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1.
Jpn J Ophthalmol ; 2024 Sep 23.
Article in English | MEDLINE | ID: mdl-39312048

ABSTRACT

PURPOSE: Enlargement of the trigeminal nerve is observed in 20-53% of patients with IgG4-related ophthalmic disease (IgG4-ROD) and is known to be a useful finding for the diagnosis of IgG4-ROD. On the other hand, enlargement of the trigeminal nerve has also been found at a certain frequency in orbital lymphoproliferative diseases other than IgG4-ROD. Therefore, we here re-evaluated the specificity of trigeminal nerve enlargement in the diagnosis of IgG4-ROD. STUDY DESIGN: Retrospective, comparative study. METHODS: A total of 149 consecutive cases of IgG4-ROD diagnosed at the Department of Ophthalmology, Tokyo Medical University Hospital were studied. As controls, 218 cases of orbital lymphoma, 13 cases of reactive lymphoid hyperplasia (RLH), and 117 cases of benign orbital tumors other than lymphoproliferative diseases were included. Enlargement of the trigeminal nerve (infraorbital or supraorbital nerve) in IgG4-ROD and all the control cases was evaluated on MRI or CT coronal images. RESULTS: Enlargement of the trigeminal nerve was observed in 35 of the 149 cases (23.5%) of IgG4-ROD and in 7 of the 218 cases (3.2%) of lymphoma, with a significantly highly frequency in IgG4-ROD (P < .0001). No cases of trigeminal nerve enlargement were observed in the cases of RLH or benign orbital tumors. The sensitivity and the specificity of trigeminal nerve enlargement in the diagnosis of IgG4-ROD were 23.5% and 96.8%, respectively. Additionally, enlargement of the trigeminal nerve was significantly more common in men than in women (P < .028). CONCLUSIONS: The present study indicates that trigeminal nerve enlargement is a characteristic imaging finding and has diagnostic value for IgG4-ROD.

2.
Helicobacter ; 29(4): e13125, 2024.
Article in English | MEDLINE | ID: mdl-39152662

ABSTRACT

BACKGROUND: The situation of Helicobacter pylori eradication therapy has been changing over time, owing to increases in antimicrobial-resistant strains, lifestyle improvements, and changes in indications for eradication. In Japan, eradication therapy is now available to all H. pylori-positive patients under the medical insurance system, and the potassium-competitive acid blocker vonoprazan has been used for eradication from 2015. Recently, with the aging of society, opportunities to provide eradication to elderly patients are increasing, but the current status and effectiveness of eradication in elderly patients remains unclear. Therefore, we aimed to investigate the trends of H. pylori eradication in a metropolitan area to determine the factors associated with successful H. pylori eradication in elderly patients older than 80 years. METHODS: Trends in the eradication rates of patients who received first- or second-line eradication at 20 hospitals in the Tokyo metropolitan area from 2013 to 2023 were investigated. RESULTS: The eradication rates in the per-protocol analysis were 82.3% (95% confidence interval [CI]: 81.2%-83.2%) for the first-line treatment (n = 6481), and 87.9% (86.9%-88.9%) for the second-line treatment (n = 4899). Multivariate analysis showed that independent factors for successful eradication in the first-line treatment were an age of older than 80 years (OR: 0.606; 95% CI: 0.448-0.822), peptic ulcers (vs. atrophic gastritis: 3.817; 3.286-4.433), and vonoprazan (vs. proton pump inhibiters (PPIs), 3.817; 3.286-4.433), and an age of older than 80 years (0.503; 0.362-0.699) and vonoprazan (1.386; 1.153-1.667) in the second-line treatment. CONCLUSION: After 2015, the eradication rate of both first- and second-line therapies were maintained at a higher level than before 2015, owing to the use of vonoprazan. As the H. pylori eradication rate in patients older than 80 years was low, an effective strategy for these patients needs to be developed in the future.


Subject(s)
Anti-Bacterial Agents , Helicobacter Infections , Helicobacter pylori , Humans , Helicobacter Infections/drug therapy , Helicobacter Infections/microbiology , Aged, 80 and over , Male , Female , Retrospective Studies , Helicobacter pylori/drug effects , Anti-Bacterial Agents/therapeutic use , Sulfonamides/therapeutic use , Treatment Outcome , Tokyo , Pyrroles/therapeutic use , Drug Therapy, Combination , Proton Pump Inhibitors/therapeutic use , Japan/epidemiology
3.
Neurogastroenterol Motil ; : e14880, 2024 Jul 26.
Article in English | MEDLINE | ID: mdl-39056471

ABSTRACT

BACKGROUND: The heterogeneous character of functional gastrointestinal disorders, recently renamed into disorders of gut-brain interaction, makes finding effective treatment options challenging. Compared to synthetic drugs, phytotherapy can have broader pharmacological effects and is often better tolerated. This study aimed to investigate the effect of peppermint oil and caraway oil (POCO) on gastric function and symptom levels in 32 healthy subjects in a single-blinded, placebo-controlled, randomized, parallel design. METHODS: Gastric emptying rate was assessed using a 13C-breath test. Intragastric pressure was measured using high-resolution manometry in fasted state and during intragastric infusion of a nutrient drink (350 mL or until full satiation). GI symptoms were rated on a 100 mm VAS. Data were analyzed using linear mixed models. KEY RESULTS: POCO had no effect on intragastric pressure in fasted or fed state (p > 0.08 for all). No significant differences in gastric emptying rate were observed (p = 0.54). In the fasted state, a stronger increase in hunger and decrease in satiety were observed following POCO (p = 0.016 and p = 0.008, respectively). No differences in hunger and satiety were observed in the fed state (p > 0.31 for all). POCO induced less epigastric burning, bloating, and fullness (p < 0.05 for all). CONCLUSIONS: Acute POCO administration did not affect gastric function in healthy subjects, but increased fasted hunger ratings. The effects of POCO on gastric function and hunger sensations in patients with disorders of gut-brain interaction, and the contribution to symptom improvement, needs to be elucidated in future studies.

4.
J Biosci Bioeng ; 137(6): 463-470, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38570220

ABSTRACT

The choice of sterilization method for hydrogels used for cell culture influences the ease of preparing the gel. We prepared interpenetrating gelatin/calcium alginate hydrogels containing 1% (w/v) alginate and 1-16% (w/v) gelatin by molding with the mixture of gelatin/sodium alginate solution, followed by the addition of calcium ions by incubation in calcium chloride solution. It is the simplest method to prepare autoclavable gelatin/sodium hydrogel. We measured various properties of the hydrogels including volume, Young's modulus in the compression test, storage modulus, and loss modulus in the dynamic viscoelasticity measurement. The gelatin/alginate hydrogel can be easily fabricated into any shape by this method. After autoclave treatment, the hydrogel was shrunk to smaller than the original shape in similar figures. The shape of the gelatin/alginate hydrogel can be designed into any shape with the reduction ratio of the volume. Human osteosarcoma (HOS) cells adhered to the gelatin/alginate hydrogel and then proliferated. Gelatin/calcium alginate hydrogels with a high concentration are considered to be autoclavable culture substrates because of their low deformation and gelatin elution rate after autoclaving and the high amount of cells attached to the hydrogels.


Subject(s)
Alginates , Gelatin , Hydrogels , Tissue Scaffolds , Gelatin/chemistry , Alginates/chemistry , Hydrogels/chemistry , Humans , Tissue Scaffolds/chemistry , Cell Line, Tumor , Sterilization , Cell Proliferation/drug effects , Glucuronic Acid/chemistry , Tissue Engineering/methods , Hexuronic Acids/chemistry , Elastic Modulus , Cell Adhesion
5.
Sci Rep ; 14(1): 378, 2024 01 03.
Article in English | MEDLINE | ID: mdl-38172327

ABSTRACT

Sweat is an essential protection system for the body, but its failure can result in pathologic conditions, including several skin diseases, such as palmoplantar pustulosis (PPP). As reduced intraepidermal E-cadherin expression in skin lesions was confirmed in PPP skin lesions, a role for interleukin (IL)-1-rich sweat in PPP has been proposed, and IL-1 has been implicated in the altered E-cadherin expression observed in both cultured keratinocytes and mice epidermis. For further investigation, live imaging of sweat perspiration on a mouse toe-pad under two-photon excitation microscopy was performed using a novel fluorescent dye cocktail (which we named JSAC). Finally, intraepidermal vesicle formation which is the main cause of PPP pathogenesis was successfully induced using our "LASER-snipe" technique with JSAC. "LASER-snipe" is a type of laser ablation technique that uses two-photon absorption of fluorescent material to destroy a few acrosyringium cells at a pinpoint location in three-dimensional space of living tissue to cause eccrine sweat leakage. These observatory techniques and this mouse model may be useful not only in live imaging for physiological phenomena in vivo such as PPP pathomechanism investigation, but also for the field of functional physiological morphology.


Subject(s)
Psoriasis , Skin , Animals , Mice , Skin/metabolism , Sweat/metabolism , Psoriasis/metabolism , Epidermis/metabolism , Eccrine Glands/metabolism , Interleukin-1/metabolism , Optical Imaging/adverse effects , Cadherins/metabolism
6.
Biol Trace Elem Res ; 202(10): 4699-4714, 2024 Oct.
Article in English | MEDLINE | ID: mdl-38180597

ABSTRACT

We measured the intracellular zinc ion concentration of murine fetal neural stem/progenitor cells (NSPCs) and that in the differentiated cells. The NSPCs cultured with 1.5 µM Zn2+ proliferated slightly faster than that in the zinc-deficient medium and the intracellular zinc concentration of the NSPCs and that of their differentiated cells (DCs) cultured with 1.5 µM Zn2+ was 1.34-fold and 2.00-fold higher than those in the zinc-deficient medium, respectively. The zinc transporter genes upregulated over the 3.5-fold change were Zip1, Zip4, Zip12, Zip13, ZnT1, ZnT8, and ZnT10 whereas the only downregulated one was Zip8 during the differentiation of NSPCs to DCs. The cell morphologies of both NSPCs and DCs in the low oxygen culture condition consisting of 2%O2 and 5%CO2, the high carbon dioxide condition consisting of 21%O2 and 10%CO2, and the normal condition consisting of 21%O2 and 5%CO2 were essentially the same each other. The expression of Zip4, Zip8, Zip12, and Zip14 was not drastically changed depending on the O2 and CO2 concentrations.


Subject(s)
Cation Transport Proteins , Cell Differentiation , Neural Stem Cells , Up-Regulation , Zinc , Animals , Neural Stem Cells/metabolism , Neural Stem Cells/cytology , Zinc/metabolism , Mice , Cation Transport Proteins/genetics , Cation Transport Proteins/metabolism , Cells, Cultured , Carrier Proteins/genetics , Carrier Proteins/metabolism
7.
Br J Clin Pharmacol ; 90(3): 900-904, 2024 03.
Article in English | MEDLINE | ID: mdl-37990649

ABSTRACT

Although diuretics play an important role in triple-whammy acute kidney injury (AKI), it is unclear whether the type of diuretic influences the risk of triple-whammy AKI. The aim of this study was to evaluate whether vasopressin receptor antagonists affect triple-whammy AKI. This cross-sectional study used disproportionality analysis of VigiBase data to assess the risk of AKI with various diuretics. Although multiple logistic regression analysis showed that aldosterone antagonists (odds ratio [OR] 2.19, 95% CI 2.01-2.37), loop diuretics (OR 4.40, 95% CI 4.07-4.76) and thiazide diuretics (OR 1.98, 95% CI 1.83-2.15) increased the risk of AKI in patients who received non-steroidal anti-inflammatory drugs (NSAIDs) and renin-angiotensin system inhibitors (RASi), vasopressin receptor antagonists did not increase the risk of AKI in those patients. Vasopressin receptor antagonists might not influence the development of triple-whammy AKI.


Subject(s)
Acute Kidney Injury , Angiotensin-Converting Enzyme Inhibitors , Humans , Angiotensin-Converting Enzyme Inhibitors/adverse effects , Antidiuretic Hormone Receptor Antagonists/adverse effects , Cross-Sectional Studies , Angiotensin Receptor Antagonists/adverse effects , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Diuretics/adverse effects , Acute Kidney Injury/chemically induced , Acute Kidney Injury/epidemiology
8.
BMC Prim Care ; 24(1): 262, 2023 12 02.
Article in English | MEDLINE | ID: mdl-38042776

ABSTRACT

BACKGROUND: Although previous studies have reported general inexperience with the Epley manoeuvre (EM) among general physicians, no report has evaluated the effect of EM on benign paroxysmal positional vertigo (BPPV) in primary care by using point estimates or certainty of evidence. We conducted this systematic review and meta-analysis and clarified the efficacy of EM for BPPV, regardless of primary-care and subspecialty settings. METHODS: Systematic review and meta-analysis of randomised sham-controlled trials of EM for the treatment of posterior canal BPPV in primary-care and subspecialty settings. A primary-care setting was defined as a practice setting by general practitioners, primary-care doctors, or family doctors. A systematic search was conducted in January 2022 across databases, including Cochrane Central Resister of Controlled Trial, MEDLINE, Embase, Cumulative Index of Nursing and Allied Health Literature, World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov. Primary outcomes were the disappearance of subjective symptoms (vertigo), negative findings (Dix-Hallpike test), and all adverse events. We evaluated the certainty of evidence using the Grading of Recommendations, Assessment, Development and Evaluation approach. RESULTS: Twenty-seven randomised controlled trials were identified. In primary-care settings, EM reduced the subjective symptoms [risk ratio (RR), 3.14; 95% confidence interval (CI), 1.96-5.02]; however, there was no applicable article for all adverse events. In the subspeciality setting, EM reduced the subjective symptoms (RR, 2.42; 95% CI, 1.64-3.56), resulting in an increase in negative findings (RR, 1.81; 95% CI, 1.40-2.34). The evidence exhibited uncertainty about the effect of EM on negative findings in primary-care settings and all adverse events in subspecialty settings. CONCLUSIONS: Regardless of primary-care and subspecialty settings, EM for BPPV was effective. This study has shown the significance of performing EM for BPPV in primary-care settings. EM for BPPV in a primary-care setting may aid in preventing referrals to higher tertiary care facilities and hospitalisation for follow-up. TRIAL REGISTRATION: The study was registered in protocols.io (PROTOCOL INTEGER ID: 51,464) on July 11, 2021.


Subject(s)
Benign Paroxysmal Positional Vertigo , General Practitioners , Humans , Benign Paroxysmal Positional Vertigo/diagnosis , Benign Paroxysmal Positional Vertigo/therapy , Hospitalization , Language , MEDLINE
9.
Cureus ; 15(8): e44042, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37746482

ABSTRACT

Infantile laryngeal hemangiomas are relatively common. However, adult vocal cord hemangiomas are extremely rare. A 46-year-old woman was referred to our department for hoarseness, which continued for 18 months. A laryngeal fiberscope revealed a small protuberant tumor resembling a polyp on her right vocal cord, and the narrow-band imaging showed abundant vascularity. Laryngeal microsurgery with a cold instrument under general anesthesia completely resected the tumor on the vocal cord. Histopathologically, the resected tumor consisted of vessels with thick walls and was diagnosed as a cavernous hemangioma of the vocal cord. After the surgery, she has never complained of hoarseness and has had no local recurrence for six months.

10.
BMJ Case Rep ; 16(9)2023 Sep 26.
Article in English | MEDLINE | ID: mdl-37751987

ABSTRACT

We report a case where tranexamic acid, which is an antifibrinolytic agent, was used to effectively treat bleeding tendency in a patient with immunoglobulin light chain (AL) amyloidosis. A male patient in his 80s without a history of bleeding disorders was admitted to our hospital for the examination of bleeding tendency and was diagnosed with a bleeding disorder due to AL amyloidosis. Blood tests revealed elevated plasmin-α2-plasmin inhibitor complex levels, suggesting fibrinolytic activation. Managing the bleeding was difficult; however, we suspected fibrinolytic activation associated with AL amyloidosis and initiated treatment with oral tranexamic acid, which markedly improved the bleeding disorder and abnormalities of the fibrinolytic system. Therefore, in cases of bleeding due to fibrinolytic activation of AL amyloidosis, tranexamic acid administration can be an effective treatment.

11.
Acta Neuropathol ; 146(4): 611-629, 2023 10.
Article in English | MEDLINE | ID: mdl-37555859

ABSTRACT

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by TDP-43 inclusions in the cortical and spinal motor neurons. It remains unknown whether and how pathogenic TDP-43 spreads across neural connections to progress degenerative processes in the cortico-spinal motor circuitry. Here we established novel mouse ALS models that initially induced mutant TDP-43 inclusions in specific neuronal or cell types in the motor circuits, and investigated whether TDP-43 and relevant pathological processes spread across neuronal or cellular connections. We first developed ALS models that primarily induced TDP-43 inclusions in the corticospinal neurons, spinal motor neurons, or forelimb skeletal muscle, by using adeno-associated virus (AAV) expressing mutant TDP-43. We found that TDP-43 induced in the corticospinal neurons was transported along the axons anterogradely and transferred to the oligodendrocytes along the corticospinal tract (CST), coinciding with mild axon degeneration. In contrast, TDP-43 introduced in the spinal motor neurons did not spread retrogradely to the cortical or spinal neurons; however, it induced an extreme loss of spinal motor neurons and subsequent degeneration of neighboring spinal neurons, suggesting a degenerative propagation in a retrograde manner in the spinal cord. The intraspinal degeneration further led to severe muscle atrophy. Finally, TDP-43 induced in the skeletal muscle did not propagate pathological events to spinal neurons retrogradely. Our data revealed that mutant TDP-43 spread across neuro-glial connections anterogradely in the corticospinal pathway, whereas it exhibited different retrograde degenerative properties in the spinal circuits. This suggests that pathogenic TDP-43 may induce distinct antero- and retrograde mechanisms of degeneration in the motor system in ALS.


Subject(s)
Amyotrophic Lateral Sclerosis , Retrograde Degeneration , Animals , Mice , Amyotrophic Lateral Sclerosis/pathology , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Motor Neurons/metabolism , Retrograde Degeneration/metabolism , Retrograde Degeneration/pathology , Spinal Cord/pathology
12.
JID Innov ; 3(4): 100205, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37441125

ABSTRACT

Nuclear IL-33 levels are high at the epidermal edges of skin wounds and facilitate wound healing. However, IL-33-mediated regulation of keratinocyte (KC) biology during wound healing remains poorly understood. During skin-wound healing, KC migration and re-epithelialization are mediated predominantly by EGFR signaling activation and depend on the function of signal transducer and activator of transcription 3 (STAT3). We found that migrating KCs at the leading edges of mouse skin wounds exhibited concomitant induction and nuclear colocalization of IL-33 and phosphorylated STAT3. In cultured human KCs, activation of EGFR signaling caused rapid elevation of nuclear IL-33, which directly interacts with phosphorylated STAT3, promoting STAT3 activation. In vitro KC migration and wound-healing assays revealed that high nuclear IL-33 levels were required for KC migration and wound closure. KC mobility associated with a lack of suprabasal epidermal keratins and extracellular matrix degradation mediated by matrix metalloproteinases (MMPs) control cell migration at the intracellular and extracellular levels, respectively. In EGFR-activated KCs, nuclear IL-33 mediated keratin 1 and 10 downregulation and MMP9 upregulation by promoting STAT3 activation and limited MMP1, MMP3, and MMP10 induction by suppressing NF-κB transactivation. Thus, epidermal nuclear IL-33 is involved in KC migration and wound closure by regulating the STAT3 and NF-κB pathways.

13.
Cureus ; 15(5): e38429, 2023 May.
Article in English | MEDLINE | ID: mdl-37273346

ABSTRACT

Diffuse aspiration bronchiolitis (DAB) is a chronic inflammatory response of the bronchioles caused by repeated aspiration of foreign bodies. It is common among older individuals with dysphagia associated with neurological diseases or dementia. Here, we present the case of a woman in her 40s who was presumed to have developed DAB due to neuromyelitis optica spectrum disorder (NMOSD). There have been no reports of DAB due to NMOSD. The absence of obvious episodes of aspiration and the fact that pneumonia was the predominant symptom delayed the diagnosis despite the appearance of specific neurological abnormalities. DAB caused by neurological diseases of the brainstem should be considered in younger patients with diffuse centrilobular opacities, even if dysphagia is not obvious.

14.
Nutrients ; 15(7)2023 Mar 24.
Article in English | MEDLINE | ID: mdl-37049410

ABSTRACT

People who drink naturally hardened water may experience longevity-enhancing effects. In this study, we investigated water hardness and longevity from both geological and epidemiological perspectives in Japan's Amami islands, where drinking water is drawn from coralline or non-coralline bedrock. We investigated drinking water hardness, limestone bedrock occupancy, and the centenarian rate (number per 10,000 population) by municipality across four adjacent islands (Amami-Oshima (non-coralline), Tokunoshima, Okinoerabu, and Yoron (predominantly coralline)). Limestone was strongly correlated with water hardness (r = 0.99; p < 0.01), occupying more than 80% of the bedrock where the water was the hardest (Tokunoshima's Isen municipality: 86.5%; Yoron: 82.9%) and being scarcely detectable in Amami-Oshima (0.0 to 0.2%), where the water was the least hard. The centenarian rate was also strongly correlated with water hardness (r = 0.84, p < 0.01), with the highest figures in Yoron (29.7) and Isen (29.2), and the lowest in Amami-Oshima (0.0 to 12.2). Therefore, we hypothesize a potentially beneficial effect of hard water on longevity when that water is drawn from coralline limestone. Water hardness is determined by the water content of calcium and magnesium and may plausibly influence life expectancy through a preventative effect against cardiovascular disease. Our findings are of interest to current debates about future global access to drinking water and its quality.


Subject(s)
Drinking Water , Aged, 80 and over , Humans , Drinking Water/analysis , Japan , Centenarians , Hardness , Calcium/analysis , Calcium Carbonate
15.
Environ Int ; 174: 107893, 2023 04.
Article in English | MEDLINE | ID: mdl-37058973

ABSTRACT

The impact of low-dose-rate radiation on genetics is largely unknown, particularly in natural environments. The Fukushima Dai-ich Nuclear Power Plant disaster resulted in the creation of contaminated natural lands. In this study, de novo mutations (DNMs) in germ line cells were surveyed from double-digest RADseq fragments in Japanese cedar and flowering cherry trees exposed to ambient dose rates ranging from 0.08 to 6.86 µGy h-1. These two species are among the most widely cultivated Japanese gymnosperm and angiosperm trees for forestry and horticultural purpose, respectively. For Japanese flowering cherry, open crossings were performed to produce seedlings, and only two candidate DNMs were detected from uncontaminated area. For Japanese cedar, the haploid megagametophytes were used as next generation samples. The use of megagametophytes from open crossing for next generation mutation screening had many advantages such as reducing exposure to radiation in contaminated areas because artificial crossings are not needed and the ease of data analysis owing to the haploid nature of megagametophytes. A direct comparison of the nucleotide sequences of parents and megagametophytes revealed an average of 1.4 candidate DNMs per megagametophyte sample (range: 0-40) after filtering procedures were optimized based on the validation of DNMs via Sanger sequencing. There was no relationship between the observed mutations and the ambient dose rate in the growing area or the concentration of 137Cs in cedar branches. The present results also suggest that mutation rates differ among lineages and that the growing environment has a relatively large influence on these mutation rates. These results suggested there was no significant increase in the mutation rate of the germplasm of Japanese cedar and flowering cherry trees growing in the contaminated areas.


Subject(s)
Disasters , Fukushima Nuclear Accident , Radiation Monitoring , Soil Pollutants, Radioactive , Trees/genetics , Radiation Monitoring/methods , Soil Pollutants, Radioactive/analysis , Cesium Radioisotopes/analysis , Japan
16.
Cureus ; 15(1): e33493, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36779101

ABSTRACT

Central nervous system (CNS) tuberculosis (TB) remains a serious disease with high morbidity and mortality but is often difficult to diagnose owing to less sensitive microbiological techniques. Herein, we present a case where the main complaint was staggering gait; however, the patient was diagnosed with CNS TB associated with pulmonary TB. A woman in her 70s was admitted to our hospital with a two-month history of progressive ataxia. Cerebrospinal fluid examination showed an elevated lymphocyte count; however, cranial imaging studies did not show significant findings. However, we performed positron emission tomography-computed tomography imaging owing to suspicions of paraneoplastic syndrome, which showed substantial 18F-fluorodeoxyglucose accumulation in the lungs. A subsequent bronchoscopy exam led to a pulmonary TB diagnosis for which the patient was treated, and the patient's symptoms fully resolved. Finally, we diagnosed ataxia due to CNS TB with pulmonary TB after excluding other causes of ataxia and because of a lymphocyte-predominant increase of cells in the spinal fluid. Thus, TB infection should be considered in cases of cerebellar ataxia of unknown etiology.​​.

17.
J Gastroenterol ; 58(4): 358-366, 2023 04.
Article in English | MEDLINE | ID: mdl-36781490

ABSTRACT

BACKGROUND: Vonoprazan, a potassium-competitive acid blocker (VPZ), significantly reduces postoperative bleeding after gastric ESD; however, there is no consensus on the appropriate treatment duration. We conducted a randomized controlled study to demonstrate that the 3-week administration of VPZ is not inferior to the 8-week administration for ulcer healing. METHODS: This is a prospective, open-label multicenter randomized controlled trial. Patients aged 20-85 years undergoing gastric ESD were included in this study. The key exclusion criteria were patients with bleeding tendencies and those taking NSAIDs, steroids, PPIs, or VPZ medications. Eligible patients were randomly assigned to the VPZ 3w or 8w treatment group. The primary endpoint was the proportion of patients with complete closure of the post-ESD wound at 24 weeks after ESD. The key secondary endpoints included the proportion of patients with complete closure of the post-ESD wound at 8 weeks and the proportion of bleeding or perforation more than 3 weeks after ESD. RESULTS: From May 2018 to October 2020, 234 patients were included. The proportion of patients with complete ulcer closure was significantly lower in the 3w group than in the 8w group (70.8% vs. 90.6%) at 8 weeks post-treatment. The complete closure rates at 24 weeks in the 3w and 8w groups were 99.1% and 99.2%, respectively. The absolute difference in the closure rate at 24 weeks was - 0.059% [95% confidence interval (CI) -3.4% to 3.2], and the lower limit of the 95% CI exceeded -10%, the preset threshold. None of the patients developed delayed bleeding 3 weeks after ESD. CONCLUSION: This multicenter randomized study demonstrated that 3 weeks of treatment with VPZ is sufficient for ulcer healing. Trial registry number. UMIN000031564.


Subject(s)
Endoscopic Mucosal Resection , Stomach Neoplasms , Stomach Ulcer , Humans , Ulcer , Proton Pump Inhibitors/therapeutic use , Stomach Ulcer/drug therapy , Stomach Ulcer/etiology , Prospective Studies , Stomach Neoplasms/drug therapy , Endoscopic Mucosal Resection/adverse effects , Treatment Outcome
18.
Commun Biol ; 6(1): 13, 2023 01 06.
Article in English | MEDLINE | ID: mdl-36609486

ABSTRACT

Trehalose is the nonreducing disaccharide of glucose, evolutionarily conserved in invertebrates. The living skin equivalent (LSE) is an organotypic coculture containing keratinocytes cultivated on fibroblast-populated dermal substitutes. We demonstrated that human primary fibroblasts treated with highly concentrated trehalose promote significantly extensive spread of the epidermal layer of LSE without any deleterious effects. The RNA-seq analysis of trehalose-treated 2D and 3D fibroblasts at early time points revealed the involvement of the CDKN1A pathway, the knockdown of which significantly suppressed the upregulation of DPT, ANGPT2, VEGFA, EREG, and FGF2. The trehalose-treated fibroblasts were positive for senescence-associated ß-galactosidase. Finally, transplantation of the dermal substitute with trehalose-treated fibroblasts accelerated wound closure and increased capillary formation significantly in the experimental mouse wounds in vivo, which was canceled by the CDKN1A knockdown. These data indicate that high-concentration trehalose can induce the senescence-like state in fibroblasts via CDKN1A/p21, which may be therapeutically useful for optimal wound repair.


Subject(s)
Skin , Trehalose , Humans , Animals , Mice , Trehalose/pharmacology , Trehalose/metabolism , Skin/metabolism , Keratinocytes/metabolism , Wound Healing/physiology , Fibroblasts/metabolism , Cyclin-Dependent Kinase Inhibitor p21/genetics , Cyclin-Dependent Kinase Inhibitor p21/metabolism
19.
Mod Rheumatol ; 33(1): 182-186, 2023 Jan 03.
Article in English | MEDLINE | ID: mdl-35134992

ABSTRACT

OBJECTIVE: This study clarifies the involvement of gender and pre-existing diabetes mellitus (DM) in the clinical characteristics of polymyalgia rheumatica (PMR). METHODS: The clinical records of patients diagnosed with PMR in our department between January 2011 and June 2021, especially in terms of gender and DM were retrospectively analysed. RESULTS: We identified 89 patients with the median age of 75.37 cases were men and 52 cases were women. Pre-existing DM was found in 21 patients (23.6%). Male PMR patients exhibited a higher complication rate of pre-existing DM and C-reactive protein (CRP) levels at diagnosis (p = .04 and p < .01, respectively) than female patients, and men were more common in the patient group with pre-existing DM (p = .04). The CRP levels of male PMR patients without pre-existing DM were higher than female PMR patients without pre-existing DM. CONCLUSION: Male PMR patients might have a varying pathophysiology from female patients in terms of high inflammation levels accompanied by a high prevalence rate of pre-existing DM and need a gender-specific approach.


Subject(s)
Diabetes Mellitus , Giant Cell Arteritis , Polymyalgia Rheumatica , Humans , Male , Female , Polymyalgia Rheumatica/complications , Polymyalgia Rheumatica/epidemiology , Polymyalgia Rheumatica/diagnosis , Retrospective Studies , East Asian People , Giant Cell Arteritis/complications , Diabetes Mellitus/epidemiology
20.
Peptides ; 160: 170905, 2023 02.
Article in English | MEDLINE | ID: mdl-36436612

ABSTRACT

Motilin is a gastrointestinal hormone secreted by the duodenum. This peptide regulates a characteristic gastrointestinal contraction pattern, called the migrating motor complex, during the fasting state. Motilin also affects the pressure of the lower esophageal sphincter, gastric motility and gastric accommodation in the gastrointestinal tract. Furthermore, motilin induces bile discharge into the duodenum by promoting gallbladder contraction, pepsin secretion in the stomach, pancreatic juice and insulin secretion from the pancreas. In recent years, it has been shown that motilin is associated with appetite, and clinical applications are expected for diseases affected by food intake, e.g. obesity, by regulating motilin levels. Gastric acid and bile are the two major physiological regulators for motilin release. Caloric foods have varying effects on motilin levels, depending on their composition. Among non-caloric foods, bitter substances reduce motilin levels and are therefore expected to have an appetite-suppressing effect. Various motilin receptor agonists and antagonists have been developed but have yet to reach clinical use.


Subject(s)
Gastrointestinal Hormones , Motilin , Gastrointestinal Motility/physiology , Stomach , Gastrointestinal Hormones/pharmacology , Myoelectric Complex, Migrating/physiology , Duodenum
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