反対側で偶発的に発見し，二期的に修復した不顕性閉鎖孔ヘルニアの1例

Institutional Repositories DataBase (IRDB) · 2025-02-13

Obturator hernias are relatively rare, accounting for 0.05% to 2.2% of all hernias. They are often discovered due to bowel obstruction and can become severe if incarcerated. In some cases, obturator hernias are incidentally identified during laparoscopic surgery. However, no established treatment guidelines exist for such cases. We encountered a case of an obturator hernia found on the contralateral side during surgery for an incarcerated obturator hernia. A 76-year-old female presented to the emergency department with worsening lower back pain and vomiting for five days. A detailed examination led to the diagnosis of an incarcerated left obturator hernia, and laparoscopic surgery was performed using the transabdominal preperitoneal (TAPP) approach. The small intestine was incarcerated in a Richter-type hernia but was successfully reduced with forceps, allowing preservation of the affected intestine. Since a right obturator hernia was also identified, we discussed the condition with the patient and her family and performed an elective TAPP procedure for the right hernia one month later. The patient’s postoperative recovery was uneventful, with no major complications. This case highlights the importance of awareness regarding the potential coexistence of inguinal and contralateral obturator hernias. Laparoscopic surgery proved useful for detecting contralateral lesions and performing prophylactic repair.

Characterization of ene reaction products of Cookson-type fluorescent reagents and their application for recognizing amyloid β aggregation

Analytical Sciences · 2025-05-23

Pyridoxamine as a potential scavenger of neurotoxic dopamine quinone: Inhibition of dopamine-induced α-synuclein oligomerization

Research Square · 2025-05-12

Pyridoxamine inhibits dopamine-induced α-synuclein oligomerization through scavenging neurotoxic dopamine quinone

Scientific Reports · 2025-12-26

Parkinson’s disease (PD) is a neurodegenerative disease characterized by loss of dopaminergic neurons causing reduced levels of dopamine (DA), and the presence of Lewy bodies, whose main component is fibrillar α-synuclein (α-Syn). DA is easily oxidized to DA o-quinone (DAQ), which is a key mechanism for neuronal cell death and α-Syn accumulation. Therefore, a DAQ-quenching molecule should prevent DA-induced pathogenicity in PD. Pyridoxamine (PM) is a promising drug candidate for various chronic diseases, including diabetes, because it scavenges reactive carbonyl species. In this study, we found that PM traps DAQ through stable adduct formation. The initial reaction of PM occurred at the DAQ carbonyl carbon to yield pyridoxal (PL) after hydrolysis. DA then reacted with the PL aldehyde, followed by intramolecular cyclization to produce a PL–DA adduct. The adduct structure was shown by LC-MS and NMR analyses to be 1-(2-methyl-3-hydroxy-5-hydroxymethyl-4-pyridyl)-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline. The PL–DA adduct was also detected under intracellular-like conditions. DA caused α-Syn oligomerization via oxidation of methionine residues, which was inhibited by PM in a dose-dependent manner. Therefore, PM could prevent DA-induced adverse effects in the brains of PD patients by forming the PL–DA adduct, suggesting a possible therapeutic use of PM for scavenging DAQ.

A Case of Left Obturator Hernia Repaired by Contralaterally Extending the TAPP Technique for Right Inguinal Hernia

Nihon Rinsho Geka Gakkai Zasshi (Journal of Japan Surgical Association) · 2024-01-01

症例は76歳，女性．右鼠径および大腿ヘルニアに対して腹腔鏡下にTAPP法で手術を施行した．手術中に反対側（左）に不顕性閉鎖孔ヘルニアを認めた．患側（右）鼠径部の腹膜剥離を反対側へ延長する「対側アプローチ」で不顕性閉鎖孔ヘルニアをメッシュで修復した．反対側（左）は過去の鼠径ヘルニア手術でメッシュプラグ法により修復されていたが，手術中に大きな合併症なく手術を完遂した．手術後，右鼠径部の症状は消失し大きな合併症は認めていない．腹腔鏡手術が普及する中，偶発的に閉鎖孔ヘルニアを発見することがある．腸閉塞のリスクを考慮して修復する際，対側アプローチは治療の選択肢になり得ると考えられた．

Lower Extremity Traumatic Wound Management: Relative Significance of Negative Pressure Wound Therapy in the Orthopedic Setting

Advances in Wound Care · 2024-07-13 · 4 citations

Significance: Lower extremity traumatic wounds are associated with numerous perioperative challenges. Their etiologies determine the characteristics and extent of the injury. The timing of subsequent surgical intervention and wound healing optimization after lower extremity trauma are integral to successful perioperative lower extremity wound management. Recent Advances: Managing trauma to the lower extremities uses a multidisciplinary surgical approach. The objective of this review is to summarize lower limb trauma assessment, advancements in lower extremity trauma management, and the clinical applications of advanced wound care in lower limb traumatic wounds. The advent of lower limb reconstruction and the development of advanced wound care modalities have helped to improve the management of these complex injuries. Critical Issues: The extensive involvement of bone, soft tissues, nerves, and blood vessels of severe lower extremity trauma wounds presents a challenge for clinicians in both the acute care setting and during patient rehabilitation. If not properly managed, these injuries may be subject to a decline in limb function and may possibly result in limb loss. To reveal developing limb-threatening conditions, serial examinations should be performed. Future Directions: The majority of lower limb traumatic wound will benefit from the perioperative administration of an appropriate negative pressure wound therapy (NPWT)-based system, which can help to promote granulation tissue and remove wound exudate before definitive closure and/or reconstruction. NPWT should be included as an important adjunct in the surgical management of lower limb traumatic wounds.

Tyrosine modifications of insulin-degrading enzyme enable favorable control of substrate specificity for both Alzheimer’s disease and type-2 diabetes mellitus

Bioorganic Chemistry · 2024-10-25 · 4 citations

• 4-Phenyl-1,2,4-triazoline-3,5-dione (PTAD) was used for tyrosine modification. • The modification sites on insulin-degrading enzyme (IDE) were identified. • The substrate specificity of tyrosine-modified IDE was examined. • The modified IDE digested amyloid beta, but not insulin. • That is favorable for both Alzheimer’s disease and type-2 diabetes mellitus. Insulin-degrading enzyme (IDE) cleaves amyloid beta (Aβ), insulin, and other bioactive peptides. Because Aβ and insulin are closely related to Alzheimer’s disease (AD) and type-2 diabetes mellitus (T2DM), respectively, IDE is a candidate drug target for treating both AD and T2DM. However, the activity of IDE has opposing effects, including decreasing AD risk by degrading Aβ and increasing T2DM risk by degrading insulin. The opposed substrate specificity is associated with the exo- and active sites containing Tyr 314 and Tyr 831 residues, the plausible modification targets for controlling substrate specificity. In this study, we used a tyrosine-specific modification regent, Cookson reagent (4-phenyl-1,2,4-triazoline-3,5-dione, PTAD), for IDE and examined the degradation activities on Aβ 40 and insulin. Fifteen tyrosine residues, including Tyr 314 and Tyr 831 , were modified by PTAD. After incubation with PTAD-modified IDE for 3 days, insulin remained intact, whereas Aβ 40 was completely degraded. This favorable change of substrate specificity was also observed in the mixture of Aβ 40 and insulin, suggesting that tyrosine modification of IDE might be a therapeutic strategy for AD and T2DM.

SKGQA, a Peptide Derived from the ANA/BTG3 Protein, Cleaves Amyloid-β with Proteolytic Activity

Biomolecules · 2024-05-15 · 1 citations

Despite the extensive research conducted on Alzheimer’s disease (AD) over the years, no effective drug for AD treatment has been found. Therefore, the development of new drugs for the treatment of AD is of the utmost importance. We recently reported the proteolytic activities of JAL-TA9 (YKGSGFRMI) and ANA-TA9 (SKGQAYRMA), synthetic peptides of nine amino acids each, derived from the Box A region of Tob1 and ANA/BTG3 proteins, respectively. Furthermore, two components of ANA-TA9, ANA-YA4 (YRMI) at the C-terminus end and ANA-SA5 (SKGQA) at the N-terminus end of ANA-TA9, exhibited proteolytic activity against amyloid-β (Aβ) fragment peptides. In this study, we identified the active center of ANA-SA5 using AEBSF, a serine protease inhibitor, and a peptide in which the Ser residue of ANA-SA5 was replaced with Leu. In addition, we demonstrate the proteolytic activity of ANA-SA5 against the soluble form Aβ42 (a-Aβ42) and solid insoluble form s-Aβ42. Furthermore, ANA-SA5 was not cytotoxic to A549 cells. These results indicate that ANA-SA5 is a promising Catalytide and a potential candidate for the development of new peptide drugs targeting Aβ42 for AD treatment.

Oxoammonium salts exert antiviral effects against coronavirus via denaturation of their spike proteins

Scientific Reports · 2024-10-13 · 2 citations

Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV2) infection has forced social changes worldwide. Development of potent antiviral agents is necessary to prevent future pandemics. Titanium oxide, a photocatalyst, is a long-acting antiviral agent; however, its effects are weakened in the dark. Therefore, new antiviral substances that can be used in the dark are needed. Two types of nitroxyl radicals, 2,2,6,6-tetramethylpiperidine N-oxyl (TEMPO) and 2-azaadamantane N-oxyl (AZADO), are commonly used as oxidation catalysts utilizing oxygen in the air as the terminal oxidant. Therefore, in this study, we aimed to evaluate the potential of these radicals as antiviral compounds with sustained activity even in the dark. We evaluated the antiviral effects of oxoammonium salts corresponding to TEMPO and AZADO (TEMPO-Oxo and AZADO-Oxo, respectively), which are the active forms of nitroxyl radicals in oxidation reactions. TEMPO-Oxo and AZADO-Oxo inhibited the binding of SARS-CoV2 spike protein receptor-binding domain (S-RBD) to angiotensin-converting enzyme 2. Notably, AZADO-Oxo exhibited a 10-fold stronger inhibitory effect than TEMPO-Oxo. TEMPO-Oxo and AZADO-Oxo also denatured S-RBD; however, effects of AZADO-Oxo were 10-fold stronger than those of TEMPO-Oxo and did not change in the dark. Some S-RBD peptides treated with AZADO-Oxo were cleaved at the N-terminal side of tyrosine residues. TEMPO-Oxo and AZADO-Oxo exhibited concentration-dependent antiviral effects against feline coronavirus. In conclusion, active forms of the nitroxyl radicals, TEMPO-Oxo and AZADO-Oxo, exerted antiviral effects by denaturing S-RBD, regardless of the presence or absence of light, suggesting their potential as novel antiviral agents.

Stable Isotope Dilution LC/ESI-SRM/MS Analysis for Highly Polar Bioactive Dipeptides Found in Fermented Brown Rice Product using a Porous Graphitic Carbon Column

Food Analytical Methods · 2023-09-05 · 3 citations

Abstract In this study, a validated analytical method based on liquid chromatography/electrospray ionization-selected reaction monitoring/mass spectrometry (LC/ESI-SRM/MS) was developed for dipeptides in a functional food, fermented brown rice and rice bran with Aspergillus oryzae (FBRA). The aim of this study was to screen and quantify dipeptides in the water-soluble fraction of FBRA. There are few studies focusing on dipeptides in FBRA, even though FBRA is expected to contain bioactive peptides: FBRA or its aqueous extract has shown variety of biological activities. An anti-hypertensive dipeptide was found in similar rice bran products digested by thermolysin. Dipeptides are the smallest class of peptides, and many show a variety of biological activities. Some bioactive peptides are widely found in fermented foods. However, because dipeptides are generally too polar to be retained on versatile LC columns, such as octadecylsilyl columns, dipeptides have been often overlooked and not quantified because of the analytical difficulties. The LC was performed using a porous graphitic carbon column with the mobile phases of 0.1% formic acid/0.1% trifluoroacetic acid/1% tetrahydrofuran in water and acetonitrile. The stable isotope-labeled internal standards and SRM for dipeptides made it possible to develop a validated method. Five dipeptides were identified and quantified in FBRA in much higher concentrations than related materials (malted brown rice, rice bran, brown rice, and white rice) as follows: Ile-Arg, 82.1 µg/g; Ala-Phe, 27.8 µg/g; Ala-Tyr, 31.6 µg/g; Val-Phe, 46.3 µg/g; and Ile-Tyr, 49.9 µg/g. This method was simple and robust and would be applicable for other functional foods. Graphical Abstract