Metabolism of polychlorinated dibenzo-p-dioxins (PCDDs) by human cytochrome P450-dependent monooxygenase systems

Metabolism of polychlorinated dibenzo-p-dioxins (PCDDs) by monooxygenase systems dependent on 12 forms of human cytochrome P450 (CYP) was examined with the recombinant yeast microsomes containing each of the human CYP. The metabolites of PCDDs were analyzed by HPLC and GC-MS. Remarkable metabolism by the multiple CYP forms was observed toward dibenzo-p-dioxin (DD) and mono-, di-, and trichloroDDs. The metabolism contained multiple reactions such as hydroxylation at an unsubstituted position, hydroxylation with migration of a chloride substituent, and hydroxylation with elimination of a chloride substituent. Although major CYPs in human liver such as CYP2C8, CYP2C9, and CYP3A4 showed no significant metabolism toward the PCDDs, CYP1A1 and CYP1A2 showed high catalytic activity toward DD and mono-, di-, and trichloroDDs. The kinetic parameters K(m)(app) and V(max) of the CYP1A1-dependent 8-hydroxylation activity of 2,3,7-trichloro-DD (2,3,7-triCDD) were estimated to be 0.30 microM and 51 (mol/min/mol of P450), respectively, suggesting that 2,3,7-triCDD was a good substrate for CYP1A1. However, none of the CYPs showed any detectable activity [<0.01 mol/min/mol of P450)] toward 2,3,7,8-tetraCDD. Substrate-induced absorption spectrum and inhibition studies indicated that CYP1A1 could bind 2,3,7,8-tetraCDD with considerably high affinity. It was strongly suggested that the long half-life (7.1 years) of 2,3,7,8-tetraCDD in humans was due to an extremely low activity of CYPs toward 2,3,7,8-tetraCDD in addition to its chemical stability.     

Kinetics of diarrhetic shellfish poisoning toxins,okadaic acid,dinophysistoxin-1, pectenotoxin-6 and yessotoxin in scallops <Emphasis Type="Italic">Patinopecten yessoensis</Emphasis>

ABSTRACT:   Four toxins, okadaic acid (OA), dinophysistoxin-1 (DTX1), pectenotoxin-6 (PTX6), and yessotoxin (YTX), all associated with diarrhetic shellfish poisoning (DSP), were administered via syringe to Scallops Patinopecten yessoensis and their distribution in the hepatopancreas, adductor muscle, and combined other tissues (mantle, gill, gonad) was analyzed by liquid chromatography-mass spectrometry. Toxins exclusively remained in the hepatopancreas irrespective of the injection site, adductor muscle or hepatopancreas. When injected into hepatopancreas, OA, DTX1, and YTX were metabolized to 7- O -palmitoylOA, 7- O -palmitoylDTX1 and 45-hydroxyyessotoxin (45OH-YTX), respectively. Such metabolic changes were insignificant when toxins were injected into the adductor muscle. The residual ratio for each toxin in the hepatopancreas was less than 20%. Mortalities of scallops treated with PTX6 were lower than those treated with other toxins.     

Skeletal development and deformities in cultured larval and juvenile seven-band grouper, Epinephelus septemfasciatus (Thunberg)

The seven‐band grouper, Epinephelus septemfasciatus (Thunberg), is currently recognized as a potential new species for aquaculture in Japan. This study describes normal and abnormal skeletal development of the jaw and vertebrae in cultured larvae and early juveniles of E. septemfasciatus. The ontogenetic stages at which skeletal deformities of jaw and vertebra developed were also described for this species. Osteological observations were made using a clearing and staining method for larvae and soft X‐ray photographs for juveniles. A high incidence of skeletal deformities was observed in the jaws and vertebral column during the larval and juvenile stages. Most of the jaw deformities were explained by an abnormal maxilla curvature. Jaw deformities were visually evident from flexion stage after ossification of the deformed elements. Deformities in the vertebral column (mostly lordosis) were observed from the post‐larval stage and became more evident as growth proceeded. The lordosis generally occurred on the positions of the 8–11th vertebra. These types of deformities are compared with those of other species, and possible causative factors of the skeletal deformities are discussed.
     

Photoinduced oxidation of the insecticide phenothrin on soil surfaces

Photodegradation profiles of the pyrethroid insecticide phenothrin on a moistened U.S. soil thin layer was investigated by using its predominant component, the 1R-trans-isomer (I), under continuous exposure to light at >290 nm from a xenon arc lamp. Its degradation was moderately accelerated by irradiation with half-lives of 5.7-5.9 days (dark control 21-24 days), mainly via successive oxidation of the 2-methylprop-1-enyl group and ester cleavage followed by mineralization to carbon dioxide. Spectroscopic and cochromatographic analyses showed that the major degradates were the alcohol and ketone derivatives of I formed via photoinduced oxidation of the 2-methylprop-1-enyl group by singlet oxygen. The photoinduced generation of singlet oxygen in/on the soil surface was confirmed by using chemical trapping reactions together with ESR spectroscopy.     

Plasma concentration and cardiovascular effects of lidocaine during continuous epidural administration in dogs anesthetized with isoflurane

The cardiovascular effects of continuous epidural administration (CEA) of lidocaine were investigated in anesthetized dogs. Loading epidural injections of 2, 4, or 6 mg/kg of lidocaine were followed by CEA with 1, 2, or 3 mg/kg/hr lidocaine, respectively, for 2 hr under 2.0% isoflurane anesthesia. Heart rate, direct blood pressure, cardiac index, and stroke volume decreased dose-dependently during CEA, whereas systemic vascular resistance did not significantly differ with dose, and no characteristic changes were observed in any groups. Plasma lidocaine concentration reached a steady state during CEA and increased in a dose-dependent manner. Circulatory suppression caused by lidocaine CEA was not attributable to peripheral vasodilation, but rather to the direct cardiac action of systemic lidocaine absorption from the peridural space.     

Functional study of the central nervous system for farm animal husbandry

The purpose of this mini-review is to describe the recent approaches for revealing the function of the central nervous system in farm animals. The sensory organs are the first sites to gain environmental information. The behavior of the animals is outputted as a result of changes in the integrated neuronal systems, and is largely influenced by the external environment. Therefore, it is necessary to know how farm animals catch and recognize environmental changes. To understand the mechanisms of sensing and behavioral output, approaches for analyzing the brain function are required. Neuroscientific approaches are able to give cues for resolving abnormal behaviors such as stereotypy, and may lead to the improved housing and management of farm animals.     

Conversion of pectenotoxin-2 to pectenotoxin-2 seco acid in the New Zealand scallop, Pecten novaezelandiae

SUMMARY: Comparison of pectenotoxin (PTX) profiles between the toxic dinoflagellate Dinophysis acuta and scallops Pecten novaezelandiae collected at Wedge Point, Queen Charlotte Sound, New Zealand was carried out by liquid chromatography–mass spectrometry (LC-MS) with turbo-ionspray ionization. Although the major PTX homolog in D. acuta was pectenotoxin-2 (PTX2), the scallops contained pectenotoxin-2 seco acid (PTX2SA) as the predominant toxin. Pectenotoxin-2 isolated from D. acuta was rapidly converted to PTX2SA and its epimer 7- epi -pectenotoxin-2 seco acid (7- epi -PTX2SA) in the scallop extracts. These results indicate that PTX2SA and 7- epi -PTX2SA arose from the conversion of PTX2 by scallop tissue. The results indicate that New Zealand scallops have an ability to reduce the cytotoxicity of PTX2 by conversion to PTX2SA.     

Clinico-pathological findings in peripartum dairy cows fed anion salts lowering the dietary cation-anion difference: involvement of serum inorganic phosphorus, chloride and plasma estrogen concentrations in milk fever

In our previous study, it was demonstrated that the administration of anion salts, which slightly lower the dietary cation-anion difference (DCAD), in the prepartum period is safe and effective for preventing milk fever in multiparous cows. In the present study, several clinico-pathological constituents in serum and urine, which might be related to milk fever, were analyzed using stored samples from the previous study to identify clinico-pathological parameters for easily evaluating the efficacy of lowering DCAD and to further investigate the mechanism by which lowering DCAD prevents milk fever. Among the parameters analyzed in the present study, inorganic phosphorus (iP) was involved in milk fever because the serum concentration and urinary excretion of iP were significantly higher in the group of primiparous cows (heifer group), which did not develop hypocalcemia, than those in other groups of multiparous cows. Serum chloride concentrations in the heifer group and the group of multiparous cows fed anion salts (anion group) tended to remain higher than those in other control groups of multiparous cows suggesting that serum chloride concentration may be utilized for evaluating the status of metabolic acidosis and the efficacy of lowerng DCAD in dairy cows fed anion salts. In addition, plasma estradiol-17beta concentration in the heifer group tended to be lower at parturition compared with that in other multiparous groups suggesting that estrogen known as a potent inhibitor of bone resorption may be involved in developing milk fever.     

Current status of leptospirosis in Japan and Philippines

Leptospirosis is an acute febrile illness with a wide variety of clinical manifestations and is encountered throughout the world, prominently in tropical areas with high rainfall. In this paper, we review the current status of leptospirosis in two Asian countries, Japan and Philippines, which have quite different situations in terms of economy, environment, infrastructures and prevailing infectious diseases. In Japan, until 1960, more than 200 deaths due to leptospirosis had been reported yearly. After 1960, the number of reported cases had rapidly decreased. Now, leptospirosis cases notified every year were less than 20. After the early 1960s, modernization of agriculture was introduced, at the same time, inactivated vaccine against Leptospira was applied for humans and there was good maintenance of infrastructures such as water works and sewage systems.

In Philippines, on the other hand, leptospirosis patients tend to be frequently found in flood-prone areas of urban setting such as Metro Manila, which was found to be the endemic foci of leptospirosis. Morbidity in a rural area (Cabatuan, Iloilo) was 147 cases per 100,000 populations. From 1998 to 2001, about 70% of 1200 suspected leptospirosis patients in Philippines were serologically positive. The average age of patients was 32 years old where 87% of the cases were males and 70% were outdoor workers. Case fatality rate was found to be 12–14%. The estimated major serovars in Metro Manila and neighboring provinces were Manilae, Losbanos, Tarassovi, Poi and an unknown serovar. Outbreaks of leptospirosis in the Philippines are thought to be associated with heavy rainfall, rapid urbanization (dramatic increase in populations), deforestation, increasing number of flood-prone areas, poor infrastructures and many others.     

Characterization of Escherichia coli strains obtained from layer chickens affected with colibacillosis in a commercial egg-producing farm

The present study reports colibacillosis of layer chickens in a commercial egg-producing farm in western Japan. Three flocks of chicken at 18-21 weeks of age were affected during the initiation of egg lay. Postmortem examination revealed pericarditis, perihepatitis, airsacculitis, subcutaneous inguinal lesion, and injured cloaca. Escherichia coli was isolated from the lesions of the affected birds. Twenty-two of 26 E. coli isolates (84.6%) obtained from 18 birds in the 3 flocks showed pulsed-field gel electrophoresis (PFGE) patterns that were considered to be closely associated to each other and arbitrarily designated as pattern A. All the 22 isolates with the PFGE pattern A harbored the putative virulence genes, astA, iss, iucD, tsh, and cva/cvi. Additional 2 PFGE patterns (B and C) were also found in E. coli isolates obtained from the affected flocks and had the putative virulence genes in combinations different from those in the pattern A strains. The results suggested that certain E. coli virulence genes and host factors, such as initiation of egg lay may be associated with occurrence of colibacillosis.