Reduced antiviral seropositivity among patients with inflammatory bowel disease treated with immunosuppressive agents.

BACKGROUND: Although live-attenuated vaccines are contraindicated under immunosuppression, the immune status of patients with inflammatory bowel disease (IBD) has not been fully assessed prior to immunosuppressive therapy. AIMS: To investigate antiviral serostatus against viruses requiring live vaccines for prevention in IBD patients undergoing immunosuppressive therapy. METHODS: This multicenter study included IBD patients who were aged <40 years and were treated with thiopurine monotherapy, molecular-targeted monotherapy, or combination therapy. Gender- and age-matched healthy subjects (HS) living in the same areas were included as control group. Antibody titers against measles, rubella, mumps, and varicella were measured by enzyme-linked immunosorbent assays. RESULTS: A total of 437 IBD patients (163 ulcerative colitis [UC] and 274 Crohn's disease [CD]) and 225 HS were included in the final analysis. Compared with HS, IBD patients had lower seropositivity rates for measles (IBD vs. HS = 83.91% vs. 85.33%), rubella (77.55% vs. 84.89%), mumps (37.50% vs. 37.78%), and varicella (91.26% vs. 96.44%). Gender- and age-adjusted seropositivity rates were lower in UC patients than in both CD patients and HS for measles (UC, CD, and HS = 81.60%, 85.29%, and 85.33%), rubella (76.40%, 78.23%, and 84.89%), mumps (27.16%, 43.70%, and 37.78%), and varicella (90.80%, 91.54%, and 96.44%); the difference was significant for all viruses except measles. Divided by the degree of immunosuppression, there were no significant differences in seropositivity rates among IBD patients. CONCLUSIONS: IBD patients, especially those with UC, exhibit reduced seropositivity rates and may benefit from screening prior to the initiation of immunosuppressive therapy.

A Partial Clamp During Off-Pump Coronary Artery Bypass Grafting Can be Safely Used When Utilizing the Calcium Score with Computed Tomography For Evaluating The Ascending Aorta.

BACKGROUND: No previous study has shown that the volume of calcium score is useful for evaluating the aorta when performing a partial clamp (PC). The purpose of this study was to examine the effect of different clamping strategies during off-pump coronary artery bypass grafting (OPCAB), in terms of the incidence of postoperative stroke using the calcium score of the ascending aorta. METHODS: We retrospectively reviewed 339 patients, who underwent isolated OPCAB between August 2013 and March 2021. There were two groups of patients, depending on the procedure. A PC was used for proximal anastomoses in 130 (38.3%) patients. A clampless proximal facilitating anastomotic device (CFD) was used in 107 (31.5%) patients. We prescribed preoperative CT for all patients, and the Agatston score was used. RESULTS: The calcium score significantly was higher in the CFD group than in the PC group (29.7 ± 66.5 vs. 1819.8 ± 2391.5, < 0.001). The number of distal anastomoses and operative time were not significantly different between the two groups. There was no mortality and three strokes occurred at the 30-day follow up. Two strokes occurred in the PC group (1.5%) and one in the CFD group (0.9%), which was not significantly different (P = 0.98). CONCLUSION: A PC does not increase postoperative stroke incidence compared with a CFD, when utilizing calcium score evaluation in OPCAB.

Endoscopic Internal Thoracic Artery Harvesting with Changes in Scope Position.

Although minimally invasive direct coronary artery bypass (MIDCAB) is a less invasive procedure, internal thoracic artery (ITA) harvesting is difficult. A 65-year-old woman was advised to undergo MIDCAB for recurrent in-stent restenosis. We harvested the ITA using three-dimensional endoscopy without robotics and determined the scope position using enhanced computed tomography. We changed the camera installation between the wound and the camera port, according to the harvesting site with a harmonic scalpel using the skeletonized technique. We harvested the ITA from the subclavian vein level superiorly to the xyphoid process level inferiorly.

Mild Systemic Hypothermic Circulatory Arrest Using a Frozen Elephant Trunk Graft with Endo-Balloon Occlusion for Total Arch Replacement.

BACKGROUND: Stroke and paraplegia are serious complications of total aortic arch replacement (TAR). Hypothermic circulatory arrest and cerebral perfusion reduce the risk of neurologic complications, but longer circulatory arrest time remains a risk factor for such complications. We utilized a frozen elephant trunk (FET) with endo-balloon occlusion under mild systemic hypothermia, which allowed us to shorten circulatory arrest time. METHODS: Between April 2007 and May 2020, 72 patients underwent elective TAR using antegrade cerebral perfusion (ACP). They were divided into 2 groups. 64 patients received conventional TAR with moderate systemic hypothermic (bladder temperature, 25-28°C) circulatory arrest (group C). We used a FET with endo-balloon occlusion and retrograde perfusion through the femoral artery for the newest 8 patients who had mild hypothermic (bladder temperature of 30°C) circulatory arrest (group B). RESULTS: The mean operation time (257.5 ± 42.1 versus 327.8 ± 84.9 min, P = .023), CPB time (144.4 ± 28.1 versus 178.2 ± 26.4 min, P = .003), cardiac arrest time (75.5 ± 21.2 versus 95.7 ± 56.4 min, P < .001), SCP time (100.8 ± 25.5 versus 124 ± 23.2 min, P < .001), lower body circulation arrest time (17.2 ± 4.2 versus 62.5 ± 19.3 min, P < .001) were significantly shorter in the endo-balloon occlusion group. There were no perioperative neurological and renal complications or mortality in FET group. The new technique enabled a decrease in mechanical ventilation time (8.6 ± 1.4 versus 13.9 ± 5.7 min, P = .015) and hospital length of stay (9.7 ± 1.8 versus 18.3 ± 4.6 min, P = .005). CONCLUSION: FET using an endo-balloon occlusion with mild hypothermia is a safe and an effective approach in TAR.

[Lung Adenocarcinoma Combined with Minute Pulmonary Meningothelial-like Nodule (MPMN) in Young Patient;Report of a Case].

We report a rare case of lung adenocarcinoma combined with minute pulmonary meningothelial-like nodule (MPMN) in a young adult. A 39-year-old woman was referred to our department for abnormal shadow of the right lower lobe. Chest computed tomography (CT) showed a mass shadow, 11 mm in size, in right S6. Since fluorodeoxyglucose-positron emission tomography (FDG-PET) demonstrated a lesion with FDG activity, with an increased uptake value of 2.2, this lesion was suspected to be a lung cancer. Wedge resection of right S6 was performed via thoracoscopy. The intraoperative pathological diagnosis was invasive lung adenocarcinoma, and additional right S6 segmentectomy and lymph node dissection (ND1a) was performed. The final pathological diagnosis of the tumor was adenocarcinoma of the lung, and MPMN was incidentally found by pathology in reseced specimen.

Long-term course of inflammatory bowel disease after the Great East Japan Earthquake.

BACKGROUND AND AIM: This study analyzed inflammatory bowel disease activity for 2 years after the Great East Japan Earthquake. METHODS: We compared the relapse rates of patients with ulcerative colitis or Crohn's disease 1 and 2 years after the earthquake with rates immediately after the earthquake. To evaluate continuous disease courses, we also performed multivariate time-to-event analyses from the time of the earthquake to the onset of additional treatments. RESULTS: Of 903 patients with ulcerative colitis or Crohn's disease in our previous study, we could evaluate 2-year courses in 677 patients (394 ulcerative colitis and 283 Crohn's disease). Compared with the relapse rates of ulcerative colitis and Crohn's disease immediately after the earthquake (15.8% and 7.0%, respectively), those in the corresponding periods in 2012 (2.5% and 1.1%, respectively) and 2013 (2.3% and 2.5%, respectively) significantly decreased. There were 226 patients who required additional treatments after the earthquake. Multivariate time-to-event analyses revealed that only patients who had experienced the death of family members or friends were likely to need additional treatments (hazard ratio = 1.77, 95% confidence interval = 1.25-2.47). No other factors had a significant influence. CONCLUSIONS: The relapse rates 1 and 2 years after the earthquake significantly decreased. The factors that influenced long-term relapse were different from those that influenced short-term relapse.

Simultaneous development of sarcoidosis and cutaneous vasculitis in a patient with refractory Crohn's disease during infliximab therapy.

BACKGROUND: Paradoxical inflammations during anti-TNF-α therapy are defined as adverse effects such as psoriasiform skin lesions, uveitis and sarcoidosis-like granulomas induced by immune reactions, not by infectious agents. Here, we report a very rare case of the simultaneous development of sarcoidosis and cutaneous vasculitis in a patient with refractory Crohn's disease during infliximab therapy and both of which resolved spontaneously without the cessation of infliximab. CASE PRESENTATION: In September 2000, 23-year old Japanese male was diagnosed with Crohn's disease. Prednisolone in combination with mesalazine was introduced at first and succeeded for almost one year. In June 2002, since his gastrointestinal symptoms relapsed and were refractory, infliximab (IFX) therapy 5 mg/kg was introduced. In February 2011, because he had repeated arthralgia almost every intravenous IFX administration, IFX was increased to 10 mg/kg under the diagnosis of a secondary failure of IFX. In December 2012, he complained of slight dry cough and an itchy eruption on both lower limbs, and he was referred to our hospital due to the appearance of bilateral hilar lymphadenopathy on chest X-ray examination. Chest computed tomogram revealed bilateral hilar lymphadenopathy and fine reticulonodular shadows on the bilateral upper lungs. Serum calcium, angiotensin-converting enzyme and soluble interleukin 2 receptor levels were not elevated, but the titer of antinuclear antibody was considerably elevated. Mycobacterium infection was carefully excluded. Trans-bronchial lung biopsy showed non-caseating epithelioid cell granulomas compatible with sarcoidosis. The skin biopsy of the right limb was diagnosed as leukocytoclastic vasculitis. The patient was diagnosed as having a series of paradoxical inflammations during anti-TNF-α therapy. Since his paradoxical inflammations were not severe and opportunistic infections were excluded, IFX was cautiously continued for refractory Crohn's disease. Nine months later, not only his intrathoracic lesions but also his cutaneous lesions had spontaneously resolved. CONCLUSION: Physicians caring for patients with anti-TNF-α therapy should know that, based on a careful exclusion of infectious agents and thoughtful assessment of the patient's possible risks and benefits, paradoxical inflammations can be resolved without the cessation of anti-TNF-α therapy.

Strategy for acute DeBakey type I aortic dissection considering midterm results: a retrospective cohort study comparing ascending aortic replacement and total arch replacement with frozen elephant trunk technique.

BACKGROUND: Acute type A aortic dissection is treated with an emergency procedure that uses ascending aortic replacement (AAR). However, to avoid a residual dissected aorta with a false lumen, total arch replacement (TAR) is required. The frozen elephant trunk (FET) technique is a promising surgical approach that promotes false lumen obliteration in a single step. Therefore, this retrospective single-center study aimed to evaluate the operative outcomes of AAR and TAR with FET. METHODS: Between 2007 and 2021, 143 patients with acute DeBakey type I aortic dissection underwent a central repair using AAR (n = 95) or TAR with FET (n = 43). All perioperative variables, the duration of all-cause mortality, and aortic events defined as dilatation of the distal aorta > 5 cm, new occurrences of aortic dissection, distal aortic surgery, and distal aortic rupture were recorded. We compared these perioperative variables and mid-term results with an additional focus on distal aortic events. RESULTS: Patient background data did not differ between the two groups. Perioperative results for the TAR with FET group vs the AAR group showed similar operative times (306 vs 298 min, P = 0.862), but the TAR group had longer cardiopulmonary bypass times (154 vs 179 min, P < 0.001). The freedom from all-cause death for the TAR vs AAR groups using the Kaplan-Meier method was 81.9% vs 85.4% and 78.0% vs 85.4% (P = 0.407) at 1 and 3 years, respectively. Freedom from aorta-related events was 90.6% vs 97.6% and 69.3% vs 87.0% (P = 0.034) at 1 and 3 years, respectively. CONCLUSIONS: TAR with FET had comparable perioperative results to AAR in acute DeBakey type I aortic dissection and was considered a valuable method to avoid aorta-related events in the midterm.

Thoracic Endovascular Aortic Repair Without Subclavian Revascularization of a Ruptured Kommerell Diverticulum.

A ruptured Kommerell diverticulum is extremely rare. This is the first report of thoracic endovascular aortic repair without subclavian revascularization of a ruptured Kommerell diverticulum with a right-sided aortic arch. However, decisions regarding subclavian revascularization should be individualized based on the patient's anatomy and clinical presentation.

Prognostic and diagnostic significance of tumor budding associated with ß-catenin expression in submucosal invasive colorectal carcinoma.

Endoscopic resection has become a major curative treatment for early colorectal carcinoma without lymph node metastasis. However, lymph node metastasis, a poor prognostic factor in colorectal carcinoma, occurs in about 10% of the patients with submucosal invasive colorectal carcinoma. Therefore, it is important to identify a high-risk factor for lymph node metastasis in submucosal invasive colorectal carcinoma. This study was designed to identify the relationship between tumor budding with ß-catenin expression and lymph node metastasis in submucosal invasive colorectal carcinoma. We investigated the immunohistochemistry of tumor budding in the 142 patients who underwent surgical resection for submucosal invasive colorectal carcinomas between 1984 and 1999 and the expression pattern of ß-catenin in budding tumor cells. Accordingly, all the patients were followed up for at least 10 years or until death. Among the 142 patients, lymph node metastasis was detected in 14 patients (9.9%). Univariate analysis showed that tumor budding with ≥ 5 tumor cells or cell clusters with expression of ß-catenin in the nucleus was significantly associated with lymph node metastasis (P = 0.005). In contrast, tumor budding detected by hematoxylin and eosin staining was not associated with lymph node metastasis. Multivariate logistic regression analysis showed that tumor budding with ≥ 5 tumor cells or cell clusters with expression of ß-catenin in the nucleus was a significant risk factor for lymph node metastasis (odds ratio, 7.124; 95% confidence interval, 1.407-36.062). Thus, tumor budding associated with ß-catenin expression is a risk factor for lymph node metastasis in submucosal invasive colorectal carcinoma.

Concomitant surgery of minimally invasive direct coronary artery bypass with left atrium appendage closure.

Surgical approaches of minimally invasive direct coronary artery bypass and left atrial appendage exclusion are different, and issues may arise in cases of concomitant surgery. Moreover, the safety of concomitant procedures has not been established. A man in his 80s with a history of stroke required minimally invasive coronary artery bypass grafting and left atrial appendage closure for the stenosis of the left anterior descending artery and atrial fibrillation. He suffered from bladder bleeding, which required early reduction of anticoagulant and antiplatelet medication. Therefore, he wished for surgical treatment. A lateral incision was necessary for left atrial appendage closure in minimally invasive surgery. We performed totally endoscopic harvest of the internal thoracic artery without a robotic system. This method allowed the incision to be made more laterally. Combining the endoscopic harvest of the internal mammary artery with left atrial appendage closure via lateral incision may be a reasonable technique.

Combination of endoscopic internal thoracic artery harvest and proximal anastomoses on the descending aorta in minimally invasive coronary artery bypass grafting.

Minimally invasive coronary artery bypass grafting is less invasive. Proximal anastomoses at the ascending aorta, in contrast, are technically difficult to perform because of the limited field of view. A man in his 60s undergoing haemodialysis required minimally invasive coronary artery bypass grafting for left anterior descending artery and circumflex arterial restenosis. We successfully performed minimally invasive coronary artery bypass grafting with a proximal graft anastomosis of the descending aorta. A thoracotomy was performed to extend the lateral approach to the descending aorta. We performed a minithoracotomy using three-dimensional endoscopy for internal thoracic artery harvesting. Endoscopic internal thoracic artery harvesting minimises incision length. The combination of endoscopic and lateral thoracotomy incisions in minimally invasive coronary artery bypass grafting enabled small and lateral thoracotomy incisions.

Revascularization for controlling hypertension and improving cardiorenal failure in Leriche syndrome.

Leriche syndrome usually occurs when atherosclerotic obstructions result in luminal narrowing of the abdominal aorta or iliac arteries and leads to thrombosis; it rarely causes heart or renal failure. We report the case of a 58-year-old Asian man with heart and renal failure as the dominant clinical manifestations of renovascular hypertension caused by Leriche syndrome. We performed an aorto-bifemoral bypass and unilateral renal artery stenting. Post-operative echocardiography showed improved cardiac function, with the left ventricular ejection fraction increasing from 30% before surgery to 54.2% after surgery. Moreover, his heart rate and blood pressure became stable, and his serum creatinine and brain natriuretic peptide levels decreased from 3.46 to 1.08 mg/dL and 685 to 4 pg/mL, respectively. Our case report shows that aorto-bifemoral bypass and unilateral renal artery stenting can effectively treat heart and renal failure resulting from renovascular hypertension caused by Leriche syndrome.

TNFSF15 transcripts from risk haplotype for Crohn's disease are overexpressed in stimulated T cells.

TNFSF15 is a susceptibility gene for Crohn's disease (CD). It remains to be elucidated how the associated single nucleotide polymorphisms (SNPs) in TNFSF15 affect the susceptibility to CD. Because there are no non-synonymous SNPs in TNFSF15, we speculated that one or more of the SNPs associated with CD may act as cis-regulatory SNPs. To reveal the effects of the SNPs on the transcriptional activity of TNFSF15, we first examined the allelic expression imbalance of TNFSF15 in peripheral blood mononuclear cells (PBMCs). When PBMCs stimulated by phytohemagglutinin (PHA) were examined, the allelic ratio of mRNA transcribed from the risk haplotype to the non-risk haplotype increased, compared with the ratio without stimulation. When peripheral blood T cells and Jurkat cells stimulated by phorbol 12-myristate 13-acetate + ionomycin were examined, an allelic expression imbalance similar to that observed in PBMCs stimulated by PHA was confirmed. The promoter assay in stimulated Jurkat cells showed that the luciferase activity of the promoter region (-979 to +35) of the risk haplotype was significantly higher than that of the non-risk haplotype, and deletion and mutagenesis analysis demonstrated that this difference resulted from the -358T/C SNP. The promoter activity of -358C (risk allele) was higher than that of -358T (non-risk allele) in stimulated T cells. This effect of -358T/C on the transcriptional activity in stimulated T cells may confer susceptibility to CD.

Stent graft in abdominal aortic aneurysm collapsed suddenly after thoracic endovascular aortic repair.

Stent graft collapse due to aortic dissection is an extremely rare event. Although endovascular aneurysm repair (EVAR) and thoracic endovascular aortic repair (TEVAR) are increasingly being performed, various complications can occur. We report a case of collapse of a stent graft, which was used to repair an abdominal aortic aneurysm (AAA) after TEVAR for thoracic aortic aneurysm (TAA). A 72-year-old man with a 77 mm AAA and 60 mm TAA underwent EVAR and a TEVAR 2 months later, respectively. CT performed after the TEVAR showed thoracic aorta dissection with associated AAA stent graft collapse. The graft collapsed was due to superior mesenteric artery obstruction. An emergency TEVAR was performed, and the procedure improved the collapsed graft; however, the endoleak of the AAA stent graft persisted. The AAA expanded over several days, warranting an open repair. Our case provides an insight into the cautionary indications for endovascular therapy.

Late-onset total anomalous pulmonary venous connection in a 70-year-old woman.

Total anomalous pulmonary venous connection (TAPVC) is a rare congenital cardiac anomaly. There are a few reports of untreated TAPVC diagnosed in patients older than 60 years. Herein, we report the successful surgical treatment of TAPVC in a 70-year-old woman. A 70-year-old woman with TAPVC presented with symptoms of acute heart failure. We closed an atrial septal defect and performed tricuspid annuloplasty and commissurotomy of the pulmonary valve. Postoperative CT showed no residual shunt, and the pulmonary veins drained into the left atrium. She had an uneventful postoperative course. This report describes the case of the oldest known patient who underwent surgical treatment for TAPVC. Surviving into adulthood with little or no symptoms is uncommon in patients with TAPVC, and cases of late-onset TAPVC, such as our case, are rare. Nevertheless, close vigilance is necessary to prevent misdiagnosis in patients with this clinical presentation.

What determines the later clinical course of patients who do not undergo colectomy at the first attack? A Japanese cohort study on ulcerative colitis.

BACKGROUND/AIMS: Several earlier studies on factors predicting the long-term outcome of ulcerative colitis only encompassed treatment failure for one severe episode, or suffered from a lack of multivariate analyses. We aimed to identify factors assessable at diagnosis or after the first induction therapy which predicted relapse or later colectomy in patients with mild to severe ulcerative colitis. METHODS: Clinical parameters (age, sex, disease extent, and disease activity at diagnosis) and laboratory data (hemoglobin, albumin, C-reactive protein, and erythrocyte sedimentation rate at diagnosis and 4 weeks after the first induction therapy) were evaluated in 296 patients (median follow-up 87 months). Factors predicting relapse and later colectomy were sought using the Cox proportional hazard model. RESULTS: The presence of moderate or severe disease at diagnosis were significant predictors of relapse [adjusted hazard ratio (95% CI) 2.07 (1.48-2.89) and 1.70 (1.06-2.72), respectively] and later colectomy [3.40 (1.09-10.54) and 6.77 (1.92-23.86)]. After the first induction therapy, hemoglobin and albumin were associated with relapse [0.87 (0.76-0.99) and 0.58 (0.41-0.83)] and later colectomy [0.60 (0.47-0.77) and 0.11 (0.06-0.22)]. CONCLUSION: Relapse and later colectomy were associated with (1) disease activity at diagnosis and (2) lower levels of hemoglobin and albumin after the first induction therapy.

Scheduled maintenance therapy with infliximab improves the prognosis of Crohn's disease: a single center prospective cohort study in Japan.

The main goal of Crohn's disease (CD) treatment at present is to induce and maintain remission for as long as possible, and several approaches have been used as induction and maintenance therapies. There are no reports that have compared the effects on mid- and long-term prognosis among the induction and maintenance therapies, especially between infliximab, a chimeric antibody to tumor necrosis factor-alpha, and nutritional therapies. A total of 262 CD patients with induced remission were enrolled in the cohort study. Patients who failed to achieve remission, and patients who were lost to follow-up within 12 months were excluded. Induction therapies for CD included total elemental enteral nutrition, total parenteral nutrition, infliximab, prednisolone, and surgical resection. Maintenance therapies included home elemental diet, 5-aminosalicylates, immunomodulators, and scheduled infliximab therapy. We evaluated the possible predictive factors of relapse and surgical recurrence including the clinical backgrounds of the patients and medical therapies, using the Cox multivariate hazard analysis. The main factors that strongly affected the first relapse were scheduled infliximab therapy (hazard ratio (HR) = 0.24, p < 0.0001), surgical induction (HR = 0.19, p < 0.0001) and high frequency of previous relapse (HR = 2.56, p = 0.002). Penetrating (HR = 3.33, p = 0.009) and stricturing (HR = 6.60, p < 0.0001) disease behavior were main risk factors of surgical recurrence. Scheduled infliximab therapy is the most effective maintenance therapy in a real clinical setting with respect to the mid- and long-term prognosis.

Relapse of aortopulmonary window 41 years after patch closure.

In this study, we describe a rare case of a 45-year-old man with a recurrence of aortopulmonary window (APW) 41 years after the initial patch closure for an APW at the age of 4. He presented with persistent cough and exertional dyspnoea. Imagings revealed a recurrence of APW, ascending aorta saccular aneurysm, and severe mitral and tricuspid regurgitation. Re-patch closure, ascending aortic replacement, and mitral and tricuspid annuloplasties were performed, followed by an uneventful postoperative course. The relapse of APW in the remote postoperative period is extremely rare.

Effects of estrogens on striatal damage after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxicity in male and female mice.

Emerging evidence shows a beneficial effect of estrogens for Parkinson's disease, yet the exact potency of these compounds implicated remain obscured. In this study, we investigated the neuroprotective effect of 17beta-estradiol and estrone against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced striatal toxicity in mice. The neuroprotective effects of both compounds were evaluated by HPLC and Western blot analyses 5 days after the last of 4 consecutive injections of MPTP at 1-h intervals to mice. Subacute treatment (10 days) with estrone or 17beta-estradiol at low doses (0.05 and 0.2mg/kg) showed no significant changes against MPTP-induced damage of striatal dopamine terminals in mice. Furthermore, acute treatment with estrone at high doses (0.5 and 2.0mg/kg) showed no significant alterations against MPTP-induced damage of striatal dopamine terminals in mice. In contrast, acute treatment with 17beta-estradiol at high doses exhibited a neuroprotective effect against the damage of striatal dopamine terminals in both male and female mice after MPTP treatments. The results demonstrate that estrogen therapy with high doses may have a neuroprotective effect on the damage of striatal dopamine terminals in the MPTP-induced mice. These findings may lead to be development of estrogen therapy for the prevention and treatment of Parkinson's disease.