뇌하수체 선종 연구에 있어서 sAIPKO 마우스 모델의 유용성

의과대학/석사Acromegaly results from the chronic hypersecretion of GH, which primarily originates from GH secreting pituitary adenoma. Although transsphenoidaladenomectomy is the treatment of choice, some patients do not achieve biochemical remission after surgery and require medical treatment. However, there are not many available drugs due to the limitations of GH-secreting pituitary adenoma which include the poorly understood pathogenesis and lack of a proper animal model. Recently, Igenerated an animal model that develops GH secreting pituitary adenoma, which has the deletion of the aryl hydrocarbon receptor interacting protein (AIP) in somatotroph. To investigate the usefulness of somatotroph-specific AIP knock out (sAIPKO) mice in developing therapeutics for GH secreting pituitary adenoma, I evaluated the biochemical effects of somatostatin analogs on sAIPKO mice. I generated sAIPKO mice using a Cre-loxp strategy. Twelvemale sAIPKO mice were assessed. The mice received a subcutaneous injection of octreotide LARor pasireotide LAR. Imeasured serum IGF-1 levels, body weight and blood glucose levels three times a month. There were significant decreases in serum IGF-1 levels in the pasireotide group. However, serum IGF-1 levels inthe octreotide group showed a decreasing trend, although it was not statistically significant. Body weight in the pasireotide group significantly decreased on the 14th day, not on the 28th day while there was no significant change in the octreotide group. Blood glucose levels in the pasireotide group increased significantly on 28th day.Pasireotide which is a multireceptor targeted somatostatin analog, had stronger inhibitory effects on biochemical activity in sAIPKO mice suggesting that this mouse model represent more aggressive GH secreting pituitary adenoma. Thus, this mouse model will be useful for drug development and efficacy evaluation in GH secreting pituitary adenoma.ope

Clinical and Biochemical Characteristics and Treatment of Patients with Thyrotropin-Secreting Pituitary Adenomas

Background/Aims : Thyrotropin (TSH)-secreting pituitary adenoma (TSHoma) is rare and represents 1~2% of all pituitaryadenomas. TSHoma should be distinguished from the thyroid hormone resistance syndrome. Patients with TSHoma may bemisdiagnosed with primary hyperthyroidism and often receive inappropriate thyroid gland treatment. Methods : We assessed the clinical characteristics of patients with TSHoma who presented to Severance Hospital at the YonseiUniversity College of Medicine, Seoul, Korea between 2005 and 2009. Results : Of 484 patients who underwent pituitary tumor resection, eight (1.65%; five women and three men) were found to haveTSHoma. The mean age was 40.6±8.9 years at diagnosis (range, 28~55 years). The median duration from onset of symptoms todiagnosis was 17 months (range, 4~60 months). Four patients had overt symptoms of hyperthyroidism and two had visual fielddefect. Six patients had elevated free thyroxine (FT4) levels with elevated or inappropriately normal TSH levels, and two patientshad symptoms associated with Hashimoto’s thyroiditis. The serum levels of free α-subunit measured in two patients were elevated.Six of the tumors were macroadenomas (>10 mm) and two were microadenomas. Complete tumor removal was achieved in allpatients. Five patients had preoperative anterior pituitary dysfunction; three patients recovered from this after surgery. Threepatients were lost to follow up and five patients showed no evidence of recurrence or hyperthyroidism in the follow-up period(mean, 30.8 months, range, 3~57). Conclusions : Early diagnosis and complete removal of the tumor mass may improve the neurological and endocrine deficits. (Korean J Med 2011;80:47-55)ope

Effects of ulinastatin treatment on myocardial and renal injury in patients undergoing aortic valve replacement with cardiopulmonary bypass.

BACKGROUND: We determined the protective effects of a high dose of ulinastatin on myocardial and renal function in patients undergoing aortic valve replacement with cardiopulmonary bypass (CPB). METHODS: Sixty patients were assigned randomly to either the ulinastatin group (n = 30) or the control group (n = 30). In the ulinastatin group, ulinastatin (300,000 U) was given after the induction of anesthesia, ulinastatin (400,000 U) was added to the CPB pump prime, and then ulinastatin (300,000 U) was administered after weaning from CPB. In the control group, the same volume of saline was administered at the same time points. Creatine kinase-MB levels were assessed 1 day before surgery, and on the first and second postoperative day (POD 1 and 2). Serum creatinine and cystatin C levels were assessed 1 day before surgery, upon intensive care unit arrival, and on POD 1 and 2. The level of plasma neutrophil gelatinase-associated lipocalin was assessed before induction of anesthesia, upon ICU arrival, and on POD 1. RESULTS: No significant differences were observed in serum levels of creatine kinase-MB and biomarkers of renal injury between the two groups at any point during the study period. CONCLUSIONS: Ulinastatin showed no cardiac or renal protective effects after CPB in patients undergoing aortic valve replacement.ope

A Case of Pituitary Adenoma with Simultaneous Secretion of TSH and GH

Thyrotropin (TSH)-secreting pituitary adenoma is a very rare disease. In one-quarter of patients suffering from this disease, the pituitary tumor secretes other anterior pituitary hormones. Herein, we report a case of pituitary adenoma with simultaneous secretion of TSH and growth hormone (GH). A 34-year-old female visitied local hospital complaining of sweating, intermittent palpitation, and weight loss of 8 kg within 1 year. The patient had undergone trans-sphenoidal surgery 3 years prior for resolution of a TSH and GH co-secreting pituitary adenoma. She had been administered somatostatin analogue prior to visiting our hospital. The patient's GH levels were suppressed to below 1 ng/mL on the 75 g oral glucose tolerance test, and her basal insulin-like growth factor-I (IGF-I) level was within normal range. Thyroid function tests demonstrated increased levels of both free thyroxine and TSH. Sella-MRI revealed pituitary adenoma at the floor of the pituitary fossa, approximately 2 cm in height. Therefore, she was diagnosed with residual TSH-secreting pituitary adenoma. The patient again underwent trans-sphenoidal surgery and entered complete remission, based on hormone levels and MRI findings.ope

Comparison of Dexmedetomidine and Remifentanil on Airway Reflex and Hemodynamic Changes during Recovery after Craniotomy.

PURPOSE: During emergence from anesthesia for a craniotomy, maintenance of hemodynamic stability and prompt evaluation of neurological status is mandatory. The aim of this prospective, randomized, double-blind study was to compare the effects of dexmedetomidine and remifentanil on airway reflex and hemodynamic change in patients undergoing craniotomy. MATERIALS AND METHODS: Seventy-four patients undergoing clipping of unruptured cerebral aneurysm were recruited. In the dexmedetomidine group, patients were administered dexmedetomidine (0.5 μg/kg) for 5 minutes, while the patients of the remifentanil group were administered remifentanil with an effect site concentration of 1.5 ng/mL until endotracheal extubation. The incidence and severity of cough and hemodynamic variables were measured during the recovery period. Hemodynamic variables, respiration rate, and sedation scale were measured after extubation and in the post-anesthetic care unit (PACU). RESULTS: The incidence of grade 2 and 3 cough at the point of extubation was 62.5% in the dexmedetomidine group and 53.1% in the remifentanil group (p=0.39). Mean arterial pressure (p=0.01) at admission to the PACU and heart rate (p=0.04 and 0.01, respectively) at admission and at 10 minutes in the PACU were significantly lower in the dexmedetomidine group. Respiration rate was significantly lower in the remifentanil group at 2 minutes (p<0.01) and 5 minutes (p<0.01) after extubation. CONCLUSION: We concluded that a single bolus of dexmedetomidine (0.5 μg/kg) and remifentanil infusion have equal effectiveness in attenuating coughing and hemodynamic changes in patients undergoing cerebral aneurysm clipping; however, dexmedetomidine leads to better preservation of respiration.ope

Undiagnosed light chain systemic amyloidosis: does it matter to anesthesiologists? -a case report-

Light chain systemic amyloidosis is rare but may accompany laryngeal or pulmonary involvement, which may increase the risk in airway management. We present a case of a patient planned for resection of cervical epidural mass. The patient had face and neck ecchymoses and purpuras with an unknown cause. Mask ventilation and intubation were successful, but the operation was cancelled to evaluate bleeding from facial skin lesions. A diagnosis of light chain systemic amyloidosis prompted evaluation of involvement of other organs and treatment. This case shows the importance of preoperative evaluation and careful airway management in patients with systemic amyloidosis.ope

Association between opioid receptor gene polymorphism and postoperative pain response in Koreans

Background:The objective of this study was to investigate the association between A118G single nucleotide polymorphism (SNP) of human Ռ-opioid receptor (OPRM1) gene and the postoperative pain response in Korean patients undergoing thyroidectomy. Methods:Fifty two adult patients undergoing thyroidectomy were enrolled in this study. Their blood samples were genotyped for the A118G polymorphism. Pain intensity was assessed by a verbal numerical rating scale (VNRS) at postanesthesia care unit, postoperative 6, 24, and 48 hours. Mechanical pain threshold was assessed using electronic von Frey preoperatively and repeated at postoperative 24 and 48 hours on the forearm and periincisional regions. Results:Of the 50 patients, 23 patients were A118 homozygous (AA), 19 patients were heterozygous (AG), and 8 patients were 118G homozygous (GG). The VNRS score was higher in patients with GG genotype than other genotypes at PACU (P ＜ 0.05). Mechanical pain thresholds on the forearm and periincisional area were decreased at postoperative 24 and 48 hours from the preoperative values in all genotypes (P ＜ 0.05). However, the changes in pain thresholds were similar among the genotypes. Conclusions:A118G SNP of OPRM1 gene is associated with inter-individual difference in immediate postoperative pain score in Korean population.ope

Application of intraoperative lung-protective ventilation varies in accordance with the knowledge of anaesthesiologists: a single-Centre questionnaire study and a retrospective observational study

BACKGROUND: The benefits of lung-protective ventilation (LPV) with a low tidal volume (6 mL/kg of ideal body weight [IBW]), limited plateau pressure (/=5 cm H2O) between 2004 and 2014 (0/818 [0.0%] vs. 280/818 [34.2%]; p < 0.001). CONCLUSIONS: Our study suggests that the knowledge of LPV is directly related to its implementation, and can explain the increase in LPV use in general anaesthesia. Further studies should assess the impact of using intraoperative LPV on clinical outcomes and should determine the efficacy of education on intraoperative LPV implementation.ope

Metformin Restores Parkin-Mediated Mitophagy, Suppressed by Cytosolic p53

Metformin is known to alleviate hepatosteatosis by inducing 5' adenosine monophosphate (AMP)-kinase-independent, sirtuin 1 (SIRT1)-mediated autophagy. Dysfunctional mitophagy in response to glucolipotoxicities might play an important role in hepatosteatosis. Here, we investigated the mechanism by which metformin induces mitophagy through restoration of the suppressed Parkin-mediated mitophagy. To this end, our ob/ob mice were divided into three groups: (1) ad libitum feeding of a standard chow diet; (2) intraperitoneal injections of metformin 300 mg/kg; and (3) 3 g/day caloric restriction (CR). HepG2 cells were treated with palmitate (PA) plus high glucose in the absence or presence of metformin. We detected enhanced mitophagy in ob/ob mice treated with metformin or CR, whereas mitochondrial spheroids were observed in mice fed ad libitum. Metabolically stressed ob/ob mice and PA-treated HepG2 cells showed an increase in expression of endoplasmic reticulum (ER) stress markers and cytosolic p53. Cytosolic p53 inhibited mitophagy by disturbing the mitochondrial translocation of Parkin, as demonstrated by immunoprecipitation. However, metformin decreased ER stress and p53 expression, resulting in induction of Parkin-mediated mitophagy. Furthermore, pifithrin-α, a specific inhibitor of p53, increased mitochondrial incorporation into autophagosomes. Taken together, these results indicate that metformin treatment facilitates Parkin-mediated mitophagy rather than mitochondrial spheroid formation by decreasing the inhibitory interaction with cytosolic p53 and increasing degradation of mitofusins.ope

Protocol-Based Resuscitation for Septic Shock: A Meta-Analysis of Randomized Trials and Observational Studies

PURPOSE: Owing to the recommendations of the Surviving Sepsis Campaign guidelines, protocol-based resuscitation or goal-directed therapy (GDT) is broadly advocated for the treatment of septic shock. However, the most recently published trials showed no survival benefit from protocol-based resuscitation in septic shock patients. Hence, we aimed to assess the effect of GDT on clinical outcomes in such patients. MATERIALS AND METHODS: We performed a systematic review that included a meta-analysis. We used electronic search engines including PubMed, Embase, and the Cochrane database to find studies comparing protocol-based GDT to common or standard care in patients with septic shock and severe sepsis. RESULTS: A total of 13269 septic shock patients in 24 studies were included [12 randomized controlled trials (RCTs) and 12 observational studies]. The overall mortality odds ratio (OR) [95% confidence interval (CI)] for GDT versus conventional care was 0.746 (0.631-0.883). In RCTs only, the mortality OR (95% CI) for GDT versus conventional care in the meta-analysis was 0.93 (0.75-1.16). The beneficial effect of GDT decreased as more recent studies were added in an alternative, cumulative meta-analysis. No significant publication bias was found. CONCLUSION: The result of this meta-analysis suggests that GDT reduces mortality in patients with severe sepsis or septic shock. However, our cumulative meta-analysis revealed that the reduction of mortality risk was diminished as more recent studies were added.ope