Ischaemia-reperfusion injury of the peripheral nerve: An experimental study

Although the neuropathology of ischaemic fibre degeneration is relatively well known, its pathogenesis is poorly understood. One of the presumed mechanisms is oxidative stress, causing the breakdown of the blood-nerve barrier (BNB) and ending in lipid peroxidation. We evaluated the effect of ischaemia and reperfusion on the sciatic-tibial nerve of the rat and investigated the biochemical, pathological, and functional evidence of BNB disruption and lipid peroxidation. The distal portion and trifurcation of the sciatic nerve were rendered ischaemic by clamping the femoral vessels for 3 h and followed by varying durations of reperfusion. Reperfusion resulted in an increase in lipid peroxidation beginning from the first hour and increasing until the seventh day, followed by a gradual decline over the following weeks. Nerve oedema and ischaemic fibre degeneration (IFD) consistently became more severe and prominent with reperfusion, indicating that oxidative stress damages the BNB and causes IFD. Results of functional testing by the sciatic function index correlated with other parameters as walking track analysis results got worse as reperfusion periods increased. Impairment of walking patterns was more striking after the first day and continued up to the third week. These data indicate that severe ischaemia of the peripheral nerve results in reperfusion injury, functional impairment, and disruption of the BNB. Microvascular events, which may occur during reperfusion, may be important in amplifying the nerve fibre degeneration that initiated during ischaemia.     

Augmentation of Shoulder Contour Using a Calf Implant

Sprengel deformity is a rare orthopedic condition that is associated with functional and cosmetic impairment. Results of orthopedic procedures are usually inconsistent and cosmetic results are far from satisfactory in these patients. A silicone-gel-filled calf prosthesis was used to correct the shoulder contour in a patient with Sprengel deformity. Cosmetically the deformity can be restored by using a calf implant for patients in whom orthopedic procedures are not likely to yield a satisfactory outcome.     

Differential Interleukin-8 thresholds for chemotaxis and netosis in human neutrophils

In humans, IL-8 (CXCL8) is a key chemokine for chemotaxis of polymorphonuclear leukocytes and monocytes/macrophages when acting on CXCR1 and CXCR2. CXCL8 activity on neutrophils includes chemotaxis and eliciting the extrusion of neutrophil extracellular traps (NETs). In this study, we show that concentrations of IL-8 that induce NETosis surpass in at least one order of magnitude those required to elicit chemoattraction in human neutrophils. IL-8-induced NETosis was less dependent on G-proteins than migration, while extracellular Ca⁺² chelation similarly inhibited both processes. Reactive oxygen species (ROS) were more important for NETosis than for chemotaxis as evidenced by neutralization with N-acetyl -cysteine. Interestingly, selective blockade with anti-CXCR1 mAb inhibited NETosis much more readily than chemotaxis, while pharmacological inhibition of both CXCR1 and CXCR2, or selective inhibition for CXCR2 alone, similarly inhibited both functions. Together, these results propose a model according to which low concentrations of IL-8 in a gradient attract neutrophils to the inflammatory foci, while high receptor-saturating concentrations of IL-8 give rise to NETosis once leukocytes reach the core of the inflammatory insult.     

Affinin and hexahydroaffinin: Chemistry and toxicological profile

The present work aimed to determine the safety parameters of two new alkamides, affinin and hexahydroaffinin, with antinociceptive activity. To predict the preliminary acute toxicity, we used the acute and subchronic toxicity (50 mg/kg, orally [po]) in Swiss Webster mice. Genotoxicity assayed via analysis of cell micronuclei of the femoral bone marrow in mice; at the same time, metabolic parameters determined from peripheral blood samples. Furthermore, to discard the neuropharmacological effects, we assessed the ambulatory activity in mice to determine the possible effects in the central nervous system. Finally, we used capsaicin as a positive control of alkamides. According to our results, hexahydroaffinin (LD₅₀ ≥ 5,000 mg/kg, po) is significantly less noxious than affinin (LD₅₀ = 1,442.2 mg/kg, po) or capsaicin (LD₅₀ = 489.9 mg/kg, po). In subchronic administration, we did not observe any changes in hematological or biochemical parameters in any compound analyzed from peripheral blood samples. Finally, the data from the genotoxicity assay showed micronuclei formation in 28%, 5%, and 3% of mice in the capsaicin, affinin, and hexahydroaffinin groups, respectively. With the results obtained in the present investigation, we suggest that affinin and hexahydroaffinin are not only useful candidates for possible new drugs but also safe compounds.     

Effect of trapidil in ischemia/reperfusion injury of peripheral nerves

OBJECTIVE: Ischemia plays an important role in the development of pathological changes in nerve tissue, and restoration of blood flow results in injury (ischemia/reperfusion [I/R] injury) mediated by toxic oxygen free radicals. Trapidil is currently used as a coronary artery vasodilating agent and is also used for the prevention of ischemic symptoms of cerebral vasospasm. The purpose of this study was to determine the effects of trapidil on I/R injury and the ischemic tolerance of rat peripheral nerves. METHODS: Preischemia or prereperfusion administration of trapidil (8 mg/kg) was evaluated in the rat sciatic nerve I/R injury model. Nerve tissue samples from the I/R injury site were assayed for malondialdehyde (MDA), nitrites, and nitrates, as markers of I/R injury, and pathological changes were evaluated by electron microscopy. RESULTS: I/R resulted in an increase in MDA levels, which remained elevated for 2 weeks in control nerves. Rats that received trapidil before ischemia exhibited decreased MDA levels, and rats that received trapidil after the standard 3 hours of ischemia demonstrated increased tolerance to reperfusion, as reflected in significantly decreased MDA levels. Nitrite and nitrate levels in trapidil-treated rats were significantly higher than those in control animals. Histological evaluations of the sciatic nerve segments demonstrated that preischemia and postischemia trapidil treatments had a sparing effect against the myelin damage and axonal edema that are consistently noted in untreated ischemic reperfused nerves. CONCLUSION: The results confirm that pretreatment with trapidil before the ischemic insult or before reperfusion provides marked protection against I/R injury in peripheral nerves.     

Tourniquet application and epinephrine injection to penile skin: is it safe?

Although a tourniquet is frequently used in penile surgery there is still no consensus on safe application time. The aim of the present study is to investigate the effect of malondialdehyde (MDA) levels and histological changes in skin flaps after penile tourniquet application and epinephrine injection. A total of 36 male white New Zealand rabbits were randomly divided into six groups each containing six animals. A Mathieu-like flap was raised in all of the groups and a tourniquet was applied and the penis was subjected to ischemia for 10, 20 and 40 min in groups 1, 2 and 3, respectively. The flaps were then allowed to reperfuse for 5 min. Biopsies for MDA measurement were harvested in these groups. Subcutaneous 1/200,000 epinephrine was injected into penile skin in group 4 and 5 rabbits and biopsies for MDA measurement were harvested 10 and 40 min after injection. The control group was anesthetized without tourniquet usage or epinephrine injection. Specimens taken from the harvested flaps of all groups were submitted for histological evaluation. The mean MDA levels in all experimental groups were higher than in the control group and the difference was statistically significant. Edema, congestion and extravasation were observed in groups 1, 2 and 3. Minimal congestion and edema were observed in group 4 and severe edema and extravasation in group 5. Tourniquet usage for a duration of less than 10 min is clearly safer than prolonged usage. Epinephrine injection to penile skin may show a deleterious effect on wound healing.     

Familial aquagenic acrokeratoderma: case reports and review of the literature

In recent years, a number of authors have described the development of palmar or palmoplantar keratoderma after brief exposure to water. Herein, we report a father and son with this condition, which we prefer to call aquagenic acrokeratoderma. These cases are interesting because they mark the first documentation of this entity in males. Also, they provide further evidence of familial occurrence.     

Effects of obstructive jaundice on the peripheral nerve: an ultrastructural study in rats

Obstructive jaundice (OJ) and hepatic disorders have been shown to be associated with peripheral neuropathy in several clinical studies. The study evaluated the effect of OJ on the ultrastructure of the rat sciatic nerve. In the OJ group, jaundice was created by ligation of common bile duct in Wistar-Albino rats. In the sham-operated control group the same procedure was performed without ligation of the bile duct. On day 7, all rats were re-operated and sciatic nerves were explored to harvest 2-cm-long nerve segments for quantitative and qualitative histopathological analysis by light and electron microscopy. Bilirubin was measured on serum samples. Bilirubin levels were significantly higher in jaundiced rats compared with that of controls (8.46 +/- 0.45 vs. 0.80 +/- 0.14 mmol/l, means +/- SD, p < 0.01). Control nerves did not show anything other than the normal histology. In the OJ group, degenerative changes such as irregularities, thinning, ruffling and invaginations, irregularshaped bodies, vacuolizations and focal segmental demyelination were observed in the myelin sheath. Myelin clusters were noted in the axoplasm. A varying degree of swelling was noted in the nucleus and cytoplasm of the Schwann cells. Morphometric analysis of specimens obtained from sciatic nerves showed that myelin injury (370.9 +/- 51.3 vs. 11.6 +/- 0.5 axons), axonal edema (142.1 +/- 24.2 vs. 10.6 +/- 0.5 edematous axons) and Schwann cell degeneration (50.3 +/- 11.6 vs. 3.2 +/- 0.2 Schwann cells) was significantly higher in the jaundiced rats than in the control group (p < 0.01). The ultrastructural alterations spotted in the rat peripheral nerve were attributed to hyperbilirubinemia and increased concentrations of several neurotoxic substances released from the Kupffer cells in OJ. Neuropathy in jaundiced patients seems to result from accompanying degenerative changes in the peripheral nervous system. However, the exact nature and initiating factors of this nerve injury remains to be unveiled.