalin revealed that somnolence and dizziness were the two frequent adverse events followed by constipation, weight gain and edema. However, it was noticed that female patients aged less than 50 years were found to be at a higher risk in comparison with men. Moreover, those patients having one comorbid complication (i.e. hypertension or diabetes mellitus alone) were at a higher risk of somnolence, weight gain and dry mouth. Conclusion: Naranjo’s quantification for the possibility and probability of adverse events reflect that all the events were probable. Age, gender and comorbid medical conditions are some of the factors that might have clinical association with the occurrence of the AEs.     

Anatomical variations of the frontal and supraorbital transcranial passages

In this study, 500 frontal and supraorbital transcranial passages were studied in 50 cadavers and 200 crania of 500 samples. One hundred six specimens had a frontal foramen (notch), and all the samples had a supraorbital foramen (notch). The frontal passage was a foramen in 7 samples and a notch in 99 samples. As for the supraorbital passage, it was found as a foramen in 133 of specimens and as a notch in 358 of specimens. In 9 of the specimens, there were double notches or foramina. The distances from the foramina (notches) to angulus oculi medialis were measured in the cadavers. The average distance from the angulus oculi medialis to the frontal foramen (notch) was 4.50 mm, and the average distance to the supraorbital foramen (notch) was 9.87 mm. The distances from the foramina (notches) to the midline were measured in the crania. The average distances from the midline to the frontal foramen (notch) and the supraorbital foramen (notch) were 20.24 mm and 25.23 mm, respectively. The average distance between the frontal foramen (notch) and supraorbital foramen (notch) was 5.37 mm in cadavers and 4.99 mm in crania. In 200 crania, the distances of the frontal and supraorbital transcranial passages to the midline were measured. Types of these passages were also evaluated, and frequencies were calculated. Measurements were made using a digital compass, and the student t test was used in the statistical evaluation of results.     

Cancellous bone grafting in alveolar cleft repair: new experience

Bone grafting plays an important role in the dental rehabilitation of patients with alveolar cleft. During the period between 1993 and 2001, 12 patients with alveolar clefts have been treated in our clinic. Cancellous iliac bone grafts were used in all 12 patients. Seven patients had left and five patients had right complete unilateral cleft lip and complete cleft palate operations. All patients had palatal fistulas. The ages were between 4 and 18 years (mean age, 10.5 y). Seven of them were female (58.4%) and 5 were male (41.6%). All the cancellous grafts survived. Enough filling and the closure of the fistulas were achieved except one patient who had wound dehiscence and partial graft loss. The patients experienced a limp for 2 days (mean time) because of the donor site. This surgical procedure achieves successful results if it is used with the proper indication in suitable cases.