Stratification of Volunteers According to Flavanone Metabolite Excretion and Phase II Metabolism Profile after Single Doses of ‘Pera’ Orange and ‘Moro’ Blood Orange Juices

Large interindividual variations in the biological response to citrus flavanones have been observed, and this could be associated with high variations in their bioavailability. The aim of this study was to identify the main determinants underlying interindividual differences in citrus flavanone metabolism and excretion. In a randomized cross-over study, non-obese and obese volunteers, aged 19–40 years, ingested single doses of Pera and Moro orange juices, and urine was collected for 24 h. A large difference in the recovery of the urinary flavanone phase II metabolites was observed, with hesperetin-sulfate and hesperetin-sulfo-O-glucuronide being the major metabolites. Subjects were stratified according to their total excretion of flavanone metabolites as high, medium, and low excretors, but the expected correlation with the microbiome was not observed at the genus level. A second stratification was proposed according to phase II flavanone metabolism, whereby participants were divided into two excretion groups: Profiles A and B. Profile B individuals showed greater biotransformation of hesperetin-sulfate to hesperetin-sulfo-O-glucuronide, as well as transformation of flavanone-monoglucuronide to the respective diglucuronides, suggestive of an influence of polymorphisms on UDP-glucuronosyltransferase. In conclusion, this study proposes a new stratification of volunteers based on their metabolic profiles. Gut microbiota composition and polymorphisms of phase II enzymes may be related to the interindividual variability of metabolism.

Uji Klirens dan Uji Pirogenitas sebagai Bagian dari Penentuan Mutu Biologi Sediaan 90Y-EDTMP

Cancer is one of the causes of death in Indonesia and even the world. Nuclear medicine techniques with radiopharmaceuticals and SPECT are one of the ways to treat cancer, but their use in Indonesia is not yet popular. Radiopharmaceuticals marked with radionuclide emitting beta (β) radiation are proven to be used for cancer therapy, one that has been developed in PTRR-BATAN is 90Y-EDTMP. Yttrium-90 is used in nuclear medicine by utilizing β radiation (E max 2.28 MeV). The β energy which is produced from the decay process of 90Y radionuclides to 90Zr can kill cancer cells. This study aimed to provide information about the substances biological effects so that preventive measures can be taken to protect humans. This study conducted evaluation of the 90Y-marked radiopharmaceutical (90Y produced from a 90Sr / 90Y generator which is 90Y-EDTMP) encompasses clearance test, pyrogen test, and dose safety test in experimental animals. The clearance test utilized mice, the pyrogen test utilized rabbits, and the dose safety test utilized mice. The results of the clearance test showed that 90Y-EDTMP compound which was excreted in 192 hour was 49.70% through urine and 14.59% through feces. The total excretion of 90Y-EDTMP within 192 hours was 64.57%. Based on the results of clearance tests with calculations, 90Y of 90Sr / 90Y generators in 90Y-EDTMP dosage form had 84.2 hours of half-life, 36.5 hours of an effective half-life and 52.7 hours of a residence time. Pyrogen test results showed pyrogen-free. The 90Y-EDTMP dose safety test showed that the dose is safe and not deadly. The development of 90Y-EDTMP is expected to be improved to produce radiopharmaceuticals for cancer therapy in order to make a real contribution in public health services.

Estimasi Sintesis Protein Mikrobia Rumen Menggunakan Ekskresi Derivat Purin dalam Urin dengan Teknik Spot Sampling pada Kambing Bligon dan Kambing Kejobong

This study were aimed to determine the correlation between concentration of purine derivatives (PD) in spot sample with PD total excretion in Bligon and Kejobong goats and determine the appropriate sampling time, in order to predicting microbial protein synthesis in both breeds. Six male Bligon goats and six male Kejobong goats with age range from 8 to 14 months and body weight from 16 to 21 kg were placed in metabolism cages. Peanut straw and water were given to both groups of goats through ad libitum feeding and drinking. The study was done in 14 days for adaptation, 3 days for collection. Sample of feeds, feed residues, and feces were collected and then analyzed to determine dry matter and organic matter content. Spot urine and the total daily urine samples were also collected. Samples collection of spot sampling technique was run by taking the urine periodically with 3 hours intervals at 24 hours. Urine samples were analyzed for the content of creatinine and PD which includes allantoin, uric acid, xanthine, and hypoxanthine. Data were tested for the correlation between concentration of PD spot urine sample with total PD daily excretion. It is known that the concentration of PD and creatinine (µmol/L) for Bligon were 1,418.40 and 202.85 respectively, while for Kejobong were 1,547.40 and 219.68 respectively. Total excretion of PD, allantoin, uric acid, xanthyne and hypoxanthine and creatinine (µmol/W0,75/day) for Bligon were 114.14, 95.86, 17.31, 0.97, and 16.40 respectively, with microbial protein synthesis efficiency was 4.61 g N/kg degraded of organic matter in rumen (DOMR). Total excretion of PD allantoin, uric acid, xanthyne and hypoxanthine and creatinine (µmol/W0,75/day) for Kejobong were 180.18, 158.17, 20.60, 1.40, and 24.87 respectively, with microbial protein synthesis efficiency was 6.90 g N/kg DOMR. Based on this study also known that the best time for spot sampling to determine the total excretion of PD in Bligon was in the range time of 11.00 am to 2.00 pm, with equation Y=1.474X+48.81, while Kejobong goat in the range of 2.00 to 5.00 pm, with equation Y=2.678X+5.692.

Biodistribution of60Co–Co/Graphitic-Shell NanocrystalsIn Vivo

The magnetic nano-materials, Co/graphitic carbon- (GC-) shell nanocrystals, were madeviachemicalvapour deposition (CVD) method, and their biodistribution and excretion in mice were studied by using postintravenously (i.v.) injecting with60Co–Co/GC nanocrystals. The results showed that about 5% of Co was embedded into graphitic carbon to form multilayer Co/GC nanocrystals and the size of the particle was ~20 nm, the thickness of the nanocrystal cover layer was ~4 nm, and the core size of Co was ~14 nm. Most of the nanocrystals were accumulated in lung, liver, and spleen after 6, 12, 18, and 24 h afteri.v.with60Co–Co/GC nanocrystals. The nanoparticles were cleared rapidly from blood and closed to lower level in 10 min after injection. The60Co–Co/GC nanocrystals were eliminated slowly from body in 24 h after injection, ~6.09% of60Co–Co/GC nanocrystals were excreted by urine, ~1.85% by feces in 24 h, and the total excretion was less than 10%.

Residues of penicillin in the milk after intrauterine treatment of lactating cows

The penicillin is a broad-spectrum antibiotic, active against a large number of Gram-positive and Gram-negative microorganisms. A total of 14 cows (East Friesian sort) were divided into two equal experimental groups, and one group was administered a dose of 400.000 IJ/ i.u./cow, and the order group 800.000 IJ/ i.u./cow penicillin. The penicillin residues in milk was determined using of Delvo test SP method with B. stearothermophilus var. calidolactis, as the test microorganism. In the first group, the average duration of the presence of its residue in milk of treated cows was 37,7 (0-60) hours. After the intrauterine dose of 800.000 I.U./cow, this time period was an average of 53,8 (36-72) hours. The concentrations of penicillin residues at the intrauterine treatment dairy cows were determinined an average of 0,003-0,143 I.U./ml milk for dose of 400.000 I.U./cow, and an average of 0,008-0,325 I.U./ml milk for dose of 800.000 I.U./cow. Total excretion of penicillin residues per cow were an average of 1.288,2 (0-2.538) I.U./cow for dose of 400.000 I.U./cow, and an average of 6.149,1 (1.452-15.330) I.U./cow for dose of 800.000 I.U./cow.

Impact of chronic catheterization and automated blood sampling (Accusampler) on serum corticosterone and fecal immunoreactive corticosterone metabolites and immunoglobulin A in male rats

Jugular catheters were inserted in nine male rats under general isofluorane anesthesia and the catheters were connected to a commercially available computerized blood sampling device (Accusampler). Blood samples (150 microl) were collected every 4 h during the first 24 h after surgery and every 12 h during the following 72 h until 94 h after surgery, when the animals were killed. All fecal pellets were collected at blood sampling. Serum corticosterone and fecal concentrations of immunoreactive corticosterone metabolites and immunoglobulin A (IgA) were quantified by ELISAs. In blood, high corticosterone concentrations (>200 ng/ml) were recorded in the first samples obtained after surgery, but the concentrations decreased steadily during the day and became cyclical, showing a diurnal variation with high levels during evenings and low levels in the mornings. The automatic blood sampling itself did not result in recordable increases in serum corticosterone concentrations. The time delay between the presence of elevated corticosterone levels in blood and in feces was approximately 12 h. Fecal immunoreactive corticosterone metabolite levels remained elevated during the 94 h study period after surgery. The fecal concentrations of IgA showed substantial between-animal variation and decreased non-significantly after the surgery. Like serum corticosterone, fecal IgA showed a diurnal variation in amounts excreted, in this case with high values in the morning and low values in the evening. The concentrations of fecal corticosterone and IgA were negatively correlated in samples obtained before surgery but no correlation existed after surgery. This indicates that fecal immunoreactive corticosterone metabolites, but not IgA, constitute a good marker of acute stress. For immunoreactive corticosterone metabolites as well as for IgA, the concentration in feces correlated well with total excretion, making single fecal samplings usable as a measure of total secretion.

Extracorporeal Shock Wave Lithotripsy and Glycosaminoglycans in Urine

In 50 calcium-oxalate stone-forming patients, the total excretion of glycosaminoglycans (GAGs) and four of its subgroups [chondroitin-4-sulfate (CS-A), chondroitin-6-sulfate (CS-C), dermatan sulfate (DS), and hyaluronic acid (HY)] was investigated before ESWL and in the following 5 days. The standard value was determined by reference to a group of healthy test subjects. The excretion of GAGs was significantly higher in healthy test persons than in stone-forming patients. Twenty-four hours after ESWL administration, GAG excretion enhanced significantly but returned to normal values in the course of three days. ESWL had no influence on the proportional composition of GAG subgroups CS-A, CS-C, DS and HY. The increase in GAG excretion after ESWL indicates a transient injury of renal tissue, i.e. of the mucus layer lining the urothelium. This lesion, however, can be regarded as temporary with later restitutio ad integrum.