Studies on somnolence in the daytime caused by drugs used for neuropathic pain

In the present study, the characteristics of the sleep features of amitriptyline, mexiletine, and N-(4-tertiarybutylphenyl)-4-(3-cholorphyridin-2-yl)tetrahydropyradine-1(2H)-carbox-amide (BCTC) were studied. Electrodes were chronically implanted into the frontal cortex and the dorsal neck muscles of rats for electroencephalogram (EEG) and electromyogram (EMG) measurements, respectively. EEG and EMG were recorded with an electroencephalograph, and SleepSign ver. 2.0. was used for sleep-wake state analysis. Recordings were performed from 11:00 to 17:00. Amitriptyline caused significant decreases in sleep latency and total wake time and an increase in total non-rapid eye movement (non-REM) sleep time. Mexiletine caused a significant decrease in sleep latency, but no significant effect was observed in total wake time and total non-REM sleep time. On the other hand, BCTC, which is an antagonist of transient receptor potential vaniloid 1 (TRPV1), showed no significant effect on sleep latency, total wake time, total non-REM sleep time, and total REM sleep time. From these results, it can be concluded that a TRPV1 antagonist may become a useful drug for neuropathic pain without sedative side effects in the daytime, different from amitriptyline and mexiletine.     

Pyogenic liver abscess related to dental disease in an immunocompetent host

A 59-year-old man with poor oral hygiene presented to our hospital because of fever and chills. Abdominal ultrasonography and enhanced computed tomography (CT) revealed a liver abscess. The patient had no history of immunodeficiency and we confirmed the patient had no immunologic abnormalities. Blood culture revealed Fusobacterium nucleatum, a bacterium commonly found in the oral cavity. Even if a patient is immunocompetent, poor oral hygiene might be an independent risk factor for a pyogenic liver abscess. Professional mechanical tooth cleaning (PMTC) and appropriate self-care are recommended as a prophylaxis against not only dental, but also systemic diseases.     

Lesion of the isthmo-optic nucleus impairs target selection for visually guided reaching

Flavonoids, which are polyphenolic compounds, have been reported to possess remarkable antioxidant and anti-inflammatory activities. Among the dietary flavonoids, fisetin (3,3′,4′,7-tetrahydroxyflavone) possesses a significant spectrum of biochemical and pharmacological actions. The present study aimed to investigate the antidepressant potential of fisetin and its possible mechanism. Two mouse models of despair tests were used to evaluate the antidepressant-like effect of fisetin. The results suggested that fisetin (10 and 20 mg/kg, p.o.) dose dependently inhibited the immobility time in both behavioral tests, while the doses that affected the immobile response did not affect locomotor activity. Two behavioral models, reserpine-induced hypothermia and ptosis, and p-chlorophenylalanine (PCPA)-induced depletion of serotonin, were used to explore the possible involvement of fisetin in the noradrenergic and serotonergic system. The higher dose of fisetin was found to effectively antagonize the hypothermia, but not ptosis, induced by reserpine. Pre-treatment with PCPA abolished the anti-immobility effect of fisetin in the forced swimming and tail suspension tests. Moreover, neurochemical assays showed that fisetin produced an increase in serotonin and noradrenaline levels in the frontal cortex and hippocampus. Monoamine oxidase (MAO) activity in the mouse brain was inhibited by 14.7% after treatment with fisetin, while MAO-B activity was not affected. These findings indicate that the antidepressant-like effect of fisetin involves the regulation of the central serotonin and noradrenaline levels.     

Zinc L-carnosine protects against mucosal injury in portal hypertensive gastropathy through induction of heat shock protein 72

BACKGROUND AND AIMS: Increased susceptibility to gastric mucosal injury is observed in portal hypertensive gastropathy (PHG). In this study, the effects of zinc L-carnosine, an anti-ulcer drug, were evaluated on expression of heat shock protein (hsp) 72 and cytoprotection in gastric mucosa in a rat model of PHG. METHODS: Portal hypertensive gastropathy with liver cirrhosis was induced by bile duct ligation for 4 weeks in male Sprague-Dawley rats. Expression of gastric mucosal hsp72 was evaluated by Western blotting at 6 h after intragastric administration of L-carnosine, zinc sulfate, or zinc L-carnosine. Blood was also collected for determination of serum zinc level. Mucosal protective abilities against hydrochloric acid (HCl) (0.6N) followed by pretreatment with L-carnosine, zinc sulfate or zinc L-carnosine were also studied. RESULTS: L-carnosine, zinc sulfate, and zinc L-carnosine induced hsp72 in gastric mucosa of rats with bile duct ligation. Zinc sulfate and zinc L-carnosine suppressed HCl-induced mucosal injury. However, L-carnosine could not suppress HCl-induced mucosal injury. Serum zinc levels were significantly elevated after zinc L-carnosine administration. Furthermore, pretreatment with zinc L-carnosine (30-300 mg/kg) increased the expression of hsp72 in gastric mucosa and prevented HCl-induced mucosal injury in rats with bile duct ligation in a dose-dependent manner. CONCLUSIONS: Zinc derivatives, especially zinc L-carnosine, protected portal hypertensive gastric mucosa with increased hsp72 expression in cirrhotic rats. It is postulated that zinc L-carnosine may be beneficial to the mucosal protection in PHG as a 'chaperone inducer'.     

Treatment of infantile spasms by pediatric neurologists in Japan

Objective

To clarify changes in clinical practice for infantile spasms, including West syndrome, in Japan over the past two decades.

Biallelic loss‐of‐function UBA5 mutations in a patient with intractable West syndrome and profound failure to thrive

Mutation of the gene encoding ubiquitin‐like modifier‐activating enzyme 5 (UBA5) causes autosomal recessive early‐onset epileptic encephalopathy. UBA5 acts as an E1‐activating enzyme in the ubiquitin‐fold modifier 1 pathway, which is important for unfolded protein elimination and regulation of apoptosis, and has been linked to human diseases. We identified biallelic mutations in UBA5 in a Japanese boy with intractable West syndrome, profound failure to thrive, and severe cerebral and cerebellar atrophy. The boy presented with epileptic spasms and hypsarrhythmia at the age of three months. He was diagnosed with West syndrome, however, treatments with adrenocorticotropic hormone and several antiepileptic drugs were ineffective. MRI findings were initially normal, but subsequently showed a progression of cerebellar and cerebral atrophy. By the age of seven years, he had not achieved any developmental milestones; he had daily epileptic spasms and tonic seizures and profound failure to thrive. Gene analysis revealed novel compound heterozygous mutations in UBA5; a microdeletion encompassing the entire UBA5 gene and a putative disease‐causing missense mutation in the catalytic domain. These biallelic variants may have caused loss of function, accounting for the observed clinical symptoms. Intractable infantile epileptic spasms, failure to thrive, and severe neurological impairment may be characteristic of patients with UBA5 mutations.     

Measurement over 1 Year of Neutralizing Antibodies in Cattle Immunized with Trivalent Vaccines Recombinant Alpha,Beta and Epsilon of Clostridium perfringens

The alpha (CPA), beta (CPB) and epsilon (ETX) toxins of Clostridium perfringens are responsible for causing diseases that are difficult to eradicate and have lethal potential in production animals. Vaccination of herds is still the best control strategy. Recombinant clostridial vaccines have shown good success at inducing neutralizing antibody titers and appear to be a viable alternative to the conventional production of commercial clostridial toxoids. Research is still needed on the longevity of the humoral immune response induced by recombinant proteins in immunized animals, preferably in target species. The objective of this study was to measure the humoral immune response of cattle immunized with trivalent vaccines containing the recombinant proteins alpha (rCPA), beta (rCPB) and epsilon (rETX) of C. perfringens produced in Escherichia coli at three different concentrations (100, 200, and 400 µg) of each protein for 12 months. The recombinant vaccines containing 200 (RV2) and 400 µg (RV3) yielded statistically similar results at 56 days. They performed better throughout the study period because they induced higher neutralizing antibody titers and were detectable for up to 150 and 180 days, respectively. Regarding industrial-scale production, RV2 would be the most economical and viable formulation as it achieved results similar to RV3 at half the concentration of recombinant proteins in its formulation. However, none of the vaccines tested induced the production of detectable antibody titers on day 365 of the experiment, the time of revaccination typically recommended in vaccination protocols. Thus, reiterating the need for research in the field of vaccinology to achieve greater longevity of the humoral immune response against these clostridial toxins in animals, in addition to the need to discuss the vaccine schedules and protocols adopted in cattle production.