Antipruritic effect of curcumin on histamine-induced itching in mice

Itching is a common clinical symptom of skin disease that significantly affects a patient's quality of life. Transient receptor potential vanilloid 1 (TRPV1) receptors of keratinocytes and peripheral nerve fibers in skin are involved in the regulation of itching as well as pain. In this study, we investigated whether curcumin, which acts on TRPV1 receptors, affects histamine-induced itching in mice, using behavioral tests and electrophysiological approaches. We found that histamine-induced itching was blocked by topical application of curcumin in a concentration-dependent manner. In ex-vivo recordings, histamine-induced discharges of peripheral nerves were reduced by the application of curcumin, indicating that curcumin acts directly on peripheral nerves. Additionally, curcumin blocked the histamine-induced inward current via activation of TRPV1 (curcumin IC₅₀=523 nM). However, it did not alter chloroquine-induced itching behavior in mice, which is associated with transient receptor potential ankyrin 1 (TRPA1). Taken together, our results suggest that histamine-induced itching can be blocked by topical application of curcumin through the inhibitory action of curcumin on TRPV1 receptors in peripheral nerves.

DAMGO modulates two-pore domain K⁺ channels in the substantia gelatinosa neurons of rat spinal cord

The analgesic mechanism of opioids is known to decrease the excitability of substantia gelatinosa (SG) neurons receiving the synaptic inputs from primary nociceptive afferent fiber by increasing inwardly rectifying K⁺ current. In this study, we examined whether a µ-opioid agonist, [D-Ala2,N-Me-Phe4, Gly5-ol]-enkephalin (DAMGO), affects the two-pore domain K⁺ channel (K2P) current in rat SG neurons using a slice whole-cell patch clamp technique. Also we confirmed which subtypes of K2P channels were associated with DAMGO-induced currents, measuring the expression of K2P channel in whole spinal cord and SG region. DAMGO caused a robust hyperpolarization and outward current in the SG neurons, which developed almost instantaneously and did not show any time-dependent inactivation. Half of the SG neurons exhibited a linear I~V relationship of the DAMGO-induced current, whereas rest of the neurons displayed inward rectification. In SG neurons with a linear I~V relationship of DAMGO-induced current, the reversal potential was close to the K⁺ equilibrium potentials. The mRNA expression of TWIK (tandem of pore domains in a weak inwardly rectifying K⁺ channel) related acid-sensitive K⁺ channel (TASK) 1 and 3 was found in the SG region and a low pH (6.4) significantly blocked the DAMGO-induced K⁺ current. Taken together, the DAMGO-induced hyperpolarization at resting membrane potential and subsequent decrease in excitability of SG neurons can be carried by the two-pore domain K⁺ channel (TASK1 and 3) in addition to inwardly rectifying K⁺ channel.

Changing Clinical Characteristics according to Insulin Resistance and Insulin Secretion in Newly Diagnosed Type 2 Diabetic Patients in Korea

BACKGROUND: The role of increased insulin resistance in the pathogenesis of type 2 diabetes has been emphasized in Asian populations. Thus, we evaluated the proportion of insulin resistance and the insulin secretory capacity in patients with early phase type 2 diabetes in Korea. METHODS: We performed a cross-sectional analysis of 1,314 drug-naive patients with newly diagnosed diabetes from primary care clinics nationwide. The homeostasis model assessment of insulin resistance (HOMA-IR) was used as an index to measure insulin resistance, which was defined as a HOMA-IR > or =2.5. Insulin secretory defects were classified based on fasting plasma C-peptide levels: severe ( or =1.7 ng/mL). RESULTS: The mean body mass index (BMI) was 25.2 kg/m2; 77% of patients had BMIs >23.0 kg/m2. Up to 50% of patients had central obesity based on their waist circumference (> or =90 cm in men and 85 cm in women), and 70.6% had metabolic syndrome. Overall, 59.5% of subjects had insulin resistance, and 20.2% demonstrated a moderate to severe insulin secretory defect. Among those with insulin resistance, a high proportion of subjects (79.0%) had a mild or no insulin secretory defect. Only 2.6% of the men and 1.9% of the women had both insulin resistance and a moderate to severe insulin secretory defect. CONCLUSION: In this study, patients with early phase type 2 diabetes demonstrated increased insulin resistance, but preserved insulin secretion, with a high prevalence of obesity and metabolic syndrome.

Erratum to "Assessment of Deceased Donor Kidneys Using a Donor Scoring System" by Bang K, et al. (Yonsei Med J 2010;51:870-876)

No abstract available.

Erratum to "Assessment of Deceased Donor Kidneys Using a Donor Scoring System" by Bang K, et al. (Yonsei Med J 2010;51:870-876)

No abstract available.

Cardiovascular Diseases after Kidney Transplantation in Korea

Cardiovascular disease (CVD) is the leading cause of death in renal allograft recipients with functioning graft. Our study aimed to determine the incidence and the risk factors of cardiovascular disease after renal transplantation in Korea. We retrospectively analyzed 430 adult recipients who underwent kidney transplantation between January 1997 and February 2007. CVD was defined as a composite outcome of ischemic heart disease, cerebrovascular accident and peripheral vascular disease. Mean age of recipients was 40.0+/-11.8 yr. Mean duration of follow-up was 72+/-39 months. The cumulative incidence of CVD after renal transplantation was 2.4% at 5 yr, 5.4% at 10 yr and 11.4% at 12 yr. Multivariate analysis revealed that recipient's age, diabetes mellitus and duration of dialysis before transplantation were associated with post-transplant CVD (hazard ratio 1.843 [95% CI, 1.005-3.381], 3.846 [95% CI, 1.025-14.432] and 3.394 [95% CI, 1.728-6.665] respectively). In conclusion, old age, duration of dialysis and diabetes mellitus are important risk factors for post-transplant CVD, although the incidence of post-renal transplant CVD is lower in Korea than that in western countries.

Assessment of Deceased Donor Kidneys Using a Donor Scoring System

PURPOSE: Marginal grafts should be used more actively in Asian countries where deceased donor transplantation is unpopular. We modified a quantitative donor scoring system proposed by Nyberg and his colleagues and developed a donor scoring system in order to assess the quality of deceased donor grafts and their prognostic value as an initial effort to promote usage of marginal donors. MATERIALS AND METHODS: We retrospectively evaluated 337 patients. RESULTS: A scoring system was derived from six donor variables [age, 0-25; renal function, 0-4; history of hypertension, 0-4; Human Leukocyte Antigen (HLA) mismatch, 0-3; body weight, 0-1; cause of death, 0-3 points]. Donor grafts were stratified by scores: grade A, 0-10; grade B, 11-20; grade C, 21-30; and grade D, 31-40 points. Donor grades significantly correlated with estimated glomerular filtration rate (eGFR) at 6 months (A, 64.0 mL/min/1.73 m2; B, 57.0 mL/min/1.73 m2; C, 46.8 mL/min/1.73 m2; p < 0.001). The five-year graft survival rate was also lower in grade C than grade A (74% vs. 93%, p = 0.002). Donors in grade C and D were regarded as marginal donors. The proportion of marginal donors was much lower in Korea, compared with data from the United Network for Organ Sharing (15.2% vs. 29%). CONCLUSION: Considering the scarcity of deceased donor kidneys and the relatively better graft outcome with lower grade-donors in Korea, it is worth increasing the usage of marginal grafts.

The Effect of Cobalt Chloride Pre-treatment on Experimental Ischemia-Reperfusion Renal Injury / 대한신장학회잡지

BACKGOUND: Cobalt chloride (COCL) has hypoxia-mimetic effects by inhibiting degradation of HIF-1alpha, which is a master regulator of genes activated by low oxygen tension. Heme oxygenase-1 (HO-1), an inducible heat shock protein, is known to have cytoprotective effects against ischemic injury. This study evaluated the efficacy of COCL in a bilateral renal ischemia-reperfusion (I-R) injury model of male Sprague-Dawley rats. METHODS: I-R renal injury was induced by 45 min clamping of both renal arteries. Rats in the sham (n=6) and I-R control groups (n=8) had been drinking tap water, whereas rats in the COCL treated sham (n=6) and COCL treated I-R groups (n=9) had been drinking water containing 2 mM COCL from day -10 to day 1. RESULTS: The serum level of creatinine 24 hrs after surgery was 2.6+/-1.1 (mean+/-SD) mg/dL in I-R COCL treated group, significantly lower than that in I-R control group (4.8+/-1.6 mg/dL, p<0.05). The renal HO-1 gene expression and protein signal were significantly upregulated in the COCL treated sham group compared to sham operated control rats (all, p<0.05). The expressions of TGF-beta MCP-1, TNF-alpha endothelin-1 and Fas genes in COCL treated I-R rats were significantly lower than those of I-R control rats (all, p<0.05). The level of Bcl-2 gene expression of COCL treated I-R rats was significantly higher than the level of I-R control rats (p<0.05). CONCLUSION: It is speculated that the pretreatment of COCL in I-R rat model attenuates ischemic renal injury and at least in part, upregulation of renal HO-1 is involved in this mechanism.

Efficacy of erythropoietin in renal function of pre-dialysis patients with chronic renal failure / 대한내과학회지

BACKGROUND: Anemia is one of the most important risk factors for cardiovascular morbidity and mortality in patients with chronic renal failure. The most effective treatment modality for anemia is erythropoietin injection. Besides erythropoietic effect, erythropoietin has multiple beneficial effects such as anti-oxidant, anti-hypoxic, anti-apoptotic and vasculogenetic effects, and prevents tubular lesions and interstitial fibrosis. Despite lots of advantages of erythropoietin therapy, the number of patients treated with this agent is modest, particularly during the pre-dialysis chronic renal failure. We conducted a clinical trial to evaluate the effects of erythropoietin on renal function in the anemic pre-dialysis patients with chronic renal failure. METHODS: Data of 23 pre-dialysis patients with chronic renal failure were analyzed retrospectively 6 months prior, and prospectively 6 months after the initiation of erythropoietin therapy. Erythropoietin was admitted at a dose of 3000 IU weekly with supplementary iron. RESULTS: The average hematocrit and hemoglobin rose from 22.1+/-2.5%, 7.4+/-0.8 g/dL to 28.4+/-4.2%, 9.6+/-1.5 g/dL, respectively. When linear regression analysis was applied to pre- and post-erythropoietin glomerular filtration rate and 1/Cr, mean rate of decline of glomerular filtration rate were significantly delayed (p=0.039) but that of 1/Cr had a tendency to be delayed but was not statistically meaningful (p=0.099). CONCLUSIONS: Treatment of the anemia with low dose erythropoietin in pre-dialysis patients with chronic renal failure is relatively safe and may slow the rate of renal function deterioration.

Role of gamma-aminobutyric acid B (GABA B) receptors in the regulation of kainic acid-induced cell death in mouse hippocampus

Kainic acid (KA) is well-known as an excitatory, neurotoxic substance. In mice, KA administered intracerebroventricularly (i.c.v.) lead to morphological damage of hippocampus expecially concentrated on the CA3 pyramidal neurons. In the present study, the possible role of gamma-aminobutyric acid B (GABA B) receptors in hippocampal cell death induced by KA (0.1 microgram) administered i.c.v. was examined. 5-Aminovaleric acid (5-AV; GABA B receptors antagonist, 20 microgram) reduced KA-induced CA3 pyramidal cell death. KA increased the phosphorylated extracellular signal-regulated kinase (p-ERK) and Ca2+ /calmodulin-dependent protein kinase II (p-CaMK II) immunoreactivities (IRs) 30 min after KA treatment, and c-Fos, c-Jun IR 2 h, and glial fibrillary acidic protein (GFAP), complement receptor type 3 (OX-42) IR 1 day in hippocampal area in KA-injected mice. 5-AV attenuated KA-induced p-CaMK II, GFAP and OX-42 IR in the hippocampal CA3 region. These results suggest that p-CaMK II may play as an important regulator on hippocampal cell death induced by KA administered i.c.v. in mice. Activated astrocytes, which was presented by GFAP IR, and activated microglia, which was presented by the OX-42 IR, may be a good indicator for measuring the cell death in hippocampal regions by KA excitotoxicity. Furthermore, it showed that GABA B receptors appear to be involved in hippocampal CA3 pyramidal cell death induced by KA administered i.c.v. in mice.

3 Cases of Fenoverine-Induced Rhabdomyolysis / 대한신장학회잡지

Fenoverine is a spasmolytic drug. It has been reported as a causative drug for rhabdomyolysis in France and also in Korea. Well known risk factors for fenoverine induced rhabdomyolysis are hepatic dysfunction, renal dysfunction, concomitant use of lipid lowering drug, mitochondrial myopathy, lipid storage myopathy or malignant hyperthermia. We describe the clinical findings of 3 cases of fenoverine-induced rhabdomyolysis. (Case 1) A 78 year-old male patient complained of generalized myalgia after 7 days medication of fenoverine 300 mg, daily. (Case 2) A 72 year-old female who had been on statin medication for 4 years, complained of generalized myalgia and weakness after 1 day medication of 300 mg of fenoverine. (Case 3) A 57 year-old female who was diagnosed with liver cirrhosis, complained of generalized myalgia, after 4 days medication of 300mg of fenoverine. Laboratory and Tc-99m MDP bone scan findings were compatible with rhabdomyolysis in all 3 patients: ARF was complicated in case 2 and 3. The renal function improved with supportive care. As far as our knowledge concerned, case 1 is the first report of fenoverine-induced rhabdomyolysis without previously known risk factors. So we suggest when physicians are prescribing fenoverine, careful monitoring of symptoms and signs of rhabdomyolysis should be taken to all patients.

End-stage Renal Disease Caused by Primary Hyperoxaluria / 대한신장학회잡지

Primary hyperoxaluria is a rare autosomal recessive inherited metabolic disease which results from endogenous overproduction of oxalic acid. It causes variant phenotypes from renal failure in infancy to mere urolithiasis in late adulthood. We report a case of primary hyperoxaluria in a 11-year-old boy. He presented with recurrent multiple renal stones since 3 years of age. He had renal failure and markedly increased hyperoxaluria (568.26 microgram/mg of creatinine (normal: 0.04-0.15)) and his stones consisted of a mixture of calcium oxalate (30%) and calcium phosphate (10%) in contrast to pure calcium oxalate monohydrate in the other primary hyperoxaluria type 1 patients. A renal biopsy showed interstitial cellular infiltration with crystals which are birefringent under polarized light within the tubules. His general conditions were improved after hemodialysis treatment. For definite cure of disease, combined liver-kidney transplantation is considered.

A Case of Trimethoprim-Sulfamethoxazole and Omeprazole Induced Acute Interstitial Nephritis in a Patient with Renal Transplantation / 대한신장학회잡지

A 44-year-old woman diagnosed with idiopathic chronic kidney disease was subjected to living related renal transplantation from her brother. Immunosuppressant consisted of cyclosporine, mycophenolate mofetil, and prednisolone. On the day 2 after transplantation, her serum level of BUN and creatinine (Cr) were normalized to 13.4 mg/dL and 1.06 mg/dL respectively. Urine output was also well maintained. On day 9, her body temperature was 39degrees C, serum level of BUN and Cr were increased to 20.8 mg/dL and 1.54 mg/dL respectively and urine output was decreased with weight gain. Her serum cyclosporine trough level was 118 ng/dL. DTPA renal scan and Doppler sonography suggested acute rejection. So, antirejection treatment was started with methylprednisolone pulse therapy under the cover of empirical broad spectrum antibiotics. On day 11, graft biopsy was done and the biopsy was compatible with acute interstitial nephritis. The relationship between the time of renal dysfunction and drug medication was analyzed; trimethoprim-sulfamethoxazole (TMP-SMZ) and omeparzole were suspected as causative drugs. So, TMP-SMZ and omeprazole were discontinued. Her serum Cr was slowly increased to 2.32 mg/dL until day 15. And afterward, her serum Cr decreased and normalized We suggest that acute interstitial nephritis should be considered among the many causes of early renal allograft dysfunction when using TMP- SMZ and omeprazole.

A Case of Idiopathic Light Chain Deposition Disease / 대한신장학회잡지

Light chain deposition disease (LCDD) is a systemic disorder characterized by the deposition of monoclonal immunoglobulin light chains (LCs) in various organs. As LCs are overproduced by an abnormal clone of B cells, LCDD is usually described in the course of plasma cell dyscrasias or other lymphoproliferative disorders. However, it can occur in the absence of any detectable hematological disorder even during prolonged follow-up. We experienced a case of 62-year-woman who presented generalized edema, massive proteinuria and renal insufficiency. The histologic findings showed nodular glomerular mesangial expansion and prominent ribbon like immunohistochemical staining for kappa-light chain in the glomerular capillary wall. There was no evidence of multiple myeloma in bone marrow biopsy specimen. Because she refused the intensive chemothrapy, low dose of prednisolone and cyclophosphamide were prescribed for 6 months. Her renal function was maintained relatively well without renal replacement therapy for 7 months. We report a case of idiopathic LCDD not associated with multiple myeloma or other plasma cell dysclasia.

A Case of Tuberous Sclerosis with Spontaneous Rupture of Renal Angiomyolipoma / 대한신장학회잡지

Tuberous sclerosis is an autosomal dominant disorder characterized by seizures, mental retardation and hamartomatous tumors in multiple organs, including subependymal giant cell astrocytomas, cortical tubers, cardiac rhabdomyoma, pulmonary lymphangiomyomatosis and renal angiomyolipomas. However, these clinical features are not always present. The following is a report concerning a 30-year-old woman with tuberous sclerosis who suffered a spontaneous hemorrhage into the angiomyolipoma of the kidney and underwent curative selective renal embolization. The patient had a medical history of focal seizures. Moreover, brain magnetic resonance imaging revealed typical signs of tuberous sclerosis, and a high resolution computerized tomography of the chest showed bilateral nodules with irregular margins and multiple thin-walled cystic lesions. There was no family history of renal disease or of tuberous sclerosis. As such, this case exhibited rare clinical manifestations of tuberous sclerosis involving multiple organs.

The clinical impact of the referral pattern to nephrologist in patients with chronic renal failure / 대한내과학회지

BACKGROUND: It has been speculated that many factors including age, hemoglobin serum albumin level and socioeconomic factors are closely related with the mortality and morbidity of patients with end-stage renal disease (ESRD). Optimal management of the patients with pre-dialysis chronic kidney disease has been thought to be very important for the prognosis of end-stage renal disease patients on dialysis. METHODS: In order to evaluate the clinical impact of referral pattern of chronic renal failure patients to nephrologist, 217 patients (male 129, female 88) who initiated hemodialysis from Jan. 1998 to Jul. 2002 in Chungnam National University Hospital were included in this retrospective analysis. Patients were defined as early referral (n=129) when hemodialysis was initiated at least 90 days after the first visit to nephrologist and as late referral (n=88) when hemodialysis was performed within 90 days after the first visit to nephrologist. RESULTS: Male gender and medical aid coverage were significantly more prevalent in late referral than early referral group (p<0.05, p<0.05, respectively). Late referral group had more combined medical problems than those of early referral group (p<0.05). Serum albumin level of early referral group was significantly higher than that of late referral group at the initiation of hemodialysis (p<0.001). At the initiation of hemodialysis, temporary central catheter for the blood access was needed in 85.2 % of late referral group. However, only 41.6% of early referral group needed such temporary catheter (p<0.001). One year after initiation of hemodialysis treatment, early referral group showed significantly lower mortality rate than that of late referral group (p<0.001). CONCLUSION: The early referral of chronic renal failure patients to nephrologist has beneficial effects including higher one-year survival after beginning of hemodialysis.

A Case of Carcinoid Tumor in a Patient with Focal Segmental Glomerulosclerosis / 대한신장학회잡지

A renal lesion of neoplasm-related nephrotic syndrome usually presents as membranous nephropathy. Neoplasm-related nephrotic syndrome exhibiting focal segmental glomerulosclerosis (FSGS) has been reported mainly in patients with hematological malignancies. But reports of an association between FSGS and neoplasm are extremely rare. We report a 66-year-old woman with FSGS who presented with nephrotic syndrome and was subsequently found to have carcinoid tumors in the duodenum, confirmed by tissue biopsy. After resection of carcinoid tumor, the patient received initial treatment with oral prednisolone for 2 months but her nephrotic syndrome persisted. The patient was then treated with oral cyclophosphamide. One month later, she was in complete remission of nephrotic syndrome as indicated by a normal serum albumin and no proteinuria. This case may be a coincidence or the lesions may be linked with each other but since little is known about the pathogenesis of FSGS and neoplasm, it is difficult to speculate on a pathogenetic link between these two lesions. We report a case of FSGS with nephrotic syndrome in a patient with carcinoid tumor.

A Clinical Study on Adult Thrombotic Thrombocytopenic Purpura / 대한신장학회잡지

OBJECTIVE: Thrombotic thrombocytopenic purpura (TTP) is a disorder characterized by microangiopathic hemolytic anemia, thrombocytopenia, fluctuating neurological symptoms and a variable degree of impairment of renal function, which are thought to be due to endothelial cell injury, platelet activation and subsequent formation of thrombi in the microcirculaion. It usually occurs in adults but few reports are available on etiology, clinical manifestation, progression and the outcome of disease in Korea. METHODS: We investigated 10 adult patients who had admitted and were diagnosed as TTP in Department of Internal Medicine, Chungnam National University Hospital from Dec. 1994 to Jul. 2001. RESULTS: The male to female ratio was 1 : 4. The etiologic antecedants were infectious diarrhea in 3 patients, upper respiratory infection in 3 patients and pregnancy was related with TTP in 2 patents. The clinical manifestations were variable neurologic symptoms(100%), renal involvement(90%), hemorrhagic manifestations(80%), fever(60%), and diarrhea(40%). Acute renal failure was noted in 6 patients and hemodialysis was required in 5 patients. Plasma exchange was performed in 9 patients and corticosteroid was prescribed in 8 patients, simultaneously. Vincristine, azatioprine and cyclophosphamide were added in 2 patients. One patient died of hepatic failure. Seven patients showed complete recovery. One patient progressed to end-stage renal failure. The other patient showed multiple recurrences. CONCLUSION: It is thought that a considerable number of TTP patients show very serious acute renal failure and plasma exchange should be included in therapeutic modalities of TTP.

Surgical Treatment for Burst Fracture of the Thoracolumbar Spine: Anterior approach vs posterior approach / 대한정형외과학회잡지

We present a prospective, randomized study of acute burst fracture of the thoracolumbar spine. Forty-one patients were treated either by anterior decompression and stabilization with Kaneda device or by posterior distraction instrumentation using the A-O fixateur interne. The mean follow up was 21 months. The result were as follows; 1. The mean preoperative kyphotic angle was 19.2° in those patients treated by anterior surgery and 21.4° in those patients treated by posterior surgery. At last follow-up the mean correction in kyphotic angle was 13.2° in the anterior group and 9.2° in the posterior group. There is no statistically significant difference between those two groups. 2. The mean preoperative midsagittal diameter of the canal compromise 47.4% in anterior group and 49.3% in posterior group. Postoperatively, this was reduced to 2.5% and 7.9%. There is a statistically significant difference between these two groups(P < 0.05). 3. The mean preoperative canal enchroachment 52.)% in anterior group and 47.6% in posterior group. Postoperatively, this was reduced to 3.2% and 6.0%. There is a statistically significant difference between these two group(P < 0.05). 4. Neurologic recovery was 81% in posterior surgery and 85% in anterior surgery. The improvement in Frankel grade was 1 grade in average, and showed no difference between two groups. 5. There was two cases of pedicle screw breadage in posterior group and one case of pyothorax in anterior group but no early or late vascular or neurologic complication.

Clinical Study of Ipsilateral Fracture of the Femur and Tibia / 대한정형외과학회잡지

Usually the condition of ipsilateral fracture of femur and tibia is called floating knee, it is termed applied to the flail knee joint segment. The key point of the treatment is focused to the early restoration of the knee function. We experienced 86 consecutive cases during the period from March 1978 to February 1991 in Yonsei University Wonju College of Medicine. Among them, 51 cases(above 16 years old) were analysed with the mean follow up period of 2.1 years(1.2-5.6 years). The results obtained were as follows: 1. Main cause of these fractures is traffic accident. Among them, the pedestrian accident is more than in-car accident. 2. The cases of open fracture were 13 cases (25.5%) in femur and 31 (60.8%) in tibia. The degree of open fracture was more severe in tibia. 3. There were 2 cases (3.9%) of fat embolism syndrome preoperatively. 4. At an average 25 months follow up after injury, the good and excellent result of the group 1 and 3 was 85.2%, and the group 2 and 4 was 71.4% by Karlström and Olerud criteria. 5. At the last follow up examination, the mean loss of range of motion of the knee was 5.6° in group 1 and 3, 10.9° in group 2 and 4(P < 0.05). 6. The operative treatment of the both side is better than case of one side operation and other side conservative treatment.