Effect of the Position of Immobilization Upon the Tensile Properties in Injured Achilles Tendon of Rat

OBJECTIVE: To examine the effect of the posture of immobilization upon the tensile properties in injured Achilles tendon of rat for an initial period of immobilization. METHODS: Forty-two Sprague-Dawley rats were used in the present study. Eighteen rats received a total tenotomy of the right Achilles tendon to mimic total rupture and were divided into three groups comprising of 6 rats each. Ankles of group A were immobilized at 60degrees of plantarflexion. Ankles of group B were immobilized at neutral position. Whereas, those of group C were immobilized at 60degrees of dorsiflexion. Other 18 rats received hemitenotomy to mimic partial rupture and were divided into three groups. The remaining 6 rats were kept free as control. After 14 days, we dissected the tendons and analyzed maximum force, stiffness, and energy uptake during pulling of the tendons until they ruptured. The tendons of 6 rats in each group and control were reserved for histology. Picrosirius staining was done for the analysis of collagen organization. RESULTS: In total tenotomy, tensile properties were significantly different between the control and the intervention groups (p0.05). In partial tenotomy, tensile properties were significantly different between the control and the intervention groups (p<0.05). Group C showed significantly higher value than other intervention groups in terms of maximum force and energy uptake (p<0.05). The semiquantitative histologic grading scores were assigned for collagen organization. The scores for dorsiflexion posture were higher than the ones for plantarflexion. CONCLUSION: Dorsiflexion posture in partial ruptured Achilles tendon showed better functional recovery than other immobilized postures. In total ruptured case, the tensile properties showed increasing tendency in dorsiflexion posture.

Pain modality and spinal glia expression by streptozotocin induced diabetic peripheral neuropathy in rats / 한국실험동물학회지

Pain symptoms are a common complication of diabetic peripheral neuropathy or an inflammatory condition. In the most experiments, only one or two evident pain modalities are observed at diabetic peripheral neuropathy according to experimental conditions. Following diabetic peripheral neuropathy or inflammation, spinal glial activation may be considered as an important mediator in the development of pain. For this reason, the present study was aimed to address the induction of pain modalities and spinal glial expression after streptozotocin injection as compared with that of zymosan inflammation in the rat. Evaluation of pain behavior by either thermal or mechanical stimuli was performed at 3 weeks or 5 hours after either intravenous streptozotocin or zymosan. Degrees of pain were divided into 4 groups: severe, moderate, mild, and non-pain induction. On the mechanical allodynia test, zymosan evoked predominantly a severe type of pain, whereas streptozotocin induced a weak degree of pain (severe+moderate: 57.1%). Although zymosan did not evoke cold allodynia, streptozotocin evoked stronger pain behavior, compared with zymosan (severe+moderate: 50.0%). On the other hand, the high incidence of thermal hyperalgesia (severe+moderate: 90.0%) and mechanical hyperalgesia (severe+moderate: 85.7%) by streptozotocin was observed, as similar to that of zymosan. In the spinal cord, the increase of microglia and astrocyte was evident by streptozotocin, only microglia was activated by zymosan. Therefore, it is recommended that the selection of mechanical and thermal hyperalgesia is suitable for the evaluation of streptozotocin induced diabetic peripheral neuropathy. Moreover, spinal glial activation may be considered an important factor.

Sigma-1 Receptor Antagonist BD1047 Reduces Allodynia and Spinal ERK Phosphorylation Following Chronic Compression of Dorsal Root Ganglion in Rats

Many therapeutic roles have been proposed for sigma-1 receptor (Sig-1R), but the involvement of Sig-1R in neuropathic pain has currently not been well explored. The present study aimed to evaluate the anti-nociceptive effect of Sig-1R antagonist (BD1047) in a rat model of chronic compression of the dorsal root ganglion (CCD), which is a model of human foraminal stenosis and radicular pain. When stainless steel rods were inserted into the intervertebral foramen of lumbar vertebrae 4 and 5, the CCD developed reliable mechanical (from 3 day) and cold allodynia (from 1 day) as compared with the sham operation group. The spinal expressions of Sig-1R and phosphorylation of extracellular signal-regulated kinase (pERK) were significantly increased from day 3 to day 14 after CCD surgery, as is consistent with the manifestation of allodynia. The BD 1047 (10, 30, 100 mg/kg) administered on postoperative days 0~5 dose-dependently suppressed both the induction of allodynia and the elevation of the spinal pERK expression in a manner comparable with that of gabapentin (100 mg/kg). At 7 days post-CCD surgery, BD1047 (10, 30, 100 mg/kg) administration also produced anti-nociceptive effects on the mechanical and cold allodynia similar with those of gabapentin (100 mg/kg). Therefore, this data suggested that Sig-1R may play an important role in both the development and maintenance of CCD-induced neuropathy.

An Improved Method for Intrathecal Catheterization in the Rat / 한국실험동물학회지

Catheterization of the subarachnoid space provides a useful tool to deliver drugs to spinal cord in rat. However, the passage of a long intrathecal catheter inserted via the cisterna magnum to lumbar spinal levels increases the risk of spinal cord trauma and the mislocation of catether into other places. Thus, present study was aimed to introduce direct subarachnoid catheterization of the rat lumbar spinal cord with novel shape of catheter. An intrathecal PE-10 catheter was fabricated with coil (four-time helix with 2 mm diameter) on either end and attached small silicon beads on both end of the coil. Using the silicon bead at insertion part as an anchorage, the catheter was advanced into the subarachnoid space until the silicon bead was embedded on a drilled hole over interspinous space between L4 and L5 vertebra. And then, silicon bead was tightly attached by surgical glue and dental resin with vertebra. Using the other side of silicon bead, catheter was tightly suturing with muscle layer. Finally, external portion of the catheter was placed into stainless steel protector on neck to reduce the damage by rat. Following this catheterization, it is not significantly affect the general physiology (i.e. motor function, weight gain and mechanical allodynia) of the rat without catheter loss over 2 weeks. Moreover, intrathecal injection either fluorescent dye or lidocaine further confirmed that drug diffusion site was appropriated for intended target.

The Antinociceptive Effect of Sigma-1 Receptor Antagonist, BD1047, in a Capsaicin Induced Headache Model in Rats

Intracranial headaches, including migraines, are mediated by nociceptive activation of the trigeminal nucleus caudalis (TNC), but the precise mechanisms are poorly understood. We previously demonstrated that selective blockage of spinal sigma-1 receptors (Sig-1R) produces a prominent antinociceptive effect in several types of pain models. This study evaluates whether the Sig-1R antagonist (BD1047) has an antinociceptive effect on capsaicin (a potent C-fiber activator) induced headache models in rats. Intracisternal infusion of capsaicin evoked pain behavior (face grooming), which was significantly attenuated by BD1047 pretreatment. BD1047 consistently reduced capsaicin-induced Fos-like immunoreactivity (Fos-LI), a neuronal activator, in the TNC in a dose-dependent manner. Moreover, capsaicin-induced phosphorylation of N-methyl-D-aspartate receptor subunit 1 was reversed by BD1047 pretreatment in the TNC. These results indicate that the Sig-1R antagonist has an inhibitory effect on nociceptive activation of the TNC in the capsaicin-induced headache animal model.

The Effect on Fos Expression in Rat Spinal Cord following Stimulation to Dorsal Root Ganglion by Pulsed Radiofrequency

OBJECTIVE: To reconfirm the relationship between the Fos expression and the pulsed radiofrequency which very few articles have reported. METHOD: Thirty-four male Sprague-Dawely rats were enrolled: 8 for lumbar 3rd dorsal root ganglion (DRG) stimulation, 4 for L3 and L4 DRGs, 5 for C5 and C6 DRGs, 8 for sham L3 DRGs, 5 for sham L3 and L4 DRGs, and 4 for sham C5 and C6 DRGs. Without laminectomy, each lumbar DRG was stimulated with PRF for 2 minutes 2 times with 42 degrees C. Sham group was stimulated with PRF electrode but without any stimulation. Three hours after the stimulations, spinal cord was thin sectioned for immunohistochemistry and Fos expression was calculated. Individual sections were digitized with 4096 gray levels using a computer assisted image analysis system. With laminectomy, cervical DRGs was stimulated with the same method of lumbar DRGs. Sham stimulation was applied to the sham group. RESULTS: No significant difference of Fos expression was observed on dorsal horn of rat in operated site, 3 hours later after operation, between the PRF and sham group in lumbar DRGs and the PRF and sham groups in cervical DRGs. CONCLUSION: The expression of Fos was not significantly related with the cervical and the lumbar DRGs stimulation with PRF.

Topical application of epidermal growth factor accelerates wound healing by myofibroblast proliferation and collagen synthesis in rat

Recombinant human epidermal growth factor (rhEGF) stimulates the proliferation and migration of epithelial cells in human cell culture systems and animal models of partial-thickness skin wounds. This study investigated the effect of a topical rhEGF ointment on the rate of wound healing and skin re-epithelialization in a rat full thickness wound model, and verified whether or not the rhEGF treatment affected both myofibroblast proliferation and collagen synthesis in the dermis. When rhEGF (10 microgram/g ointment) was applied topically twice a day for 14 days, there was significantly enhanced wound closure from the 5th to the 12th day compared with the control (ointment base treatment) group. A histological examination at the postoperative 7th day revealed that the rhEGF treatment increased the number of proliferating nuclear antigen immunoreactive cells in the epidermis layer. In addition, the immunoreactive area of alpha-smooth muscle actin and the expression of prolyl 4-hydroxylase were significantly higher than those of the control group. Overall, a topical treatment of rhEGF ointment promotes wound healing by increasing the rate of epidermal proliferation and accelerating the level of wound contraction related to myofibroblast proliferation and collagen deposition.

General pharmacological profiles of bee venom and its water soluble fractions in rodent models

Recently, the antinociceptive and anti-inflammatory efficacy of bee venom (BV, Apis mellifera) has been confirmed in rodent models of inflammation and arthritis. Interestingly, the antinociceptive and anti-inflammatory effect of whole BV can be reproduced by two water-soluble fractions of BV (>20 kDa:BVAF1 and<10 kDa: BVAF3). Based on these scientific findings, BV and its effective water-soluble fractions have been proposed as potential anti-inflammatory and antinociceptive pharmaceuticals. While BV's anti-inflammatory and antinociceptive properties have been well documented, there have been no careful studies of potential, side effects of BV and its fractions when administered in the therapeutic range (BV, 5 microgram/kg; BVAF1, 0.2 microgram/kg: BVAF3, 3 microgram/kg; subcutaneous or intradermal). Such information is critical for future clinical use of BV in humans. Because of this paucity of information, the present study was designed to determine the general pharmacological/physiological effects of BV and its fractions administration on the rodent central nervous, cardiovascular, respiratory and gastrointestinal system. Subcutaneous BV and its fractions treatment did not produce any significant effects on general physiological functions at the highest dose tested (200-fold and 100-fold doses higher than that used clinically, respectively) except writhing test. These results demonstrate that doses of BV or BV subfractions in the therapeutic range or higher can be used as safe antinociceptive and anti-inflammatory agents.

Electroacupuncture ameliorates experimental colitis induced by acetic acid in rat

The effect of electroacupuncture (EA) on experimental colitis was investigated in Sprague-Dawley rats. Colitis was induced by intracolonic instillation of 4% acetic acid. EA (2 Hz, 0.05 ms, 2 V for 20min) was applied to bilateral Hoku (LI-4) and Zusanli (ST-36) on 12 hrs and 36 hrs after induction of colitis. EA-treatment significantly reduced the macroscopic damage and the myeloperoxidase activity of colonic samples at 3 days post-induction of colitis. Colitic colon showed a decreased in vitro motility. However, colonic motility of EAtreated group was not significantly different from that of normal group. The anti-inflammatory effect of EA was not inhibited by a glucocorticoid receptor antagonist, RU-486, but suppressed by a beta-adrenoceptor antagonist, propranonol. These results suggest that EA-treatment has a beneficial effect on colitis, and its anti-inflammatory effect is mediated by beta-adrenoceptor activation but not by endogenous glucocorticoiddependent mechanism.

The Antinociceptive and Anti-inflammatory Effect of Ethylacetate Extracts from Bang-Poong (Radix ledebouriellae) on the Freund's Adjuvant-Induced Arthritis in Rats

In this study, we aimed to determine the antinociceptive and/or anti-inflammatory effect of Bang-Poong (BP, Radix Ledebouriellae) on Freund's adjuvant-induced arthritis in rats. Traditionally, BP has been used to treat several inflammatory diseases such as arthritis. Whole BP is extracted into two fractions that were ethylacetate and hexane-soluble fractions. Adult Sprague-Dawley rats (n=30, 130-150 g) were subcutaneously administered by the Freund's complete adjuvant (FCA) into the plantar surface of right hindpaw. Twelve days after the injection of FCA, the rats initially showed typical inflammatory edema and arthritis-related symptoms on the contralateral side (i.e. left hindpaw). Both antinociceptive (evaluation of mechanical, thermal pain threshold and analysis of spinal Fos expression) and anti- inflammatory (evaluation of paw edema, serum interleukin-6 level and x-ray analysis) effect of BP extracts were examined. The ethylacetate fraction of BP (BPE) significantly suppressed the FCA-induced paw edema as well as the serum level of interleukin-6 and it alleviated the radiological changes. Moreover, both mechanical and thermal hyperalgesia were attenuated by the treatment of BPE. In addition, spinal Fos expression that was increased by FCA- injection was suppressed in BPE group. Therefore, this study showed that BPE produced significant both antinociceptive and anti-inflammatory effects on FCA- induced arthritis in rats, while hexane fraction of BP did not show these effects. In conclusion, it is suggested that the ethylacetate fraction of BP is recommended to alleviate the arthritis-related symptoms in human according to the results of this study.

Serum Total Homocysteine as a Risk Factor for Patients with Coronary Artery Disease

BACKGROUND AND OBJECTIVES: Homocysteine is a metabolite of methionine metabolism with atherogenic and thrombotic properties. Increased blood homocysteine has been recognized as a risk factor for atherosclerotic coronary artery disease, but it is not much to be clarified in this country. MATERIALS AND METHOD: In a case-control study, we examine the relationship between the risk of atherosclerotic coronary artery disease and serum total homocysteine, folate, vitamin B12, vitamin B6, and other conventional risk factors. Thirty nine patients with significant stenosis of epicardial coronary artery and 20 healthy age-sex matched control subjects were included. Fasting venous blood was obtained and serum total homocysteine (tHCY) concentration was measured by high performance liquid chromatography and fluorescent detection method. RESULTS: Compared with control group, case group had higher tHCY concentrations (14.9+/-6.9 vs 10.8+/-4.2 mol/L, p<0.05) and lower folic acid concentration (6.7+/-3.6 vs 11.0+/-5.7 ng/mL,p<0.05). There were higher tHCY concentrations of patients with 2 vessel and 3 vessel disease than that of patients with 1 vessel disease (17.2+/-6.7 and 18.4+/-9.8 micro mol/L vs 12.4+/-3.9 micro mol/L,p<0.05). Vitamin B12 and vitamin B6 concentrations showed no significant difference between case group and control group. Compared with control group, there were more smokers (51.5% vs 25.0%, p<0.05), and patients with hypertension (39.4% vs 0%, p<0.001) and diabetes (30.3% vs 0%, p<0.001) in case group. Increased tHCY (tHCY over 14.7 mol/L) was an independent risk factor for atherosclerotic coronary artery disease (OR; 6.75, 95% CI; 1.15 - 40.99, p<0.05) together with smoking (OR; 5.4, 95% CI; 1.22 - 23.95, p<0.05). CONCLUSION: These data support the hypothesis that elevated serum tHCY concentration is a risk factor for Korean patients with atherosclerotic coronary artery disease, and low folate concentration may be responsible for elevated tHCY concentration.

A case of combined hyperlipoproteinemia / 대한내분비학회지

No abstract available.

One Case of Menetrier's Disease / 대한소화기내시경학회지

Menetrier's disease is a rare disease characterized by the presence of large rugal folds involving part or all of the stomach. Patients with hypertrophic gastropathy often have distressing abdominal symptoms, weight loss and edema due to gastric protein loss. The 48-year-old male patient was admitted to the Hangang Sacred Heart Hospital with cheif complaints of indigestion and epigastric pain. The diagnosis of Menetriers disease is established by radiologic, endoscopic, and pathologic examination. He was treated with soft diet, antacid, H2- receptor antagonist, and IV albumin. We report a case of Menetriers disease with brief review of literatures.