The role of the adipose tissue-derived mesenchymal stem cells enriched with melatonin in pancreatic cellular regeneration.

BACKGROUND: Adipose tissue-derived mesenchymal stem cells (AD-MSCs) were proved to differentiate into insulin-producing cells (IPCs), but the amount of insulin secreted was relatively low compared to the insulin secreted by mature pancreatic islets. Enrichment of MSCs culture with melatonin (MT) was found to promote cartilage matrix synthesis, osteogenic and neuronal differentiation. Therefore, the present study was conducted to evaluate the potential role of MT pre-treated AD-MSCs in enhancing the treatment and regeneration of the islet cells of Langerhans in rats with diabetes induced by streptozotocin (STZ). MATERIALS AND METHODS: Forty adult male Sprague Dawley albino rats were divided equally into groups; group I (control group), group II (STZ group), group III (STZ + AD-MSCs) and group IV (STZ+MT pre-treated AD-MSCs). Biochemical studies were implemented including measurements of the body weight, fasting blood glucose and serum insulin levels, Interleukin 17 (IL-17) and IL-10. Samples of the pancreas were taken and prepared for light, fluorescent microscopic examination, proliferating cell nuclear antigen and caspase-3 immunohistochemical studies and histomorphometric analysis. RESULTS: The present study confirmed the regenerative and therapeutic effects of AD-MSCs on the pancreatic cells. Concomitant supply of MT to the culture of AD-MSCs, in group IV, was shown to retain the normal architecture of the islet cells of Langerhans. They appeared well-defined and lightly stained, surrounded by classical pancreatic acini and contained a large number of islet cells with vesicular nuclei and prominent nucleoli. Improvement of all the biochemical parameters, in the same group, was demonstrated by increased body weight and serum insulin levels with a decrease in the fasting blood glucose levels. Significant decrease in the pro-inflammatory cytokine; IL-17 and increase in the anti-inflammatory cytokine; IL-10, compared to the STZ group, were also discovered. Significant increase in the proliferating cell nuclear antigen proliferation index, decrease in caspase-3 and increase in PKH26 labelled MSCs area per cent was recorded in the group of AD-MSCs enriched with MT compared to the group of AD-MSCs without MT. CONCLUSIONS: The present study confirmed the potential therapeutic and protective role of MT pre-treated AD-MSCs against the STZ-induced pancreatic islet cells damage. Further studies are recommended to investigate the efficacy of MT and AD-MSCs over longer experimental durations.

Effect of valproic acid administration during pregnancy on postnatal development of cerebellar cortex and the possible protective role of folic acid.

BACKGROUND: Valproic acid (VPA), one of the most important antiepileptic drugs, proved to be inevitable for epileptic pregnant women to limit the hazards of convulsions on the foetuses and mothers. Periconceptional folic acid supple-mentation was investigated to protect against several birth defects. However, its role against VPA cerebellar toxicity was not properly investigated. The present study was conducted to evaluate the protective effect of folic acid against VPA cerebellar neurotoxicity. MATERIALS AND METHODS: Twenty-four pregnant female albino rats were divided into three groups; group I (control group, did not receive any drugs), group II (given VPA at a dose of 50 mg/kg body weight once daily) and group III (given the same dose of VPA and 400 µg/kg of body weight folic acid once daily). Ten male offspring from each group were sacrificed at two ages: at 2 and 12 weeks after birth. Samples of cerebellar cortex were taken and prepared for light, electron microscopic examination, glial fibrillary acidic protein (GFAP) immunohistochemical study and histomorphometric analysis. RESULTS: The present study confirmed the neurotoxic effect of prenatal VPA on the cerebellar cortex, especially on Purkinje cells. The cells appeared shrunken, reduced in density, disorganised and surrounded by empty haloes. Nuclear damage and axon degeneration in the form of vacuolation, loss of organelles and absence of neurofilaments with myelin sheath depletion were detected. Concomitant supply of folic acid was shown to retain the normal architecture of Purkinje cells with their axons and nuclei. In many animals receiving folic acid, the thickness of all layers of the cortex increased up to that of the control groups, after being markedly reduced in VPA-treated groups. GFAP immunoreaction was also improved against the strong positive gliosis detected in VPA-treated groups. CONCLUSIONS: The present study confirmed the protective role of folic acid against the cerebellar neurotoxic effects of VPA prenatal exposure. It is recommended that folic acid supplements should be given to every epileptic pregnant mother treated with VPA. (Folia Morphol 2018; 77, 2: 201-209).

The relationship between the dimensions of the internal auditory canal and the anomalies of the vestibulocochlear nerve.

BACKGROUND: Internal auditory canal (IAC) stenosis and vestibulocochlear nerve (VCN) abnormalities have been reported to be associated with sensorineural hearing loss. Previous studies classified the normal dimensions of the IAC and its anomalies with no consideration of the VCN. Other studies categorised the VCN development in only stenotic canals. In the present study, an anatomical classification of the normal dimensions of the IAC and its anomalies and their association with malformations of the VCN and its subdivisions were described. MATERIALS AND METHODS: Retrospective review was undertaken for children ranged from 1 to 10 years. A total of 764 canals were investigated for pre-operative assessment of cochlear implantation. Other 100 canals of normal hearing ears were included as the control group. The maximum anteroposterior diameter, considered the width of the canal, was measured in axial plane and the length of the canal was identified in coronal plane. The canals were categorised normal: if they are from 3 to 8 mm, patulous: if they are more than 8 mm, stenotic: if they are less than 3 mm and atretic if absent, using multislice computed tomography. The VCN trunks and their subdivisions were investigated using magnetic resonance imaging. RESULTS: Internal auditory canals were found normal in 66% with a mean width: 5.27 ± ± 0.68, patulous in 17% with a mean width 113% more than that of the control group (p = 0.000), stenotic in 13% with a mean width 73% less as compared to that of the control group (p = 0.000) and atretic in 4% of the experimental canals. The VCN trunks were found normal with well-developed subdivisions in 77.8% of the normal canals, 98.4% of the patulous canals, and 19.2% of the stenotic canals. The VCN trunks were normal with hypoplastic subdivisions in 11.3% of the normal canals, 1.6% in the patulous canals, and 61.6% in the stenotic canals with a mean width 52% less than that of the normal trunk with developed subdivisions. Hypoplastic VCN trunks with absent subdivisions were reported in 7.3% of the normal canals, 11.1% of the stenotic canals and in 3.2% of the atretic canals. The VCN trunks were not found in 3.6% of the normal canals, in 8.1% of the stenotic canals and in 96.8% of the atretic canals. CONCLUSIONS: Internal auditory canal formation was dependent on the process of development and growth of the eighth cranial nerve and its subdivisions that greatly affected the completion of IAC canalisation. This paper could serve as a reference providing a quantitative classification of the relationship between the dimensions of the IAC and the development of the VCN trunk and its subdivisions.