Asymmetric synthesis of (−)-5,11-dideoxytetrodotoxin, an analog of puffer fish toxin, was accomplished from a common key intermediate through a novel hydroxylation at the C-8 position with ...neighboring group participation of trichloroacetamide, a highly stereoselective addition of acetylide as an equivalent of carboxylic acid, and a new guanidine synthesis from trichloroacetamide as key steps. This study presents the first asymmetric synthesis among tetrodotoxin and its analogs.
Graphic
The monitoring of the blood concentration at 2 h (C(2)) after the oral administration of a cyclosporine (CsA) microemulsion was reconfirmed to be useful for the prediction of systemic exposure, the ...area under the blood concentration-time curve from 0 to 4 h (AUC(0-4)), in a group of Japanese patients, consisting of 33 children aged 5-15 years and 19 young adults aged 16-27 years, with a greater correlation for C(2) (r = 0.927) than the trough concentration (r = 0.488). The dose-normalized AUC(0-4) was independent of gender or indications for CsA, while it depended on body size, i.e., the age (P = 0.065) and total body weight (P = 0.026). MDR1 C3435T had a weak, but insignificant effect (P = 0.072); it was about 22-31% lower in the patients with TT(3435). Co-administration of a steroid and further treatment with nifedipine had a more intensive effect (P = 0.018); co-administration resulted in a 51% increase in the dose-normalized AUC(0-4). A strong effect was also observed for the serum total cholesterol level (P = 0.001). Collectively, the discrepancies in the results on MDR1 C3435T among investigators might be due to variability in the age/total body weight, co-administration drugs or serum lipid level.
The recombinant vaccinia viruses expressing the surface protein of
Neospora caninum tachyzoite, NcSAG1 or NcSRS2, were constructed. The vaccination with these recombinant viruses could protect ...effectively the parasite invasion in a mouse model system. The vaccine efficacy of NcSRS2 was higher than that of NcSAG1. The present study indicated that a high level of IgG1 Ab production to parasite is important for clearance of parasite at the early stage of infection and that T cell response has a crucial role for protection against the intracellular infection at the late stage of infection. The recombinant vaccinia viruses might be applicable as vaccine against
N. caninum infection in a natural host.
The utility of various synthetic peptides has been investigated in clinical trials of the treatment of cancers, infectious diseases and endocrine diseases. In the process of functional gene screening ...with in silico analysis for molecules with angiogenic properties, we generated a small peptide, angiogenic peptide (AG)‐30, that possesses both antimicrobial and pro‐inflammatory activities. AG‐30 has an α‐helix structure with a number of hydrophobic or net positively charged amino acids and a propensity to fold into amphipathic structures. Indeed, AG‐30 exhibited antimicrobial activity against various bacteria, induced vascular endothelial cell growth and tube formation in a dose‐dependent manner and increased neovascularization in a Matrigel plug assay. As a result, AG‐30 up‐regulated expression of angiogenesis‐related cytokines and growth factors for up to 72 hrs in human aortic endothelial cells. To further evaluate the angiogenic effect of AG‐30 in vivo, we developed a slow‐release AG‐30 system utilizing biodegradable gelatin microspheres. In the ischaemic mouse hind limb, slow‐release AG‐30 treatment results in an increase in angiogenic score, an increase in blood flow (as demonstrated by laser Doppler imaging) and an increase in capillary density (as demonstrated by immunostaining with anti‐CD31 antibody). These data suggest that the novel peptide, AG‐30, may have therapeutic potential for ischaemic diseases.
We report a case of a 23-year-old womanwho developed pulmonary embolism(PE)during chemotherapy for advanced gastric cancer following total gastrectomy(R1). She presented with type 4 gastric cancer ...with peritoneal dissemination and positive washing cytology. Palliative total gastrectomy was performed(R1)and first-line chemotherapy with S-1(80mg/m2, days 1 to 21) plus CDDP(60mg/m2, day 8)(SP; every 35 days)was administered. PE occurred on day 15 of the 3rd courses of SP. Computed tomography(CT)revealed massive PE in both the pulmonary arteries, and ultrasonography indicated an increase in right-sided pressure. Thrombolysis using urokinase and heparin was performed immediately, and she recovered after 10 days in intensive care. Dehydration caused by the adverse event, as well as nausea and the anticancer drug itself, are risk factors for DVT and PE. Risk stratification, prevention, and early treatment are very important for PE.
A 26-year-old woman, who successfully underwent umbilical cord blood transplantation for aplastic anemia 4 years previously, had suffered from hepatosplenic microabscesses caused by unidentifiable ...grocott stain-positive spores from immediately after the transplantation. At 51 months post-transplant, we attempted bone marrow biopsy from her posterior iliac crest, but failed to penetrate the cortical bone. X-ray of her spine and pelvis showed marked and diffuse osteosclerosis. Retrospective analysis of computed tomography revealed the gradual replacement of sternal, vertebral, and pelvic bone marrow with calcified tissues in addition to the dispersed calcification of the liver, spleen, and kidneys over the last 2 years. The bone mineral density of the lumbar spine had increased but not that of the femoral neck. Biomedical parameters for bone remodeling demonstrated enhanced bone formation as well as bone resorption and secondary hyperparathyroidism. Based on the past reports, we suggest that chronic fungal infection, which caused visceral calcification, induced the production of humoral factors for osteoblastic activation.
A 42 years old female was admitted into our hospital on July 2016 complaining of pain in the lower abdomen and watery bloody stool. Colonoscopy showed ischemic change in the descending and sigmoid ...colon and multiple erosions in the ascending colon. Patient treated as ischemic colitis, and she discharged after conservative therapy for 7 days. After 4 months, colonoscopy showed linear ulcer scar in the descending and sigmoid colon and annular ulcer in the ascending colon. A diagnosis of tuberculosis was made from a biopsy sample taken at the annular ulcer that revealed positive mycobacterium culture results as well as a positive polymerase chain reaction (PCR) assay. Quantiferon (QFT) was also positive. She was placed on four-drug therapy for 6 months. Following treatment colonoscopy showed no evidence of erosions or ulcers. Findings of erosions in the ileum or ileocecal region suggest tuberculosis, and a high index of suspicion should be maintained when performing diagnostics. Workup should include QFT, which has high sensitivity and specificity and close follow up with colonoscopy should also be done.
Background and Aim: A beneficial effect of Helicobacter pylori (H. pylori) eradication in patients with H. pylori‐positive idiopathic thrombocytopenic purpura (ITP) has been reported by several ...investigators; however, it was not clear whether the recovered platelet count after H. pylori eradication was maintained for a long period.
Method: Thirty‐eight ITP patients who were examined for H. pylori infection were assessed. H. pylori‐positive patients received a standard antibiotic therapy for H. pylori eradication. We investigated the long‐term effect of H. pylori eradication on platelet recovery in patients with H. pylori‐positive ITP.
Results: Of the 38 ITP patients, 26 (68.4%) were positive for H. pylori. The response rate of platelet recovery was 56.5% (13/23 patients). Twelve patients showed complete response (CR) and one showed partial response (PR). The mean platelet counts 6 months after eradication significantly increased from 31 × 109/L to 129 × 109/L in 23 H. pylori‐eradicated patients (P < 0.001). The median platelet counts of responders 1, 2, 3, and 4 years after eradication were 168 × 109/L (n = 10), 193 × 109/L (n = 9), 168 × 109/L (n = 7), and 243 × 109/L (n = 4) after a mean follow‐up of 25.8 months.
Conclusion: Eradication therapy for H. pylori‐positive patients with ITP was effective and a favorable effect was maintained for long periods.
Aims/Introduction
The aim of the present prospective observational study was to assess long‐term efficacy and safety of insulin degludec as a part of a basal–bolus therapy for Japanese patients with ...type 1 or type 2 diabetes in routine clinical practice.
Materials and Methods
In the present study, 93 type 1 diabetes patients and 135 type 2 diabetes patients treated with insulin glargine or detemir were switched from their basal insulin to insulin degludec. The primary end‐points were the changes in glycated hemoglobin (HbA1c) from baseline at 3, 6 and 12 months. The secondary end‐points were changes in body mass index, insulin dose, frequency of hypoglycemia and adverse events.
Results
HbA1c levels from baseline were significantly reduced at 3, 6, and 12 months by 0.4, 0.4 and 0.3% in type 1 diabetes patients, respectively, and by 0.5, 0.5 and 0.3% in type 2 diabetes patients, respectively. Body mass index in type 1 diabetes patients increased significantly (P < 0.05), whereas that in type 2 diabetes patients did not change. Basal insulin dose decreased significantly at 3 months after switching (P < 0.05), and returned baseline dose at 12 months in type 1 diabetes and type 2 diabetes patients. The frequency of both total and nocturnal hypoglycemia decreased significantly in type 1 diabetes and type 2 diabetes patients (P < 0.05). The result of multiple regression analysis showed that baseline HbA1c was a significant independent variable of the percentage change in HbA1c with switching.
Conclusion
In both type 1 diabetes and type 2 diabetes patients, switching from insulin glargine or insulin detemir to insulin degludec led to improvement of glycemic control with a significant reduction of hypoglycemia.
In both T1D and T2D subjects treated with BBT, switching from insulin glargine or detemir to insulin degludec led to improvement of glycemic control with a significant reduction of hypoglycemia.
New derivatives of an intriguing marine natural product are now accessible. The first asymmetric synthesis of the simple tetrodotoxin analogue, 5,11‐dideoxytetrodotoxin (3), was achieved. ...Hydroxylation at position C8 of the key intermediate 1 relied on the neighboring trichloroacetamide group, and stereoselective elaboration of the vinyl group gave α‐hydroxylactone 2, which was transformed into the title compound through a new guanidylation method.
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