Adipose-Derived Stem Cells Enhance Axonal Regeneration through Cross-Facial Nerve Grafting in a Rat Model of Facial Paralysis.

BACKGROUND: Cross-face nerve grafting combined with functional muscle transplantation has become the standard in reconstructing an emotionally controlled smile in complete irreversible facial palsy. However, the efficacy of this procedure depends on the ability of regenerating axons to breach two nerve coaptations and reinnervate endplates in denervated muscle. The current study tested the hypothesis that adipose-derived stem cells would enhance axonal regeneration through a cross-facial nerve graft and thereby enhance recovery of the facial nerve function. METHODS: Twelve rats underwent transection of the right facial nerve, and cross-facial nerve grafting using the sciatic nerve as an interpositional graft, with coaptations to the ipsilateral and contralateral buccal branches, was carried out. Rats were divided equally into two groups: a grafted but nontreated control group and a grafted and adipose-derived stem cell-treated group. Three months after surgery, biometric and electrophysiologic assessments of vibrissae movements were performed. Histologically, the spectra of fiber density, myelin sheath thickness, fiber diameter, and g ratio of the nerve were analyzed. Immunohistochemical staining was performed for the evaluation of acetylcholine in the neuromuscular junctions. RESULTS: The data from the biometric and electrophysiologic analysis of vibrissae movements, immunohistochemical analysis, and histologic assessment of the nerve showed that adipose-derived stem cells significantly enhanced axonal regeneration through the graft. CONCLUSION: These observations suggest that adipose-derived stem cells could be a clinically translatable route toward new methods to enhance recovery after cross-facial nerve grafting.

The Notch pathway is a critical regulator of angiogenesis in a skin model of ischemia.

The Notch pathway is definitely required for normal vascular development. Although the contribution of Notch in postnatal angiogenesis is the focus of intense investigation, the implication of Notch in reparative neovascularization in the skin remains unexplored. In this study, we investigated Notch changes using a skin model of ischemia. Thirty Sprague-Dawley rats were divided into two groups. In the surgery group (n = 24), a caudally based dorsal skin flap was raised and sutured back into its initial position. In the control group, no surgical procedure was performed. Tissue biopsies were obtained at different time intervals. Tissue specimens were assessed for Delta-like ligand 4 (DLL4) and vascular endothelial growth factor (VEGF) gene expression by real-time polymerase chain reaction (PCR). Immunohistochemical staining was used for detection of DLL4 in tissue materials. Quantitative assessment of skin flap microvasculature was made. Compared with normoperfused tissue, VEGF and DLL4 expressions increased significantly (p < 0.01). Immunohistochemical analysis revealed weak and patchy expression of DLL4 in microvascular endothelial cells of normoperfused tissues. Conversely, DLL4 expression was upregulated in capillary endothelial cells after ischemia. In conclusion, in this study we have shown that the Notch ligand DLL4 is upregulated in skin tissue after ischemia. A deeper understanding of these fundamental principles will aid in the development of new avenues for the treatment of blood vessel-related skin pathologies.

Inhibition of the Notch Pathway Promotes Flap Survival by Inducing Functional Neoangiogenesis.

OBJECTIVE: The Notch pathway seems to function as an antiangiogenic factor, negatively regulating the sprouting effect of vascular endothelial growth factor (VEGF). This function is well defined in embryonic and tumor vasculature. However, little is known about its function in ischemia-induced angiogenesis. In the first part of this study, we investigated the role of Notch in reparative angiogenesis after ischemia. In the second part, we hypothesized that anti-Notch therapy will result in increased angiogenic sprouting. We analyzed the effect of Notch inhibition in the induction of angiogenic sprouting. METHODS: In the first part, we investigated the effect of ischemia on the Notch ligand delta-like ligand 4 (DLL4). Twenty rats were divided equally into 2 groups. In the surgery group, dorsal skin flap was used as model of ischemia. In the control group, no surgical procedure was performed. DLL4 and VEGF gene expressions were assessed. Immunohistochemical staining was used for detection of DLL4 in tissue materials. Plasma levels of VEGF and DLL4 were measured. In the second part, we investigated the effect of Notch inhibition using a gamma-secretase inhibitor (GSI) on inducing neoangiogenesis. Twenty rats were assigned to 2 equal groups. In all animals, dorsal skin flap was raised and sutured back into its bed. Animals in the GSI-treated group received GSI intravenously after surgery for 3 days. Saline was administered in the control group. Necrotic area measurements, microangiography, and histologic evaluations were performed to compare groups. RESULTS: In the first part, VEGF and DLL expressions increased in ischemic tissues (P < 0.01). Immunohistochemical analysis revealed that DLL4 expression was upregulated in capillary endothelial cells after ischemia. Plasma levels for VEGF and DLL4 were higher in the animals that underwent surgery (P < 0.01). In the second part, GSI treatment resulted in higher flap survival rates (P < 0.05). Microscopic analysis exhibited increase in the number of microvascular structures after GSI treatment (P < 0.05). Microangiographic evaluation showed that neovascularization increased in the GSI-applied flaps. CONCLUSIONS: We present an evidence for the importance of the Notch pathway in the regulation of ischemia-induced angiogenesis. Notch inhibition promotes flap survival by creating a neovasculature that has an increase in vascular density.

Comparison of Intraocular Pressure Measurements Between Goldmann Applanation Tonometry and Reichert 7 Noncontact Tonometry.

PURPOSE: The aim of this study was to compare the Reichert 7 (R7) noncontact tonometry with Goldmann applanation tonometry (GAT) and to determine the influence of central corneal thickness (CCT) in these measurements in the healthy population. DESIGN: A prospective cross-sectional study. METHODS: Intraocular pressure (IOP) of the right eyes of 120 patients was measured with GAT and R7. All patients were free of glaucoma. All the measurements were carried out between 7 AM and 9 AM The measurements with the R7 were taken in the automatic mode. After 15 minutes, IOP with GAT was measured followed by pachymetry. The R7 provided a Goldmann-correlated IOP (IOPg) and a corneal-compensated IOP (IOPcc). RESULTS: The mean age of the patients was 53.9±19.3 (range, 26 to 85 y). The male/female ratio was 0.9/1. When R7 measurements were compared with GAT measurements, R7 measurements (both IOPcc and IOPg) were significantly higher than GAT measurements (P≤0.001). Besides that, IOPcc was significantly higher than IOPg (P≤0.001). There was a significant positive linear relationship between IOPcc and GAT (r=0.761, P≤0.001), and similar relationship between IOPg and GAT (r(2)=0.739, P≤0.001). The mean CCT was 545.9±33.2 µm (range, 476 to 634 µm). A weak correlation was observed between CCT and GAT (r=0.196, P=0.032). There was a significant correlation between CCT and IOPg (r=0.283, P=0.02). The correlation between CCT and IOPcc was not statistically significant (r=0.123, P=0.179). CONCLUSIONS: IOP values of R7 are higher than GAT values. However, IOPg was observed more coherent to the GAT values than IOPcc. IOPcc should be an evaluation factor along with GAT or IOPg in glaucoma examination.

Consanguineous marriage and increased risk of idiopathic congenital talipes equinovarus: a case-control study in a rural area.

BACKGROUND: The purpose of this study is to evaluate if there is any relationship between consanguineous marriages and idiopathic congenital talipes equinovarus (CTEV). METHODS: A case-control study on CTEV screening was conducted in a rural eastern city of Turkey between 2009 and 2011 and a total of 28 cases (infants with idiopathic CTEV) and 575 controls (healthy infants) were recruited. Sociodemographic status of the infants, including gestational age and birth weights, maternal characteristics and, if any, the degree of consanguinity, were recorded. As an inclusion criterion, only singleton, full-term, live births were accepted. A backward stepwise logistic regression model was used to evaluate the relationship between idiopathic CTEV and parental consanguinity. Unadjusted and adjusted odds ratios (OR) with 95% confidence interval (CI) were calculated. RESULTS: Among maternal and infant characteristics, significant risk factors for idiopathic CTEV in the regression analysis were work status (employed), consanguineous marriage, sex (male), and gestational age (>42 wk). Babies born to first-cousin parents had >4 times the risk of idiopathic CTEV [OR, 4.138, (95% CI, 1.484, 11.538)] and the risk for those born to distant relatives was 2.9 times higher [OR, 2.941, (95% CI, 1.070, 8.087)] than for children of unrelated parents. CONCLUSIONS: Consanguineous marriage was significantly associated with an increased risk of idiopathic CTEV. This association remained significant even after adjusting for potential confounding variables. To obtain more accurate results, a population-based screening study with an increased number of cases and controls should be performed in future studies. LEVEL OF EVIDENCE: Case-control study investigating the effect of a patient characteristic on the outcome of disease (level-III).

Stereological volumetric evaluation of the cerebellum in benign paroxysmal positional vertigo.

OBJECTIVE: To evaluate cerebellar volume changes and the asymmetry of patients with benign paroxysmal positional vertigo (BPPV). METHODS: The cerebellar hemispheres` volumetric symmetry were evaluated using a stereological method on MR images. The study included 15 patients with BPPV, and 14 age-, and gender-matched control subjects. The cases were admitted to the Departments of Otolaryngology, Neurology, and Neurosurgery in the Faculty of Medicine, Kocatepe University, Afyonkarahisar, Turkey with the complaint of vertigo between January 2004 and December 2008. RESULTS: The right hemi cerebellum volumes of the subjects with BPPV and the controls were measured smaller than the left hemi cerebellar volumes, however, there was no statistically significant quantitative evidence detected in terms of cerebellar asymmetry between sagittal and axial plane estimates in the cases with vertigo. There was statistical significance between the right and left cerebellum in both the patient and control groups (p=0.023), however, the difference did not change according to gender. There were no statistically significant age and gender dependent cerebellar atrophy and asymmetry between BPPV and control subjects. CONCLUSION: There was no cerebellar atrophy and asymmetry between BPPV and age matched control groups. The stereological evaluation of hemi cerebellar symmetry and atrophy in humans is important for both clinicians and anatomists. The technique is simple, inexpensive, and reliable.

Evaluation of cerebellar and cerebral volume in migraine with aura: a stereological study.

Migraine is associated with an increased risk of deep white matter lesions and subclinical posterior circulation infarcts. A significant association between deep white matter hyperintensities and cerebral atrophy is true for various neurological diseases; it was not specifically proven in migraine. The aim of this study was to evaluate the cerebellar and cerebral volume and volume ratios for cerebellum using the Cavalieri principle. We also aimed to examine whether migraine with aura causes cerebellar and cerebral atrophy. Twenty three right-handed patients with migraine with aura diagnosed by means of the International Headache Society criteria and 24 age-matched subjects whose only health problem was headache due to rhinosinusitis and tension type headache were included in the study. Measurements of the cerebellar and cerebral volumes as well as cerebellar/cerebral volume ratios were made using Cavalieri's principle by utilizing the point-counting methods. There were no significant differences between the volumes of cerebrum, cerebellum, and the ratio of cerebellum to cerebrum for males (p = 0.05, p = 0.10, and p = 0.64, respectively) and for females (p = 0.18, p = 0.89, and p = 0.24, respectively). Our results suggest that patients with migraine with aura do not have a significant difference in cerebellar and cerebral volumes and cerebellar/cerebral volume ratios compared to the non-migraine group.

Effects of rosiglitazone on bone mineral density and remodelling parameters in Postmenopausal diabetic women: a 2-year follow-up study.

OBJECTIVE: To evaluate the effect of rosiglitazone on bone metabolism and bone density. DESIGN: An open-label, randomized, controlled trial of 24-month duration. Patients and measurements Obese, postmenopausal women with newly diagnosed diabetes were studied. Before and after the intervention, metabolic bone markers and bone density were assessed. RESULTS: Twenty-six patients received rosiglitazone (4 mg/day), and 23 remained on diet alone. Serum bone-specific alkaline phosphatase and osteocalcin levels decreased by 17% (P < 0.001 vs control group) and 26% (P < 0.01 vs control group), respectively, in the rosiglitazone group. There were no significant changes in the deoxypyridinoline levels between the two groups. Annual bone loss at the trochanter and at the lumbar spine associated with each year of rosiglitazone use was 2.56% (P = 0.01 vs control group) and 2.18% (P < 0.01 vs control group), respectively. Femoral neck and total hip bone density declined significantly in both groups (P < 0.01, and P = 0.01, respectively) but was not significantly different between the two groups. CONCLUSIONS: Rosiglitazone treatment adversely affects bone formation over a 2-year period. It increases bone loss at the lumbar spine and trochanter in postmenopausal, type 2 diabetic women. However, bone loss at the total hip did not differ with use of this agent.