Cyclosporine A(CsA) is a widely used immunosuppressant for transplant patients and is also used for the treatment of a wide variety of systemic diseases with immunologic disorders. However, its use is frequently limited because of complications such as nephrotoxicity or gingival hyperplasia. Although several hypotheses have been postulated for CsA-induced gingival hyperplasia, i.e. various cytokine effects of inflammatory cells, existence of plaque or CsA itself, but its pathogenesis is still unclear. For experimental chronic CsA toxicity, salt depletion has been shown to increased susceptibility of rodents to the effects of CsA, and this maneuver facilitates production of arteriolopathy and interstitial fibrosis in kidney that mimic the changes found in human. The purpose of this study was to evaluate pathogenesis of CsA-induced gingival hyperplasia by comparing changes between CsA administration groups of normal standard diet and those of low salt diet group. Specific pathogen-free, 20 to 25 days old(120 to 150 g), male Fisher-344 rats(KIST, Korea), 120 to 150g of body weight, were assigned to four groups of six animals each after one week of adaptation period for powder food. Group 1 received olive oil($300{\mu}l/g\;of\;diet$) with normal standard diet(0.4% of sodium)(NSD). Group 2 received CsA(Cypol-N, Jonggundang, Korea; $300{\mu}g/g\;of\;diet$) with normal standard diet(NSD+CsA). Group 3 received same amount of olive oil with low salt diet(0.05 % of sodium, Teklad Premier, U.S.A.)(LSD). Group 4 received same dose of CsA with low salt diet(LSD+CsA). Rats were pair fed and were sacrificed after six weeks. Renal histologic lesions associated with CsA, consisted of cortical interstitial fibrosis, tubular atrophy and hyalinization of arterioles and the impairment of renal function including increase of serum creatinine and decrease of glomerular filtration rate was more severe in low salt diet group. These were proved as the results of activated of renin-angiotensin system in the kidney by low salt condition. Meanwhile the degree of gingival hyperplasia at incisor and molar tooth was less severe in low salt diet group compared with normal sodium diet group. Hyperplastic gingiva showed mild epithelial hyperplasia and expanded underlyng stroma which consisted of matrix increasement, capillary proliferation and dilatation. While the number and the activation of fibroblasts were increased, inflammatory cells were rare in the stroma. The immunohistochemistry for TGF-${\beta}_1$ in the kidney and gingiva revealed stronger positive in LSD+CsA in kidney but in gingiva of NSD+CsA. These results suggested followings; Gingival hyperplasia can be developed without inflammatory cells infiltration and seemed not induced by CsA by itself. The major role for gingival hyperplasia by CsA would be the secondary effect of TGF-${\beta}$, which maybe upregulated by CsA administration. Low salt diet can attenuate this hyperplasia perhaps by decreasing the activation of $TGF-{\beta}$.
Suture microvascular anastomosis is time-consuming and tedious and demands long and continuous training. Techinique of anastomosis of microvessel was presented interrupted suture and continuous suture. Recently the unilink instrument system is created as a fast and simple method to achieve high patency rates without long and continuous training in the anastomosis of small vessels. The author experimentally studied the femoral artery of 20 mice(0.5-1.0mm, av. 0.7mm), the femoral vein of 20 mice(0.8-1.6mm, av. 1.2mm) after anastomosis with interrupted suture in 20 cases and continuous sutre in 20 cases. For the unilink apparatus we used the carotid arteries of 15 cases in 14 rabbits(1.0-1.6mm, av. 1.3mm) and facial veins of 12 cases in 14 rabbits(0.9mm-2.2mm, av. 1.5mm). A total of 27 arterial and venous anastomoses were performed. We examined the postoperative patency at immediate, 2 weeks, and 8 weeks. The results were as followings, 1. In the arterial anastomosis the rate of patency was 90%(18/20) in interrupted suture, 90%(18/20) in continuous suture and 93%(13/15) in unilink apparatus. In the venous anastomosis the rate of patency was 90%(18/20) in interrupted suture, 80%(16/20) in continuous suture and 100%(9/9) in unilink apparatus. 2. The mean time for completion of the arterial anastomosis were 12.2 minutes in interrupted suture group, 10.3 minutes in continouous suture group and 8.5 minutes in unillnk apparatus group. The mean time for completion of the venous anastomosis were 13.6 minutes in interrupted suture group, 11.0 minutes in continuous suture group and 6.2 minutes in unilink apparatus group. 3. At the histological examination of suture group, hyperplastic reaction of middle layer and subintimal hyperplasia were observed. In unilink apparatus group, the endothelium layer was continued and the thickness of vessel wall was decreased due to moderate atrophy of the media and mild degree of nonspecific chronic inflammation were seen around the unilink apparatus. 4. No significants was noticied in foreign body reaction among the interrupted, continuous and unilink apparatus group. 5. A case of the arterial anastomosis was released with acting out at 15 minutes after operation. 6. The important factors in the technical problems were accurate apposition of the cut vessel edges in suture group and the proper selection of the ring size and optimal fitting between two rings in unilink apparatus group. Even though the outer diamater of vessel in suture group was different from that in unilink apparatus group the unilink method provides a very safe, fast, and simple way to perform microvascular anastomoses especially in anastomosis of vein. But howerver suture was needed in vessels below 1 mm outer diamater. In that situation continuous suture was benefit than the interrupted suture in operation time.
Insulin signaling is coordinated by insulin receptor substrates (IRSs). Many insulin responses, especially for blood glucose metabolism, are mediated primarily through Irs-1 and Irs-2. Irs-1 knockout mice show growth retardation and insulin signaling defects, which can be compensated by other IRSs in vivo; however, the underlying mechanism is not clear. Here, we presented an Irs-1 truncated mutated mouse ($Irs-1^{-/-}$) with growth retardation and subcutaneous adipocyte atrophy. $Irs-1^{-/-}$ mice exhibited mild insulin resistance, as demonstrated by the insulin tolerance test. Phosphatidylinositol 3-kinase (PI3K) activity and phosphorylated Protein Kinase B (PKB/AKT) expression were elevated in liver, skeletal muscle, and subcutaneous adipocytes in Irs-1 deficiency. In addition, the expression of IRS-2 and its phosphorylated version were clearly elevated in liver and skeletal muscle. With miRNA microarray analysis, we found miR-33 was down-regulated in bone marrow stromal cells (BMSCs) of $Irs-1^{-/-}$ mice, while its target gene Irs-2 was up-regulated in vitro studies. In addition, miR-33 was down-regulated in the presence of Irs-1 and which was up-regulated in fasting status. What's more, miR-33 restored its expression in re-feeding status. Meanwhile, miR-33 levels decreased and Irs-2 levels increased in liver, skeletal muscle, and subcutaneous adipocytes of $Irs-1^{-/-}$ mice. In primary cultured liver cells transfected with an miR-33 inhibitor, the expression of IRS-2, PI3K, and phosphorylated-AKT (p-AKT) increased while the opposite results were observed in the presence of an miR-33 mimic. Therefore, decreased miR-33 levels can up-regulate IRS-2 expression, which appears to compensate for the defects of the insulin signaling pathway in Irs-1 deficient mice.
Purpose : We intend to review clinical results after Anterior cruciate ligament(ACL) reconstruction using hamstring tendon arthroscopically. Materials & Methods : Sixty two patients who had underwent arthroscopic ACL reconstruction using hamstring tendon from Mar. 1996 to Mar. 1997 were reviewed. The average follow-up was 16 months and average age at operation was 27 years old. Clinical results were evaluated with physical examination, Lysholm Knee score and instrumented anterior laxity test with Telos Results : The average preoperative Lysholm knee score was 57.0 and postoperative average of that was 91.8. All cases of 62 patients had normal range of motion of knee and were able to walk with no problems at follow-up. On the Lachmann test, there were mild(+) instability in 24 cases, moderate(++) in 24 cases, severe(+++) in 14 cases preoperatively and 48 cases were converted to negative, 14 cases mild postoperatively. On instrumented anterior laxity test with Telos, difference between normal and affected knee on 20 lb which was 13.4mm preoperatively was decreased to 4.7mm at follow-up and anterior stability was regained(P<0.05). Parapatellar complications such as crepitus in 18 cases(29.5%), atrophy of quadriceps in 23 cases(36.5%) were observed. There were 2 cases of inaccuracy of guide pin of semifix screw intraoperatively and 3 cases of malposition of semifix screw postoperatively. Conclusion : ACL reconstruction using hamstring tendon seems to be a effective procedure to establish the stability of knee joint but is technically demanding procedure and leaves some parapatellar complications.
Song Eun Kyoo;Lee Keun Bae;Shin Sang Gyoo;Kim Hyun Jong
Journal of Korean Orthopaedic Sports Medicine
/
v.1
no.1
/
pp.21-25
/
2002
Purpose: To evaluate the clinical results after anterior cruciate ligament (ACL) reconstruction with hamstring tendon and Ligament Anchor (LA) screw, which is newly designed for fixation of graft into femur. Materials and Methods: Fifty eight patients who were followed up at least more than 2 years after ACL reconstruction with four strands of Hamstring tendon and LA screw were included in this study. The graft was fixed with LA screw at femoral tunnel and with only bioabsorbable interference screw at tibial tunnel. The mean follow-up period was 28 months. The clinical results were evaluated by physical examination and Lysholm knee score. Widening of bony tunnel and anterior laxity difference compared with normal side by instrumented anterior laxity test with Telos(R) (Telos stress device; Austin & Associates, Inc., Polston, US) were evaluated. Results: The Lysholm knee score improved from 60.0 points preoperatively to 94.0 points at last follow up. On the Lachman test, there were mild (+) instability in 16 cases, moderate (++) in 24,severe (+++) in 18 preoperatively. 50 cases were converted to negative and 8 to mild instability at postoperative follow up. On instrumented anterior laxity test with Telos(R), difference between normal and affected knee on 20 lb was 12.9 mm in average preoperatively, and was decreased to 3.1mm at last follow-up. The femoral tunnel was widened from 10.6 mm postoperatively to 12.7 mm (21.1$\%$) at follow up on antero-posterior plane and from 10.7 mm to 12.4 mm (16.5$\%$) on lateral plane. Tibial tunnels was also widened from 9.8mm to 11.8mm (20.7$\%$) on antero-posterior plane and from 9.9mm to 11.7 mm ($18.9\%$) on lateral plane. Complications were: anterior knee crepitus in 17 case, quadriceps muscle atrophy(>3 cm) in 6, penetration of screw over the lateral femoral cortex in 5, saphenous nerve paresthesia in 2.Conclusions: ACL reconstruction with hamstring tendon and LA screw was one of the choice of grafts and fixation devices in restoring knee stability and in improving clinical results with little complications such as excessive widening of bony tunnel and anterior knee pain
Choi, Yu Jin;Lee, Ah Jin;Nam, Soo Hyun;Choi, Byung-Ok;Chung, Ki Wha
Journal of Life Science
/
v.29
no.7
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pp.800-808
/
2019
Charcot-Marie-Tooth disease (CMT) is a group of rare peripheral neuropathies characterized by progressive muscle weakness and atrophy and areflexia in the upper and lower extremities. The most common subtype of CMT is CMT1A, which is caused by a tandem duplication of the PMP22 gene in the 17p12 region. Patients with CMT1A show a loose genotype-phenotype correlation, which suggests the existence of secondary genetic or association factors. Recently, polymorphisms of rs71428439 (n.83A>G) and rs2292832 (n.86T>C) in the MIR149 have been reported to be associated with late onset and mild phenotypic CMT1A severity. The aim of this study was to examine the intrafamilial heterogeneities of clinical phenotypes according to the genotypes of these two SNPs in MIR149. For this study, we selected 6 large CMT1A families who showed a wide range of phenotypic variation. This study suggested that both SNPs were related to the onset age and severity in the dominant model. In particular, the AG+GG (n.83A>G) and TC+CC genotypes (n.86T>C) were associated to late onset and mild symptoms. Motor nerve conduction velocity (MNCV) was not related to the MIR149 genotypes. These results were consistent with the previous studies. Therefore, we suggest that the rs71428439 and rs2292832 variants in MIR149 may serve as genetic modifiers of CMT1A intrafamilial phenotypic heterogeneity, as they have a role in the unrelated patients. This is the first study to show an association using large families with variable clinical CMT1A phenotypes. The results will be helpful in the molecular diagnosis and treatment of patients with CMT1A.
Nine dogs presented to the Veterinary Medical Teaching Hospital of Konkuk University and Woosung Animal Hospital with a history of pelvic limb lameness. On physical examination, 9 dogs all showed a consistent weight bearing lameness and mild muscle atrophy. There was cranial drawer sign with pain in 9 dogs. Mediolateral radiographic projection revealed cranial subluxation of the tibial tuberosity in a tibial compression view. The right and left stifle joints were affected in 7 dogs and 2 dogs respectively. TightRope cranial cruciate ligament (CCL) technique for treatment of CCL deficiency was performed. Polyester and nylon were used to stabilize the stifle in 3 dogs and 6 dogs respectively. Suture sizes were 0.8 mm (n = 2), 0.9 mm (n = 4), 1.1 mm (n = 2), and $1.1mm{\times}2$ strands (n = 1) in diameter. Mean (${\pm}SD$) surgical duration was $48.3{\pm}8.5$ minutes (range 35 to 60 minutes). Preoperative and postoperative mean (${\pm}SD$) cranial drawer signs were $8.6{\pm}1.6$ mm (rage 7 to 12 mm) and $1.2{\pm}1.0$ mm (rage 0 to 3 mm) respectively. Immediate postoperative radiographs of the affected limb revealed no evidence of cranial subluxation of the tibial tuberosity in a tibial compression view of 9 dogs. Normal limb function was regained in 8 dogs within 8 weeks postoperatively. A consistent weight bearing lameness resolved in all dogs after TightRope CCL technique, but reoccurred in one dog (case No. 6) 2 weeks after surgery. Cranial subluxation of the tibial tuberosity was identified in a tibial compression test. During the second surgery, breakage of surgical button was identified and a tibial wedge osteotomy was performed. Based on surgical time, complication, stifle stability, and functional recovery, the present study indicated that TightRope CCL technique is effective treatment for the dogs with CCL deficiency.
Purpose : This study aims to examine and compare the features of rolandic epilepsy. Methods : Of 158 patients selected retrospectively, 116 had typical (group A) and 42 had atypical (group B) rolandic epilepsy, as defined by Worrall's criteria. Results : The age at onset of the seizures in group A was $8.6{\pm}2.0y$ and $6.2{\pm}1.7y$ in group B (P>0.05). Among the 40 patients who underwent neuroimaging studies (25 patients in group A and 15 patients in group B), abnormal findings in group B included ventricular dilatation, mild cortical atrophy, and partial agenesis of corpus callosum. group A had no abnormal findings. The frequency of seizures was $2.0{\pm}1.0$ and $2.3{\pm}1.2$ per month in groups A and B respectively. Seizure control from the initial anticonvulsant treatment was achieved within 3 months in group A, and 3 to 12 months in group B. A 2-year remission rate was noted in 105 patients in group A and in 38 patients in group B. Of these, the recurrence rate after 2 y was 13 in group A and 12 in group B. Conclusion : Age of onset of seizures, gender, frequency of seizures before therapy, and 2-y remission rate were not significantly different in the 2 groups. However, neuroimaging abnormalities, the time to achieving seizure control from the initial anticonvulsant treatment, and the recurrence rate after being seizure-free for 2 y were significantly different in the 2 groups.
Worm recovery rates and pathologic changes in small intestine of albino rats were observed after concurrent and challenge infections with metacercariae (MCI of Fibricota seouLensis and MetaBonimus vokogaupci, and compared with those of single Infection groups. Albino rats In concurrent Infection group were killed 20 days after feeding with 1,000 MC of each fluke. Rats in challenge. infection group were fed with 1.000 MC of f seouleni,s and challenged by 1,000 MC of M. yokogawai 10 days after primary infection, then killed 10 days thereafter. In concurrent infection group, mean number of F. seoulensis and M. yokogawai recovered, 250 and 118 respectively, were similar to those of single infection groups. However, more flukes were collected from the duodenum and less flukes were from the ileum than from single infection group. In challenge Infection group, the recovery rate of F. seoulensis was similar to that of sin91e infection group and the distribution of thIn flukes was similar to that of concurrent infection group. Mean number of M. yokogculat, 69, was signiflcantly lower than that of single infection group. Its distribution, however, extended to the duodenum and most of the flukes were recovered from the jejunum. In concurrent infection group, villi of the duodenum were more markely thickened, fused and shortened than those in F. seoulensis sing1e Infection group. The crypt epithelium appeared to be hyperplastic and inflammatory cell infiltration into the villous stroma was mild. Villous atrophy in the jrlunum and ileum was ndlder than in M. yokogawai single infection group. In challenge Infection group, the fhldlngs were simuar to those of concurrent Infection group. Crypt epithelium hyperplasla was not severe in duodenum. Inflammatory reaction was observed in submucosa of the Jrjunum and ileum. From the above results, it Is considered that F. seoulenis ikabiting in upper part of small intestine affect the settlement of M. yokoguwai introduced later In lower part of the intestine.
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