Pr-SNTX, a short-chain three-finger toxin from Papuan pigmy mulga snake, is an antagonist of muscle-type nicotinic acetylcholine receptor (α2ßδε).

Three-finger toxins (3FTxs) are one of the major components in snake venoms. In this study, we isolated a cDNA encoding a short-chain 3FTx, Pr-SNTX, from Pseudechis rossignolii. The amino acid sequence of Pr-SNTX is nearly identical to that of its ortholog in Pseudechis australis. Pr-SNTX protein inhibited muscle-type (α2ßδε), but not neuronal α7 nicotinic acetylcholine receptor (nAChR) activity.

Effects of feeding outer bran fraction of rice on lipid accumulation and fecal excretion in rats.

Outer bran fraction of rice (OBFR) contains higher concentrations of crude fiber, γ-oryzanol, and phytic acid compared to whole rice bran (WRB). In this study, we examined the effects of feeding OBFR on lipid accumulation and fecal excretion in rats. Twenty-one male rats at seven-week-old were divided into a control group and two treatment groups. The control group was fed a control diet, and the treatment groups were fed OBFR- or WRB-containing diet for 21 days. There was no significant difference in growth performance. Feeding OBFR diet increased fecal number and weight accompanied by increased fecal lipid content, while it did not affect mRNA expressions encoding lipid metabolism-related protein in liver. In addition, feeding OBFR-diet decreased the abdominal fat tissue weight and improved plasma lipid profiles, while WRB-containing diet did not affect them. These results suggested that feeding OBFR-diet might prevent lipid accumulation via enhancing fecal lipid excretion in rats.

Voriconazole-associated salt-losing nephropathy.

A 74-year-old man was diagnosed with nephrotic syndrome due to focal segmental glomerulosclerosis, and steroid therapy was initiated. Subsequently, he was affected by deep mycosis, and hence, voriconazole (VRCZ) was administered. On the 16th day, he was transferred to our hospital because of somnolence and malaise. His systolic blood pressure was approximately 80 mmHg, and he showed decreased skin turgor, indicating volume depletion. Laboratory analysis revealed hyponatremia and liver dysfunction. Discontinuation of VRCZ and drip infusion of normal saline improved the consciousness disorder, hyponatremia, and liver dysfunction. The levels of antidiuretic hormone (ADH) and plasma renin activity were elevated. This patient showed high excreted urine sodium, despite volume depletion and low serum osmolality. Therefore, this patient was diagnosed with salt-losing nephropathy (SLN). SLN should be considered for treatment of VRCZ-associated hyponatremia, together with syndrome of inappropriate secretion of ADH.

Feeding the Outer Bran Fraction of Rice Alters Hepatic Carbohydrate Metabolism in Rats.

Dietary intake of fiber-rich food has been reported to contribute to multiple health benefits. The aim of the current study is to investigate the effects of a diet containing the outer bran fraction of rice (OBFR), which is rich in insoluble fiber, on the intestinal environment and metabolite profiles of rats. Fourteen 8-week-old male Sprague-Dawley rats were divided into a control group and an OBFR group. For a period of 21 days, the control group was fed a control diet, while the OBFR group was fed a diet containing 5% OBFR. Metabolomics analysis revealed drastic changes in the cecal metabolites of the rats fed the OBFR diet. Furthermore, in the plasma and liver tissue, the concentrations of metabolites involved in pyruvate metabolism, the pentose phosphate pathway, gluconeogenesis, or valine, leucine, isoleucine degradation were changed. Concordantly, the OBFR diet increased the expression of genes encoding enzymes involved in these metabolic pathways in the livers of the rats. Collectively, these results suggest that the OBFR diet altered the concentrations of metabolites in the cecal contents, plasma, and liver, and the hepatic gene expressions of rats, and that this may have mainly contributed to carbohydrate metabolism in the liver.

Blood pressure during pregnancy is a useful predictive maker for hypertension and dyslipidemia later in life, a population-based, cross-sectional study.

OBJECTIVE: Pregnancy is an opportunity for women to become aware of their risk of cardiovascular disease (CVD), because physiologic responses to dynamic hemodynamic changes can be observed during pregnancy. Accordingly, we hypothesized that blood pressure levels during pregnancy may be associated with the risk of CVD later in life. STUDY DESIGN: We used data from the Iwaki Health Promotion Project and designed a population-based, cross-sectional study. In this study, Maternity Health Record Books were collected from women over 40 years of age in order to obtain reliable data regarding past pregnancies. Of a total of 642 women, 432 were selected according to the study criteria. MAIN OUTCOME MEASURES: The associations between blood pressure levels during pregnancy and major CVD risk factors (hypertension and dyslipidemia) were analyzed retrospectively. RESULTS: A 10 mmHg increase in the mean diastolic blood pressure level between gestational weeks 12 and 42 conferred a 1.70- and 1.55-fold increase in the risk of hypertension and dyslipidemia, respectively, in later life. CONCLUSIONS: Blood pressure levels during pregnancy may be associated with CVD risk and could therefore be a useful predictive marker.

Foreign body in the maxillary sinus--possible plastic tube: a case report.

We experienced the case of a patient who had a foreign body in the maxillary sinus. The patient complained of recurrent unilateral badly smelling rhinorrhea. The computed tomography and the magnetic resonance images revealed a foreign body in the maxillary sinus. The foreign body was removed via the Caldwell-Luc approach. The foreign body was a plastic tube, which was supposed to be designed for the drainage of the maxillary sinus. However, the patient did not remember having been subjected to a treatment using such kind of tube. After the surgical removal, the patient became free from the nasal symptoms.

Traumatic perilymph fistula in infants: a case report.

Traumatic perilymph fistula is reported to be rare in infants because of the small size of the infant external meatus. We treated an infant with a traumatic perilymph fistula in the right ear. A metallic wire had penetrated the tympanic membrane. Horizontal-rotatory nystagmus was also observed. Computed tomographic images revealed dislocation of the ossicles. The perilymph fistula was closed under general anesthesia. The incus-stapes joint was separated and the footplate of the stapes was dislocated. Leakage of the perilymph fluid was apparent from the oval window and this fistula was closed with connective tissue. The perforation of the tympanic membrane was closed with temporal fascia. After surgery, the spontaneous nystagmus disappeared. The patient is under observation as an outpatient and is growing normally.

Subcutaneous emphysema after tonsillectomy: a case report.

We experienced a case of a subcutaneous emphysema after tonsillectomy. The patient, a 24-year-old man, complained of a recurrent sore throat and was diagnosed as having chronic tonsillitis. Pre-operative general examinations revealed no abnormalities. The operation was carried out under general anesthesia. The adhesions between the tonsils and the surrounding tissues were moderate. The bi-lateral tonsils were easily removed. The recovery period was uneventful. On the next morning, marked swelling of the left cheek and submandibular area was noted. On palpation, there was a characteristic crepitation and softness in these areas. The X-ray examination revealed subcutaneous emphysema. There was no finding of airway obstruction. We diagnosed him as having a subcutaneous emphysema and administered antibiotics for 5 days. From clinical findings, the subcutaneous emphysema was thought to be caused by surgical rather than anesthetic factors. The subcutaneous emphysema gradually disappeared. One year after the tonsillectomy, the patient is under observation as an outpatient and is free from any abnormal symptoms. To avoid this kind of complication, we should pay attention to carefully separate the tonsil from its fossa and to make appropriate selection of surgical equipments.

[Stem cell factor production from cultured nasal epithelial cells--effect on SCF production by drugs].

We studied whether epithelial cells cultured in serum-free medium contained other cells or not, there were differences in SCF production from cultured nasal epithelial cells between groups of nonallergic and allergic patients, and among degrees of serum mite-CAP RAST classes of allergic patients, and how drugs inhibited SCF production. As a result, no other contaminating cells except mast cell existed in cultured cells. There was a significant difference in SCF production of cultured cells between nonallergic and class 1-2, 3-4, 5-6, and between class 1-2 and 3-4, 5-6 of mite CAP-RAST class. Cyclosporin, prednisolone, fluticasone, ketotifen, and clemastine inhibited SCF production from cultured epithelial cells, but cromoglicate and suplatast did not. Inhibition means the reduction of SCF from cells, not the growth of cultured nasal epithelial cells.

Functional characterization of Kunitz-type protease inhibitor Pr-mulgins identified from New Guinean Pseudechis australis.

Kunitz-type protease inhibitors, which consist of around 60 amino acid residues and three distinctive disulfide bridges, exhibit a broad range of physiological functions such as protease inhibitor and ion channel blocker. In this study, we identified cDNAs encoding Kunitz-type protease inhibitors, Pr-mulgins 1, 2 and 3, from the venom gland cDNA library of Papuan pigmy mulga snake (New Guinean Pseudechis australis). The deduced amino acid sequences of the Pr-mulgins are 92.4-99.3% identical with their orthologs in Australian P. australis. Pr-mulgin proteins were recombinantly prepared and subjected to inhibitory assays against proteases. Pr-mulgin 1 significantly affected matrix metalloprotease (MMP) 2; Pr-mulgins 2 and 3 showed potent inhibition to trypsin and plasma plasmin; and Pr-mulgin 2 inhibited α-chymotrypsin. Pr-mulgins 1, 2, and 3, however, had essentially no effect on Drosophila K(+) channels (Shaker) and rat K(+) channels (K(v) 1.1).

Constitutive expression of insulin receptor substrate (IRS)-1 inhibits myogenic differentiation through nuclear exclusion of Foxo1 in L6 myoblasts.

Insulin-like growth factors (IGFs) are well known to play essential roles in enhancement of myogenic differentiation. In this report we showed that initial IGF-I signal activation but long-term IGF-1 signal termination are required for myogenic differentiation. L6 myoblast stably transfected with myc-epitope tagged insulin receptor substrate-1, myc-IRS-1 (L6-mIRS1) was unable to differentiate into myotubes, indicating that IRS-1 constitutive expression inhibited myogenesis. To elucidate the molecular mechanisms underlying myogenic inhibition, IGF-I signaling was examined. IGF-I treatment of control L6 cells for 18 h resulted in a marked suppression of IGF-I stimulated IRS-1 association with the p85 PI 3-kinase and suppression of activation of Akt that correlated with a down regulation of IRS-1 protein. L6-mIRS1 cells, in contrast, had sustained high levels of IRS-1 protein following 18 h of IGF-I treatment with persistent p85 PI 3-kinase association with IRS-1, Akt phosphorylation and phosphorylation of the downstream Akt substrate, Foxo1. Consistent with Foxo1 phosphorylation, Foxo1 protein was excluded from the nuclei in L6-mIRS1 cells, whereas Foxo1 was localized in the nuclei in control L6 cells during induction of differentiation. In addition, L6 cells stably expressing a dominant-interfering form of Foxo1, Δ256Foxo1 (L6-Δ256Foxo1) were unable to differentiate into myotubes. Together, these data demonstrate that IGF-I regulation of Foxo1 nuclear localization is essential for the myogenic program in L6 cells but that persistent activation of IGF-1 signaling pathways results in a negative feedback to prevent myogenesis.

Regional divergence of phospholipase A(2)-like protein cDNAs between New Guinean and Australian Pseudechis australis.

Snake Phospholipase A(2) (PLA(2)) exhibits diverse pharmacological effects, such as hemolysis, myotoxicity, and neurotoxicity. In this study, we identified 10 novel PLA(2)-like protein cDNAs, which we named Pr 1-10, from the venom gland cDNA library of Papuan pigmy mulga snake (New Guinean Pseudechis australis). The deduced amino acid sequence of Pr 1, which ortholog has not been reported in mulaga snake (Australian P. australis) yet, shows 78.8% identity with the ortholog in Australian tiger snake (Notechis scutatus scutatus). The amino acid sequences of Pr 2-10 are 92.4-99.3% identical with their orthologs and paralogs in Australian P. australis.

Successful treatment for thrombotic thrombocytopenic purpura complicated with myeloperoxidase anti-neutrophil cytoplasmic autoantibody-associated vasculitis.

Thrombotic thrombocytopenic purpura (TTP) complicated with myeloperoxidase anti-neutrophil cytoplasmic autoantibody (MPO-ANCA)-associated vasculitis is rare and generally has a serious prognosis. We report a case wherein TTP was successfully treated with repeated plasma exchange (PE) and MPO-ANCA-associated vasculitis with corticosteroids. The renal function consequently improved such that haemodialysis could be discontinued and the patient was discharged without any significant complications.

The effect of H1 antagonists carebastine and olopatadine on histamine induced expression of CC chemokines in cultured human nasal epithelial cells.

BACKGROUND: CC chemokines have been shown to play an important role in inducing selective recruitment of inflammatory cells into local allergic inflammatory sites. CC chemokines are also known as histamine releasing factors. We previously showed that histamine enhances transcription of CC chemokines from nasal mucosa which leads to further induction of histamine release. This cyclic cascade may cause prolonged allergic inflammation. The aim of this study is to clarify the relationship between histamine and CC chemokine production by using human nasal epithelial cells (HNECs) and to examine the potential of H1 receptor (H1R) antagonists in new therapeutic approaches for the treatment of nasal allergy. METHODS: HNECs were isolated from the nasal turbinates of patients diagnosed with nasal allergy. HNEC monolayers were cultured for 48 hours with or without histamine (10(-3) to 10(-5) mol/L). Furthermore, an H1R antagonist, either carebastine or olopatadine, was added to the supernatant (10(-3) to 10(-7) mol/L) 30 minutes before incubation with histamine. The expression of Regulated on Activation, Normal T-cell Expressed and Secreted (RANTES) and monocyte chemotactic protein-1 (MCP-1) in the culture media were measured by ELISA. RESULTS: The release of RANTES and MCP-1 was significantly upregulated by histamine compared with the control group. Both carebastine and olopatadine inhibited the release of CC chemokine production to the control level in both groups. CONCLUSIONS: This study suggests that the interaction between histamine and CC chemokines may prolong allergic inflammation in human nasal mucosa. We also demonstrate the potential use of H1R antagonists in new therapeutic approaches to the treatment of nasal allergy through inhibiting this histamine-CC chemokine interaction.

Pyrazolato-bridged polynuclear palladium and platinum complexes. Synthesis, structure, and reactivity.

Cyclic trinuclear complexes [Pd(3)(mu-pz)(6)] (1) and [Pd(3)(mu-4-Mepz)(6)] (2) and dinuclear complex [Pd(2)(mu-3-t-Bupz)(2)(3-t-Bupz)(2)(3-t-BupzH)(2)] (3) have been prepared by the reactions of [PdCl(2)(CH(3)CN)(2)] with pyrazole (pzH), 4-methylpyrazole (4-MepzH), and 3-tert-butylpyrazole (3-t-BupzH), respectively, in CH(3)CN in the presence of Et(3)N. In the absence of the base, treatment of [PdCl(2)(CH(3)CN)(2)] with pzH gave the mononuclear complex, [Pd(pzH)(4)]Cl(2) (6). The reaction of [PtCl(2)(C(2)H(5)CN)(2)] with pzH in the presence of Et(3)N under refluxing in C(2)H(5)CN afforded the known dimeric Pt(II) complex, [Pt(pz)(2)(pzH)(2)](2) (7). The protons participating in the hydrogen bonding in 3 and 7 are easily replaced by silver ions to give the heterotetranuclear complex [Pd(2)Ag(2)(mu-3-t-Bupz)(6)] (4) and the heterohexanuclear complex [Pt(2)Ag(4)(mu-pz)(8)] (5). The complexes 1-6 are structurally characterized.