Effect of lymphedema on the recovery of fractures.

BACKGROUND: Lymphedema delays the healing of any wound by negatively affecting its inflammatory period. Whether it affects bone healing in a similar negative manner is unknown. Therefore, we experimentally investigated the effect of lymphedema on fracture recovery. METHODS: We used thirty 200- to 250-g Sprague-Dawley rats for the experiment. The rats were randomly divided into two groups of 15 rats each for the experimental lymphedema and control groups. Lymphedema development was confirmed by measuring the circumference and diameter of the extremities together with lymphoscintigraphy. Twenty days after the development of lymphedema, a fracture model was created in both groups in the right tibia with mid-diaphyseal osteotomy and fixing with an intramedullary Kirschner wire. After 6 weeks, all rats were sacrificed and the callus tissue that formed along the osteotomy was compared between groups with respect to radiographic, histological, and biomechanical characteristics. RESULTS: The three-point bending test yielded an average stiffness value of 1227 N/mm (n = 6) in the control group and 284 N/mm (n = 7) in the experimental lymphedema group (P < 0.05). At the end of week 6, radiographic evaluation showed that solid knitting was obtained in the control group, whereas in the lymphedema group delayed or no knitting was observed. In the control group, histological investigation revealed normal callus morphology. Trabecular bone was normal and osteoblast and osteoclast activity was clearly evident. The bone was stained homogeneously with hematoxylin and eosin, and ossification was within normal limits. In the lymphedema group, however, the histological appearance was mostly that of scar tissue. In addition, osteoblast and osteoclast activity was much less visible or absent. CONCLUSIONS: Lymphedema negatively affected bone healing in rats. However, the mechanism of this negative effect and its occurrence in humans are still unknown. Further experimental and clinical studies are needed to support and extend our findings.

Effects of gabexate mesilate on ischemia-reperfusion-induced testicular injury in rats.

The aim of this study was to determine the effects of a synthetic serine protease inhibitor, gabexate mesilate (GM), in rats with ischemia-reperfusion (I-R) damage due to unilateral testicular torsion. Thirty male Sprague-Dawley rats were separated into three groups, each containing ten rats. A sham operation was performed in group 1 (control). In group 2 (I-R/untreated), 1 h detorsion of the testis was performed after 6 h of unilateral testicular torsion. In group 3 (I-R/GM), after performing the same surgical procedures as in group II, gabexate mesilate was given intravenously. In all experimental rats, ipsilateral orchiectomies were performed for histological examination and measuring the tissue levels of malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px). MDA values and the testicular injury score decreased and SOD, CAT and GSH-Px values increased in the GM-treated group compared to the I-R/untreated group. The Tc-99m pertechnetate uptake ratio and the perfusion index were significantly decreased in the group 2 compared to the group 1 and 3 rats. In group 3, these values were significantly increased compared to group 2. Most of the specimens in the GM-treated group showed grade-I testicular injury. However, the injuries in the I-R/untreated rats varied between grade-III and grade-IV. The results of this study show that GM may play a role in reducing the injury caused by I-R.

The effect of celecoxib, a selective COX-2 inhibitor, on liver ischemia/reperfusion-induced oxidative stress in rats.

This study examined the effects of celecoxib on hepatic ischemia/reperfusion (I/R) injury in rats. A total of 40 male Sprague-Dawley rats weighing 190-210g were randomized into 4 groups of 10: (1) controls: data from unmanipulated animals; (2) sham group: rats subjected to the surgical procedure, except for liver I/R, and given saline; (3) I/R group: rats that underwent liver ischemia for 1h followed by reperfusion for 45min; (4) I-R/Celecoxib group: rats pretreated with celecoxib (3mgkg(-1), i.p.) 40min before liver I/R. Tc-99m sulfur colloid images were used to measure the uptake ratio and perfusion index. Liver tissues were taken to determine SOD, CAT, GSH-Px, and MDA levels and for biochemical and histological evaluation. The plasma ALT, AST, GGT, and LDH activities were higher in group 3 than in group 4. The uptake ratio was significantly lower in group 3 compared to groups 1, 2, and 4. In addition, in group 4, the uptake ratio and perfusion index were also significantly higher compared to group 3. MDA values and the hepatic injury score decreased, while the SOD, CAT, and GSH-Px values increased in group 4 compared to group 3. In group 3, hepatocytes were swollen with marked vacuolization. Group 4 showed well preserved liver parenchyma with hepatocytes arranged radially around the central vein; there were regular sinusoidal structures with normal morphology without any signs of congestion. We showed that celecoxib has beneficial effects in hepatic I/R injury and may protect the liver.

The effects of mibefradil, a T-type Ca2+ channels blocker, on the renal dysfunction and injury caused by ischemia-reperfusion of the rat kidney.

This study was designed to determine the possible protective effect of mibefradil on renal ischemia/reperfusion (I/R) injury. Unilaterally nephrectomized Sprague-Dawley rats were subjected to 60 min of left renal ischemia followed by 45 min of reperfusion. Group 1 were sham-operated animals; group 2, I/R/untreated animals; and group III, I/R/mibefradil-treated animals. A 99mTc-DTPA scan was taken to measure kidney perfusion, glomerular filtration rate (GFR) and the time elapsed from isotope injection to the maximum of the curve. Serum creatinine, blood urea nitrogen (BUN), kidney malondialdehyde (MDA) level were determined as well as examining the kidneys histologically. Treatment of rats with mibefradil produced a significant reduction in the serum levels of creatinine and urea nitrogen. T-max-sec (renal perfusion) was significantly lower in group 2 than in groups 1 and 3. The GFR was markedly greater in group 3 than in the group 2. The Tmax-min was significantly greater in group 2 than in group 3. Mibefradil treatment significantly decreased the MDA levels. The histopathologic score was significantly less in the group 3 rats compared with group 2 rats. Kidneys of group 2 rats showed tubular cell swelling, cellular vacuolization, pyknotic nuclei, medullary congestion, and moderate to severe necrosis. Treatment with mibefradil preserved the normal morphology of the kidney and shows normal glomeruli and slight edema of the tubular cells. These findings suggest that mibefradil reduces the renal dysfunction associated with I/R of the kidney.