Studies of new purine derivatives with acetic acid moiety in human keratinocytes

Recently we described a group of purine derivatives based on theophylline structure with acetic acid moiety. Studies in a group of these compounds demonstrated their analgesic and anti-inflammatory properties. Taking into account wide spectrum of theophylline derivatives activity and searching for their new properties. the aim of the study was to evaluate safety of newly synthesized derivatives in human keratinocytes model. The effect of new purine derivatives with acetic acid moiety: 2-(8-methoxy-1,3-dimethyl-2,6-dioxo-purin-7-yl) acetic acid and 2-(1,3-dimethyl-2,6,8-trioxo-9H-purin-7-yl) acetic acid on proliferation rate and the ability of keratinocytes to migration was carried out. The results clearly demonstrate that purine derivatives with acetic acid moiety did not affect basic keratinocytes functions. Our compounds do not inhibit cells proliferation rate as well as their ability to migration. It can be therefore concluded that new purine derivatives with acetic acid moiety are safe versus normal cells. This observation opens up additional prospects in searching for their new applications

Relationship of Metabolizable Protein Balance, Purine Derivative Excretion, and 3-Methyl Histidine Excretion to Feed Efficiency in Individually Fed Finishing Heifers

Individually fed heifers were used to determine the relationship of 3-methyl histidine, purine derivatives, and metabolizableprotein balance to feed efficiency. Heifers were fed finishing dietsthat were either deficient or sufficient in metabolizable protein. Urine samples were collected and analyzed for early, late, and entire feeding period concentrations of 3-methyl histidine, purine derivatives, and creatinine. Results from this study indicated a negative relationship between feed efficiency and metabolizable protein balance, and no relationship between 3-methyl histidine excretion and feed efficiency, suggesting that protein turnover and microbial protein synthesis are not related to feed efficienc

Relationship of Metabolizable Protein Balance, Purine Derivative Excretion, and 3-Methyl Histidine Excretion to Feed Efficiency in Individually Fed Finishing Heifers

Individually fed heifers were used to determine the relationship of 3-methyl histidine, purine derivatives, and metabolizableprotein balance to feed efficiency. Heifers were fed finishing dietsthat were either deficient or sufficient in metabolizable protein. Urine samples were collected and analyzed for early, late, and entire feeding period concentrations of 3-methyl histidine, purine derivatives, and creatinine. Results from this study indicated a negative relationship between feed efficiency and metabolizable protein balance, and no relationship between 3-methyl histidine excretion and feed efficiency, suggesting that protein turnover and microbial protein synthesis are not related to feed efficienc

Chemical markers for rumen methanogens and methanogenesis

Peer reviewedPublisher PD

Synthesis and regioselective N- and O-alkylation of 3-alkyl-5-phenyl-3H-[1,2,3]triazolo[4,5-d]pyrimidin-7(6H)-ones and 2-phenyl-9-propyl-9H-purin-6(1H)-one with evaluation of antiviral and antitumor activities

3-Alkyl-5-phenyl-3H-[1,2,3]triazolo[4,5-d]pyrimidin-7(6H)-ones were prepared by nitrosative cyclization of the appropriate 5,6-diamino-2-phenylpyrimidin-4(3H)-ones with nitrous acid and were subjected to regioselective alkylation with several alkylating agents in aprotic solvent at different temperature. Simultaneous 6-N- and 7-O-alkylation were observed and the regioselectivity varied remarkably with size and shape of the alkylating agents as well as with the reaction temperature. Similarly, N- and O-alkylation as well as selectivity was also observed in the case of 2-phenyl-9-propyl-9H-purin-6(1H)-one. Some of the synthesized compounds showed moderate antiviral and antitumor activities.</p

Methane emission by alpaca and sheep fed on lucerne hay or grazed on pastures of perennial ryegrass/white clover or birdsfoot trefoil

Based on the knowledge that alpaca (Lama pacos) have a lower fractional outflow rate of feed particles (particulate FOR) from their forestomach than sheep (San Martin 1987), the current study measured methane (CH4) production and other digestion parameters in these species in three successive experiments (1, 2 and 3): Experiment 1, lucerne hay fed indoors; Experiment 2, grazed on perennial ryegrass/white clover pasture (PRG/WC); and Experiment 3, grazed on birdsfoot trefoil (Lotus corniculatits) pasture (Lotus). Six male alpaca and six castrated Romney sheep were simultaneously and successively fed on the forages either ad libitium or at generous herbage allowances (grazing). CH4 production (g/day) (using the sulphur hexafluoride tracer technique), voluntary feed intake (VFI), diet quality, and protozoa counts and volatile fatty acid concentrations in samples of forestomach contents were determined. In addition, feed digestibility, energy and nitrogen (N) balances and microbial N supply from the forestomach (using purine derivatives excretion) were measured in Experiment 1. Diets selected by alpaca were of lower quality than those selected by sheep, and the voluntary gross energy intakes (GEI, MJ) per kg of liveweight(0.75) were consistently lower (P0.05) in their CH4 yields (% GEI) when fed on lucerne hay (5.1 v. 4.7), but alpaca had a higher CH4 yield when fed on PRG/WC (9.4 v. 7.5, P0.05) in diet N partition or microbial N yield, but alpaca had higher (P<0.05) neutral detergent fibre digestibility (0.478 v. 0.461) and lower (P<0.01) urinary energy losses (5.2 v. 5.8 % GEI) than sheep. It is suggested that differences between these species in forestomach particulate FOR might have been the underlying physiological mechanism responsible for the differences in CH4 yield, although the between-species differences in VFI and diet quality also had a major effect on it

7-Substituted pyrrolo[2,3-d]pyrimidines for the synthesis of new 1-deazapyrimido[1,2,3-cd]purines

Few examples of new heterocyclic 1-deazapyrimido[1,2,3-cd]purine derivatives were synthesized by intramolecular cyclization of methyl 7-(oxiran-2-ylmethyl)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylates. The latter were obtained by iodolactonization of 7-allylpyrrolo[2,3-d]pyrimidine-6-carboxylic acids

Urinary Purine Derivatives Excretion as a Method for Estimation of Rumen Microbial Protein Production in Swamp Buffaloes and Zebu Cattle

Prediction equations based on urinary purine derivatives (PD) excretion rate as an index to predict rumen microbial protein production have been developed for European cattle and sheep. However, there is evidence to suggest that those equations may not be applicable directly to tropical swamp buffaloes (Bubalus bubalis) and zebu cattle (Bos indicus). To establish similar equations for the above two species of ruminant, five studies were conducted. In the first study, endogenous PD excretion rate determined by fasting procedure for swamp buffaloes and the Malaysian indegenous KK. cattle (zebu cattle) were 199 and 300 Ilmol/kgO.75 /day, respectively. Urinary PD excretion rate per kg digestible organic matter intake (DOMI) for buffaloes (8.19 mmol/kg DOMI) was significantly lower than that for KK. cattle (15.45 mmol/kg DOMI). The second study examined the relationship between daily urinary PD excretion (Y, mmol) and exogenous purine bases (PB) supply via duodenal infusion (X, mmol/day). The relationship obtained were Y = O. I 2X+ 12.78 (r2= 0.45) for buffaloes and Y = 0.85X + 7.15 (r2= 0.62) for KK. cattle, suggesting that 12% and 85% of the supplied exogenous purine were excreted in the urine of buffaloes and zebu cattle, respectively. In the third study, labelled [8_14C] uric acid marker was used to test the hypothesis that the lower recovery rate of urinary PD in swamp buffaloes was due to their higher recycling of plasma PD as compared to KK cattle. The averaged non-renal PD loss of plasma PD for swamp buffaloes and KK cattle did not differ significantly

Urinary Purine Derivatives as Index for Estimation of Ruminal Microbial Nitrogen Production in Sheep and Goats

Microbial-N production in the rumen can be estimated by using urinary purine derivatives (PD) as an index. A series of experiments were conducted to establish the relationship between urinary PD (allantoin, uric acid, xanthine and hypoxanthine) and feed intake, endogenous PD excretion and recovery rate of plasma PD in sheep and goats. Studies on factors affecting PD excretion; xanthine oxidase and uricase activities of the plasma, liver and intestinal mucosa cells; uric acid kinetic; and purine-N:total-N ratio of rumen microbes were also conducted. Male Poll Dorset Cross sheep and male Ferral goats were used. The animals were fed a diet consisting of 40% oil palm frond and 60% concentrate (OPFC). Four sheep (40.232.8kg) and four goats (39.6f1.8 kg) were used to measure urinary PD excretion at 40%, 60%, 80% and 95% of voluntary intake (VI). The proportion of plasma PD excreted in the urine was determined by using ['4~]-uric acid as a marker at 40% and 80 % of VI. Endogenous PD excretion was determined by fasting in six sheep (55.4f5.1 kg) and six goats (40.2f4.6kg). The results showed that sheep excreted significantly (p<0.05) higher PD and creatinine than goats when compared at the same level of feed intake. However, the coefficient of the relationship between PD and DOMI in goats (12.57 mmollkg DOMI) was similar to that in sheep (12.49 mmolkg DOMI). The proportion of allantoin to total PD in goats (86%) was higher than that in sheep (60%). The distribution pattern of enzymes (xanthine oxidase and uricase) activities in the plasma, liver and intestinal mucosal cells were similar in both animal species, but uricase activity of the intestinal mucosa cells in sheep was significantly higher (p<0.05) than in goats. The average daily urinary endogenous PD excretion obtained by the fasting trial for sheep (201f35 p r n o l k g7~5d - 1 ) was similar to that for goats (202f17 p o l k g W075d-1). The average percentage of total recovery of plasma PD excreted in the urine determined by using [14~]-urica cid in sheep (77f2.8 %) was not significantly different from that in goats (83f2.0 %). In the uric acid kinetics study, total tracer recovered reached a peak value of about 74.2% at 12 h for goats, and 74.4% at 15 h for sheep. The conversion efficiency of [14c]-uric acid to allantoin in the plasma pool was higher (p<0.05) in goats than in sheep, with a peak value of 40% recovery at 12 h post injection for goats and 33.5% at 15 h post injection for sheep. By 15 h, no [14~]-uriacc id was detected in the urine of both animal species. The rates of [I4c]-allantoin and [I4c]-uric acid excretions in the urine of sheep (3 1.0 and 88.0% h", respectively) were significantly (p<0.05) faster than those of goats (19.0 and 64.7% h-I, respectively), but the rates of total [I4c]- tracer were not significantly different between the two animal species (42.5% h-' and 30.3% h-I for sheep and goats, respectively). The primary compartment size in the plasma (V]) was significantly (p<0.05) larger in sheep (24.4 f3.01 mg C) than in goats (17.5k1.28 mg C) and the secondary compartment size in the tissue (Vz) of sheep was also larger (129f21.6 mg C) than that of goats (65.7f23.7 mg C). The volume of distribution (L) was 45% higher in sheep (0.898 L) than in goats (0.490 L). However, the net flux tended to be higher in goats (20.3k3.82 mg C) than in sheep (16.1A2.0 mg C). Hence, the results indicated that differences exist between sheep and goats in uric acidallantoin kinetics. The equations established for sheep and goats based on the recovery of labeled PD ['4~]-urica cid and endogenous PD excretion to determine the absorption of purines (X mmoWd) estimated from PD excretion in the urine (Y mmol/d) for sheep was Y=0.77X+0.201 X B75e~u.20 Xan d for goats Y= 0 . 8 3 ~ + 0 . 2 0 2 x ~ ~ T~h~e epu~rin. e~-N~:to~ta.l- N ratios of mixed rumen liquid-associated bacteria and solid-associated bacteria for sheep were 11.2 and 10.4, and those for goats were 8.5 and 10.0, respectively. The proposed equations to ,estb-ate rumen microbial-N production based on PD excretion was 0.753X for sheep and 0.992X for goats