Assessment of Tie2-Rejuvenated Nucleus Pulposus Cell Transplants from Young and Old Patient Sources Demonstrates That Age Still Matters.

Cell transplantation is being actively explored as a regenerative therapy for discogenic back pain. This study explored the regenerative potential of Tie2 nucleus pulposus progenitor cells (NPPCs) from intervertebral disc (IVD) tissues derived from young (<25 years of age) and old (>60 years of age) patient donors. We employed an optimized culture method to maintain Tie2 expression in NP cells from both donor categories.

Repurposing of the analgesic Neurotropin for MASLD/MASH treatment.

Background: The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) has increased in recent decades. Approximately 25% of patients with MASLD progress to metabolic dysfunction-associated steatohepatitis, which is characterized by hepatic steatosis plus hepatocyte damage, inflammation, and fibrosis. We previously reported that Neurotropin (NTP), a drug used for relieving pain in Japan and China, inhibits lipid accumulation in hepatocytes by preventing mitochondrial dysfunction.

Neurotropin ameliorates chronic pain associated with scar formation in a mouse model: A gene expression analysis of the inflammatory response.

: Scar formation after trauma and surgery involves an inflammatory response and can lead to the development of chronic pain. Neurotropin (NTP) is a nonprotein extract of inflamed skin of rabbits inoculated with vaccinia virus. It has been widely used for the treatment of chronic pain.

Recombinant Laminin-511 Fragment (iMatrix-511) Coating Supports Maintenance of Human Nucleus Pulposus Progenitor Cells In Vitro.

The angiopoietin-1 receptor (Tie2) marks specific nucleus pulposus (NP) progenitor cells, shows a rapid decline during aging and intervertebral disc degeneration, and has thus sparked interest in its utilization as a regenerative agent against disc degeneration. However, the challenge of maintaining and expanding these progenitor cells in vitro has been a significant hurdle. In this study, we investigated the potential of laminin-511 to sustain Tie2 NP progenitor cells in vitro.

Stakeholders' perceived achievements and challenges after the safe motherhood project in Northern Uganda.

The Japanese Red Cross Society (JRCS) and the Uganda Red Cross Society (URCS) implemented the Safe Motherhood project to promote mother-friendly society in northern Uganda from 2010 to 2016. The follow-up study has not been conducted and the information on achievements and challenges after the project were limited. To review the safe motherhood project in northern Uganda, the purpose of the study was to explore the stakeholders' perceived achievements and challenges after the project.

Association of NAT2 genetic polymorphism with the efficacy of Neurotropin® for the enhancement of aggrecan gene expression in nucleus pulposus cells: a pilot study.

Background: Intervertebral disc degeneration, one of the major causes of low-back pain, results from altered biosynthesis/turnover of extracellular matrix in the disc. Previously, we reported that the analgesic drug Neurotropin® (NTP) had an anabolic effect on glycosaminoglycan synthesis in cultured nucleus pulposus (NP) cells via the stimulation of chondroitin sulfate N-acetylgalactosaminyltransferase 1. However, its effect on the aggrecan core protein was not significantly detected, because of the data variance.

Hippocampal diffusion abnormality after febrile status epilepticus is related to subsequent epilepsy.

Objective: To assess hippocampal signal changes on diffusion-weighted imaging (DWI) during the acute period after febrile status epilepticus (FSE) and to examine the relationship between DWI and subsequent epilepsy.

Methods: A prospective, multicenter study of children with a first episode of FSE was performed. The patients underwent magnetic resonance imaging (MRI) within 3 days of FSE, and signal intensity was evaluated on DWI.

Upregulation of glycosaminoglycan synthesis by Neurotropin in nucleus pulposus cells via stimulation of chondroitin sulfate N-acetylgalactosaminyltransferase 1: A new approach to attenuation of intervertebral disc degeneration.

It is suggested that most cases of low back pain are related to degeneration of intervertebral discs. Disc degeneration is a chronic and progressive disease and the search for effective medical treatments continues. Neurotropin is widely used in Japan and China to treat low back pain and neck-shoulder-arm syndrome.

Stress enhances gait disturbance induced by lumbar disc degeneration in rat.

Purpose: Although psychological factors are assumed to be the primary cause of stress-related back pain, there have been no studies of the relationships between stress and low back pain in an animal model. The purpose of this study was to examine the influence of specific alternation of rhythm in temperature (SART) stress on gait abnormality using the CatWalk method in a rat model of low back pain caused by lumbar facetectomy.

Methods: Sixty rats were divided into three groups: the control, sham and experimental groups.

Neurotropin inhibits calpain activity upregulated by specific alternation of rhythm in temperature in the mesencephalon of rats.

Aims: Neurotropin® (NTP), an analgesic for chronic pain, has antihyperalgesic effects in specific alternation of rhythm in temperature (SART)-stressed rats. Previous studies have shown that SART stress induces hyperalgesia, as well as post-translational modification of proteins (including substrates for calpain, a calcium-dependent cysteine protease) in the mesencephalon of rats. To better understand the mechanism of action of NTP, we investigated whether SART stress activates calpain in the mesencephalon of rats and whether NTP inhibits this activation.

Neurotropin suppresses inflammatory cytokine expression and cell death through suppression of NF-κB and JNK in hepatocytes.

Inflammatory response and cell death in hepatocytes are hallmarks of chronic liver disease, and, therefore, can be effective therapeutic targets. Neurotropin® (NTP) is a drug widely used in Japan and China to treat chronic pain. Although NTP has been demonstrated to suppress chronic pain through the descending pain inhibitory system, the action mechanism of NTP remains elusive.

Clinical and biochemical characterization of 3-hydroxyisobutyryl-CoA hydrolase (HIBCH) deficiency that causes Leigh-like disease and ketoacidosis.

3-Hydroxyisobutyryl-CoA hydrolase (HIBCH) deficiency is an autosomal recessive disorder characterized by episodes of ketoacidosis and a Leigh-like basal ganglia disease, without high concentrations of pyruvate and lactate in the cerebrospinal fluid. Only 4 cases of HIBCH deficiency have been reported. However, clinical-biochemical correlation in HIBCH deficiency by determining the detailed residual enzyme activities has not yet been elucidated.

Mutations in HADHB, which encodes the β-subunit of mitochondrial trifunctional protein, cause infantile onset hypoparathyroidism and peripheral polyneuropathy.

Mitochondrial trifunctional protein (MTP) is a hetero-octamer composed of four α- and four β-subunits that catalyzes the final three steps of mitochondrial β-oxidation of long chain fatty acids. HADHA and HADHB encode the α-subunit and the β-subunit of MTP, respectively. To date, only two cases with MTP deficiency have been reported to be associated with hypoparathyroidism and peripheral polyneuropathy.

Creatinine metabolite, HMH (5-hydroxy-1-methylhydantoin; NZ-419), modulates bradykinin-induced changes in vascular smooth muscle cells.

A creatinine metabolite, 5-hydroxy-1-methylhydantoin (HMH: NZ-419), a hydroxyl radical scavenger, has previously been shown to confer renoprotection by inhibiting the progression of chronic kidney disease in rats. In the current study, we demonstrate that HMH modulates the effects of glucose and bradykinin (BK) in vascular smooth muscle cell (VSMC). HMH a novel anti-oxidant drug completely suppressed the expression of B2-kinin receptors (B2KR) in response to high glucose (25 mM) stimulation in VSMC and was also shown to attenuate the effects of BK on VSMC remodeling.

Clinical characterization and identification of duplication breakpoints in a Japanese family with Xq28 duplication syndrome including MECP2.

Xq28 duplication syndrome including MECP2 is a neurodevelopmental disorder characterized by axial hypotonia at infancy, severe intellectual disability, developmental delay, mild characteristic facial appearance, epilepsy, regression, and recurrent infections in males. We identified a Japanese family of Xq28 duplications, in which the patients presented with cerebellar ataxia, severe constipation, and small feet, in addition to the common clinical features. The 488-kb duplication spanned from L1CAM to EMD and contained 17 genes, two pseudo genes, and three microRNA-coding genes.

Molecular analysis of X-linked inborn errors of purine metabolism: HPRT1 and PRPS1 mutations.

Mutations of two enzyme genes, HPRT1 encoding hypoxanthine guanine phosphoribosyltransferase (HPRT) and PRPS1 encoding a catalytic subunit (PRS-I) of phosphoribosylpyrophosphate synthetase, cause X-linked inborn errors of purine metabolism. Analyzing these two genes, we have identified three HPRT1 mutations in Lesch-Nyhan families following our last report. One of them, a new mutation involving the deletion of 4224 bp from intron 4 to intron 5 and the insertion of an unknown 28 bp, has been identified.

MBTPS2 mutation causes BRESEK/BRESHECK syndrome.

BRESEK/BRESHECK syndrome is a multiple congenital malformation characterized by brain anomalies, intellectual disability, ectodermal dysplasia, skeletal deformities, ear or eye anomalies, and renal anomalies or small kidneys, with or without Hirschsprung disease and cleft palate or cryptorchidism. This syndrome has only been reported in three male patients. Here, we report on the fourth male patient presenting with brain anomaly, intellectual disability, growth retardation, ectodermal dysplasia, vertebral (skeletal) anomaly, Hirschsprung disease, low-set and large ears, cryptorchidism, and small kidneys.

Acute encephalopathy in children with Dravet syndrome.

Purpose: The occurrence of acute encephalopathy in children with Dravet syndrome has been reported sporadically. This study clarified the features of acute encephalopathy in children with Dravet syndrome.

Methods: Through the mailing list of the Annual Zao Conference on Pediatric Neurology, we collected 15 patients with clinically diagnosed Dravet syndrome, who had acute encephalopathy, defined as a condition with decreased consciousness with or without other neurologic symptoms, such as seizures, lasting for >24 h in association with infectious symptoms.

[Age-, period-, and birth-cohort-specific effects on the male proportion in Japanese newborns and projections for male proportion for 20 periods (2008-2027)].

Objectives: To determine the age-, period-, and cohort-specific effects on the male proportion in Japanese newborns, we performed an age-period-cohort (APC) analysis in this study. In addition, projections for the male proportion were analyzed.

Methods: We obtained data on live births of newborns for Japanese women in 1947-2007 from the National Vital Statistics.

Molecular analysis of two enzyme genes, HPRT1 and PRPS1, causing X-linked inborn errors of purine metabolism.

Inherited mutation of hypoxanthine guanine phosphoribosyltransferase (HPRT) gives rise to Lesch-Nyhan syndrome or HPRT-related gout. On the other hand, PRPS1 mutations cause PRPP synthetase superactivity associated with hyperuricemia and gout, sometimes including neurodevelopmental abnormalities. We have identified two mutations in two Lesch-Nyhan families after our last report.

Involvement of post-translational modification of neuronal plasticity-related proteins in hyperalgesia revealed by a proteomic analysis.

To clarify roles of an endogenous pain modulatory system of the central nervous system (CNS) in hyperalgesia, we tried to identify qualitative and quantitative protein changes by a proteomic analysis using an animal model of hyperalgesia. Specifically, we first induced functional hyperalgesia on male Wistar rats by repeated cold stress (specific alternation of rhythm in temperature, SART). We then compared proteomes of multiple regions of CNS and the dorsal root ganglion between the hyperalgetic rats and non-treated ones by 2-D PAGE in the pI range of 4.

Effect of corticosteroids in a twin child with idiopathic localization-related epilepsy.

Corticosteroids have been used only in the treatment of special epileptic syndromes or epileptic encephalopathies, such as infantile spasms. We report an antiepileptic effect of corticosteroids that were used for treatment of nephropathy in a monozygotic twin child with idiopathic localization-related epilepsy (I-LRE). The patient and her monozygotic twin sister exhibited repeated partial seizures at two years of age and electroencephalogram (EEG) showed focal spikes in the occipital area and, on other occasions, the centro-parietal areas.

Hippocampal volumes and diffusion-weighted image findings in children with prolonged febrile seizures.

Objectives: To assess hippocampal volumes (HV) and signal changes on diffusion-weighted imaging (DWI) within 5 days of prolonged febrile seizures (PFS) and compare them with the PFS duration and EEG.

Methods: We studied 12 children (mean age: 32 +/- 21 months, range 10 months-5 years) within 5 days of a first episode of PFS (a seizure or series of seizures lasting for 30 min or longer, without return of consciousness between the seizures). The HV measurements were carried out using high-resolution magnetic resonance imaging and signal intensity abnormalities were evaluated visually on DWI.