Hak Hadhanah dalam Putusan Pengadilan Agama

The purpose of the research is to reveal the rights of custody of children that have not been mumajiz if there is a divorce seen from the requirements set by the ulama in Islamic law or the benefit of the child. Today\u27s condition often happens to mothers or apostates who cause divorce, or the condition of mothers who have divorced their husbands as career women. Does it have implications for hadhanah rights for mothers or fathers? The normative qualitative approach was applied in this study. The results of the discussion of the four cases decided by the Religious Court which became the object of research gave foster rights (hadhanah) to fathers because fathers have competence in child care, such as having good moral, having competence in the science of education and social competence that is responsible and prioritizes the benefit of children from to determine the rights of mothers as child care. In this condition the father fulfills the requirements of the hadhin compared to the mother

Physiologically based biokinetic (PBBK) modeling and validation of dose-, species-, interindividual- and matrix dependent effects on the bioactivation and detoxification of safrole

Keywords: safrole, PBBK model, DNA adduct, mace Safrole has been demonstrated to be carcinogenic in rodent studies at high doses of the pure compound. The use of pure safrole in foodshas already been prohibited. As a result, the main exposure to safrole occurs through the use of herbs and spices containing low levels of safrole, such as nutmeg, mace, star anise, pimento, cinnamon, and black pepper, and food products containing these herbs and spices or their essential oils. The Scientific Committee on Food of the European Union concluded in their evaluation that safrole is genotoxic and carcinogenic and that reductions in the exposure and restriction in the use levels are indicated. This opinion is based on carcinogenicity data from rodent studies as adequate human data were not available. Therefore, translation from animal bioassays at high dose levels of the pure compound to the risk for the human population exposed to safrole at relatively low levels via dietary intake within the complex food matrix is obviously needed. The aim of this thesis was to obtain insight into the dose-, species-, interindividual- and matrix dependent effects on the bioactivation and detoxification of safrole using physiologically based biokinetic (PBBK) modeling. PBBK models for safrole in male rats and humans were developed based on in vitro metabolic parameters determined, in silico derived partition coefficients, and physiological parameter values taken from literature. The performance of the PBBK model for rats was evaluated by comparison of predicted levels of 1,2-dihydroxy-4-allylbenzene, 1′-hydroxysafrole glucuronide and total urinary safrole metabolites to the reported levels of these metabolites in urine of rats exposed to safrole. This evaluation revealed that the predictions adequately matched observed experimental values. The PBBK model for humans was evaluated by comparison of the PBBK predicted and the reported experimental data on the level of total safrole metabolites detected in the urine of human volunteers exposed to safrole whichshowed an adequately match. The comparison of the PBBK model for rats and humans revealed that the predicted level of formation of 1ʹ-hydroxysafrole in human liver is fourfold higher than that for rat liver and the predicted formation of 1ʹ-sulfooxysafrole is about fivefold higher than that for rat liver. This indicates that the interspecies differences in toxicokinetics for bioactivation of safrole between rat an human are in line with the uncertainty factor normally taken into account for interspecies differences in toxicokinetics of 4. Species differences between humans and rats in the nature of the detoxification pathways of 1ʹ-hydroxysafrole were larger, with the formation of 1ʹ-oxosafrole being the main detoxification pathway in humans but a minor pathway in rats and glucuronidation of 1ʹ-hydroxysafrole being less important in humans than in rats. Monte Carlo simulations revealed that the formation of 1′-sulfooxysafrole was predicted to vary 4- to 17-fold in the population (fold-difference between the 95th and median, and 95th and 5th percentile, respectively). Risk assessment of safrole resulting from consumption of herbs and spices containing safrole should be performed taking into account the possible modulating effect of other compounds present in these herbs or spices. In this study, mace was chosen as the model spice of interest because it contains significant levels of safrole. Mace fraction with the highest SULT inhibiting activity was identified as malabaricone C. Studies using human HepG2 cells exposed to 1ʹ-hydroxysafrole and in the presence of mace extract showed that formation of the DNA adduct N2-(trans-isosafrol-3′-yl)-2′-deoxyguanosine was inhibited. To investigate the possible effects on safrole bioactivation to 1′-sulfooxysafrole by malabaricone C-containing mace extract could also be expected in vivo, the SULT inhibition was integrated into the PBBK model. The PBBK models predicted that at a dose of 50 mg/kg bw safrole and a ratio of malabaricone C-containing mace extract to safrole similar to the level of these constituents in mace, inhibition of 1′-sulfooxysafrole formation by malabaricone C-containing mace extract for rats and humans amounts to 90 and 100%, respectively. To see whether the inhibition of safrole DNA adduct formation by malabaricone C-containing mace extract is also observed in in vivo, to the end, Sprague-Dawley rats were orally exposed to mace extract and safrole. The results demonstrated that safrole DNA adduct formation in the liver of Sprague-Dawley rats by the mace extract was reduced by 55%. The results of the in vitro and in vivo studies that demonstrated inhibition of the formation of safrole DNA adducts by mace extract, support that combination effects should be taken into account in the risk assessment when safrole is tested in the presence of a relevant food matrix. To integrate thefood matrix dependent modulation of safrole bioactivation in the risk assessment of safrole, the so-called Margin of Exposure (MOE) approach can be used. This revealed that when safrole would be tested in rodent bioassays in the presence of a matrix containing SULT inhibitors the MOE values would be higher and the need for risk management actions would be lower. </p

Efficacy of Honey on Sex Reversal of Guppy (Poecilia reticulata Peters)

This study was performed to determine effectiveness of honey on sex reversal of guppy.  Guppy broodstock was dipped on 1 L of water containing 0, 20, 40 or 60 mL of honey, for 10 hours.  Sex identification was carried out by morphologically and histological method.  The results of study show that percentage of male progeny tends to increase by increasing the dose of honey used.  Higher percentage of male fish is obtained by the dose of 60 ml/L (59.5% male), about 2.4 fold higher than that of control (24.3% male).  Dipping of honey has no effect on survival of broodstock and larvae.  Keywords: honey, sex reversal, monosex, Poecilia reticulata   ABSTRAK Penelitian ini dilakukan untuk mengetahui efektivitas madu dalam pengarahan diferensiasi kelamin ikan gapi. Induk ikan gapi direndam dalam 1 L air yang mengandung 0, 20, 40 atau 60 mL madu, selama 10 jam.  Jenis kelamin ikan gapi diidentifikasi secara morfologis dan metode histologi. Hasil penelitian menunjukkan bahwa persentase anak ikan gapi jantan cenderung meningkat seiring dengan peningkatan dosis madu yang diberikan. Persentase tertinggi ikan gapi jantan diperoleh pada perlakuan 60 mg/l media (59,5%), sekitar 2,4 kali lebih tinggi daripada kontrol (24,3%). Perendaman dengan madu terbukti tidak mempengaruhi tingkat kelangsungan hidup induk dan larva. Kata kunci: madu, pengarahan kelamin, monoseks, Poecilia reticulat

Profil Gliserida, Dan Kandungan EPA (Eicosapentaenoat) Dan DHA (Docosaheksaenoat) Hasil Hidrolisis Minyak Hati Ikan Cod Oleh Lipase Teramobil Dari Mucor Miehei

Hydrolysis of cod liver oil by immobilized lipase from Mucor miehei was studied to observe the hydrolysis level, glycerides profile and EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid) contents in the form of glycerides and free fatty acid on various hydrolysis temperatures. Enzymatic hydrolysis of cod liver oil was carried out in a waterbath shaker at temperatures ranging from 30-60°C for 48 hours. Up to 12 hours reaction time, higher temperature gave higher hydrolysis level. Reaction time longer than 12 hours did not improve level of hydrolysis and all of them beyond 67%. This result indicated that there was possibility of acyl migration during hydrolysis. Though the hydrolysis level was high, after 48 hours reaction, EPA and DHA contents in the form of free fatty acid were low

Physiologically Based Biokinetic (PBBK) Modeling of Safrole Bioactivation and Detoxification in Humans as Compared With Rats

A physiologically based biokinetic (PBBK) model for the alkenylbenzene safrole in humans was developed based on in vitro- and in silico-derived kinetic parameters. With the model obtained, the time- and dose-dependent formation of the proximate and ultimate carcinogenic metabolites, 1'-hydroxysafrole and 1'-sulfooxysafrole in human liver were estimated and compared with previously predicted levels of these metabolites in rat liver. In addition, Monte Carlo simulations were performed to predict interindividual variation in the formation of these metabolites in the overall population. For the evaluation of the model performance, a comparison was made between the predicted total amount of urinary metabolites of safrole and the reported total levels of metabolites in the urine of humans exposed to safrole, which adequately matched. The model results revealed no dose-dependent shifts in safrole metabolism and no relative increase in bioactivation at dose levels up to 100 mg/kg body weight/day. Species differences were mainly observed in the detoxification pathways of 1'-hydroxysafrole, with the formation of 1'-oxosafrole being a main detoxification pathway of 1'-hydroxysafrole in humans but a minor pathway in rats, and glucuronidation of 1'-hydroxysafrole being less important in humans than in rats. The formation of 1'-sulfooxysafrole was predicted to vary 4- to 17-fold in the population (fold difference between the 95th and median, and 95th and 5th percentile, respectively), with the median being three to five times higher in human than in rat liver. Comparison of the PBBK results for safrole with those previously obtained for the related alkenylbenzenes estragole and methyleugenol revealed that differences in 1'-sulfooxy metabolite formation are limited, being only twofold to fivefold

Physiologically based biokinetic (PBBK) model for safrole bioactivation and detoxification in rats

A physiologically based biokinetic (PBBK) model for alkenylbenzene safrole in rats was developed using in vitro metabolic parameters determined using relevant tissue fractions. The performance of the model was evaluated by comparison of the predicted levels of 1,2-dihydroxy-4-allylbenzene and 1'-hydroxysafrole glucuronide to levels of these metabolites reported in the literature to be excreted in the urine of rats exposed to safrole and by comparison of the predicted amount of total urinary safrole metabolites to the reported levels of safrole metabolites in the urine of safrole exposed rats. These comparisons revealed that the predictions adequately match observed experimental values. Next, the model was used to predict the relative extent of bioactivation and detoxification of safrole at different oral doses. At low as well as high doses, P450 mediated oxidation of safrole mainly occurs in the liver in which 1,2-dihydroxy-4-allylbenzene was predicted to be the major P450 metabolite of safrole. A dose dependent shift in P450 mediated oxidation leading to a relative increase in bioactivation at high doses was not observed. Comparison of the results obtained for safrole with the results previously obtained with PBBK models for the related alkenylbenzenes estragole and methyleugenol revealed that the overall differences in bioactivation of the three alkenylbenzenes to their ultimate carcinogenic 1'-sulfooxy metabolites are limited. This is in line with the generally less than 4-fold difference in their level of DNA binding in in vitro and in vivo studies and their almost similar BMDL10 values (lower confidence limit of the benchmark dose that gives 10% increase in tumor incidence over background level) obtained in in vivo carcinogenicity studies. It is concluded that in spite of differences in the rates of specific metabolic conversions, overall the levels of bioactivation of the three alkenylbenzenes are comparable which is in line with their comparable carcinogenic potential

Malabaricone C-containing mace extract inhibits safrole bioactivation and DNA adduct formation both in vitro and in vivo

Safrole, present in mace and its essential oils, causes liver tumors in rodents at high dose levels due to formation of a DNA reactive 1'-sulfooxysafrole. The present study identifies malabaricone C as a mace constituent able to inhibit safrole DNA adduct formation at the level of sulfotransferase mediated bioactivation. This inhibition was incorporated into physiologically based biokinetic rat and human models. Dosing safrole at 50 mg/kg body weight and malabaricone C-containing mace extract at a ratio reflecting the relative presence in mace, and assuming 100% or 1% uptake of malabaricone C-containing mace extract, the model predicted inhibition of 1'-sulfooxysafrole formation for rats and humans by 90% and 100% or 61% and 91%, respectively. To validate the model, mace extract and safrole were co-administered orally to Sprague-Dawley rats. LC-ECI-MS/MS based quantification of DNA adduct levels revealed a significant (p <0.01) 55% reduction of safrole DNA adduct formation by malabaricone C-containing mace extract in the liver of rats exposed to safrole. The data obtained were used to perform a refined risk assessment of safrole. Overall, the results suggest a lower tumor incidence when safrole would be tested within a relevant food matrix containing sulfotransferase inhibitors compared to dosing pure safrole

Malabaricone C-containing mace extract inhibits safrole bioactivation and DNA adduct formation both in vitro and in vivo

Safrole, present in mace and its essential oils, causes liver tumors in rodents at high dose levels due to formation of a DNA reactive 1'-sulfooxysafrole. The present study identifies malabaricone C as a mace constituent able to inhibit safrole DNA adduct formation at the level of sulfotransferase mediated bioactivation. This inhibition was incorporated into physiologically based biokinetic rat and human models. Dosing safrole at 50 mg/kg body weight and malabaricone C-containing mace extract at a ratio reflecting the relative presence in mace, and assuming 100% or 1% uptake of malabaricone C-containing mace extract, the model predicted inhibition of 1'-sulfooxysafrole formation for rats and humans by 90% and 100% or 61% and 91%, respectively. To validate the model, mace extract and safrole were co-administered orally to Sprague-Dawley rats. LC-ECI-MS/MS based quantification of DNA adduct levels revealed a significant (p <0.01) 55% reduction of safrole DNA adduct formation by malabaricone C-containing mace extract in the liver of rats exposed to safrole. The data obtained were used to perform a refined risk assessment of safrole. Overall, the results suggest a lower tumor incidence when safrole would be tested within a relevant food matrix containing sulfotransferase inhibitors compared to dosing pure safrole