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1.
J Vet Med Sci ; 2024 Apr 16.
Article in English | MEDLINE | ID: mdl-38631888

ABSTRACT

The present study analyzed B-cell clonality and bovine leukemia virus (BLV) provirus integration sites in cattle with enzootic bovine leukosis (EBL) having BLV proviral copy numbers less or greater than the number of bovine nucleated cells. EBL cattle with BLV copy numbers less than the number of bovine nucleated cells showed monoclonal and biclonal proliferation of B-cells with one BLV provirus integration site. On the other hand, EBL cattle with BLV copy numbers greater than the number of bovine nucleated cells showed monoclonal proliferation of B-cells with two BLV provirus integration sites. These results suggest that superinfection of BLV can occur in EBL cattle.

2.
Clin Transl Sci ; 17(4): e13803, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38651283

ABSTRACT

Drug safety communications (DSCs) are essential tools for communicating important postmarket serious drug safety information to healthcare professionals and patients. Previous studies characterized DSCs issued by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA); however, knowledge about the activities of the Pharmaceuticals and Medical Devices Agency (PMDA)/the Ministry of Health, Labor and Welfare (MHLW) is limited. This study characterized DSCs by the PMDA/MHLW in comparison with previously reported DSCs by the FDA and the EMA. We retrospectively analyzed 37 DSCs of 41 adverse drug reactions (ADRs) for 33 drugs in Japan from 1997 to 2022. Most DSCs were related to non-oncology drugs (30/37, 81.1%), and the median (interquartile range) time from approval to DSC issuance was 19 (10-51) months. Notably, the regulatory review reports and the latest labels before DSC issuance did not describe 16/28 (57.1%) and 12/37 (32.4%) of the ADRs related to DSCs, respectively. Most DSCs resulted in label revisions (36/37, 97.3%) and seven drugs were eventually withdrawn. Some DSC characteristics are similar among the PMDA/MHLW, the FDA, and the EMA; however, the number, contents, and range of new safety issues addressed by DSCs differ among the three jurisdictions. Our study emphasized the importance of continuous efforts to gather postmarket drug safety information because substantial ADRs that led to DSCs were recognized after approval and were associated with critical label revisions and withdrawals. Future studies are required to address global challenges for regulatory harmonization of safety-related regulatory actions.


Subject(s)
Drug Approval , Drug-Related Side Effects and Adverse Reactions , Product Surveillance, Postmarketing , Japan , Humans , Product Surveillance, Postmarketing/statistics & numerical data , Retrospective Studies , Drug-Related Side Effects and Adverse Reactions/epidemiology , United States Food and Drug Administration/standards , Drug Labeling/standards , United States , Adverse Drug Reaction Reporting Systems/statistics & numerical data
3.
Neuromolecular Med ; 26(1): 16, 2024 Apr 26.
Article in English | MEDLINE | ID: mdl-38668900

ABSTRACT

Toll-like receptor (TLR) 7 plays an important role in recognizing virus-derived nucleic acids. TLR7 signaling in astrocytes and microglia is critical for activating immune responses against neurotrophic viruses. Neurons express TLR7, similar to glial cells; however, the role of neuronal TLR7 has not yet been fully elucidated. This study sought to determine whether resiquimod, the TLR7/8 agonist, induces the expression of inflammatory chemokines in SH-SY5Y human neuroblastoma cells. Immunofluorescence microscopy revealed that TLR7 was constitutively expressed in SH-SY5Y cells. Stimulation with resiquimod induced C-C motif chemokine ligand 2 (CCL2) expression, accompanied by the activation of nuclear factor-kappa B (NF-κB) in SH-SY5Y cells. Resiquimod increased mRNA levels of C-X-C motif chemokine ligand 8 (CXCL8) and CXCL10, while the increase was slight at the protein level. Knockdown of NF-κB p65 eliminated resiquimod-induced CCL2 production. This study provides novel evidence that resiquimod has promising therapeutic potential against central nervous system viral infections through its immunostimulatory effects on neurons.


Subject(s)
Chemokine CCL2 , Chemokine CXCL10 , Imidazoles , Interleukin-8 , Toll-Like Receptor 7 , Transcription Factor RelA , Humans , Cell Line, Tumor , Chemokine CCL2/genetics , Chemokine CCL2/biosynthesis , Chemokine CXCL10/genetics , Chemokine CXCL10/biosynthesis , Imidazoles/pharmacology , Interleukin-8/genetics , Interleukin-8/biosynthesis , Neuroblastoma , Neurons/drug effects , Neurons/metabolism , NF-kappa B/metabolism , RNA, Messenger/genetics , RNA, Small Interfering/genetics , Signal Transduction/drug effects , Toll-Like Receptor 7/agonists , Toll-Like Receptor 7/genetics , Toll-Like Receptor 8/agonists , Toll-Like Receptor 8/genetics , Transcription Factor RelA/metabolism , Transcription Factor RelA/genetics
4.
Surg Endosc ; 38(5): 2834-2841, 2024 May.
Article in English | MEDLINE | ID: mdl-38605169

ABSTRACT

BACKGROUND: Stoma prolapse (SP) is a common stoma-related complication, particularly in loop colostomies. This study aimed to investigate potential risk factors for SP development after laparoscopic loop colostomy. METHODS: In total, data from 140 patients who underwent laparoscopic loop colostomy were analyzed between September 2016 and March 2022. Risk factors for SP were investigated retrospectively. RESULTS: The median follow-up duration after colostomy was 12.5 months, and SP occurred in 33 (23.6%) patients. Multivariate analysis showed that being overweight (body mass index ≥ 25; odds ratio [OR], 8.69; 95% confidential interval [CI], 1.61-46.72; p = 0.012) and having a thin rectus abdominis penetration of the stoma (< 8.9 mm; OR, 8.22; 95% CI, 2.50-27.05; p < 0.001) were independent risk factors for SP. Other patient characteristics and surgical factors associated with stoma construction were unrelated to SP development. CONCLUSIONS: Being overweight and the route penetrating the thinner rectus abdominis during stoma construction was associated with a significantly higher incidence of SP after laparoscopic loop colostomy. Selecting a construction site that penetrates the thicker rectus abdominis muscle may be crucial for preventing SP.


Subject(s)
Colostomy , Laparoscopy , Surgical Stomas , Humans , Colostomy/adverse effects , Colostomy/methods , Female , Laparoscopy/methods , Laparoscopy/adverse effects , Male , Risk Factors , Middle Aged , Retrospective Studies , Surgical Stomas/adverse effects , Prolapse , Aged , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Adult , Incidence , Rectus Abdominis , Overweight/epidemiology , Aged, 80 and over
5.
J Equine Sci ; 35(1): 15-19, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38524753

ABSTRACT

Equine testicular arteritis commonly occurs as a consequence of the migration of nematode larvae or equine arteritis virus (EAV) infection. However, testicular arteritis without evidence of these infections has been reported, and the underlying pathogenesis remains unclear. We encountered testicular arteritis without evidence of nematode or EAV infection in a 3-year-old male heavy draft horse with scrotal enlargement. Grossly, the volume of the pampiniform plexus was markedly increased due to edema. Histologically, non-suppurative and necrotizing testicular arteritis, characterized by lymphocyte infiltration and fibrinoid necrosis of the arterial walls, was diffusely observed in the spermatic cord, pampiniform plexus (most severe), testis, and epididymis. We were unable to identify the cause of arteritis, such as a viral infection or autoimmune abnormality.

6.
Mol Biol Rep ; 51(1): 417, 2024 Mar 14.
Article in English | MEDLINE | ID: mdl-38483660

ABSTRACT

BACKGROUND: Bronchial epithelial cells are at the front line of viral infections. Toll-like receptor 3 (TLR3) cascade causes the expression of interferon (IFN)-ß and IFN-stimulated genes (ISGs), which in turn induce an antiviral response. Members of the transmembrane protein (TMEM) family are expressed in various cell types. Although the prognostic value of TMEM2 in various cancers has been reported, its association with infectious diseases remains unknown. In this study, we investigated the effects of TMEM2 on antiviral immunity in BEAS-2B bronchial epithelial cells. METHODS AND RESULTS: TMEM2 protein was found in the cytoplasm of normal human bronchial epithelial cells and differed between organs using immunohistochemistry. Cultured BEAS-2B cells were transfected with TMEM2 siRNA, followed by administration of TLR3 ligand polyinosinic-polycytidylic acid (poly IC) or recombinant human (r(h)) IFN-ß. The expression of TMEM2, IFN-ß, ISG56, C-X-C motif chemokine ligand 10 (CXCL10) and hyaluronan were evaluated appropriately by western blotting, quantitative reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay. TMEM2 expression was not altered by poly IC stimulation. Knockdown of TMEM2 increased poly IC-induced expression of IFN-ß, CXCL10, and ISG56, while IFN-ß-induced expression of ISG56 and CXCL10 were not changed by TMEM2 knockdown. The hyaluronan concentration in the medium was decreased by either TMEM2 knockdown or poly IC, but additive or synergistic effects were not observed. CONCLUSIONS: TMEM2 knockdown enhanced TLR3-mediated IFN-ß, CXCL10, and ISG56 expression in BEAS-2B cells. This implies that TMEM2 suppresses antiviral immune responses and prevents tissue injury in bronchial epithelial cells.


Subject(s)
Hyaluronic Acid , Toll-Like Receptor 3 , Humans , Toll-Like Receptor 3/genetics , Toll-Like Receptor 3/metabolism , Ligands , Poly I-C/pharmacology , Epithelial Cells/metabolism , Cells, Cultured , Chemokine CXCL10/genetics
7.
Acta Trop ; 254: 107185, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38494059

ABSTRACT

Animal African trypanosomosis (AAT) is an important global disease of livestock that causes economic losses of up to 4.5 billion US dollars per year. Thus, eliminating AAT in endemic countries will improve agricultural productivity and economic growth. To prevent AAT, vector control and the development of prophylactic drugs are crucial. Ascofuranone (AF) is a bioactive fungal compound with proven in vitro trypanocidal potency and in vivo treatment efficacy. However, the complex stereoselective synthesis of AF has prevented its cost-effective industrial production. Recently, a genetically modified strain of Acremonium egyptiacum fungus that produces a high yield of AF was developed. Therefore, we hypothesized that the oral administration of the AF-producing fungus itself may be effective against AAT. Hence, this study aimed to evaluate the prophylactic activity of orally administered dry-heat-sterilized A. egyptiacum against Trypanosoma congolense IL3000 infection using a mouse model. The survival rate was significantly prolonged (p = 0.009), and parasitemia was suppressed in all AF-fungus-treated groups (Group 1-9) compared with that in the untreated control group (Group 10). Hence, the trypanocidal activity of AF was retained after dry-heat-sterilization of the AF-producing fungus and that its oral administration effectively prevented AAT. Since AAT is endemic to rural areas with underdeveloped veterinary infrastructure, dry-heat-sterilized A. egyptiacum would be the most cost-effective potential treatment for AAT.


Subject(s)
Acremonium , Disease Models, Animal , Trypanosoma congolense , Trypanosomiasis, African , Animals , Trypanosomiasis, African/prevention & control , Trypanosomiasis, African/drug therapy , Trypanosomiasis, African/veterinary , Trypanosoma congolense/drug effects , Administration, Oral , Mice , Female , Parasitemia/prevention & control , Parasitemia/drug therapy , Mice, Inbred BALB C
8.
Gynecol Oncol Rep ; 52: 101346, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38404911

ABSTRACT

Lymphatic ascites is a postoperative complication of lymph node dissection. Most symptomatic cases improve with conservative treatments. However, optimal management strategies for intractable lymphatic ascites remain controversial, and clinicians sometimes encounter intractable lymphatic ascites that does not respond to conservative management. We herein report a case of postoperative intractable lymphatic ascites that was successfully treated with intranodal lymphangiography (LG) from inguinal lymph nodes under microsurgery. A 56-year-old woman was diagnosed with stage II endometrial cancer and underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy, and pelvic and para-aortic lymphadenectomies. On postoperative day (POD) 13, the patient presented with abdominal distention, and lymphatic ascites was diagnosed. Although the patient was treated with conservative management and lymphaticovenular anastomosis, her lymphatic ascites did not resolve. Finally, intranodal LG from the inguinal region was performed under microsurgery. A 2-cm incision was made on each side of the inguinal region. Once the lymph nodes were identified, a 23-gauge needle was inserted into the lymph node and lipiodol was injected. Extravasation of lipiodol into the abdomen from the left side of the lower pelvic region was confirmed. The postoperative course was uneventful. The ascites gradually decreased and disappeared within two weeks after LG.

9.
Opt Express ; 32(2): 1802-1824, 2024 Jan 15.
Article in English | MEDLINE | ID: mdl-38297724

ABSTRACT

It has been well established that photonic crystal nanocavities with wavelength sized mode volume enable various integrable photonic devices with extremely small consumption energy and small footprint. In this study, we explore the possibility of non-volatile functionalities employing photonic crystal nanocavities and phase change material, Ge2Sb2Te5 (GST). Recently, non-volatile photonic devices based on GST have attracted significant interest and are expected to enable energy-efficient photonic processing, especially for optical computing. However, the device size and the area of GST in previous studies have been rather large. Here, we propose and fabricate Si photonic crystal nanocavities on which submicron-square GST patterns are selectively loaded. Because of the strong light confinement, extremely small area of GST is sufficient to manipulate the cavity mode. We have succeeded to fabricate 30-nm-thick and several-100nm-square GST blocks patterned at the center of photonic crystal cavity with a high alignment accuracy. We confirmed that the resonant wavelength and Q-factor of cavity modes are controlled by the phase change of GST. Moreover, cavity formation controlled by submicron-sized GST is also demonstrated by GST-loaded photonic-crystal line-defect waveguides. Our approach in which we place sub-micron-sized GST inside a photonic crystal nanocavity is promising for realizing extremely energy-efficient non-volatile integrable photonic devices, such as switches, modulators, memories, and reconfigurable novel devices.

10.
J Vet Med Sci ; 86(3): 258-265, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38233195

ABSTRACT

Oral squamous cell carcinoma (oSCC) is a highly invasive malignant neoplasm in cats. Recently, tumor stroma, known as tumor microenvironments, have been considered to play an essential role in tumor progression. However, their role in feline squamous cell carcinoma (SCC) remains unclear. This study aimed to reveal the cancer microenvironment of feline oSCC and evaluate the pathological mechanisms of progression. We used 19 samples from 17 cats with oSCC, which were examined using light microscopy, immunohistochemistry, and in situ hybridization (RNAscope®). Feline oSCCs had two types of stroma, namely fibrotic and myxoid stromal reaction patterns, which were easily distinguished using hematoxylin-eosin staining. The myxoid stroma was rich in hyaluronic acid, which seems to be produced by neoplastic cells. Furthermore, the presence of myxoid stroma was correlated with histological parameters, including the appearance of cancer-associated fibroblasts and tumor budding. Periostin protein expression was also frequently observed in the stroma of feline oSCC and was significantly more common in the myxoid stromal reaction pattern group than in the fibrotic group. Positive signals for periostin mRNA were detected in stromal cancer-associated fibroblasts. This study indicates that the interaction between neoplastic cells and stromal reaction pattern components, such as hyaluronic acid and periostin, may be involved in tumor malignancy. Therefore, we propose that focus be placed not only on the tumor tissue but also on the characterization of the stroma for analyzing feline oSCC.


Subject(s)
Carcinoma, Squamous Cell , Cat Diseases , Head and Neck Neoplasms , Mouth Neoplasms , Cats , Animals , Mouth Neoplasms/veterinary , Mouth Neoplasms/metabolism , Mouth Neoplasms/pathology , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/veterinary , Squamous Cell Carcinoma of Head and Neck/veterinary , Hyaluronic Acid , Head and Neck Neoplasms/veterinary , In Situ Hybridization/veterinary , Tumor Microenvironment
11.
Echocardiography ; 41(1): e15735, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38284671

ABSTRACT

OBJECTIVES: We previously reported a higher left atrial volume index (LAVI) was independently associated with left atrial (LA) appendage (LAA) thrombus formation in 737 patients with non-valvular atrial fibrillation (NVAF) receiving appropriate oral anticoagulation therapy. Since our previous study was a retrospective single-center study, we designed and conducted a prospective multi-center study to verify our findings for LAVI as a predictor of LAA thrombus in patients with NVAF receiving appropriate oral anticoagulation therapy. METHODS: This prospective multi-center study comprised 746 consecutive patients with NVAF recruited between December 2021 and March 2023 from eight institutions in Japan, who were receiving appropriate oral anticoagulation therapy, had undergone transthoracic echocardiography and transesophageal echocardiography (TEE). RESULTS: LAA thrombi were observed in 21 patients (2.8%). The prevalence of LAA thrombus formation in patients with paroxysmal AF (PAF) was significantly lower than that in patients with non-PAF (0.7% vs. 4.1%, p = .006). LAA thrombus formation was detected in none (0/171) of the patients with normal size LA (LAVI ≤ 34 mL/m2 ). The prevalence of LAA thrombus formation in patients with mildly dilated LA (LAVI: 34-49.9 mL/m2 ) was 2.1% (6/283), but that in PAF patients was low at 1.0% (1/104). Furthermore, this prevalence in patients with severely dilated LA (LAVI ≥ 50 mL/m2 ) was high at 5.1% (15/292). CONCLUSIONS: The findings of this prospective multi-center study are consistent with those of our previous study. Thus, the need for TEE prior to catheter ablation or electrical cardioversion can be determined by the level of LAVI.


Subject(s)
Atrial Appendage , Atrial Fibrillation , Heart Diseases , Thrombosis , Humans , Atrial Appendage/diagnostic imaging , Atrial Fibrillation/complications , Atrial Fibrillation/drug therapy , Atrial Fibrillation/epidemiology , Retrospective Studies , Prospective Studies , Heart Atria/diagnostic imaging , Echocardiography, Transesophageal , Thrombosis/complications , Anticoagulants/therapeutic use
12.
Biosens Bioelectron ; 249: 116006, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38199081

ABSTRACT

The rapid identification of pathogenic bacteria is crucial across various industries, including food or beverage manufacturing. Bacterial microcolony image-based classification has emerged as a promising approach to expedite identification, automate inspections, and reduce costs. However, conventional imaging methods have significant practical limitations, namely low throughput caused by the limited imaging range and slow imaging speed. To address these challenges, we developed an imaging system based on a line image sensor for rapid and wide-field imaging compared to existing colony imaging methods. This system can image a standard Petri dish (92 mm in diameter) completely within 22 s, successfully acquiring bacterial microcolony images. This process yielded a set of discrimination parameters termed as colony fingerprints, which were employed for machine learning. We demonstrated the performance of our system by identifying Staphylococcus aureus in food products using a machine learning model trained on a colony fingerprint dataset of 15 species from 9 genera, including foodborne pathogens. While conventional mass spectrometry-based methods require 24 h of incubation, our colony fingerprinting approach achieved 96% accuracy in just 10 h of incubation. Line image sensor offer high imaging speeds and scalability, allowing for swift and straightforward microbiological testing, eliminating the need for specialized expertise and overcoming the limitations of conventional methods. This innovation marks a transformative shift in industrial applications.


Subject(s)
Biosensing Techniques , Bacteria , Machine Learning
13.
Respir Investig ; 62(1): 77-84, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37976917

ABSTRACT

BACKGROUND: Transbronchial biopsy using an ultrathin bronchoscope (UTB) has a high diagnostic yield for peripheral pulmonary lesions (PPLs). When combined with peripheral transbronchial needle aspiration (pTBNA), it improves the diagnostic yield of "adjacent to" radial endobronchial ultrasonography (rEBUS) findings. However, pTBNA is a complicated technique, and the specimen volume is often inadequate for diagnostic and multiplex analyses. Recently, transbronchial cryobiopsy (TBCB) using a 1.1-mm cryoprobe that could be inserted into an UTB has been available. We investigated whether TBCB combined with forceps biopsy using a 1.1-mm cryoprobe with an UTB improved the diagnostic yield of "adjacent to" lesions. METHODS: The data of 66 consecutive patients who underwent TBCB and forceps biopsy using UTB (hemostasis using two-scope method) under rEBUS for small PPLs (≤30 mm) were retrospectively analyzed. The histological diagnosis rate using TBCB and forceps biopsy, TBCB alone, or forceps biopsy alone was compared between cases where the rEBUS probe was "within" and "adjacent to" lesions. RESULTS: The diagnosis rate using TBCB and forceps biopsy was 81.8 % for all lesions ("within" vs. "adjacent to" cases: 88.4 % vs. 69.6 %; p = 0.093). The corresponding rate using TBCB alone was 80.3 % (86.0 % vs. 69.6 %; p = 0.19), and that using forceps biopsy alone was 62.1 % (74.4 % vs. 39.1 %; p = 0.008). Bleeding leading to discontinuation of the examination occurred in four (6.1 %) patients; however, in all cases, bleeding could be controlled endoscopically. CONCLUSION: Forceps biopsy with TBCB during ultrathin bronchoscopy for small PPLs improved the diagnostic yield when the lesions were adjacent to the rEBUS probe.


Subject(s)
Bronchoscopes , Lung Neoplasms , Humans , Retrospective Studies , Biopsy , Bronchoscopy/methods , Endosonography , Biopsy, Fine-Needle , Lung Neoplasms/pathology , Lung/diagnostic imaging , Lung/pathology
14.
Front Chem ; 11: 1307254, 2023.
Article in English | MEDLINE | ID: mdl-38075500

ABSTRACT

Protein ubiquitination is involved in nearly all biological processes in Eukaryotes. To gain precise insights into the function of ubiquitination in these processes, researchers frequently employ ubiquitinated protein probes with well-defined structures. While chemical protein synthesis has afforded a variety of ubiquitinated protein probes, there remains a demand for efficient synthesis methods for complex probes, such as ubiquitinated glycoproteins and ubiquitinated cysteine-containing proteins. In this study, we introduce a new method to obtain ubiquitinated proteins through isopeptide bond formation mediated by δ-selenolysine residues. We synthesized δ-selenolysine derivatives in both L- and D-forms starting from DL-δ-hydroxy-DL-lysine, accomplished by substituting the δ-mesylate with KSeCN and by enzymatic optical resolution with L- and D-aminoacylase. We synthesized ubiquitin (46-76)-α-hydrazide with a δ-seleno-L-lysine residue at position 48, as well as ubiquitin (46-76)-α-thioester, using solid-phase peptide synthesis. Subsequently, the δ-selenolysine-mediated ligation of these peptides, followed by one-pot deselenization, provided the desired isopeptide-linked ubiquitin peptide. The new δ-selenolysine-mediated isopeptide bond formation offers an alternative method to obtain complex ubiquitin- and ubiquitin-like probes with multiple post-translational modifications. These probes hold promise for advancing our understanding of ubiquitin biology.

15.
Intern Med ; 2023 Dec 04.
Article in English | MEDLINE | ID: mdl-38044155

ABSTRACT

A 48-year-old man presented with a fever and back pain and was referred to our hospital with multiple bone destruction and abscess formation. A sputum examination revealed Mycobacterium intracellulare, and pathological findings revealed an indistinct granuloma and acid-fast bacilli, leading to a diagnosis of disseminated nontuberculous mycobacteriosis. Anti-interferon-γ-neutralizing autoantibodies were detected in the serum, and acquired immunodeficiency was suspected to be the etiology. Antimicrobial chemotherapy was initiated, and the lesions generally regressed. However, only the skull lesions worsened, requiring local resection to control the disease. Currently, the patient is continuing to receive drug therapy with good disease control after debridement.

16.
Biol Pharm Bull ; 46(11): 1639-1642, 2023.
Article in English | MEDLINE | ID: mdl-37914368

ABSTRACT

The oral bioavailability of berberine is quite low due to extensive first-pass metabolism. To increase the bioavailability of berberine (BBR), the efficacy of rectal administration that can avoid intestinal and hepatic first-pass metabolism partly was evaluated using BBR sulfate in rats. BBR sulfate was administered intravenously (1 mg/kg as BBR), orally (10 mg/kg as BBR) and rectally (1, 3, or 10 mg/kg as BBR) using Witepsol® H15 suppository base to evaluate bioavailability in rats. Concentrations of BBR in plasma were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS). When BBR sulfate was administered orally, the average oral bioavailability was 0.26%. When BBR sulfate was administered rectally, the average bioavailabilities were 17.0% at 1 mg/kg, 24.3% at 3 mg/kg, and 12.3% at 10 mg/kg as BBR, respectively. Thus, rectal administration of BBR sulfate greatly increased the bioavailability of BBR as compared with oral administration, which would also increase the pharmacological activities of BBR in vivo.


Subject(s)
Berberine , Rats , Animals , Rats, Sprague-Dawley , Chromatography, Liquid , Biological Availability , Administration, Rectal , Tandem Mass Spectrometry/methods , Administration, Oral , Sulfates
17.
Curr Med Res Opin ; : 1-10, 2023 Oct 26.
Article in English | MEDLINE | ID: mdl-37881860

ABSTRACT

OBJECTIVE: Acute myeloid leukemia (AML) is the most common form of leukemia among adults in Japan. This study aimed to understand the treatment patterns, health care resource utilization, and costs of FMS-like tyrosine kinase 3 mutation-positive (FLT3m+) AML patients in Japan. METHODS: A retrospective cohort study of Japanese FLT3m + AML patients was conducted using data extracted from a national hospital-based claims database provided by Medical Data Vision Co. Ltd. (MDV; Tokyo, Japan). Patients were identified from the MDV database between April 2008 and April 2021 inclusive. RESULTS: A total of 360 patients were included in this study. The study results suggest that cytarabine + anthracyclines was the most common first-line (1 L) treatment, accounting for 41.3% of the patients. FLT3 inhibitors (FLT3i) was the most common treatment across the study period (95.7%). The mean age of patients was 62.4 years, and most were 65 years or older. The median overall survival (OS) after initiating FLT3i treatment was 394 days. The median treatment duration of FLT3i was 88.5 days, while it was 66.0 days for patients treated with FLT3i within 60 days after hematopoietic stem cell transplantation (HSCT). The overall mean monthly total treatment cost was JPY 2,009,531.7/per patient per month (PPPM) (USD 17,967.9/PPPM). CONCLUSIONS: The study found specific treatment patterns, trends and features in patients with FLT3m + AML. FLT3i was the most prescribed treatment across the study period and the overall median OS after initiating FLT3i treatment was over 1 year. The findings of this study could be helpful for clinicians to optimize treatment strategies for FLT3m + AML in Japan.

18.
Nihon Shokakibyo Gakkai Zasshi ; 120(10): 845-851, 2023.
Article in Japanese | MEDLINE | ID: mdl-37821374

ABSTRACT

A 78-year-old female patient presented to our hospital with abdominal pain and melena. Abdominal ultrasonography detected a multiple concentric ring sign and retrograde invagination mass near the hepatic flexure. Colonoscopy revealed a 40-mm diameter type 1 tumor in the transverse colon near the splenic flexure, and the biopsy specimen demonstrated a well-differentiated adenocarcinoma. Retrograde intussusception due to transverse colon cancer was diagnosed, and laparoscopic transverse colon resection with lymph node dissection was performed. The resected specimen revealed a 48×40mm diameter type 1 tumor in the transverse colon and was diagnosed as pT2N0M0 pStage I. Contrast-enhanced computed tomography was unavailable, but real-time assessment of the invaginated mass and bowel blood flow was possible by abdominal ultrasonography, which was useful in determining the diagnosis and treatment strategy.


Subject(s)
Colon, Transverse , Colonic Neoplasms , Intussusception , Female , Humans , Aged , Colon, Transverse/diagnostic imaging , Colon, Transverse/surgery , Colon, Transverse/pathology , Intussusception/diagnostic imaging , Intussusception/etiology , Intussusception/surgery , Colonic Neoplasms/complications , Colonic Neoplasms/diagnostic imaging , Colonic Neoplasms/surgery , Abdomen/pathology , Colonoscopy
19.
Yakugaku Zasshi ; 143(9): 721-727, 2023.
Article in Japanese | MEDLINE | ID: mdl-37661438

ABSTRACT

Lipid-based formulations (LBFs) are isotropic mixtures typically comprising lipids, surfactants, and/or co-solvents, in which drugs are pre-solubilized. After oral administration, LBFs are piggybacked into endogenous lipid digestion pathways. This triggers drug super-saturation and improves absorption. However, super-saturation poses a risk of drug precipitation, which generally leads to poor drug absorption. Furthermore, a series of aqueous colloidal species including digestion products (typically fatty acids and monoglycerides) and endogenous molecules (bile acids and phospholipids) increase the drug solubilization capacity of the intestinal fluid (compared with that of the normal intestinal fluid). However, the solubilization/precipitation behavior may change according to the LBF composition (e.g., the drug loading amount and type of formulation excipients), which may ultimately lead to differences in oral absorption. This review summarizes the results of the evaluation and prediction of the effect of LBFs composition on oral absorption and provides an in-depth understanding of the drug absorption mechanisms when using LBFs.


Subject(s)
Fatty Acids , Water , Pharmaceutical Preparations , Administration, Oral , Chemical Phenomena
20.
Surg Neurol Int ; 14: 191, 2023.
Article in English | MEDLINE | ID: mdl-37404484

ABSTRACT

Background: Extra-axial cerebellopontine angle (CPA) hemangioblastomas are rare clinical entity and surgical treatment is challenging due to the anatomical difficulties and multi-directional blood supplies. On the other hand, the risk of endovascular treatment for this disease has also been reported. Herein, we successfully applied a posterior transpetrosal approach to remove a large solid CPA hemangioblastoma without preoperative feeder embolization. Case Description: A 65-year-old man presented with a complaint of diplopia during downward gaze. Magnetic resonance imaging revealed a solid tumor with homogeneous enhancement measuring about 35 mm at the left CPA, and the tumor compressed a left trochlear nerve. Cerebral angiography disclosed tumor-staining fed by both left superior cerebellar and left tentorial arteries. After the operation, the patient's trochlear nerve palsy improved dramatically. Conclusion: This approach offers more optimal surgical working angle to the anteromedial part compared to the lateral suboccipital approach. In addition, the devascularization from the cerebellar parenchyma can be performed more reliably than the anterior transpetrosal approach. After all, this approach can be particularly useful when vascular-rich tumors receive blood supplies from multiple directions.

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