Effects of the Antiepileptic Drugs Phenytoin, Gabapentin, and Levetiracetam on Bone Strength, Bone Mass, and Bone Turnover in Rats.

Long-term treatment with antiepileptic drugs (AEDs) is accompanied by reduced bone mass that is associated with an increased risk of bone fractures. Although phenytoin has been reported to adversely influence bone metabolism, little is known pertaining to more recent AEDs. The aim of this study was to evaluate the effects of gabapentin or levetiracetam on bone strength, bone mass, and bone turnover in rats.

Effects of the antiepileptic drugs topiramate and lamotrigine on bone metabolism in rats.

Long-term treatment with antiepileptic drugs (AED) is associated with an elevated risk of bone fracture due to decreased bone mineral density (BMD). Phenytoin has been shown to affect bone metabolism adversely, whereas newly developed AEDs have not been studied. This study evaluated the effects of topiramate and lamotrigine on bone metabolism in rats.

Effect of the antidiabetic agent pioglitazone on bone metabolism in rats.

Thiazolidinediones (TZDs) are synthetic peroxisome proliferator-activated receptor gamma (PPARγ) agonists used as therapy for type 2 diabetes. However, clinical studies reported that the therapeutic modulation of PPARγ activity using TZDs may induce negative effects on bone metabolism. This study aimed to evaluate the effect of the TZD pioglitazone on bone metabolism in rats.

Linkage between coenzyme a metabolism and inflammation: roles of pantetheinase.

Pantetheinase is an enzyme hydrolyzing pantetheine, an intermediate of the coenzyme A degradation pathway. Pantetheinase has long been considered as the enzyme that recycles pantothenic acid (vitamin B5) generated during coenzyme A breakdown. Genetic analyses showed that mammals have multiple genes known as vanin family genes.

Involvement of reactive oxygen species in sonodynamically induced apoptosis using a novel porphyrin derivative.

In this study, we investigated the induction of apoptosis by ultrasound in the presence of the novel porphyrin derivative DCPH-P-Na(I). HL-60 cells were exposed to ultrasound for up to 3 min in the presence and absence of DCPH-P-Na(I), and the induction of apoptosis was examined by analyzing cell morphology, DNA fragmentation, and caspase-3 activity. Reactive oxygen species were measured by means of ESR and spin trapping technique.

Identification of novel short peptide inhibitors of soluble 37/48 kDa oligomers of amyloid β42.

Since the soluble oligomers of 42-residue amyloid β (Aβ42) might be neurotoxins at an early stage of Alzheimer's disease (AD), inhibition of soluble Aβ42 oligomerization should be effective in the treatment of AD. We have found by phage display that a 7-residue peptide, SRPGLRR, exhibited inhibitory activity against soluble 37/48 kDa oligomers of Aβ42. In the present study, we newly prepared 3- and 4-residue random peptides libraries and performed pannings of them against soluble Aβ42 to search for important factors in the inhibition of Aβ42 oligomerization.

Sonodynamically-induced antitumor effect of mono-l-aspartyl chlorin e6 (NPe6).

Background: The sonodynamically-induced in vitro and in vivo antitumor effects of mono-l-aspartyl chlorin e6 (NPe6) was investigated.

Materials And Methods: Both in vitro and in vivo antitumor effects were tested in combination with ultrasound at 2 MHz.

Results: The rate of ultrasonically-induced damage on isolated sarcoma 180 cells in air-saturated suspension was enhanced two-fold with 80 μM NPe6.

Partial involvement of NMDA receptors and glial cells in the nociceptive behaviors induced by intrathecally administered histamine.

The involvement of spinal glial cells in the nociceptive behaviors induced by 800 pmol of histamine was determined in mice. Histamine at 800 pmol injected intrathecally (i.t.

Involvement of glial cells in the nociceptive behaviors induced by a high-dose of histamine administered intrathecally.

The involvement of spinal glial cells in the nociceptive behaviors induced by 1600 pmol of histamine was determined in mice. Histamine injected intrathecally (i.t.

Selection of peptide inhibitors of soluble Aβ(1-42) oligomer formation by phage display.

There have been many reports suggesting that soluble oligomers of amyloid β (Aβ) are neurotoxins causing Alzheimer's disease (AD). Although inhibition of the soluble oligomerization of Aβ is considered to be effective in the treatment of AD, almost all peptide inhibitors have been designed from the β-sheet structure (H14-D23) of Aβ(1-42). To obtain more potent peptides than the known inhibitors of the soluble-oligomer formation of Aβ(1-42), we performed random screening by phage display.

Analyses of conditions for KMSSS loop in tyrosyl-tRNA synthetase by building a mutant library.

The KMSKS motif is the ATP binding motif for aminoacylation process of class I aminoacyl-tRNA synthetases. Although researches based on natural proteins inform us about the contribution of natural amino acid sequences for the catalysis, they have difficulties in discussing the other alternative sequences and prohibited sequences for the motif to maintain the catalytic ability. In order to reveal such the conditions for the alternative and prohibited sequences, it is important to investigate a library of various mutants for the motif.

Intrathecal high-dose histamine induces spinally-mediated nociceptive behavioral responses through a polyamine site of NMDA receptors.

Previous research has demonstrated that a high dose of histamine (1600 pmol) injected i.t. in mice can evoke nociceptive behaviors consisting of biting/licking along with occasional scratching.

Selection for 3'-end triplets for polymerase chain reaction primers.

Primer extension by thermostable DNA polymerase in PCR starts from the 3'-end of a primer. If the PCR starting process fails, the entire PCR fails. Primer sequences at the 3'-end often interfere with success in PCR experiments.

Evaluations of molecular docking programs for virtual screening.

Structure-based virtual screening is carried out using molecular docking programs. A number of such docking programs are currently available, and the selection of docking program is difficult without knowing the characteristics or performance of each program. In this study, the screening performances of three molecular docking programs, DOCK, AutoDock, and GOLD, were evaluated with 116 target proteins.

Involvement of dopamine D1 receptors and alpha1-adrenoceptors in the antidepressant-like effect of chlorpheniramine in the mouse tail suspension test.

It has been reported that chlorpheniramine, a classical antihistamine, has antidepressant-like effects in animal models of depression. In this study, we examined the involvement of dopaminergic (dopamine D(1) and dopamine D(2) receptors), noradrenergic (alpha(1)- and beta-adrenoceptors) and serotonergic (5-HT(1A) and 5-HT(2) receptors) receptors in the antidepressant-like effect of chlorpheniramine in the mouse tail suspension test. We also investigated the involvement of these monoamine receptors in the antidepressant-like effect of imipramine for comparison with the mechanisms of the effect of chlorpheniramine.

Effects of histamine H(1) receptor antagonists on depressive-like behavior in diabetic mice.

We previously reported that streptozotocin-induced diabetic mice showed depressive-like behavior in the tail suspension test. It is well known that the central histaminergic system regulates many physiological functions including emotional behaviors. In this study, we examined the role of the central histaminergic system in the diabetes-induced depressive-like behavior in the mouse tail suspension test.

Role of delta-opioid receptor subtypes in anxiety-related behaviors in the elevated plus-maze in rats.

Rationale: Recent studies have shown that endogenous opioid systems are associated with the regulation of emotional responses. In particular, it has been reported that delta-opioid receptors act naturally to inhibit stress and anxiety.

Objective: The present study was designed to examine the possible involvement of opioid delta-receptor subtypes in the anxiety-related behavior in the elevated-plus-maze test.

Effects of first- and second-generation histamine-H1-receptor antagonists on the pentobarbital-induced loss of the righting reflex in streptozotocin-induced diabetic mice.

The second-generation histamine-H(1)-receptor antagonists, such as epinastine and cetirizine, are used as non-sedating antihistamines for treating allergic symptoms due to their poor ability to penetrate blood-brain barrier. Because it has been reported that the blood-brain barrier system is disturbed in diabetes, it is possible that second-generation histamine-H(1)-receptor antagonists may easily penetrate the blood-brain barrier and cause potent sedation in diabetics. In the present study, we investigated the effects of first-generation (diphenhydramine) and second-generation (epinastine and cetirizine) histamine-H(1)-receptor antagonists on the duration of pentobarbital-induced loss of the righting reflex (LORR) in non-diabetic and diabetic mice.

Selection for 3' end triplets for polymerase chain reaction primers.

The 3' end of a primer is a key component of PCR primer design. Many recommendations for the composition and sequence of the 3' end have been suggested based on theoretical considerations, but have not been verified experimentally. We analyzed 3' end triplets of PCR primer sequences obtained from refereed journal articles, to test those recommendations and to make empirical recommendations for primer design.

[KiBank: a database for computer-aided drug design based on protein-chemical interaction analysis].

KiBank is a database for computer-aided drug design and consists of binding affinities and chemical and target protein structures. Each chemical or protein structure with hydrogen atoms added was optimized by energy minimization and stored in PDB or MDL MOL file format, so that the structural data can be directly used for in silico binding studies. To describe the extent of inhibition, the inhibition constant (K(i)) value is used to simplify comparisons of strengths among chemical-protein bindings.

Involvement of histaminergic system in the discriminative stimulus effects of morphine.

The interactions between morphine and the histaminergic system are not yet fully clarified. More especially, the involvement of the histaminergic system in the discriminative stimulus effects of morphine has not been determined. Therefore, the effects of histamine-related compounds on the discriminative stimulus effects of morphine were examined in rats.

Molecular detection and identification of influenza viruses by oligonucleotide microarray hybridization.

Microarrays of virus-specific oligonucleotides may provide a method of screening samples for the presence or absence of a large variety of viruses simultaneously. Influenza viruses are ideal for evaluating such microarrays because of their genetic and host diversity, and the availability of an extensive sequence database. A collection of 476 influenza virus-specific oligonucleotides was spotted onto glass slides as probes.

Simultaneous determination of vitamin K analogs in human serum by sensitive and selective high-performance liquid chromatography with electrochemical detection.

Objectives: We report a sensitive and selective method for the simultaneous determination of vitamin K1 and K2 analogs (VKs) with high-performance liquid chromatography in which a platinum catalyst reduction column and an electrochemical detector operated in the oxidation mode are incorporated into the detection system. We also applied this trace analysis method to the simultaneous determination of VKs in human serum to investigate the physiologic and pathophysiologic roles of VKs in the bone metabolism.

Methods: Our high-performance liquid chromatographic method with postcolumn catalyst reduction and electrochemical detection was applied for the simultaneous determination of VKs in human serum samples.

Effects of chronic administration of zonisamide, an antiepileptic drug, on bone mineral density and their prevention with alfacalcidol in growing rats.

We investigated the effects of chronic administration of zonisamide, an antiepileptic agent, on bone metabolism in growing rats. Administration of zonisamide at a dose of 80 mg/kg per day, s.c.