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Clonidine hydrochloride has been used for pre-anesthetic medication to provide a pre-operative sedation in pediatric surgery. The purpose of this study is to determine the plasma clonidine concentration, which gives satisfactory sedation in pediatric surgery. Sixteen pediatric patients (age: 1-11 years, weight: 9-33 kg) received either 2 or 4 microg/kg of clonidine lollipop before entering the operating room. Plasma clonidine concentrations were determined 120 min after administration of clonidine lollipop. Pre-operative sedation was evaluated by 5-point scoring systems at entering the operating room. The changes in systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR) were also assessed before and after administration of clonidine lollipop. The patients with satisfactory sedation had higher plasma clonidine concentration than that of the patients with unsatisfactory sedation (0.45+/-0.16 ng/ml vs. 0.26+/-0.16 ng/ml, p<0.05). The clonidine concentrations in the satisfactory group ranged from 0.28 to 0.81 ng/ml. There was no significant difference in hemodynamic parameters (SBP, DBP and HR) before and after administration of clonidine lollipop in both satisfactory and unsatisfactory sedation groups. Plasma clonidine concentration of 0.3-0.8 ng/ml would be sufficient to produce satisfactory sedation without changes in hemodynamic parameters in pediatric surgery.

The intestinal bacteria, Eubacterium sp. and Biˆdobacterium sp., participate in the metabolism of active kampo-ingredients, glycyrrhizin (GL), sennoside (SEN) and baicalin (BL). Since antibiotics and bacterial preparations, Bidobacterium longum ( LAC  B ) , Clostridium butyricum ( MIYA  BM ) , and Streptococcus faecalis (BIOFERMIN ), aŠect the bacterial population in intestinal bacterial ‰ora, metabolism of the active kampo-ingredients in the bacterial ‰ora may be altered by their combined administration. We investigated 1199 prescriptions including kampo-medicines for 308 patients. Combination use of kampo-medicines with antibiotics and bacterial preparations occurred with 7％ and 10％ of the kampo-prescription, respectively. Most antibiotics have activity against intestinal bacteria, except that cephems and macrolides are not active against to E. coli. This means that antibiotics may lower the metabolism of GL, SEN and BL when administered in combination. On the other hand, it is also highly possible that bacterial preparations increase the number of Eubacterium sp. and Biˆdobacterium sp., resulting in enhanced metabolism of GL and SEN when they are used concomitantly with kampo-medicines. The present results suggested that the drug interactions of kampo-medicines with antibiotics and bacterial preparations should be conˆrmed in clinical studies.

This paper reports a series of studies leading to the discovery of a submarine hydrothermal field (called Nakayama Field) at an arc seamount (12∞43¢ N, 143∞32¢ E) in the southernmost part of the Mariana Trough, western Pacific Ocean. We first detected hydrothermal plumes characterized by water column anomalies of temperature, light transmission, Mn, Fe, Al, O 2 , CH 4 , and d 13 C of CH 4 above the summit caldera of the seamount. Then deep-tow camera surveys confirmed the existence of hydrothermal activity inside the caldera, and an ROV dive finally discovered white smoker-type fluid venting associated with vent fauna. A high concentration of aluminum in the plume and white smoker-type emissions imply acidic hydrothermal activity similar to that observed at the DESMOS Caldera in the eastern Manus Basin, Papua New Guinea. Anomalously low d 13 C (CH 4 ) of -38‰ of a vent fluid sample compared to other arc hydrothermal systems along the IzuBonin and Mariana Arcs suggests an incorporation of biogenic methane based on a subsurface microbial ecosystem.

BackgroundFood is known to affect drug absorption by delaying gastric emptying time, altering gastrointestinal pH, stimulating bile flow, increasing splanchnic blood flow, or physically interacting with drugs. Although food is known to affect the pharmacokinetics of oral antineoplastic drugs, the relationship between the effects of food and the physicochemical properties of drugs remains unclear.MethodsIn this study, we surveyed the literature on three kinds of pharmacokinetic changes, AUC ratio, Cmax ratio and Tmax ratio, in the fasted and fed state for 72 oral antineoplastic drugs that were listed on the drug price standard in May 2018 in Japan. We further predicted the physicochemical properties from the 2D chemical structure of the antineoplastic drugs using in silico predictions.ResultsAs a result of analyzing the relationship between the effects of food and physicochemical properties, we found that compounds that show increased absorption in the fed state had higher logP and lower solubility in fasted-state simulated intestinal fluid (FaSSIF). However, compounds with delayed absorption had higher solubility in FaSSIF. Furthermore, as a result of decision tree analysis, it was classified as AUC increase with logP ≥4.34. We found that an AUC increase in the fed state did not occur with compounds with low lipid solubilities (logP < 1.59). From these results, it is predicted that 7 compounds out of the 24 compounds for which the effects of food are unknown are at risk for increased absorption in the fed state and that no increase in absorption would occur in 13 compounds.ConclusionIn this study, we found that drugs that will show increased absorption in the fed state and drugs for which absorption is not dependent on food can generally be predicted by logP. These results suggest that logP can be a useful parameter for predicting the effects of food on drug absorption.

The genomic DNA encoding the inorganic pyrophosphatase from an extremely thermophilic bacterium, Thermus thermophilus HB8 (ATCC27634), was isolated by colony hybridization with a probe designed as a part of gene amplified by the PCR method, which was derived from the partial amino acid sequence of the enzyme. The DNA was cloned into a plasmid vector, pUC118, after digestion with BamHI. The inserted nucleotide fragment was about 1.8 kbp in length and the nucleotide sequence included a 525 bp open reading frame. The deduced amino acid sequence was completely identical with that of the enzyme determined by automated Edman analysis of peptide fragments isolated from digests obtained with Staphylococcus aureus V8 protease and Achromobacter protease I, and also from products obtained on chemical cleavage with cyanogen bromide and 70% formic acid. The subunit of this enzyme is composed of 174 amino acid residues with a calculated molecular weight of 19,084. Then, the gene was overexpressed in Escherichia coli BL21 (DE3) using a plasmid vector, pET15b, system. The recombinant enzyme was fully active, and exhibited higher thermostability than the E. coli enzyme. Amino acid residues located on the surface of the recombinant enzyme were determined by means of limited proteolysis, and the results revealed that the environment of Lys residues is almost the same as the crystal structure reported previously [Teplyakov, A. et al. (1994) Protein Sci. 3, 1098-1107]. Furthermore, the roles of two tryptophan residues were investigated by site-directed mutagenesis, which indicated that they may be responsible for the structural integrity and thermostability.

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BackgroundPatients with Sjögren’s syndrome (SS) typically present clinically with xerostomia (dry mouth) because of progressive damage to the exocrine glands. We developed a new, low-dose pilocarpine/sodium alginate (LPA) solution with pilocarpine hydrochloride to inhibit systemic adverse effects by administering via the oral mucosa. The purpose of this study was to assess its stability, safety, and efficacy.MethodsThe pilocarpine concentration in an LPA liquid formulation was measured 3, 7, 14, and 28 days after preparation to assess its stability. A prospective clinical trial was undertaken to assess the efficacy and safety of the LPA solution as a symptomatic treatment for dry mouth in SS. Patients (n = 24) with clinically significant xerostomia were enrolled after providing written informed consent. Whole-mouth salivary flow rate was measured twice; immediately before and 60 min after LPA application. Symptoms were assessed by questionnaire with visual analog scales or checkboxes before the first application (baseline), and then once daily for 7 days.ResultsThe pilocarpine content 3, 7, 14, and 28 days after preparation showed no marked change, confirming its stability. Salivary flow was significantly increased from 0.076 ± 0.092 g/30 s to 0.122 ± 0.140 g/30 s 60 min after LPA administration (P < 0.001). Dry mouth and thirstiness showed significant improvement compared with that of baseline (P ≤ 0.01). The only adverse effect was sweating, and no serious drug-related adverse events were reported.ConclusionsThis new, low-dose pilocarpine formulation was well-tolerated and resulted in significant improvements in symptoms of dry mouth and other xerostomic conditions in patients with SS.Trial registrationThe study approval number in the institution; 08–068-2. Registered January 19, 2009. UMIN000029307. Registered 27 September 2017 (retrospectively registered).