A Pilot Study of A2NTX, a Novel Low-Molecular-Weight Neurotoxin Derived from Subtype A2 for Post-Stroke Lower Limb Spasticity: Comparison with OnabotulinumtoxinA.

All the currently used type A botulinum neurotoxins for clinical uses are of subtype A1. We compared the efficacy and safety for the first time head-to-head between a novel botulinum toxin A2NTX prepared from subtype A2 and onabotulinumtoxinA (BOTOX) derived from A1 for post-stroke spasticity. We assessed the modified Ashworth scale (MAS) of the ankle joint, the mobility scores of Functional Independence Measure (FIM), and the grip power of the unaffected hand before and after injecting 300 units of BOTOX or A2NTX into calf muscles.

Clinical Safety and Tolerability of A2NTX, a Novel Low-Molecular-Weight Neurotoxin Derived from Botulinum Neurotoxin Subtype A2, in Comparison with Subtype A1 Toxins.

All the botulinum type A neurotoxins available for clinical use are of the A1 subtype. We developed a subtype A2 low-molecular-weight (150 kD (kilo Dalton)) neurotoxin (A2NTX) with less spread and faster entry into the motor nerve terminal than A1 in vitro and in vivo. Preliminary clinical studies showed that its efficacy is superior to A1 toxins.

Increased IP-10 production by blood-nerve barrier in multifocal acquired demyelinating sensory and motor neuropathy and multifocal motor neuropathy.

Objective: Dysfunction of the blood-nerve barrier (BNB) plays important roles in chronic inflammatory demyelinating polyneuropathy (CIDP) and multifocal motor neuropathy (MMN). The aim of the present study was to identify the candidate cytokines/chemokines that cause the breakdown of the BNB using sera from patients with CIDP and MMN.

Methods: We determined the levels of 27 cytokines and chemokines in human peripheral nerve microvascular endothelial cells (PnMECs) after exposure to sera obtained from patients with CIDP variants (typical CIDP and multifocal acquired demyelinating sensory and motor neuropathy [MADSAM]), MMN and amyotrophic lateral sclerosis (ALS), and healthy controls (HC), using a multiplexed fluorescent bead-based immunoassay system.

Increased proinflammatory cytokines in sera of patients with multifocal motor neuropathy.

Background: Multifocal motor neuropathy (MMN) is characterized by clinical improvement with intravenous immunoglobulin and the frequent detection of anti-ganglioside antibodies. However, the immunological background of the neuronal damage in MMN is still unclear.

Objective: The aim of this study is to investigate abnormalities in the cytokine and chemokine profiles of MMN patients.

Are multifocal motor neuropathy patients underdiagnosed? An epidemiological survey in Japan.

Introduction: Our objective was to do an epidemiologic survey of patients with multifocal motor neuropathy (MMN) in comparison with those with amyotrophic lateral sclerosis (ALS) in Japan.

Methods: In this retrospective study, we examined 46 patients with MMN and 1,051 patients with ALS from major neuromuscular centers in Japan from 2005 to 2009. Diagnosis was based on the European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) and the revised El Escorial criteria.

[Treatment of spasticity with botulinum toxin].

The beneficial effects of rehabilitation are known to plateau around 6 months after stroke. But there are some reports that motor functions are improved with using botulinum neurotoxin A (BoNT-A) for limb spasticity in the maintenance stage of stroke. Though it has been thought that BoNT-A works in the peripheral nerves so far, Caleo showed BoNT-A can affect the central nervous system.

Sera from patients with multifocal motor neuropathy disrupt the blood-nerve barrier.

Objective: In multifocal motor neuropathy (MMN), the destruction of the blood-nerve barrier (BNB) has been considered to be the key step in the disease process. The purpose of the present study was to ascertain whether sera from patients with MMN can open the BNB, and which component of patient sera is the most important for this disruption.

Methods: We evaluated the effects of sera from patients with MMN, patients with amyotrophic lateral sclerosis, and control subjects on the expression of tight junction proteins and vascular cell adhesion molecule-1 (VCAM-1), and on the transendothelial electrical resistance (TEER) in human peripheral nerve microvascular endothelial cells (PnMECs).

[Update of multifocal motor neuropathy].

We surveyed patients with multifocal motor neuropathy (MMN) in comparison with those with amyotrophic lateral sclerosis (ALS) in Japan. This retrospective study consisted of 47 patients with MMN and 1,051 patients with ALS from major neuromuscular centers in Japan from 2005 to 2009. The ratio of MMN to ALS patients (0-0.

[A case of cerebral air embolism developed during pleural lavage].

We report a patient with cerebral air embolism in whom we could perform serial brain magnetic resonance images (MRIs). A 78-year-old man was admitted to our hospital because of recurrent empyema after surgery for esophageal cancer. He suddenly demonstrated left hemiparesis in the middle of pleural lavage.

[Treatment and indication of botulinum toxin type A for limb spasticity - can we break the 6 months barrier?].

It is common knowledge that recovery of motor function is limited at 6 months after the onset of stroke. But there are some reports that motor functions are improved with using botulinum toxin type A for limb spasticity in the maintenance stage of stroke. Though it has been thought that botulinum toxin type A works in the peripheral nerves so far, Caleo showed botulinum toxin can affect the central nervous system.

Strict red blood cell transfusion guideline reduces the need for transfusions in very-low-birthweight infants in the first 4 weeks of life: a multicentre trial.

Background And Objectives: Very-low-birthweight infants are among the most heavily transfused patients. The objective of this study was to verify if the introduction of a strict guideline would reduce the need for red blood cell transfusions in the first 4 weeks of life in these neonates.

Materials And Methods: This was a multicentre prospective study of two cohorts of very-low-birthweight infants transfused in accordance with the recommendations of a neonatologist (Phase 1) or according to previously published guidelines (Phase 2).

Trisodium nitriloacetate monohydrate: promoting effect in urinary bladder carcinogenesis in rats treated with N-butyl-N-(4-hydroxybutyl)nitrosamine.

The effect of trisodium nitrilotriacetate monohydrate [(Na3NTA X H2O) CAS: 18662-53-8] on development of urinary bladder tumors in rats initiated with N-butyl-N-(4-hydroxybutyl)nitrosamine [(BBN) CAS: 3817-11-6] was studied. Twenty-one male inbred W rats 6 weeks of age were given drinking water containing 500 ppm of BBN for 4 weeks and then put on diet containing 10,000 ppm of Na3NTA X H2O for 28 weeks. Na3NTA X H2O promoted the development of urinary bladder tumors in rats treated with BBN.

Effect of propylthiouracil on the thyroid tumorigenesis induced by N-bis(2-hydroxypropyl)nitrosamine in rats.

The effect of 0.15% propylthiouracil (PTU) on thyroid tumorigenesis was studied in male Wistar rats given a single i.p.

Trisodium nitrilotriacetate monohydrate: promoting effects on the development of renal tubular cell tumors in rats treated with N-ethyl-N-hydroxyethylnitrosamine.

The effect of trisodium nitrilotriacetate monohydrate [N,N-bis(carboxymethyl)glycine trisodium salt] (Na3NTA X H2O) on development of renal tubular cell tumors induced with N-ethyl-N-hydroxyethylnitrosamine [CAS:13147-25-6; 2-(ethylnitrosamino)-ethanol] (EHEN) was studied. Six-week-old male inbred W rats were given a diet containing 1,000 ppm of EHEN for 2 weeks and then a diet containing a high (10,000 ppm) or low (500 ppm) concentration of Na3NTA X H2O for 30 weeks. The rats were killed during week 32.

Basic lead acetate: promoting effect on the development of renal tubular cell tumors in rats treated with N-ethyl-N-hydroxyethylnitrosamine.

The development of renal tubular cell tumors by the end of experimental week 32 was studied in inbred Wistar male rats fed a diet containing 1,000 or 500 ppm N-ethyl-N-hydroxyethylnitrosamine (EHEN) for 2 weeks and then given 1,00 ppm basic lead acetate (LA) for 20 weeks. A low dose of LA enhanced the development of renal tubular cell tumors in rats treated with EHEN and increased the number and size of the tumors. The incidence of renal tubular cell tumors at the end of week 32 was 50% in rats treated with 1,000 ppm EHEN for 2 weeks and 100% in rats treated with 1,000 ppm EHEN for 2 weeks and then given 1,000 ppm LA for 20 weeks.

Promoting effects of phenobarbital and barbital on development of thyroid tumors in rats treated with N-bis(2-hydroxypropyl)nitrosamine.

Phenobarbital (PB) and barbital (BB) promoted the development of thyroid tumors in rats treated with a sub-effective dose of N-bis(2-hydroxypropyl)nitrosamine (DHPN) for thyroid tumorigenesis. Rats were given s.c.