Positive effect of ulnar nerve fascicle transfer to musculocutaneous nerve seeded with allogeneic adipose tissue derived stem cells on nerve regeneration for repairing upper brachial plexus injury in a rat model: A preliminary study.

BACKGROUND: Traumatic peripheral nerve injury, with an annual incidence reported to be approximately 13-23 per 100,000 people, is a serious clinical condition that can often lead to significant functional impairment and permanent disability. Although nerve transfer has become increasingly popular in the treatment of brachial plexus injuries, satisfactory results cannot be obtained even with total nerve root transfer, especially after serious injuries. To overcome this problem, we hypothesize that the application of stem cells in conjunction with nerve transfer procedures may be a viable alternative to more aggressive treatments that do not result in adequate improvement. Similarly, some preliminary studies have shown that adipose stem cells combined with acellular nerve allograft provide promising results in the repair of brachial plexus injury. The purpose of this study was to assess the efficacy of combining adipose-derived stem cells with nerve transfer procedure in a rat brachial plexus injury model. METHODS: Twenty female Wistar rats weighing 300-350 g and aged 8-10 weeks were randomly divided into two groups: a nerve transfer group (NT group) and a nerve transfer combined adipose stem cell group (NT and ASC group). The upper brachial plexus injury model was established by gently avulsing the C5-C6 roots from the spinal cord with microforceps. A nerve transfer from the ulnar nerve to the musculocutaneous nerve (Oberlin procedure) was performed with or without seeded allogeneic adipose tissue-derived stem cells. Adipose tissue-derived stem cells at a rate of 2 × 106 cells were injected locally to the surface of the nerve transfer area with a 23-gauge needle. Immunohistochemistry (S100 and PGP 9.5 antibodies) and electrophysiological data were used to evaluate the effect of nerve repair 12 weeks after surgery. RESULTS: The mean latency was significantly longer in the NT group (2.0 ± 0.0 ms, 95% CI: 1.96-2.06) than in the NT and ASC group (1.7 ± 0.0 ms, 95% CI: 1.7-1.7) (p < .001). The mean peak value was higher in the NT group (1.7 ± 0.0 mV, 95% CI: 1.7-1.7) than in the NT and ASC group (1.7 ± 0.3 mV, 95% CI: 1.6-1.9) with no significant difference (p = .61). Although S100 and PGP 9.5 positive areas were observed in higher amounts in the NT and ASC group compared to the NT group, the differences were not statistically significant (p = .26 and .08, respectively). CONCLUSIONS: This study conducted on rats provides preliminary evidence that adipose-derived stem cells may have a positive effect on nerve transfer for the treatment of brachial plexus injury. Further studies with larger sample sizes and longer follow-up periods are needed to confirm these findings.

Impact of Smoking on the Ocular Surface, Tear Function, and Tear Osmolarity.

PURPOSE: This study evaluated the effects of cigarette smoking on the ocular surface, tear function, and tear osmolarity. MATERIALS AND METHODS: A total of 50 smokers with at least 5 years of heavy smoking (defined as 1 pack/day) and 51 nonsmoking, healthy individuals were enrolled. Tear osmolarity was measured with an osmometer (TearLab™ Osmolarity System). Ocular surface examinations involved corneal fluorescein staining, measurement of the tear film breakup time (TBUT), the Schirmer 1 test, measurement of corneal sensitivity with a Cochet-Bonnet esthesiometer, and conjunctival impression cytology. Dry eye symptoms were scored using the Ocular Surface Disease Index (OSDI) questionnaire. The results were compared with those from an age and sex-matched control group. The Chi-squared and independent sample t-tests were used for statistical analyses. RESULTS: The smokers had significantly higher tear osmolarity values (305.38 ± 9.81 vs. 301.14 ± 7.04 mOsm/L; p = 0.014) and OSDI scores (34.13 ± 16.58 vs. 18.09 ± 9.61; p < 0.001) than the healthy controls. However, the TBUT, corneal sensitivity, and goblet cell density were significantly lower in smokers compared to healthy controls, but the fluorescein staining and Schirmer 1 test results were not statistically different between the smokers and controls. CONCLUSION: Smoking results in increased osmolarity of the tear film, which can damage the ocular surface and tear function.

Neuroprotective effects of sildenafil in experimental spinal cord injury in rabbits.

Neuroprotective agents such as methylprednisolone and sildenafil may limit damage after spinal cord injury. We evaluated the effects of methylprednisolone and sildenafil on biochemical and histologic changes after spinal cord injury in a rabbit model. Female New Zealand rabbits (32 rabbits) were allocated to 4 equal groups: laminectomy only (sham control) or laminectomy and spinal trauma with no other treatment (trauma control) or treatment with either methylprednisolone or sildenafil. Gelsolin and caspase-3 levels in cerebrospinal fluid and plasma were determined, and spinal cord histology was evaluated at 24 hours after trauma. There were no differences in mean cerebrospinal fluid or plasma levels of caspase-3 between the groups or within the groups from 0 to 24 hours after injury. From 0 to 24 hours after trauma, mean cerebrospinal fluid gelsolin levels significantly increased in the sildenafil group and decreased in the sham control and the trauma control groups. Mean plasma gelsolin level was significantly higher at 8 and 24 hours after trauma in the sildenafil than other groups. Histologic examination indicated that general structural integrity was better in the methylprednisolone in comparison with the trauma control group. General structural integrity, leptomeninges, white and grey matter hematomas, and necrosis were significantly improved in the sildenafil compared with the trauma control group. Caspase-3 levels in the cerebrospinal fluid and blood were not increased but gelsolin levels were decreased after spinal cord injury in trauma control rabbits. Sildenafil caused an increase in gelsolin levels and may be more effective than methylprednisolone at decreasing secondary damage to the spinal cord. 

Antiangiogenic effect of itraconazole on corneal neovascularization: a pilot experimental investigation.

PURPOSE: To investigate the antiangiogenic effect of itraconazole for the prevention of experimentally induced corneal neovascularization and whether the efficacy depends on the route of administration. MATERIALS AND METHODS: Thirty-six rats were randomly divided into 6 groups with 6 rats in each group. Chemical cauterization of the cornea was performed using silver nitrate/potassium nitrate sticks, and the rats were subsequently treated daily with topical (10 mg/ml), subconjunctival (10 mg/ml) or intraperitoneal (19 mg/kg) itraconazole for 7 days. Control rats received topical, subconjunctival or intraperitoneal 0.9% saline. On the 8th day of the experiment, the rat corneas were photographed to determine the percentage area of the cornea covered by neovascularization. The maximum density of corneal neovascularization was determined by microscopy. RESULTS: The median percentage of corneal neovascularization for group 1 was 31.5% (95% confidence interval, 27.5-35.5%); in group 3, it was 32% (23.5-39.8%); in group 5, it was 47% (36.3-60.0%). The percentages of corneal neovascularization in groups 2, 4 and 6 (the control groups) were 70% (95% confidence interval, 60.7-77.3%), 69% (63.0-77.7%) and 68% (56.5-78.5%), respectively. The area of neovascularization was smaller after itraconazole treatment as compared to saline treatment. Further, the area of neovascularization was smaller after topical and subconjunctival administration than after intraperitoneal administration. Histological evaluation of the corneas showed the most extensive corneal neovascularization in the control group. No local or systemic adverse effects were seen from either treatment group. CONCLUSION: Itraconazole reduces corneal neovascularization shortly after chemical burn. However, a larger experimental study is necessary to confirm the data of this investigation.