Synthesis of the A/D/E-ring Core Compounds of Maoecrystal V†.

Synthesis of the A/D/E-ring core compounds of maoecrystal V was achieved. The key Diels-Alder reactions between tricyclic α-methylene lactones and Kitahara-Danishefsky dienes afforded the spirocyclic core compounds in a regioselective and stereoselective manner.

Cost-effectiveness Analysis of Second-Generation Antihistamine 1 Receptor Blockers and Japanese Kampo Shoseiryuto for Treating Perennial Allergic Rhinitis in Outpatient Settings in Japan.

Objectives: Perennial allergic rhinitis (PAR) is common in Japan. Second-generation antihistamines (SGAs) are commonly used for its treatment; however, it remains unclear which SGA is the most cost-effective. Additionally, the pharmacoeconomics of Japanese Kampo shoseiryuto (which was traditionally prescribed to treat PAR in Japan) remains poorly understood. In this study, we aimed to investigate the effectiveness of various SGAs and shoseiryuto for the treatment of PAR in Japanese outpatients, from the healthcare payer's perspective. Methods: The most cost- and clinically effective SGAs were determined from a list of 6 SGAs (bepotastine, 10 mg; cetirizine, 10 mg; ebastine, 10 mg; epinastine, 20 mg; loratadine, 10 mg; and olopatadine, 5 mg) together with shoseiryuto, using the overall improvement rate through a model-based analysis. The time horizon was 28 days. Costs were determined based on the Medical Fee Index in 2020. Deterministic and probabilistic sensitivity analyses were conducted to address the uncertainty of the base-case results. Results: Overall, bepotastine (10 mg) and ebastine (10 mg) were cost-effective. Shoseiryuto was less cost-effective than ebastine (10 mg) (dominated). Ebastine (10 mg) was the most cost-effective option based on deterministic and probabilistic sensitivity analyses. Conclusions: Ebastine (10 mg) was the most cost-effective treatment strategy for PAR among the agents evaluated in this study. This insight could aid in establishing an appropriate formulary for treating PAR in hospitals and communities.

Postreperfusion Syndrome Presenting as Posttransplant Portal Hypertension due to Prolonged Elevation of Pulmonary Vascular Resistance and the Role of Nitroglycerin in Diagnosis and Treatment: A Case Report of Budd-Chiari Syndrome.

Postreperfusion syndrome is one of the responsible mechanisms of portal hypertension in patients undergoing liver transplantation. And post-transplant portal hypertension causes graft dysfunction. Postreperfusion syndrome is characterized by a decrease in arterial pressure and cardiac output, and an increase in central venous pressure, pulmonary artery pressure, and pulmonary vascular resistance that occurs after the release of the portal vein clamp. Although early recovery from postreperfusion syndrome is desired, there is a little medication therapy such as the administration of calcium chloride, sodium bicarbonate, and beta-agonist for postreperfusion syndrome. We present a case of postreperfusion syndrome manifested as post-transplant portal hypertension and reversed after nitroglycerin administration. A 49-year-old Asian woman was scheduled for liver transplantation because of Budd-Chiari syndrome. After portal vein reperfusion, she experienced severe postreperfusion syndrome. Administration of ephedrine and calcium restored arterial pressure; however, pulmonary artery pressure, pulmonary vascular resistance, and central venous pressure elevations were sustained, causing right ventricular overload. This condition did not improve after hepatic artery reperfusion, and caused post-transplant portal hypertension. After nitroglycerin administration, pulmonary vascular resistance and central venous pressure decreased, mean arterial pressure increased, right heart contractility recovered, and portal hypertension disappeared. Hemodynamic improvement by nitroglycerin administration helped in diagnosing postreperfusion syndrome and avoiding unnecessary splenectomy. If portal vein pressure increases after liver transplantation, the change in hemodynamic parameters by nitroglycerin administration should be assessed, which will lead to accurate diagnosis and appropriate treatment. Furthermore, postreperfusion syndrome should be listed as a differential diagnosis of post-transplant portal hypertension.

Synthesis of (12R,13S)-pyriculariol and (12R,13S)-dihydropyriculariol revealed that the rice blast fungus, Pyricularia oryzae, produces these phytotoxins as racemates.

Synthesis of assumed natural (12R,13S)-enantiomers of pyriculariol (1) and dihydropyriculariol (2), phytotoxins isolated from rice blast disease fungus, Pyricularia oryzae, was achieved using Wittig reaction or microwave-assisted Stille coupling reaction as the key step. The synthesis revealed that the natural 1 and 2 are racemates. Foliar application test on a rice leaf indicated that both the salicylaldehyde core and side chain were necessary for phytotoxic activity. The fungus is found to produce optically active phytotoxins when incubated with rotary shaker, but racemic ones when cultured using an aerated jar fermenter.

Gamma Knife Radiosurgery for Symptomatic Cavernous Malformations: Tokyo Women's Medical University Experience.

OBJECTIVE: This retrospective study evaluated the results of Gamma Knife surgery (GKS) for symptomatic cavernous malformations (CM) of the brain. METHODS: From 1993 till 2014, 11 patients (mean age 44 years) with a symptomatic CM underwent GKS at Tokyo Women's Medical University. In six cases, the disease manifested with hemorrhaging. Seizures and a neurological deficit were noted in four patients each. The CM were located in the brainstem (in 5 cases), basal ganglia (in 2 cases), thalamus (in 2 cases), and cerebral lobe (in 2 cases). The mean lesion volume was 1.46 cc. The mean marginal dose was 15.3 Gy. The mean length of follow-up after GKS was 78.5 months. RESULTS: At the last follow-up, the general status was considered excellent, fair, and poor in 8 patients (73%), 1 patient (9%), and 2 patients (18%), respectively. The annual hemorrhage rates per case-year were 2.94% from birth till GKS, 20.20% from the first hemorrhage till GKS, 4.54% within the first 2 years after GKS, and 1.39% within the entire follow-up period after GKS. Two patients attained seizure-free status after treatment. CONCLUSION: GKS may be considered as a possible management option for symptomatic CM, since it reduces the subsequent hemorrhage risk after the initial bleeding episode. Moreover, in some patients, cessation of symptomatic epilepsy after treatment may be expected.

Effect of edaravone against cisplatin-induced chronic renal injury.

Cisplatin has been widely used as an anticancer agent for a wide range of tumors, but it had nephrotoxicity that was mainly caused by oxidative stress. Edaravone, a free radical scavenger, has reportedly been validated to have a protective effect against renal injury induced by reactive oxygen species. However, most of these reports are against AKI, and few studies have examined the effect of chronic renal injury. In this study, we investigate the effect of edaravone on cisplatin nephropathy in the chronic phase. Twenty-five male Wistar rats were divided into five groups: control, cisplatin, cisplatin + edaravone 1 mg kg-1, cisplatin + edaravone 10 mg kg-1, and cisplatin + edaravone 100 mg kg-1. Edaravone was administrated intraperitoneally every other day for 5 weeks, starting 1 week before cisplatin administration (6 mg kg-1, i.p.). As a result, proximal tubule injury, interstitial fibrosis, and mononuclear cell infiltration were ameliorated histologically in the group of rats treated with high edaravone dose. In the cisplatin group, the number of α-SMA-, CD68-, and CD3-positive cells increased markedly compared with the Control group, but these numbers were significantly decreased by higher doses of co-administered edaravone. While there was no clear mRNA expression variation in antioxidant enzymes, the apoptosis-promoting factors, caspase8, were markedly reduced in the high-dose edaravone co-administration group compared with the cisplatin group. In conclusion, our results suggested that cisplatin-induced renal injury in the chronic phase was ameliorated by edaravone.

[An autopsy case of anaplastic pancreatic carcinoma with diffuse liver metastases in acute hepatic failure].

A 76-year-old man presented to our hospital with continuous abdominal pain and vomiting. The results of the computed tomography indicated a pancreatic head mass with multiple liver metastatic tumors. Multiple liver tumors progressed rapidly, and the patient died of the resulting acute hepatic failure approximately 1 month after the onset of symptoms. The results of the postmortem examination indicated anaplastic pancreatic carcinoma (pleomorphic type) with multiple liver metastases. The tumor cells in the primary pancreatic lesion and liver metastases were replaced with normal tissue, and they showed a decrease in stainability by E-cadherin staining. Overall, the pathological findings suggested that the inhibition of E-cadherin may be related to the proliferation and infiltration of anaplastic cancer cells.

Molecular detection of apicomplexan protozoa in Hokkaido brown bears (Ursus arctos yesoensis) and Japanese black bears (Ursus thibetanus japonicus).

Many tick-borne pathogens (TBPs) are present in wildlife. The objective of this study is to reveal the role of wild bears in maintaining TBPs. A total of 49 brown bears (Ursus arctos yesoensis) from Hokkaido, and 18 Japanese black bears (Ursus thibetanus japonicus) from Tochigi, and 66 Japanese black bears from Nagano were examined by two molecular methods, reverse line blot (RLB) hybridization, and nested PCR. A total of 5 TBPs (Hepatozoon ursi, Babesia sp. UR2-like group, Cytauxzoon sp. UR1, Babesia sp. UR1, and Babesia microti) were detected from bear blood DNA samples. B. microti was detected from blood DNA samples of Japanese black bear for the first time, with the prevalence of 6.0% (5/84). Out of detected pathogens, H. ursi, Babesia sp. UR2-like pathogens, and Cytauxzoon sp. UR1 were considered as three of the most prevalent TBPs in bears. The prevalence of H. ursi were significantly higher in Japanese black bear (0% vs 96.4%) while that of Babesia sp. UR2-like group was higher in Hokkaido brown bears (89.8% vs 40.5%). The prevalence of Babesia sp. UR1 were significantly higher in Japanese black bears from Tochigi (44.4%), comparing with those from Nagano (18.2%). The prevalence of the detected TBPs were significantly higher in adult bears, comparing with those in younger bears. The present study suggests that Japanese bear species contribute in the transmission of several TBPs in Japan. The expanding distribution of bears might cause the accidental transmission of TBPs to humans and domestic animals.

Dimethyl fumarate ameliorates cisplatin-induced renal tubulointerstitial lesions.

Dimethyl fumarate (DMF) has an antioxidant effect by activating the nuclear factor erythroid 2-related transcription factor 2 (Nrf2). Cisplatin (CIS) has nephrotoxicity as a frequently associated side effect that is mainly mediated by oxidative stress. In this study, we investigated whether the DMF-mediated antioxidative mechanism activated by Nrf2 can ameliorate CIS-induced renal tubulointerstitial lesions in rats. In Experiments 1 and 2, 25 five-week-old male Wistar rats were divided into five groups: control, CIS, and 3 CIS+DMF groups (300, 1,500, and 7,500 ppm in Experiment 1; 2,000, 4,000, and 6,000 ppm in Experiment 2). Rats were fed their respective DMF-containing diet for 5 weeks. CIS was injected 1 week after starting DMF administration, and the same volume of saline was injected into the control group. CIS-induced severe tubular injury, such as necrosis and degeneration in the outer segment of the outer medulla, was inhibited in the 7,500 ppm DMF group and ameliorated in all DMF groups in Experiment 2. Increased interstitial mononuclear cell infiltration and increased Sirius red-positive areas were also observed in CIS-administered groups, and these increases tended to be dose-dependently inhibited by DMF co-administration in Experiments 1 and 2. The numbers of α-smooth muscle actin (SMA)-positive myofibroblasts, CD68-positive macrophages, and CD3-positive lymphocytes observed in the peritubular area also increased with CIS administration, and these increases were dose-dependently inhibited by DMF co-administration. Moreover, renal cortical mRNA expression of Nrf2-related genes such as NQO1 increased in DMF groups. This investigation showed that DMF ameliorates CIS-induced renal tubular injury via NQO1-mediated antioxidant mechanisms and reduces the consequent tubulointerstitial fibrosis.

[A case of intracholecystic papillary neoplasm of the gallbladder (ICPN) examined using contrast-enhanced endoscopic ultrasonography].

A 78-year-old woman was found to have gallbladder wall thickening on ultrasonography during a routine health check-up and was referred to our clinic. On contrast-enhanced endoscopic ultrasonography, a papillary lesion measuring 14mm was detected in the fundus, which showed a heterogeneous enhancement at the early phase. She underwent cholecystectomy and gallbladder bed resection. Histological examination revealed that the tumor consisted of mucinous atypical cells, regularly arranged in a high-papillary architecture with delicate fibrovascular cores, which led to the diagnosis of intracholecystic papillary neoplasm of the gallbladder.

A case of esophageal mucosa-associated lymphoid tissue lymphoma diagnosed using endoscopic ultrasound-guided fine-needle aspiration.

A 65-year-old man presenting with an esophageal lesion underwent esophagogastroduodenoscopy and computed tomography and an upper esophageal submucosal mass was found. Endoscopic ultrasound-guided fine-needle aspiration led to the diagnosis of mucosa-associated lymphoid tissue lymphoma of the esophagus. Positron emission tomography showed abnormal uptake in the internal iliac lymph nodes, and laparoscopic biopsy findings confirmed the diagnosis of esophageal cancer. The patient declined treatment of any kind and has been followed up for 39 months with no progression of the lymphoma.

Image Quality Characteristics of the 3D-parallel Imaging Method (CAIPIRINHA) in Abdominal MRI.

This study investigated the image quality using controlled aliasing in parallel imaging results in higher acceleration (CAIPIRINHA) to shorten the imaging time in dynamic abdominal examinations. Comparisons with the conventional generalized autocalibrating partially parallel acquisitions (GRAPPA) method were made by changing the sampling shift in CAIPIRINHA using a 3.0 T MRI. The measurements included the visual evaluation of five stages, the signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) in phantom experiments. The visual evaluation (five stages) and SNR were determined using a nickel sulfate bottle phantom attached to the MRI device. Each evaluation was performed on the middle slice of the 3D image. The SNR was compared with the mean region of interest value calculated from five locations within the phantom. The CNR was determined using custommade phantoms that mimic the T1 and T2 values of the liver and spleen. In the results, at reduction factor (Rf) = 6 and 8, the SNR per unit imaging time was reduced with GRAPPA, while there was no decrease in SNR and CNR with CAIPIRINHA. By performing imaging using an appropriate sampling shift, it is possible to acquire an equivalent GRAPPA in a short period of time using CAIPIRINHA.

[Can fruits and vegetables be used as substitute phantoms for normal human brain tissues in magnetic resonance imaging?].

Various custom-made phantoms designed to optimize magnetic resonance imaging (MRI) sequences have been created and subsequently reported in JSRT. However, custom-made phantoms that correctly match the T1-value and T2-values of human brain tissue (gray matter and white matter) cannot be made easily or quickly. The aim of this project was to search for alternative materials, such as fruits and vegetables, for optimizing MRI sequences. The following eight fruits and vegetables were investigated: apple, tomato, melon, apple mango (Mangifera indica), banana, avocado, peach, and eggplant. Their potential was studied for use in modeling phantoms of normal human brain tissues. MRI (T1- and T2-weighted sequences) was performed on the human brain and the fruits and vegetables using various concentrations of contrast medium (gadolinium) in the same size tubes as the custom-made phantom. The authors compared the signal intensity (SI) in human brain tissue (gray matter and white matter) with that of the fruits and the custom-made phantom. The T1 and T2 values were measured for banana tissue and compared with those for human brain tissue in the literature. Our results indicated that banana tissue is similar to human brain tissue (both gray matter and white matter). Banana tissue can thus be employed as an alternative phantom for the human brain for the purpose of MRI.

Cross-modal and subliminal effects of smell and color.

In the present study, we examined whether the cross-modal effect can be obtained between odors and colors, which has been confirmed under olfactory recognizable conditions and also occurs under unrecognizable conditions. We used two flavors of red fruits such as strawberries and tomatoes for this purpose. We also aimed to compare whether similar cross-modal effects could be achieved by setting the flavors at recognizable (liminal) and unrecognizable (subliminal) concentrations in the experiment. One flavor at a normal concentration (0.1%, Liminal condition) and one at a concentration below the subliminal threshold (0.015%, Subliminal condition), were presented, and the color that resembled the smell most closely from among the 10 colors, was selected by participants. Except for the subliminal tomato condition, each odor was significantly associated with at least one color (p < 0.01). Participants selected pink and red for liminal strawberry (0.1%) (p < 0.05), pink for subliminal strawberry (0.015%) (p < 0.05), and orange for liminal tomato (0.1%) (p < 0.05), but there was no color selected for subliminal tomato (0.015%) (p < 0.05). The results of this study suggest that the flavor of tomato produced a cross-modal effect in liminal conditions, but not in subliminal conditions. On the other hand, the results of the present study suggest that the flavor of strawberries produces a cross-modal effect even under subliminal conditions. This study showed that cross-modal effects might exist, even at unrecognizable levels of flavor.

[A case report of primary small cell esophageal carcinoma responding successfully to radiochemotherapy].

Primary small cell esophageal carcinoma is a rare cancer with a poor prognosis, for which to date there is no recommended standard treatment. We present a 60-year-old male with this disease who was successfully managed by the combination of radiation and chemotherapy. The patient was referred to our hospital for liver dysfunction of unknown cause. On admission, he was diagnosed as having a primary small cell esophageal carcinoma and multifocal metastasis in the liver. He received cisplatin and 5-fluorouracil(CDDP 40mg/m2-days 1, 8, 5-FU 400 mg/m2-days 1-5, 8-12)and local radiation of 50 Gy for the esophagus, followed by 4 courses of chemotherapy the same as listed above. At the end of therapy, radiological findings showed that both primary and metastatic lesions completely disappeared. Unfortunately, he died of liver failure due to the recurrence of metastatic small cell carcinoma in the liver 13 months after the end of initial therapy. However, the primary cancer lesion had not recurred by that time. These findings suggest the beneficial effect of the combination of radiotherapy and chemotherapy for advanced-stage small cell esophageal carcinoma.

Folinic Acid, Fluorouracil, and Oxaliplatin Therapy for Recurrent Esophageal Cancer with Syndrome of Inadequate Antidiuretic Hormone Secretion (SIADH) After Preoperative Cisplatin/5-Fluorouracil Therapy.

BACKGROUND Cisplatin/5-fluorouracil therapy is the standard therapy for unresectable and recurrent esophageal cancer. Cisplatin-based chemotherapy often causes adverse effects, such as nausea, vomiting, and renal dysfunction, which may necessitate dose modification or treatment prolongation. Therefore, novel combination therapies are urgently needed to improve the efficacy and overcome drug toxicity in this setting. CASE REPORT A 77-year-old man with advanced esophageal cancer received cisplatin/5-fluorouracil therapy as neoadjuvant chemotherapy. On day 8 of administration, the patient had lightheadedness, diaphoresis, and nausea and became unconscious and developed severe hyponatremia. We diagnosed the patient with cisplatin-induced syndrome of inadequate antidiuretic hormone secretion (SIADH). Subsequently, water restriction was started, and treatment with a salt-added diet and 3% hypertonic saline infusion was initiated. The hyponatremia improved and the patient was discharged on day 16 of administration. Therefore, neoadjuvant chemotherapy was discontinued, and surgical treatment was performed. However, the tumor recurred and chemotherapy was required. The patient developed severe hyponatremia while receiving neoadjuvant chemotherapy; hence, folinic acid, fluorouracil, and oxaliplatin therapy (FOLFOX) were administered as an alternative treatment. The patient completed the FOLFOX therapy without developing SIADH. CONCLUSIONS The cisplatin/5-fluorouracil therapy is currently the standard chemotherapy regimen for esophageal cancer. However, SIADH is a known adverse effect when using cisplatin. In patients with esophageal cancer, oxaliplatin appears to have a lower risk of SIADH than cisplatin, suggesting that oxaliplatin can be a therapeutic option for patients with esophageal cancer who are at high risk of SIADH.

white regulates proliferative homeostasis of intestinal stem cells during ageing in Drosophila.

Tissue integrity is contingent on maintaining stem cells. Intestinal stem cells (ISCs) over-proliferate during ageing, leading to tissue dysplasia in Drosophila melanogaster. Here we describe a role for white, encoding the evolutionarily conserved ATP-binding cassette transporter subfamily G, with a particularly well-characterized role in eye colour pigmentation, in ageing-induced ISC proliferation in the midgut. ISCs increase expression of white during ageing. ISC-specific inhibition of white suppresses ageing-induced ISC dysregulation and prolongs lifespan. Of the proteins that form heterodimers with White, Brown mediates ISC dysregulation during ageing. Metabolomics analyses reveal previously unappreciated, profound metabolic impacts of white inhibition on organismal metabolism. Among the metabolites affected by White, tetrahydrofolate is transported by White, is accumulated in ISCs during ageing and is indispensable for ageing-induced ISC over-proliferation. Since Thomas Morgan's isolation of a white mutant as the first Drosophila mutant, white mutants have been used extensively as genetic systems and often as controls. Our findings provide insights into metabolic regulation of stem cells mediated by the classic gene white.

A case of insulinoma diagnosed postpartum with hypoglycemic symptoms that were masked during pregnancy.

The diagnosis of insulinoma in perinatal women can be difficult, as hypoglycemic symptoms may be masked by pregnancy-associated insulin resistance. In addition, when multiple insulinomas are observed, it is necessary to consider the possibility not only of MEN1, but also of insulinomatosis.