• Parasites, Hosts and Diseases
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• v.51 no.2
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• pp.165-175
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• 2013

The fear that schistosomes will become resistant to praziquantel (PZQ) motivates the search for alternatives to treat schistosomiasis. The antimalarials quinine (QN) and halofantrine (HF) possess moderate antischistosomal properties. The major metabolic pathway of QN and HF is through cytochrome P450 (CYP) 3A4. Accordingly, this study investigates the effects of CYP3A4 inhibitor, ketoconazole (KTZ), on the antischistosomal potential of these quinolines against Schistosoma mansoni infection by evaluating parasitological, histopathological, and biochemical parameters. Mice were classified into 7 groups: uninfected untreated (I), infected untreated (II), infected treated orally with PZQ (1,000 mg/kg) (III), QN (400 mg/kg) (IV), KTZ (10 mg/kg)+QN as group IV (V), HF (400 mg/kg) (VI), and KTZ (as group V)+HF (as group VI) (VII). KTZ plus QN or HF produced more inhibition (P<0.05) in hepatic CYP450 (85.7% and 83.8%) and CYT b5 (75.5% and 73.5%) activities, respectively, than in groups treated with QN or HF alone. This was accompanied with more reduction in female (89.0% and 79.3%), total worms (81.4% and 70.3%), and eggs burden (hepatic; 83.8%, 66.0% and intestinal; 68%, 64.5%), respectively, and encountering the granulomatous reaction to parasite eggs trapped in the liver. QN and HF significantly (P<0.05) elevated malondialdehyde levels when used alone or with KTZ. Meanwhile, KTZ plus QN or HF restored serum levels of ALT, albumin, and reduced hepatic glutathione (KTZ+HF) to their control values. KTZ enhanced the therapeutic antischistosomal potential of QN and HF over each drug alone. Moreover, the effect of KTZ+QN was more evident than KTZ+HF.

• Archives of Pharmacal Research
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• v.26 no.11
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• pp.979-983
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• 2003

The pharmacokinetic of tolbutamide was studied after the oral administration to normal rabbits or rabbits with mild to medium folate-induced renal failure. The plasma concentrations of tolbutamide were significantly elevated (p<0.05) during 9 to 24 h in rabbits with mild or medium folate-induced renal failure. Consequently, the area under the plasma concentration-time curves (AUC) was significantly higher in mild (p<0.05) and medium (p<0.01) folate-induced renal failure rabbits (i.e., 2906 $\mu$g/mL$.$h for mild renal failure and 4074 $\mu$g/mL$.$h for moderate renal failure) than that in normal rabbits (i.e., 2295 $\mu$g/mL$.$h). The cumulative urinary excretion of tolbutamide was significantly depressed (p<0.05) in medium folate-induced renal failure rabbits (i.e., 3.3 mg) compared with that in normal rabbits (i.e., 5.9 mg). The elimination rate constant (Kel) of tolbutamide was significantly decreased in medium renal failure rabbits (i.e., 0.027 $h^{-1}$) than that in normal rabbits (i.e., 0.044 $h^{-1}$ ); As a result, the terminal half-life of tolbutamide in medium folate-induced renal failure rabbits (i.e., 25.5 h) was significantly longer (p<0.01) than that in normal rabbits (i.e., 15.7 h). The change in pharmacokinetic parameters is consistent with the hypothesis that the alteration is mediated by the depressed metabolic elimination of the drug by the induction of renal failure. Therefore, these observations indicated that the dosage adjustment may be necessary for tolbutamide in patients with renal insufficiency.

• Safety and Health at Work
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• v.8 no.2
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• pp.183-188
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• 2017

Background: Recommendations have been proposed for minimum aerobic fitness among firefighters but it is unclear if those criteria relate to performance on the fireground. Less fit individuals fatigue more quickly than fit individuals when working at comparable intensity and may have gait changes, increasing risk of falls. We evaluated the effect of fatigue during a live burn evolution on gait parameters and functional balance comparing them to aerobic fitness levels. Methods: A total of 24 firefighters had gait and balance tested before and after a live burn evolution. Data were stratified by aerobic fitness of greater/less than 14 metabolic equivalents (METs). Results: Analysis of gait cycles measurements before and after the live burn evolution revealed that single leg stance, cycle, and swing time decreased (p < 0.05) but there were no differences in the other measures. There were no differences in time to complete the functional balance test, or errors committed before or after a live burn evolution. When firefighters were sorted by fitness level of 14 METs, there were no differences for errors or time before or after the live burn evolution. Balance data were analyzed using a linear regression. Individuals with lower fitness levels required more time to complete the test. Conclusion: A 14-MET criterion failed to distinguish gait or balance characteristics in this group. However, less fit firefighters did require more time to complete the balance test (p = 0.003). Aerobic fitness alone does not predict gait changes among firefighters following a live burn evolution but does appear to influence functional balance.

• Korean Journal of Environmental Agriculture
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• v.31 no.3
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• pp.264-270
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• 2012

BACKGROUND: The purpose of this study was that serum metabolic and hematological variables were measured to investigate the detoxication effect of Taraxacum mongolicum extract on male albino rat exposed with lead and mercury. METHODS AND RESULTS: For this study, Pb and Hg-exposed( 50 ppm) albino rats was used, and the treatments were carried out in three doses of 100 mg/kg, 200 mg/kg and 500 mg/kg as dry weight of T. mongolicum extract. T. mongolicum extract could improved the body weight gain and feed efficiency ratio, except to food intake. The levels of biochemical factors elevated by Pb-Hg mix exposure, which are Bilirubin, Alkaline phosphatase(ALP), glutamic oxaloacetate transaminase(GOT), glutamic pyruvate transaminase (GPT), lactate dehydrogenase(LDH), ceatinine and blood urea nitrogen(BUN), were significantly reduced in all treated groups as compared to Pb-Hg mix exposure alone. T. mongolicum extract was shown to suppress the accumulation of Hg and Pb in serum by dose dependent manner. CONCLUSION: Therefore, this study suggest that T. mongolicum extract might have the potential effect to minimize the toxic effects of Pb and Hg.

• Asian-Australasian Journal of Animal Sciences
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• v.16 no.9
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• pp.1291-1296
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• 2003

Effects of feeding of 9.95 mg free gossypol/kg live weight through cottonseed meal (CSM) were studied in 20 intact male calves fed barley or sorghum as source of cereal during the experimental duration of 210 days. Serum concentration of total protein, albumin, globulin and their ratio did not vary because of protein (gossypol) or cereal sources. Serum level of cholesterol and urea were lower (p<0.05) in sorghum than barley fed calves. Feeding of gossypol through CSM enhanced (p<0.05) serum cholesterol. An interaction between protein and period was observed with respect to serum concentrations of urea, creatinine and alanine transferase. The levels of serum creatinine and alanine transferase increased (p<0.05) following 120 days of experimental feeding in calves fed CSM diets compared to the control animals fed groundnut meal diets. No effect of feeding gossypol was, however, evident on the serum enzymes viz. alanine and aspartate transferases and alkaline phosphatase. Moreover, the source of cereal and protein did not appear to influence the metabolic profile of the calves. Humoral immune response, measured through antibody titre against Brucella abortus S99 innoculation, revealed a delayed and depressed seroreactivity indicative of immunocompromisation because of the phytotoxin gossypol. In conclusion, the feeding of gossypol at the designated levels, although had no deleterious clinico-biochemical manifestations, affected the humoral immune response of the calves.

• Asian-Australasian Journal of Animal Sciences
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• v.33 no.12
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• pp.2039-2049
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• 2020

Objective: This study was conducted to provide models to accurately predict nitrogen (N) and phosphorus (P) excretion of dairy cows on smallholder farms in Indonesia based on readily available farm data. Methods: The generic model in this study is based on the principles of the Lucas equation, describing the relation between dry matter intake (DMI) and faecal N excretion to predict the quantity of faecal N (Q_FN). Excretion of urinary N and faecal P were calculated based on National Research Council recommendations for dairy cows. A farm survey was conducted to collect input parameters for the models. The data set was used to calibrate the model to predict Q_FN for the specific case. The model was validated by comparing the predicted quantity of faecal N with the actual quantity of faecal N (Q_FNACT) based on measurements, and the calibrated model was compared to the Lucas equation. The models were used to predict N and P excretion of all 144 dairy cows in the data set. Results: Our estimate of true N digestibility equalled the standard value of 92% in the original Lucas equation, whereas our estimate of metabolic faecal N was -0.60 g/100 g DMI, with the standard value being -0.61 g/100 g DMI. Results of the model validation showed that the R² was 0.63, the MAE was 15 g/animal/d (17% from Q_FNACT), and the RMSE was 20 g/animal/d (22% from Q_FNACT). We predicted that the total N excretion of dairy cows in Indonesia was on average 197 g/animal/d, whereas P excretion was on average 56 g/animal/d. Conclusion: The proposed models can be used with reasonable accuracy to predict N and P excretion of dairy cattle on smallholder farms in Indonesia, which can contribute to improving manure management and reduce environmental issues related to nutrient losses.

• Journal of Pharmaceutical Investigation
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• v.28 no.2
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• pp.73-80
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• 1998

In order to elucidate the effect of N-demethylation on the in vivo metabolite kinetics, especially hepatic first-pass effect of trimebutine(TMB), the N-demethylation of TMB to N-monodesmethyl trimebutine(N-TMB) was studied in rats. TMB(10 mg/kg) and N-TMB(10 mg/kg) were injected into the femoral and the portal vein, respectively. And the pharmacokinetic parameters were obtained from the plasma concentration-time profiles of TMB and N-TMB determined by the simultaneous analysis using high-performance liquid chromatography. It was supposed that these drugs were almost metabolized in vivo because the urinary and biliary excreated amounts of TMB and N-TMB were lower than 0.1% of the administered dose. According to the hepatic biotransformation model and metabolic pathways of TMB proposed, it was found that the fraction of systemic clearance of TMB which formed N-TMB in liver$(G_{mi})$ was 0.826, that of TMB which furnishes the available N-TMB to the systemic circulation$(F_{mi})$ was 0.083, and the absolute hepatic bioavailability of N-TMB formed trom TMB$(F_{mi.p})$ was 0.1. These results showed that TMB was suspected of the sequential hepatic first-pass metabolism and N-demethylated by 82.6%. Therefore, the residue would be hydrolyzed by the esterase in the liver. That is, the ability of N-demethylation of TMB was 4.75-fold larger than that of hydrolysis by the esterase in rats.

• Journal of Pharmaceutical Investigation
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• v.31 no.4
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• pp.209-216
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• 2001

The purpose of the present study was to investigate the hepatic uptake and biliary excretion of l-anilino-8-naphthalene sulfonate (ANS) in vivo. The plasma concentration and liver concentration of ANS were determined after its i.v. bolus administration at a dose of $30\;{\mu}mol/kg$ in rats. The hepatic uptake clearance $(CL_{uptake})$ of ANS was 0.1 ml/min/g liver. On the basis of the unbound concentration of ANS, the permeability-surface area product $(PS_{influx})$ was calculated to be l0.4 ml/min/g liver, being comparable of in vitro data. On the other hand, we determined the plasma concentration, liver concentration and biliary excretion rate of ANS at steady-state after its i. v. infusion $(0.2-1.6\;{\mu}mol/min/kg)$ in rats. The excretion clearance $(CL_{excretion})$ of ANS showed Michaelis-Menten kinetics with increasing the infusion rate. The permeability-surface area product $(PS_{excretion})$ based on the unbound concentration in the liver was calculated to be 0.0165 ml/min/g liver, which is negligible compared with the intrinsic clearance $(CL_{int}=3.3\;ml/min/g\;liver)$ by rat liver microsomes. The sequestration process of ANS, therefore, was considered to be mainly due to the metabolic process in the liver $(PS_{seq}{\risingdotseq}CL_{int})$. Furthermore, $PS_{efflux}$ value calculated from $PS_{influx}$ and $PS_{seq}$ was 4.4 ml/min/g liver, which was comparable of in vitro data. In conclusion, in vivo parameters such as $PS_{influx}$, $PS_{efflux}$ and $PS_{seq}$ in the present study showed good in vivo-in vitro relationship. Thus, the kinetic analysis method proposed in the present study would be useful to analyze the hepatic transport of drugs in vivo.

• Asian-Australasian Journal of Animal Sciences
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• v.33 no.8
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• pp.1323-1331
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• 2020

Objective: Three types of dietary fiber were fed to sows during gestation and lactation stages to monitor their physiological and metabolic adaptations during the pre-partum period and to determine how these effects may influence the lactation period and sow performance. Methods: Soon after breeding, 54 sows were selected and were fed with 20% supplementation as fed of wheat bran (WB), soya hulls (SH), or rice hulls (RH) in diets during gestation and lactation. Sows were weighed, backfat thickness was measured ultrasonically and jugular blood samples were collected from all sows. The litter size was equalized to 10, by fostering piglets from sows on the same treatment. Results: Sows gained 22.0, 21.8, and 25.5 kg of net maternal body weight during gestation (for WB, SH, and RH sows, respectively; p = 0.007). There was no treatment effect on the body weight change during lactation (p = 0.158), however RH sows consumed an average of 133.66 kg of feed, WB sows took 121.29 kg and SH sows took 126.77 kg during lactation (p<0.001). The SH litters gained an average of 59.34 kg of weight during lactation, while other litters gained 51.58 and 49.98 kg (for WB and RH litters, respectively; p<0.001). Exception for aspartate aminotransferase and alanine aminotransferase, measured serum biochemical values were broadly in agreement with earlier reports. Despite the use of additional vegetable oil to balance the energy level, RH sows still had lower concentrations of serum triglycerides in late gestation. Conclusion: Different types of fibrous ingredients in the gestation diet influenced most of the investigated reference values for sows. The values of serum biochemical parameters were generally not affected by fiber type during the lactation stage. The SH supplementation for sows is an effective approach to give heavier litters at birth and weaning and to increase voluntary feed intake in early lactation.

• Radiation Oncology Journal
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• v.36 no.2
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• pp.95-102
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• 2018

Purpose: To evaluate the prognostic value of $^{18}F$-fluorodeoxyglucose positron-emission tomography (FDG PET) with computed tomography (CT) before and during radiotherapy (RT) in patients with head and neck cancer. Methods: Twenty patients with primary head and neck squamous cell carcinoma were enrolled in this study, of whom 6 had oropharyngeal cancer, 10 had hypopharyngeal cancer, and 4 had laryngeal cancer. Fifteen patients received concurrent cisplatin and 2 received concurrent cetuximab chemotherapy. FDG PET/CT was performed before RT and in the 4th week of RT. The parameters of maximum standardized uptake value, metabolic tumor volume, and total lesion glycolysis (TLG) of the primary tumor were measured, and the prognostic significance of each was analyzed with the Cox proportional hazards model. Results: Higher TLG (>19.0) on FDG PET/CT during RT was a poor prognostic factor for overall survival (OS) (p = 0.001) and progression-free survival (PFS) (p = 0.007). In the multivariate analysis, TLG during RT as a continuous variable was significantly associated with OS and PFS rate (p = 0.023 and p = 0.016, respectively). Tumor response worse than partial remission at 1 month after RT was another independent prognostic factor for PFS (p = 0.024). Conclusions: Higher TLG of the primary tumor on FDG PET/CT during RT was a poor prognostic factor for OS and PFS in patients with head and neck cancer.