Elective surgery for liver injury and misinserted tube into the inferior vena cava associated with chest tube replacement: A case report.

Background: Several reports on organ injury and death due to incorrect chest tube insertion exist; however, reports on the chest tube penetrating the liver and reaching the inferior vena cava are limited. Case Presentation: A 79-year-old man presented with a clamped tube because of massive bleeding from the tube following right chest tube replacement in the hospital of origin. The tube entered the inferior vena cava from the hepatic parenchyma via the right hepatic vein and was removed 15 h later because his hemodynamics stabilized. A ruptured pseudoaneurysm necessitated further transcatheter arterial embolism on the second hospitalization day, and the patient was transferred back to the referring hospital on day 17. Conclusion: Liver injury caused by an inferior vena cava misinsertion-associated chest tube can be treated with elective surgery in anticipation of the tube's tamponade effect. However, due to the risk of rebleeding, imaging follow-up is necessary soon after surgery.

Biosynthesis and Degradation of Free D-Amino Acids and Their Physiological Roles in the Periphery and Endocrine Glands.

It was long believed that D-amino acids were either unnatural isomers or laboratory artifacts, and that the important functions of amino acids were exerted only by L-amino acids. However, recent investigations have revealed a variety of D-amino acids in mammals that play important roles in physiological functions, including free D-serine and D-aspartate that are crucial in the central nervous system. The functions of several D-amino acids in the periphery and endocrine glands are also receiving increasing attention. Here, we present an overview of recent advances in elucidating the physiological roles of D-amino acids, especially in the periphery and endocrine glands.

Evaluating the relationship between ocular blood flow and systemic organ blood flow in hemorrhagic shock using a rabbit model.

This study aimed to investigate the feasibility of utilizing noninvasive ocular blood flow measurements as potential indicators of systemic circulation in rabbits experiencing hemorrhagic shock. Using Laser speckle flowgraphy, ocular blood flow indices, relative flow volume (RFV), and mean blur rate in the choroidal area (MBR-CH) were assessed in New Zealand White rabbits (n = 10) subjected to controlled blood removal and return. Hemodynamic parameters and biochemical markers were monitored alongside ocular circulation during blood removal and return phases. Additionally, correlations between ocular parameters and systemic indices were examined. The results indicated that RFV and MBR-CH exhibited significant correlations with renal and intestinal blood flows, with stronger correlations observed during blood removal. Additionally, ocular blood flow changes closely mirrored systemic dynamics, suggesting their potential as real-time indicators of shock progression and recovery. These findings indicate that ocular blood flow measurements may serve as real-time indicators of the systemic circulation status during hemorrhagic shock, offering potential insights into shock management and guiding tailored interventions. Thus, noninvasive ocular blood flow evaluation holds promise as an innovative tool for assessing systemic circulation dynamics during hemorrhagic shock.

Novel tetrahydrofolate-dependent d-serine dehydratase activity of serine hydroxymethyltransferases.

d-Serine plays vital physiological roles in the functional regulation of the mammalian brain, where it is produced from l-serine by serine racemase and degraded by d-amino acid oxidase. In the present study, we identified a new d-serine metabolizing activity of serine hydroxymethyltransferase (SHMT) in bacteria as well as mammals. SHMT is known to catalyze the conversion of l-serine and tetrahydrofolate (THF) to glycine and 5,10-methylenetetrahydrofolate, respectively. In addition, we found that human and Escherichia coli SHMTs have d-serine dehydratase activity, which degrades d-serine to pyruvate and ammonia. We characterized this enzymatic activity along with canonical SHMT activity. Intriguingly, SHMT required THF to catalyze d-serine dehydration and did not exhibit dehydratase activity toward l-serine. Furthermore, SHMT did not use d-serine as a substrate in the canonical hydroxymethyltransferase reaction. The d-serine dehydratase activities of two isozymes of human SHMT were inhibited in the presence of a high concentration of THF, whereas that of E. coli SHMT was increased. The pH and temperature profiles of d-serine dehydratase and serine hydroxymethyltransferase activities of these three SHMTs were partially distinct. The catalytic efficiency (kcat /Km ) of dehydratase activity was lower than that of hydroxymethyltransferase activity. Nevertheless, the d-serine dehydratase activity of SHMT was physiologically important because d-serine inhibited the growth of an SHMT deletion mutant of E. coli, ∆glyA, more than that of the wild-type strain. Collectively, these results suggest that SHMT is involved not only in l- but also in d-serine metabolism through the degradation of d-serine.

Acute Hydrocephalus Associated with Streptococcus anginosus Meningitis.

Introduction: Meningitis-related acute hydrocephalus is rare, challenging to diagnose, and has a high mortality rate. Case description: Here we describe the case of a 76-year-old patient diagnosed with bacterial meningitis who developed acute hydrocephalus and subsequently died. Discussion: Although meningitis-related acute hydrocephalus is usually non-occlusive, occlusive hydrocephalus may also occur. Moreover, worsening hydrocephalus despite cerebrospinal fluid drainage should prompt a diagnosis of obstructive hydrocephalus. In such conditions, potential management strategies include ventriculoperitoneal shunt and endoscopic third ventriculostomy. Conclusion: In patients with meningitis-related hydrocephalus, worsening despite appropriate antibiotic administration, treatment may be complicated by ventriculitis and obstructive hydrocephalus, which can be fatal. If intracranial pressure is not medically controlled, bilateral decompression craniectomy should be considered as a potential management strategy. LEARNING POINTS: The extreme rarity of obstructive hydrocephalus caused by bacterial meningitis can lead to delayed diagnosis and treatment.Ventriculoperitoneal shunt and endoscopic third ventriculostomy are the indicated management strategies for early diagnosis of obstructive hydrocephalus.Bilateral decompression craniectomy may be an option in such cases.

Transcatheter arterial embolization for traumatic injury to the pharyngeal branch of the ascending pharyngeal artery: Two case reports.

BACKGROUND: The ascending pharyngeal artery (APhA) comprises the pharyngeal trunk (PT) and neuromeningeal trunk. The PT feeds the nasopharynx and adjacent tissue, which potentially connects with the sphenopalatine artery (SPA), branched from the internal maxillary artery (IMA). Due to its location deep inside the body, the PT is rarely injured by trauma. Here, we present two cases that underwent transcatheter arterial embolization (TAE) of the PT of the APhA due to trauma and iatrogenic procedure. CASE SUMMARY: Case 1 is a 49-year-old Japanese woman who underwent transoral endoscopy under sedation for a medical check-up. The nasal airway was inserted as glossoptosis occurred during sedation. Bleeding from the nasopharynx was observed during the endoscopic procedure. As the bleeding continued, the patient was referred to our hospital for further treatment. Contrast-enhanced computed tomography (CT) demonstrated extravasation in the nasopharynx originating from the right Rosenmuller fossa. TAE was performed and the extravasation disappeared after embolization. Case 2 is a 28-year-old Japanese woman who fell from the sixth floor of a building and was transported to our hospital. Contrast-enhanced CT demonstrated a complex facial fracture accompanying extravasation in the left pterygopalatine fossa to the nasopharynx. Angiography demonstrated an irregular third portion of the IMA. As angiography after TAE of the IMA demonstrated extravasation from the PT of the APhA, additional TAE to the artery was performed. The bleeding stopped after the procedure. CONCLUSION: Radiologists should be aware that the PT of the APhA can be a bleeding source, which has a potential connection with the SPA.

YgeA is involved in L- and D-homoserine metabolism in Escherichia coli.

Noncanonical D-amino acids are involved in peptidoglycan and biofilm metabolism in bacteria. Previously, we identified amino acid racemases with broad substrate specificity, including YgeA from Escherichia coli, which strongly prefers homoserine as a substrate. In this study, we investigated the functions of this enzyme in vivo. When wild-type and ygeA-deficient E. coli strains were cultured in minimal medium containing D-homoserine, the D-homoserine level was significantly higher in the ygeA-deficient strain than in the wild-type strain, in which it was almost undetectable. Additionally, D-homoserine was detected in YgeA-expressed E. coli cells cultured in minimal medium containing L-homoserine. The growth of the ygeA-deficient strain was significantly impaired in minimal medium with or without supplemental D-homoserine, while L-methionine, L-threonine or L-isoleucine, which are produced via L-homoserine, restored the growth impairment. Furthermore, the wild-type strain formed biofilms significantly more efficiently than the ygeA-deficient strain. Addition of L- or D-homoserine significantly suppressed biofilm formation in the wild-type strain, whereas this addition had no significant effect in the ygeA-deficient strain. Together, these data suggest that YgeA acts as an amino acid racemase and plays a role in L- and D-homoserine metabolism in E. coli.

Postpartum reversible cerebral vasoconstriction with cortical subarachnoid hemorrhage and posterior reversible encephalopathy syndrome concomitant with vertebral artery dissection diagnosed by MRI MSDE method: A case report and review of literature.

Headache is one of the most common symptoms encountered during the postpartum period. The cause may be unknown, or the following illnesses are possible: cervical artery dissection (CAD), reversible posterior cerebral encephalopathy syndrome (PRES), and reversible cerebral vasoconstrictor syndrome (RCVS). It is suggested that they are interrelated and share a similar mechanism such as small vessel endothelial dysfunction, deficiencies in self-regulation, and decreased sympathetic innervation of the posterior circulation. However, there are few reports of neuroradiological findings. We experienced a rare case of multiple postpartum vascular disease occurring at the same time. A 38-year-old woman suddenly developed thunderclap headache after giving birth. She was clear and had no neuropathy. Computed tomography revealed subarachnoid hemorrhage, including the cortical surface of the frontal lobe. Magnetic resonance image fluid-attenuated inversion recovery revealed high-intensity area in the bilateral basal ganglia and right occipital cortex. Angiography showed "string sausage" and extracranial left vertebral artery stenosis, but no aneurysm. Based on the clinical course and neuroradiological findings, we diagnosed her as postpartum vascular disease including CAD, PRES, RCVS, and cortical subarachnoid hemorrhage (SAH). Three-dimensional black blood T1-weighted images using a motion-sensitized driven equilibrium three-dimensional turbo spin echo (MSDE) sequencing method revealed an intramural hematoma consistent with the extracranial vertebral artery. After 3 months, MSDE lost its abnormal signal. Our case was rare in that multiple phenomena of postpartum vascular disease occurred at the same time. In particular, we could reveal that this speculation was reversible in the MRI MSDE sequencing.

Characterization of human cystathionine γ-lyase enzyme activities toward d-amino acids.

Various d-amino acids play important physiological roles in mammals, but the pathways of their production remain unknown except for d-serine, which is generated by serine racemase. Previously, we found that Escherichia coli cystathionine ß-lyase possesses amino acid racemase activity in addition to ß-lyase activity. In the present work, we evaluated the enzymatic activities of human cystathionine γ-lyase, which shares a relatively high amino acid sequence identity with cystathionine ß-lyase. The enzyme did not show racemase activity toward various amino acids including alanine and lyase and dehydratase activities were highest toward l-cystathionine and l-homoserine, respectively. The enzyme also showed weak activity toward l-cysteine and l-serine but no activity toward d-amino acids. Intriguingly, the pH and temperature profiles of lyase activity were distinct from those of dehydratase activity. Catalytic efficiency was higher for lyase activity than for dehydratase activity.

Identification of a novel d-amino acid aminotransferase involved in d-glutamate biosynthetic pathways in the hyperthermophile Thermotoga maritima.

The hyperthermophilic bacterium Thermotoga maritima has an atypical peptidoglycan that contains d-lysine alongside the usual d-alanine and d-glutamate. We previously identified a lysine racemase involved in d-lysine biosynthesis, and this enzyme also possesses alanine racemase activity. However, T. maritima has neither alanine racemase nor glutamate racemase enzymes; hence, the precise biosynthetic pathways of d-alanine and d-glutamate remain unclear in T. maritima. In the present study, we identified and characterized a novel d-amino acid aminotransferase (TM0831) in T. maritima. TM0831 exhibited aminotransferase activity towards 23 d-amino acids, but did not display activity towards l-amino acids. It displayed high specific activities towards d-homoserine and d-glutamine as amino donors. The most preferred acceptor was 2-oxoglutarate, followed by glyoxylate. Additionally, TM0831 displayed racemase activity towards four amino acids including aspartate and glutamate. Catalytic efficiency (kcat /Km ) for aminotransferase activity was higher than for racemase activity, and pH profiles were distinct between these two activities. To evaluate the functions of TM0831, we constructed a TTHA1643 (encoding glutamate racemase)-deficient Thermus thermophilus strain (∆TTHA1643) and integrated the TM0831 gene into the genome of ∆TTHA1643. The growth of this TM0831-integrated strain was promoted compared with ∆TTHA1643 and was restored to almost the same level as that of the wild-type strain. These results suggest that TM0831 is involved in d-glutamate production. TM0831 is a novel d-amino acid aminotransferase with racemase activity that is involved in the production of d-amino acids in T. maritima.

Bioresorbable plate fracture after cranioplasty caused by head injury: a pediatric case.

BACKGROUND: Recently, bone fixation materials have been developed as surgical materials. Bioabsorbable materials offer several advantages over other materials and are widely used. We report a rare case of the fracture of bioresorbable plates caused by head injury and describe some considerations. CASE DESCRIPTION: A 6-year-old boy suffered from consciousness disturbance. He was admitted to our hospital and diagnosed with left frontal subcortical hemorrhage due to ruptured arteriovenous malformation (AVM). He received the surgery of removal of the AVM with decompressive craniectomy. He was discharged without any neurologic deficit and underwent the cranioplasty 4 months after the initial surgery. Two months after the last treatment, he was fallen and hit his left frontal head. The next day, he noticed an abnormal bulge in the injured area. We diagnosed the bulging as cerebrospinal fluid leakage because of the dural tear. The repairment of dural tear was performed. We found that two bioresorbable plates used by cranioplasty were both cracked, and the dura mater beneath them was torn. We repaired the damaged dura with an artificial dura mater. After surgery, cerebrospinal fluid leakage did not occur. CONCLUSION: It has been reported that the durability of bioresorbable plates is no less than that of titanium plates. We experienced a relatively rare case in which bioabsorbable plate used for bone fixation was damaged due to head trauma. After craniotomy or cranioplasty using bioresorbable plates, special attention should be paid to head trauma that involves bone flap sinking force and side bending stress.

Acetylornithine aminotransferase TM1785 performs multiple functions in the hyperthermophile Thermotoga maritima.

The hyperthermophilic bacterium Thermotoga maritima peptidoglycan contains unusual d-lysine alongside typical d-alanine and d-glutamate. We previously identified lysine racemase and threonine dehydratase, but knowledge of d-amino acid metabolism remains limited. Herein, we identified and characterized T. maritima acetylornithine aminotransferase TM1785. The enzyme was most active towards acetyl-l-ornithine, but also utilized l-glutamate, l-ornithine and acetyl-l-lysine as amino donors, and 2-oxoglutarate was the preferred amino acceptor. TM1785 also displayed racemase activity towards four amino acids and lyase activity towards l-cysteine, but no dehydratase activity towards l-serine, l-threonine or corresponding d-amino acids. Catalytic efficiency (kcat /Km ) was highest for aminotransferase activity and lowest for racemase activity. TM1785 is a novel acetylornithine aminotransferase associated with l-arginine biosynthesis that possesses two additional distinct activities.

Glyoxylate reductase/hydroxypyruvate reductase regulates the free d-aspartate level in mammalian cells.

Multiple d-amino acids are present in mammalian cells, and these compounds have distinctive physiological functions. Among the free d-amino acids identified in mammals, d-aspartate plays critical roles in the neuroendocrine and endocrine systems, as well as in the central nervous system. Mammalian cells have the molecular apparatus necessary to take up, degrade, synthesize, and release d-aspartate. In particular, d-aspartate is degraded by d-aspartate oxidase (DDO), a peroxisome-localized enzyme that catalyzes the oxidative deamination of d-aspartate to generate oxaloacetate, hydrogen peroxide, and ammonia. However, little is known about the molecular mechanisms underlying d-aspartate homeostasis in cells. In this study, we established a cell line that overexpresses cytoplasm-localized DDO; this cell line cannot survive in the presence of high concentrations of d-aspartate, presumably because high levels of toxic hydrogen peroxide are produced by metabolism of abundant d-aspartate by DDO in the cytoplasm, where hydrogen peroxide cannot be removed due to the absence of catalase. Next, we transfected these cells with a complementary DNA library derived from the human brain and screened for clones that affected d-aspartate metabolism and improved cell survival, even when the cells were challenged with high concentrations of d-aspartate. The screen identified a clone of glyoxylate reductase/hydroxypyruvate reductase (GRHPR). Moreover, the GRHPR metabolites glyoxylate and hydroxypyruvate inhibited the enzymatic activity of DDO. Furthermore, we evaluated the effects of GRHPR and peroxisome-localized DDO on d- and l-aspartate levels in cultured mammalian cells. Our findings show that GRHPR contributes to the homeostasis of these amino acids in mammalian cells.

Identification and biochemical characterization of threonine dehydratase from the hyperthermophile Thermotoga maritima.

The peptidoglycan of the hyperthermophile Thermotoga maritima contains an unusual component, D-lysine (D-Lys), in addition to the typical D-alanine (D-Ala) and D-glutamate (D-Glu). In a previous study, we identified a Lys racemase that is presumably associated with D-Lys biosynthesis. However, our understanding of D-amino acid metabolism in T. maritima and other bacteria remains limited, although D-amino acids in the peptidoglycan are crucial for preserving bacterial cell structure and resistance to environmental threats. Herein, we characterized enzymatic and structural properties of TM0356 that shares a high amino acid sequence identity with serine (Ser) racemase. The results revealed that TM0356 forms a tetramer with each subunit containing a pyridoxal 5'-phosphate as a cofactor. The enzyme did not exhibit racemase activity toward various amino acids including Ser, and dehydratase activity was highest toward L-threonine (L-Thr). It also acted on L-Ser and L-allo-Thr, but not on the corresponding D-amino acids. The catalytic mechanism did not follow typical Michaelis-Menten kinetics; it displayed a sigmoidal dependence on substrate concentration, with highest catalytic efficiency (kcat/K0.5) toward L-Thr. Interestingly, dehydratase activity was insensitive to allosteric regulators L-valine and L-isoleucine (L-Ile) at low concentrations, while these L-amino acids are inhibitors at high concentrations. Thus, TM0356 is a biosynthetic Thr dehydratase responsible for the conversion of L-Thr to α-ketobutyrate and ammonia, which is presumably involved in the first step of the biosynthesis of L-Ile.

D-Amino acid metabolism in bacteria.

Bacteria produce diverse d-amino acids, which are essential components of cell wall peptidoglycan. Incorporation of these d-amino acids into peptidoglycan contributes to bacterial adaptation to environmental changes and threats. d-Amino acids have been associated with bacterial growth, biofilm formation and dispersal and regulation of peptidoglycan metabolism. The diversity of d-amino acids in bacteria is primarily due to the activities of amino acid racemases that catalyse the interconversion of the d- and l-enantiomers of amino acids. Recent studies have revealed that bacteria possess multiple enzymes with amino acid racemase activities. Therefore, elucidating d-amino acid metabolism by these enzymes is critical to understand the biological significance and behaviour of d-amino acids in bacteria. In this review, we focus on the metabolic pathways of d-amino acids in six types of bacteria.

Identification of an l-serine/l-threonine dehydratase with glutamate racemase activity in mammals.

Recent investigations have shown that multiple d-amino acids are present in mammals and these compounds have distinctive physiological functions. Free d-glutamate is present in various mammalian tissues and cells and in particular, it is presumably correlated with cardiac function, and much interest is growing in its unique metabolic pathways. Recently, we first identified d-glutamate cyclase as its degradative enzyme in mammals, whereas its biosynthetic pathway in mammals is unclear. Glutamate racemase is a most probable candidate, which catalyzes interconversion between d-glutamate and l-glutamate. Here, we identified the cDNA encoding l-serine dehydratase-like (SDHL) as the first mammalian clone with glutamate racemase activity. This rat SDHL had been deposited in mammalian databases as a protein of unknown function and its amino acid sequence shares ∼60% identity with that of l-serine dehydratase. Rat SDHL was expressed in Escherichia coli, and the enzymatic properties of the recombinant were characterized. The results indicated that rat SDHL is a multifunctional enzyme with glutamate racemase activity in addition to l-serine/l-threonine dehydratase activity. This clone is hence abbreviated as STDHgr. Further experiments using cultured mammalian cells confirmed that d-glutamate was synthesized and l-serine and l-threonine were decomposed. It was also found that SDHL (STDHgr) contributes to the homeostasis of several other amino acids.

Cerebrospinal fluid and serum d-serine concentrations are unaltered across the whole clinical spectrum of Alzheimer's disease.

The diagnosis of Alzheimer's disease (AD) relies on the presence of amyloidosis and tauopathy, as reflected in cerebrospinal fluid (CSF), independently from the clinical stage. Recently, CSF d-serine has been proposed as a possible new AD biomarker, reflecting dysfunctional activation of neuronal glutamatergic N-methyl-d-aspartate receptor (NMDAR). In this study, we measured blood serum and CSF concentration of two NMDAR modulators, such as d-serine and d-aspartate, in a cohort of drug-free subjects encompassing the whole AD clinical spectrum. In addition, we also analyzed d-serine levels in a cohort of post-mortem AD and control cortex samples. We reported unaltered serum and CSF concentrations of d-serine and d-aspartate in AD patients both during the AD progression and compared to non-demented controls. Accordingly, no correlation was detected between serum or CSF d-serine content and mini-mental state examination or Clinical Dementia Rating. Similarly, cortical d-serine levels were also unaltered in post-mortem samples of AD patients. Overall, our results failed to confirm previous findings indicating the CSF d-serine as a novel biomarker for AD.

Dysfunctional d-aspartate metabolism in BTBR mouse model of idiopathic autism.

BACKGROUND: Autism spectrum disorders (ASD) comprise a heterogeneous group of neurodevelopmental conditions characterized by impairment in social interaction, deviance in communication, and repetitive behaviors. Dysfunctional ionotropic NMDA and AMPA receptors, and metabotropic glutamate receptor 5 activity at excitatory synapses has been recently linked to multiple forms of ASD. Despite emerging evidence showing that d-aspartate and d-serine are important neuromodulators of glutamatergic transmission, no systematic investigation on the occurrence of these D-amino acids in preclinical ASD models has been carried out. METHODS: Through HPLC and qPCR analyses we investigated d-aspartate and d-serine metabolism in the brain and serum of four ASD mouse models. These include BTBR mice, an idiopathic model of ASD, and Cntnap2-/-, Shank3-/-, and 16p11.2+/- mice, three established genetic mouse lines recapitulating high confidence ASD-associated mutations. RESULTS: Biochemical and gene expression mapping in Cntnap2-/-, Shank3-/-, and 16p11.2+/- failed to find gross cerebral and serum alterations in d-aspartate and d-serine metabolism. Conversely, we found a striking and stereoselective increased d-aspartate content in the prefrontal cortex, hippocampus and serum of inbred BTBR mice. Consistent with biochemical assessments, in the same brain areas we also found a robust reduction in mRNA levels of d-aspartate oxidase, encoding the enzyme responsible for d-aspartate catabolism. CONCLUSIONS: Our results demonstrated the presence of disrupted d-aspartate metabolism in a widely used animal model of idiopathic ASD. GENERAL SIGNIFICANCE: Overall, this work calls for a deeper investigation of D-amino acids in the etiopathology of ASD and related developmental disorders.

[A Case of Unruptured Internal Carotid Artery Aneurysm with Improved Endocrinological Function after Treatment].

We experienced a case of unruptured internal carotid artery aneurysm improved endocrinological function after the treatment. A 68-year-old woman was admitted to our hospital complaining of general fatigue, dizziness, and decreased visual acuity. Radiological examination revealed unruptured large aneurysm at the right anterior carotid artery compressing on the pituitary gland. We underwent right STA-MCA bypass and trapping of right internal carotid artery. Post-operative course was uneventful. Although visual function was not improved, her endocrinological function was improved 8 months after surgery by thrombosed and shrunken aneurysm. The mechanism of panhypopituitarism due to aneurysm has been suggested to involve mechanical compression on the pituitary gland, pituitary stalk, or hypophyseal artery. Although it was unclear about the improvement of endocrine function after the treatment of aneurysm, some cases could recover the hypopituitarism after enough follow-up period.