Mercapturic acid formation from lindane in rats

4-Chloro-, 2,4-dichloro-, 3,4-dichloro-, 2,3,5-trichloro-, and 2,4,5-trichlorophenylmercapturic acids were identified as main metabolites of lindane, γ-isomer of 1,2,3,4,5,6-hexachloro-cyclohexane, in rat urine. Pathways to these metabolites were shown to include $\text{(}\text{36}\text{45}\text{)-}\text{hexachlorocyclohexene}$ as the most important intermediary metabolite. $\text{(}\text{346}\text{5}\text{)-}\text{Pentachlorocyclohexene}$ and $\text{(}\text{346}\text{5}\text{)-}\text{tetrachlorocyclohexene}$ also seem to be involved in these pathways, while $\text{(}\text{36}\text{45}\text{)-}\text{pentachlorocyclohexene}$ plays a minor role in the pathway. Glutathione conjugation, using the rat liver soluble fraction, occurred directly on the polychlorocyclohexenes, not on their further transformed products. In in vivo biodegradation, $\text{(}\text{36}\text{45}\text{)-}\text{hexachlorocyclohexene}$ may be dechlorinated and dehydrochlorinated at the endoplasmic reticulum before it undergoes the glutathione conjugation in cytosol, although other polychlorocyclohexenes generally react in a manner similar to that in the in vitro reaction.     

Mechanism of herbicidal activity of a new cyclohexane-1,3-dione, tepraloxydim to Poa annua L.

Tepraloxydim [(EZ)‐(RS)‐2‐{1‐[(2E)‐3‐chloroallyloxyimino]propyl}‐3‐hydroxy‐5‐perhydropyran‐4‐ylcyclohex‐2‐en‐1‐one] showed high activity against annual bluegrass (Poa annua L.), which is relatively tolerant to sethoxydim [(±)‐2‐(1‐ethoxyiminobutyl)‐5‐[2‐(ethylthio)propyl]‐3‐hydroxycyclohex‐2‐en‐1‐one]. Absorption and translocation rates of tepraloxydim and sethoxydim were higher in P. annua than in Setaria faberi, but the absorption and translocation patterns of tepraloxydim in the two plants were similar to those of sethoxydim. Metabolic rates of tepraloxydim and sethoxydim in P. annua and S. faberi were found to be similar. The concentration for 50% inhibition (I₅₀) of acetyl‐coenzyme A carboxylase (ACCase) with tepraloxydim was approximately 3 × 10^?6 mol L^?1 for P. annua and 7 × 10^?7 mol L^?1 for S. faberi. For sethoxydim, the I₅₀ was found to be 2 × 10^?6 mol L^?1 with the enzyme of S. faberi, while sethoxydim showed a slight effect on ACCase from P. annua activity, even at 10^?4 mol L^?1. The strong inhibition of ACCase with tepraloxydim is considered to be the major factor contributing to the high herbicidal activity against P. annua. Measuring the whole plant growth response, the ratio of the tepraloxydim I₅₀ dose of P. annua to that of S. faberi (P/S) was found to be 2.4, while the P/S ratio of sethoxydim and a tepraloxydim analog with a propyl chain at R₂ were 56.3 and 73.3, respectively. The herbicidal activity against P. annua was remarkably influenced by the length of the R₂ alkyl chain, while the effect on S. faberi was not affected. Acetyl‐coenzyme A carboxylase from P. annua also exhibited a higher resistance to the tepraloxydim analog with a propyl chain than to tepraloxydim. These results suggest that a binding site structure of cyclohexane‐1,3‐diones in the ACCase differs between P. annua and S. faberi.     

Hydrolytic activation/decomposition pathways of herbicidally active ethyl 5-[N-(5,7-dimethoxy-2H-1,2,4- thiadiazolo[2,3-a] pyrimidin-2-ylidene)sulfamoyl]-1,3- dimethylpyrazole-4-carboxylate

Potent herbicidal ethyl 5-[N-(5,7-dimethoxy2H-1,2,4-thiadiazolo-[2,3-a] pyrimidin-2-ylidene)sulfamoyl]-1,3-dimethylpyrazole-4-carboxylate (I) was hydrolyzed under weakly basic conditions to afford a sulfonylurea (VII) , a 2-pyrimidylcyanamide (IV) and a mercaptopyrazole (VI) . The formation of these products was explained by nucleophilic attack at the 1 and 2-positions of the 1,2,4-thiadiazolo[2,3-alpyrimidine ring. This is believed to mimic the process which occurs on application to the plant. I appears to be a pro-pesticide for the sulfonylurea, VII .     

AAL-toxin,a potent natural herbicide which disrupts sphingolipid metabolism of plants

AAL-toxin, a product of Alternaria alternata (Fr.) Keissl., is effective as a herbicide at low concentrations against a range of broadleaf plants (e.g. jimsonweed, prickly sida and black nightshade). However, monocotyledonous crops such as maize and wheat, as well as some varieties of tomato, are tolerant to it. The IC50 values for cellular electrolyte leakage and chlorophyll loss in duckweed (Lemna pausicostata L.) after 72 h treatment were 20–40 nM. Similar results were obtained with a susceptible tomato variety. AAL-toxin caused rapid cellular leakage of electrolytes, followed by cellular collapse; the first symptom at the ultrastructural level is disruption of the plasma membrane. The effects of the toxin are not light-dependent and appear to be associated with dysfunction of the plasma membrane. Fumonisins and sphingoid bases such as phytosphingosine cause similar effects, although these compounds are less potent (fumonisins, about 10-fold; sphingoid bases, about 100-fold). Recent studies suggest that in duckweed and in susceptible tomato varieties, AAL-toxin- and fumonisin B1 -induced disruption of sphingolipid metabolism is an early event in the cascade of events leading to phytotoxic injury and cell death.     

Inotropic and lusitropic effects of incremental doses of dobutamine in dogs with right ventricular apical pacing‐induced cardiac dysfunction

This study aimed to assess the effects of incremental doses of dobutamine on diastolic function in healthy and rapid ventricular apical pacing (RVAP)‐induced cardiac dysfunction anesthetized dogs. Inotropic and lusitropic effects of dobutamine (2, 4, 8, and 12 μg kg^?1 min^?1) were assessed through left ventricle (LV) pressure–volume relation and Doppler echocardiography in six female dogs before and after 8 weeks of RVAP. Peak rate of LV pressure fall (?dP/dt_min) improved with doses >4 μg kg^?1 min^?1 in healthy (4,490 ± 970 vs. 3,265 ± 471 mmHg/s, p < 0.05) and >8 μg kg^?1 min^?1 in RVAP dogs (3,385 ± 1,122 vs. 1,864 ± 849 mmHg/s, p < 0.05) while the time constant of relaxation (tau) reduced with doses >4 μg kg^?1 min^?1 in both groups (healthy: 24.0 ± 3.7 vs. 28.2 ± 4.9 ms; RVAP: 32.6 ± 8.5 vs. 37.5 ± 11.4 ms, p < 0.05) comparing with baseline. Indices of relaxation (?dP/dt_min and tau) suggested preserved lusitropic response in contrast with markedly reduced indices of contractility in the RVAP group compared with healthy group at same infusion rates. Doppler echocardiography showed significant reduction of elastic recoil in failing hearts. The results of this study demonstrated maximal positive lusitropic effects of dobutamine at a dose of 8 μg kg^?1 min^?1 in ventricular pacing‐induced cardiac dysfunction without further impairment of ventricular filling.     

Contrast‐enhanced computed tomography may be helpful for characterizing and staging canine gastric tumors

In humans, computed tomography (CT) is a widely performed technique for the diagnosis and staging of gastric tumors. The purpose of this retrospective case series study was to describe CT findings in a group of dogs with confirmed gastric tumors. For each included dog, the following CT parameters were recorded: gastric tumor location, tumor shape, gastric involvement pattern, tumor enhancement pattern in early and late phases, presence and location of lymphadenopathy, gastric tumor attenuation values, attenuation values of enlarged lymph nodes, maximum short‐axis diameter (mm) of enlarged lymph node, maximum long‐axis diameter (mm) of enlarged lymph node, and short‐axis diameter to long‐axis diameter ratio (short axis/long axis). A total of 16 dogs met inclusion criteria and had the following final diagnoses: five lymphoma, six adenocarcinoma, three inflammatory polyps, and two leiomyoma. In the early‐ and delayed‐phase postcontrast images, the mean CT attenuation value for lymphoma was lower than that of other gastric tumors. Lymphadenopathy was widespread in lymphomas and regional in adenocarcinomas. Lymphadenopathy was not detected in leiomyomas. Lymph node measurements in lymphoma were larger than lymph node measurements in adenocarcinoma. Although there were overlapping findings for the different types of gastric tumors, contrast‐enhanced CT provided helpful information for characterizing gastric tumors based on the following criteria: early and late enhancement patterns, the site of origin of the mass lesion, and extent of local invasion and distant metastases. Lymphoma should be considered for canine gastric tumors with low mean attenuation values during early‐ and delayed‐phase postcontrast images, and widespread, bulky, and rounded lymphadenopathy.     

Cloning,molecular analysis,and developmental expression of 3 oleosin cDNA isoforms in coconut (Cocos nucifera L.)

Coconut stores its lipid reserves in the endosperm, specifically in oil bodies that contain proteins called oleosins which stabilise their structure. This study reports the complete cDNA sequences of 3 genes for 3 isoforms of oleosin termed CnOLE500a, CnOLE500c, and CnOLE300a with 396, 375, and 381 nucleotides, respectively. Their predicted amino acid sequences were 131, 124, and 126 residues in length, respectively, with molecular weights of 13,787, 12,982, and 12,988 Da, respectively. The complete CnOLE500a cDNA sequence had 83.1% similarity with that of CnOLE500c, while CnOLE300a cDNA had only 50.7% and 46.5% similarity with CnOLE500a and CnOLE500c, respectively. None of the 3 coconut oleosins had the 18 amino acid insertion characteristics of H-class oleosins, thus they belonged to the L-class of oleosins. However, phylogenetic analysis showed that CnOLE300a was more related to H-class oleosins from dicots. All 3 isoforms were highly expressed at all stages of coconut endosperm development. CnOLE500c exhibited 6% higher expression than CnOLE500a and 15% higher than CnOLE300a at all stages of coconut endosperm development. However, oleosin proteins were barely detectable in the solid endosperm of coconut at 5–6 months, but this increased 20-fold at 6–7 months, and increased by a further 2- and 12-fold, at 7–8 and 8–9 months, respectively.     

Effects of correcting missing daily feed intake values on the genetic parameters and estimated breeding values for feeding traits in pigs

Daily feed intake (DFI) is an important consideration for improving feed efficiency, but measurements using electronic feeder systems contain many missing and incorrect values. Therefore, we evaluated three methods for correcting missing DFI data (quadratic, orthogonal polynomial, and locally weighted (Loess) regression equations) and assessed the effects of these missing values on the genetic parameters and the estimated breeding values (EBV) for feeding traits. DFI records were obtained from 1622 Duroc pigs, comprising 902 individuals without missing DFI and 720 individuals with missing DFI. The Loess equation was the most suitable method for correcting the missing DFI values in 5–50% randomly deleted datasets among the three equations. Both variance components and heritability for the average DFI (ADFI) did not change because of the missing DFI proportion and Loess correction. In terms of rank correlation and information criteria, Loess correction improved the accuracy of EBV for ADFI compared to randomly deleted cases. These findings indicate that the Loess equation is useful for correcting missing DFI values for individual pigs and that the correction of missing DFI values could be effective for the estimation of breeding values and genetic improvement using EBV for feeding traits.     

Expression of HIF-1α ODD domain fused canine caspase 3 by EGFR promoter-driven adenovirus vector induces cytotoxicity in canine breast tumor cells under hypoxia

Adenovirus (Ad) vectors are widely used in cancer gene therapies. However, compared to human patients, relatively limited information is available on gene transduction efficiency or cell-specific cytotoxicity in canine tumor cells transduced with Ad vectors. Since epidermal growth factor receptor (EGFR) is highly expressed on canine breast tumor cells, we sought to develop an Ad vector based on the RGD fiber-mutant adenovirus vector (AdRGD) that expresses canine caspase 3 under the control of EGFR promoter. The aims of this study were to achieve high transduction efficiency with transgene expression restricted to canine breast tumor cells. Using EGFR promoter-driven AdRGD, we were able to restrict transgene expression to canine breast tumor cells with no evidence of expression in normal cells. Canine breast tumor cells transduced with EGFR promoter-driven AdRGD carrying canine caspase 3 gene showed cytotoxic activity. We constructed a second AdRGD vector that expressed oxygen-dependent degradation (ODD)-caspase 3 under the control of the EGFR promoter; the fusion protein contains a core part of the ODD domain of hypoxia inducible factor-1 alpha (HIF-1α) fused to caspase 3. Transduction of canine breast tumor cells with EGFR promoter-driven AdRGD expressing ODD-caspase 3 induced a higher rate of cell death under hypoxic conditions compared with under normoxia. The results indicate that the EGFR promoter-driven AdRGD vectors will be of value for tumor-specific transgene expression and safe cancer gene therapy in dogs.