Combined antiallodynic effects of Neurotropin®-tramadol and Neurotropin®-mirogabalin in rats with L5-spinal nerve ligation.

We aimed to examine the efficacy of combination therapies of Neurotropin® with tramadol and Neurotropin with mirogabalin for neuropathic pain management. A neuropathic pain model (L5 spinal nerve ligation model: L5-SNL) using male Wistar rats was generated through tight ligation of the left fifth lumbar nerve using silk sutures. Mechanical allodynia was assessed using the 50% paw withdrawal threshold.

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.

Combined effect of Neurotropin® and methylcobalamin on postherpetic neuralgia in mice infected with herpes simplex virus type-1.

Background: Postherpetic pain (PHP) is difficult to control. Although Neurotropin® (NTP) and methylcobalamin (MCB) are often prescribed to treat the pain, the efficacy of combined treatment for PHP remains imcompletely understood.

Objective: In this study, we investigate the combined effects of NTP and MCB on PHP in mice.

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.

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.

Excitatory effect of Neurotropin(®) on noradrenergic neurons in rat locus coeruleus.

Aims: Although the clinical use of Neurotropin® as an analgesic for chronic pain has been firmly established, its analgesic mechanism is still unclear. In this study, we investigate the direct effects of Neurotropin using an electrophysiological method.

Main Methods: Blind patch-clamp recordings were made from rat locus coeruleus (LC) and periaqueductal gray (PAG) neurons in brainstem slices of normal rats.

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.

Combined antiallodynic effect of Neurotropin® and pregabalin in rats with L5-spinal nerve ligation.

Aims: In this study, we investigated the combined effect of Neurotropin® and pregabalin for L5-spinal nerve ligation (L5-SNL) model in rats and thiopental-induced sleep in mice.

Main Methods: The left fifth lumbar nerve of rats was tightly ligated with silk sutures under pentobarbital anesthesia. The hindpaw withdrawal threshold was measured by application of von Frey filaments.

The antiallodynic effect of Neurotropin is mediated via activation of descending pain inhibitory systems in rats with spinal nerve ligation.

Background: Neurotropin, a nonprotein extract isolated from inflamed skin of rabbits inoculated with vaccinia virus, is widely used in Japan to treat chronic pain such as neuropathic pain. Although some studies have been conducted on the mechanism of the antiallodynic action of Neurotropin, this mechanism has yet to be adequately clarified.

Methods: The left fifth lumbar nerve of rats was tightly ligated with silk sutures under pentobarbital anesthesia.

Urinary excretion of creatol, an in vivo biomarker of hydroxyl radical, in patients with chronic renal failure.

Creatol (CTL) is a hydroxyl radical adduct of creatinine (Cr). The serum methylguanidine (MG) level and the MG/Cr molar ratio are reported to be biomarkers for oxidative stress. The aim of this study was to examine whether urinary excretion of CTL, another oxidative stress-related marker, is increased in patients with chronic renal failure (CRF).

Mechanisms of analgesic action of neurotropin on chronic pain in adjuvant-induced arthritic rat: roles of descending noradrenergic and serotonergic systems.

Neurotropin((R)), a non-protein extract from the inflamed skin of rabbits inoculated with vaccinia virus, has been clinically used as an analgesic drug for treatment of chronic pain. In this study, we investigated the analgesic mechanisms of Neurotropin in the adjuvant-induced arthritic rat, a chronic pain model with inflammation. Neurotropin caused dose-dependent inhibition of hyperalgesia in the adjuvant-induced arthritic rat after single intravenous (10 - 100 NU/kg) and oral (30 - 200 NU/kg) administration.

Comparative molecular active site analysis (CoMASA). 1. An approach to rapid evaluation of 3D QSAR.

We have developed a rapid evaluation method, comparative molecular active site analysis (CoMASA), for obtaining 3D QSAR. CoMASA has three major advantages: (1) the CoMASA results would easily transform to pharmacophore and/or queries required for 3D database searches, (2) the CoMASA method is not required to consider orientation and translation of molecules against a lattice, and (3) standard PCs can be used to perform the analysis. The potential of these improvements and possible further enhancements are discussed.

Developmental considerations of sperm protein 17 gene expression in rheumatoid arthritis synoviocytes.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by proliferative synovial tissue. We used mRNA differential display and library subtraction to compare mRNA expression in RA and osteoarthritis (OA) synoviocytes. We initially compared the mRNA expression patterns in 1 female RA and 1 OA synovia and found a differentially expressed 350 bp transcript in the RA synoviocytes which was, by sequence analysis, 100% homologous to sperm protein 17 (Sp17).

Hypertension associated with reduced plasma thrombomodulin levels and a hypercoagulable state in rats.

The plasma thrombomodulin (TM) level, an indicator of systemic endothelial cell damage, was measured in spontaneously hypertensive rats (SHR), deoxycorticosteron acetate (DOCA)-induced hypertensive rats and normotensive Wistar-Kyoto (WKY) rats to clarify its changes in hypertension. Plasma TM levels, measured by enzyme-linked immuno-sorbent assay, decreased with aging (5-20-weeks-old) in both SHR and WKY, and they were lower in SHR than age-matched WKY in all ages examined. Deoxycorticosteron acetate-induced hypertensive WKY also showed decreased TM levels compared with normotensive WKY.

Rapid evaluation of molecular shape similarity index using pairwise calculation of the nearest atomic distances.

Rapid evaluation method for obtaining molecular shape similarity index using pairwise calculation of the nearest atomic distance respected to the template atoms was investigated. This method for calculations of similarity indices remarkably reduced required time compared with hitherto methods (especially 2 or 3 orders of magnitude faster than the previous grid-based evaluation technique) and gave without clear loss of preciseness. The potential of these improvements and possible further enhancements are discussed.

A new nonpeptide tachykinin NK1 receptor antagonist isolated from the plants of Compositae.

To find new tachykinin NK1 receptor antagonists from natural sources, we examined the tachykinin antagonist activity in the extracts of approximately 200 species of plants by the use of isolated guinea pig ileum. As a result, we discovered a novel and potent NK1 receptor antagonist in the extract of dried flowers of Matricaria chamomilla L. (chamomile).

B cells are selectively associated with thymic cortical but not medullary pathology in NZB mice.

Abnormal expansion of autoantibody-synthesizing B cells and self-reactive T cells, which most likely escape negative selection within the thymus, have both been characterized and reasoned to play a role in the pathogenesis of autoimmunity in NZB mice. Support for this thesis has been our observation that NZB mice have severe cortical and medullary thymic microarchitectural defects. As a means to dissect the roles of T and B cells in the induction of such abnormalities, B cell-deficient NZB mice were bred by backcrossing the Igh6(null)allele on to the NZB background (NZB-muMT mice).

Neurotropin induces antinociceptive effect by enhancing descending pain inhibitory systems involving 5-HT3 and noradrenergic alpha2 receptors in spinal dorsal horn.

Neurotropin, a non-protein extract from the inflamed skin of rabbits inoculated with vaccinia virus, has been clinically used as an analgesic drug in Japan. Its analgesic effect has been demonstrated by reduced mechano-nociception in hyperalgesic rats exposed to SART-stress (a repeated cold stress) for 5 days. In order to clarify the mechanism of the analgesic effect of neurotropin at the spinal cord level, we examined the effects of several neurotransmitter receptor antagonists given by intrathecal (i.

Naturally occurring 2'-O-methylpurine nucleosides with hypotensive properties.

2'-O-Methylinosine (1) has been isolated for the first time and shown to be an intrinsic hypotensive principle. Its probable in vivo precursor, 2'-O-methyladenosine (3), showed stronger and even orally potent hypotensive activity. Resistance of the methyladenosine (3) against adenosine deaminase is thought to contribute to its long-lasting activity.

A complex of histamine/mouse gamma-globulin preferentially inhibits allergen-induced peritoneal accumulation of eosinophils, but not neutrophils, in mice.

A complex of histamine/human gamma-globulin (HhG) has been widely used in Japan for more than 25 years as a nonspecific hyposensitization drug in the treatment of allergic diseases. It has been reported that HhG decreases the number of eosinophils in the nasal secretions and peripheral blood of patients with allergy. In this study we used a mouse system to explore the possibility that HhG may actively inhibit the accumulation of eosinophils at inflammation sites.