Pharmacokinetics of fentanyl after single intravenous injection and constant rate infusion in dogs

OBJECTIVE: To determine the plasma concentration and define the pharmacokinetic characteristics of fentanyl (10 microg kg(-1)) administered as a single intravenous (IV) injection followed by: (a) no further drug; or (b) a constant rate infusion (CRI) of fentanyl 10 microg kg(-1) hour(-1) lasting 1, 3 or 4 hours in dogs. Animals Fourteen healthy adult beagles (seven males and seven females). EXPERIMENTAL DESIGN: Randomized cross-over design. MATERIALS AND METHODS: Dogs were randomly assigned to four treatment groups. Drugs were administered to each dog in a randomized cross-over design with at least a 14-day washout interval between experiments. All dogs received an IV loading dose of fentanyl (10 microg kg(-1)). One group received no further fentanyl. In others, the loading dose was followed by a CRI of fentanyl (10 microg kg(-1) hour(-1)) for 1, 3 or 4 hours. Blood samples were collected and plasma fentanyl concentrations determined using high-performance liquid chromatography-mass spectrometry. Plasma pharmacokinetic estimates were obtained by plotting plasma concentrations versus time data and by fitting the change in concentration to a pharmacokinetic model, using a purpose-built program written by the Graduate School of Pharmaceutical Sciences (Kyoto University) in Visual Basic (VBA) on Excel (Microsoft Corporation). RESULTS: Plasma fentanyl concentration decreased rapidly after single IV injection: the plasma concentration-time curve best fitted a two-compartment model. Pharmacokinetic variables for IV injection were characterized by a short distribution half-time (t1/2alpha was 4.5 minutes), a relatively long elimination half time (t1/2beta was 45.7 minutes), a large volume of distribution (approximately 5 L kg(-1)) and high total body clearance (77.9 mL minute(-1) kg(-1)). Stable plasma fentanyl levels were obtained in all CRI groups although pharmacokinetic variables were influenced by the duration of administration. CONCLUSIONS AND CLINICAL RELEVANCE: While this study clarified the pharmacokinetic features of rapid IV fentanyl injection and CRI in dogs, the plasma concentration achieving analgesia was not and so further research is needed. Further studies on the effects of other sedatives and/or anaesthetics on fentanyl's disposition are also required as the drug is commonly used with other agents.     

Cetacean Toll-like receptor 4 and myeloid differentiation factor 2, and possible cetacean-specific responses against Gram-negative bacteria

Toll-like receptor 4 (TLR4) and myeloid differentiation factor 2 (MD-2) are essential for recognizing the lipopolysaccharides (LPS) of Gram-negative bacteria. We determined the sequences of cDNAs encoding TLR4 and MD-2 from cetaceans and generated three-dimensional (3D) models for a better understanding of their modes of interaction and LPS recognition. The 3D reconstructions showed that cetacean TLR4 and MD-2 formed a horseshoe-like structure comprised of parallel β-strands and a β-cup structure consisting of two anti-parallel β-sheets, respectively. The (TLR4-MD-2)₂ duplex-heterodimer was shown to form a symmetrical structure. Comparison with the interfaces of the complexes in other mammals revealed that cetacean TLR4s have some amino acid residue substitutions involved in duplex-heterodimer formation and in species variation for LPS recognition. These substitutions in the changed amino acid residues may alter the interaction among TLR4, MD-2, and LPS and modify the TLR4/MD-2 immunological responses.     

Effect of the span length of Granier-type thermal dissipation probes on sap flux density measurements

? Granier-type thermal dissipation sensors measure sap flux density (u) by using the temperature difference between the heater and the reference probe. To detect u correctly, heat must not be transferred to the reference probe by thermal conduction. The distance across which heat can be transferred by conduction is important for the span length of a sensor and spacing of a number of sensors.

? To validate span lengths and spacing of sensors, we used numerical simulations to calculate the potential distance across which heat can be transferred by conduction. We compared measurements with an original and a modified sensor for a Japanese red pine (Pinus densiflora) from December 2004 to May 2005. The span length of the original and the modified sensor is 15 and 4 cm, respectively.

? Numerical simulations showed that span length and spacing of Granier sensors should be more than 10 cm for trees in which u ceases for a few hours before the predawn period. The modified sensor underestimated u by 18–46% in winter (December–March) because its reference temperature was increased by heat transferred by conduction. The modified sensor measured u correctly in warm seasons, and only underestimated the annual amount of transpiration by 6%.

     

The effects of nitrogen uptake before and after heading on grain protein content and the occurrence of basal- and back-white grains in rice (Oryza sativa L.)

Chalky rice (Oryza sativa L.) grains are induced by high temperature during the grain-filling period. Plant nitrogen status also affects the occurrence of basal- and back-white grains (BBWG). The objective of this study was to elucidate the relations between nitrogen availability per spikelet during the grain-filling period (N_GF) and each of the percentage of BBWG and grain protein content (GPC). We further compared the effect of the components of N_GF determined before heading (N_BH) and after heading (N_AH) on BBWG and GPC. We grew the rice cultivar ‘Koshihikari’ in pots in 2012 and 2013, and top-dressed nitrogen at the panicle formation and heading stages, under two (2012) or three (2013) temperature regimes during the grain-filling period. GPC was explained well by N_GF, but BBWG was not. BBWG was best explained in a multiple-regression equation by mean air temperature after heading and by N_BH and N_AH. The partial correlation coefficients for N_BH were 1.6 and 3.0 times those for N_AH in 2012 and 2013, respectively. On the other hand, in a multiple-regression equation for GPC, the partial correlation coefficients for N_BH were 0.91 and 0.71 times those for N_AH in 2012 and 2013, respectively. These results suggest that rice grains are most sensitive to plant nitrogen status before heading for BBWG but after heading for GPC, and that there is an optimal timing for nitrogen top-dressing that would maximize the reduction in BBWG per unit increment of GPC.     

Mapping a gene conferring resistance to <Emphasis Type="Italic">Wheat yellow mosaic virus</Emphasis> in European winter wheat cultivar ‘Ibis’ (<Emphasis Type="Italic">Triticum aestivum</Emphasis> L.)

Wheat yellow mosaic, caused by Wheat yellow mosaic virus (WYMV), is one of the most devastating soil-borne diseases of winter wheat (Triticum aestivum L.) in Japan. Yellow-striped leaves and stunted spring growth, symptomatic of WYMV infection, result in severe yield loss. A new putative WYMV resistance gene in the European wheat cultivar ‘Ibis’ was mapped in the cluster of microsatellite markers including Xcfd16, Xwmc41, Xcfd168 and Xwmc181 on the long arm of chromosome 2D at the distances of 2.0 cM, 4.0 cM, 7.1 cM and 12.4 cM, respectively. WYMV-resistant cultivars contained a common haplotype of the four markers, whereas moderately susceptible and susceptible cultivars did not. These results should be useful in marker-assisted selection for WYMV resistance in wheat.     

Confirmation of yessotoxin production by the dinoflagellate <Emphasis Type="Italic">Protoceratium reticulatum</Emphasis> in Mutsu Bay

ABSTRACT:   Yessotoxin (YTX) is a shellfish toxin and its contamination in bivalves has seriously damaged shellfish industries. The biogenetic origin of YTX was identified as the dinoflagellate Protoceratium reticulatum (Claparède et Lachmann) Bütschli collected in New Zealand and Yamada Bay, Iwate in Japan. Scallops cultured in Mutsu Bay, Japan, were frequently contaminated with YTX, however, occurrence of P. reticulatum in this bay and YTX production by the local strains have not been investigated. Eight strains of P. reticulatum , isolated from the bay, were cultured in the laboratory, and analyzed by fluorometric high-pressure liquid chromatography and liquid chromatography/mass spectrometry methods for YTX production and composition. All strains tested were confirmed to produce YTX, and none of them produced known YTX analogs. Toxin amount and composition differed from strain to strain. This result is also confirmation of one of the biogenetic origins of YTX in Mutsu Bay.     

低温胁迫和氮素营养对番茄畸形果发生的影响

研究表明,番茄幼苗生长点的碳、氮水平因氮肥的多寡而异,且经低温胁迫之后变化急剧。氮素较多（4 ～8mmol/L）和低温胁迫（3～8℃）,产生畸形果30%左右。氮素较多加之较低温度胁迫（3～5℃）,会显著加重畸形程度,畸形果病情指数达17.5%以上;低氮(2mmol/L)低温胁迫时,产生椭圆果和链斑果较多,合计达到88.7% ～90.6%;中氮(4mmol/L)或高氮(8mmol/L)低温胁迫时,产生窗孔果、顶裂果的比率增大。不同类型的畸形果单果重差异明显。     

Milky hemolymph syndrome associated with an intranuclear bacilliform virus in snow crab <Emphasis Type="Italic">Chionoecetes opilio</Emphasis> from the Sea of Japan

Milky hemolymph syndrome (MHS) is a previously undescribed disease in snow crab Chionoecetes opilio. Outbreaks of this disease occurred in reared and wild populations from the Sea of Japan when the water temperature was 2–3°C. The common symptom of the disease was a distinct milky or opaque coloration of the hemolymph. Some severely affected crabs also showed yellow or ivory discoloration on the ventral shell and uncalcification of the arthrodial membranes of walking legs. Histopathological changes consisted of widespread cellular degeneration characterized by enlarged nuclei with marginal hyperchromatosis and basophilic intranuclear inclusions in the interstitial connective tissues of various organs. Electron microscopy analyses of degenerated cells revealed a nonoccluded, enveloped bacilliform virus within the nuclei. The virus morphologically resembles white spot syndrome virus (WSSV) or unassigned intranuclear bacilliform viruses (IBVs) reported from other crustaceans. However, we could not detect WSSV from diseased tissues by PCR using WSSV-specific primers, and the tissues targeted by the virus differed from those targeted by IBVs. This is the first report of a virus from the genus Chionoecetes. Thus, we have tentatively designated the virus presumably associated with MHS as Chionoecetes opilio bacilliform virus (CoBV) until its relationship with other crustacean viruses can be clarified.     

Changes in endogenous cytokinin-like substances and growth inhibitors in freesia corms during high-temperature treatment for breaking dormancy

High summer temperatures are required to break dormancy of freesia corms and cormels. Endogenous cytokinin levels were low in corms at the lifting-date, 25 May, but increased after 3 months storage at 30°C. Cytokinin levels in cormels increased gradually during summer storage at natural room temperature, reaching a maximum on 25 August when cormels had the capacity to sprout, then decreased to low levels on 25 September. Inhibitor levels in cormels decreased gradually during storage. A zeatin riboside-like compound, water-soluble cytokinins and an abscisic acid-like compound were present in freesia corms. Dormant corms, soaked for 18 h in 1000 mg/l benzyladenine solution, showed 100% sprouting. We conclude that high temperatures cause a decrease in inhibitors and an increase in cytokinins, which together result in the breaking of the dormant state of corms and cormels of freesia.