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Effects of microbial phytase, low calcium and phosphorus, and removing the dietary trace mineral premix on carcass traits, pork quality, plasma metabolites, and tissue mineral content in growing-finishing pigs.

An experiment was conducted to determine the effects of phytase addition, reduced Ca and available P (aP), and removing the trace mineral premix (TMP) on growth performance, plasma metabolites, carcass traits, pork quality, and tissue mineral content in growing-finishing swine. One hundred twenty cross-bred pigs (initial and final BW of 22 and 109 kg, respectively) were allotted to five dietary treatments on the basis of weight within gender in a randomized complete block design. There were three replications of barrows and three replications of gilts, with four pigs per replicate pen. The dietary treatments were as follows: 1) corn-soybean meal (C-SBM), 2) C-SBM with reduced Ca and aP, 3) C-SBM with reduced Ca and aP plus 500 phytase units/kg of diet, 4) Diet 1 without the TMP, and 5) Diet 3 without the TMP. The Ca and aP were reduced by 0.10% in the low Ca and aP diets and the diets with added phytase. Daily gain, hot carcass weight, dressing percent, kilograms of carcass lean, bone ash percent, and bone strength were decreased (P = 0.10), but liver and kidney weight were increased (P = 0.10) in pigs fed diets with reduced Ca and aP; adding phytase reversed these responses (P = 0.10). The Commission Internationale de I'Eclairage L* was decreased (P = 0.09) in pigs fed the low Ca and aP diet plus phytase relative to those fed the control diet. Removing the TMP had no effect on overall growth performance, but it increased (P = 0.03) 10th-rib backfat thickness and fasting glucose and decreased (P = 0.03) carcass length and ham weight. Liver weight and liver weight as a percentage of final BW were not affected when phytase was added to the control diet, but removing the TMP increased liver weight and liver weight as a percentage of final BW; adding phytase reversed these responses (phytase x TMP, P = 0.06). Removing the TMP decreased (P = 0.08) Zn concentrations in the bone, muscle, and liver, and Cu and Fe concentrations in the bile but increased (P = 0.08) Mn concentrations in the bile and liver of pigs. The addition of phytase reversed the negative effects of the reduced Ca and aP diets. These data indicate that removing the TMP in diets for growing-finishing pigs has no negative effects on growth performance or pork quality, but it had negative effects on carcass traits and had variable effects on tissue mineral content.

6-Phytase↗

Tetramethylpyrazine stimulates cystic fibrosis transmembrane conductance regulator-mediated anion secretion in distal colon of rodents.

AIM: To investigate the effect of tetramethylpyrazine (TMP), an active compound from Ligustium Wollichii Franchat, on electrolyte transport across the distal colon of rodents and the mechanism involved. METHODS: The short-circuit current (I(SC)) technique in conjunction with pharmacological agents and specific inhibitors were used in analyzing the electrolyte transport across the distal colon of rodents. The underlying cellular signaling mechanism was investigated by radioimmunoassay analysis (RIA) and a special mouse model of cystic fibrosis. RESULTS: TMP stimulated a concentration-dependent rise in I(SC), which was dependent on both Cl(-) and HCO(3)(-), and inhibited by apical application of diphenylamine-2,2'-dicarboxylic acid (DPC) and glibenclamide, but resistant to 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid disodium salt hydrate (DIDS). Removal of Na(+) from basolateral solution almost completely abolished the I(SC) response to TMP, but it was insensitive to apical Na(+) replacement or apical Na(+) channel blocker, amiloride. Pretreatment of colonic mucosa with BAPTA-AM, a membrane-permeable selective Ca(2+) chelator, did not significantly alter the TMP-induced I(SC). No additive effect of forskolin and 3-isobutyl-1-methylxanthine (IBMX) was observed on the TMP-induced I(SC), but it was significantly reduced by a protein kinase A inhibitor, H(89). RIA results showed that TMP (1 mmol/L) elicited a significant increase in cellular cAMP production, which was similar to that elicited by the adenylate cyclase activator, forskolin (10 micromol/L). The TMP-elicited I(SC) as well as forskolin- or IBMX-induced I(SC) were abolished in mice with homozygous mutation of the cystic fibrosis transmembrane conductance regulator (CFTR) presenting defective CFTR functions and secretions. CONCLUSION: TMP may stimulate cAMP-dependent and CFTR-mediated Cl(-) and HCO(3)(-) secretion. This may have implications in the future development of alternative treatment for constipation.

Adrenergic beta-Agonists↗

Determination of trimethoprim and its oxidative metabolites in cell culture media and microsomal incubation mixtures by high-performance liquid chromatography.

A high-performance liquid chromatographic method is presented for the determination of trimethoprim (TMP), 3'-hydroxy-TMP, 4'-hydroxy-TMP, alpha-hydroxy-TMP and two TMP N-oxides. The last two metabolites appear to decompose on liquid extraction. TMP and its oxidative metabolites are separated using a C18 radial-compression column and quantified by UV detection at 230 nm. Calibration curves are linear from 0.5 to at least 50 microM. The limit of detection is 0.05-0.15 micrograms/ml. In in vitro rat liver metabolism studies. 3'- and 4'-hydroxylation of TMP appear to be important metabolic pathways whereas TMP N-oxides are minor metabolites.

Animals↗

[Effect of hypotensive anesthesia on tissue oxygen tension of the heart, kidney and liver].

The effects of hypotensive anesthesia by prostaglandin E1 (PGE1: 8 dogs) or trimetaphan (TMP: 8 dogs) on tissue oxygenation were studied in 16 mongrel dogs anesthetized with pentobarbital. Mean blood pressure (MBP), heart rate (HR), cardiac output (CO), blood gases (BG), the blood flow and tissue oxygen tension of the heart, the kidney and the liver were measured. The blood flow and oxygen tension were measured by electromagnetic flowmeters and by polarographic oxygen electrodes respectively. PGE1 or TMP was injected intravenously to decrease MBP by 30%. MBP, CO, HR and BG of PGE1 were not significantly different with those of TMP. Coronary blood flow decreased for 12% with PGE1 and for 33% with TMP. Though blood flows of the renal and the hepatic arteries were well maintained with PGE1, they decreased for 36% and 34% respectively with TMP. Oxygen tensions of the myocardium (both outer and inner layers) and the liver were well maintained with PGE1. But with TMP, oxygen tension decreased for 23% in outer layer, for 16% in inner layer and for 31% in the liver. Oxygen tension of the kidney remained unchanged with PGE1 and TMP. The results suggest that PGE1 is more useful for the maintenance of the tissue oxygenation than TMP during hypotensive anesthesia.

Anesthesia↗

Ceftibuten and trimethoprim-sulfamethoxazole for treatment of Shigella and enteroinvasive Escherichia coli disease.

In a prospective randomized study at two clinical sites, ceftibuten was compared with trimethoprim-sulfamethoxazole (TMP-SMX), both given orally for a period of 5 days, for the treatment of dysentery. Twenty-two children were found to have bacillary dysentery caused by Shigella and/or enteroinvasive Escherichia coli. All organisms isolated were susceptible to ceftibuten; 6 of 20 Shigella strains and 4 of 5 enteroinvasive E. coli were resistant to TMP-SMX. The diarrhea persisted for a mean (+/- SD) period of 2.4 +/- 1.4 days in the ceftibuten-treated patients vs. 3.4 +/- 1.7 days in the TMP-SMX-treated patients. The duration of fever was similar for both treatment groups. Patients treated with ceftibuten or TMP-SMX had equivalent clinical responses unless the pathogen was found to be TMP-SMX-resistant. Those who were randomized to receive TMP-SMX but who were eventually found to have TMP-SMX-resistant organisms had significantly more stools at days 3, 4 and 5 (P less than 0.02 to less than 0.00006) with more watery consistency for these days (P less than 0.02 to less than 0.005) compared to patients treated with ceftibuten. No clinical relapses were reported and no drug-related side effects were observed. We conclude that ceftibuten is at least as effective as TMP-SMX in the treatment of diarrhea caused by Shigella and enteroinvasive E. coli in children.

Adolescent↗

[Protective effect of tetramethylpyrazine and L-arginine on rats with acute myocardial infarction].

OBJECTIVE: To compare the protective effects of tetramethylpyrazine (TMP) alone and TMP and L-arginine (TMP-LA) combination on rats with acute myocardial infarction (AMI), and to explore its mechanism. METHODS: The rat model of AMI was established by via caudal vein injection of pituitrin. Experimental animal groups of normal, model, TMP treated and TMP-LA (via abdominal cavity and caudal vein respectively) treated groups were established. Expression of P- and E-selectin, serum creatine phosphokinase (CK) and troponin T (TnT), and marrow peroxidase (MPO) concentration in myocardial tissue were determined by immunohistochemical stain. RESULTS: As compared with the normal group, serum CK and TnT level, and MPO concentration in myocardial tissue were significantly higher in the model group (P < 0.01), with P- and E-selectin significantly up-regulated (P < 0.01). As compared with the model group, the above-mentioned parameters in the TMP or TMP-LA treated group was significantly lower (P < 0.05). CONCLUSION: Combined use of TMP and LA showed obvious synergism in treating AMI, by way of multi-link inhibition on expression of adhesive factors and decrease of leucocyte infiltration.

Animals↗

[Effects of tetramethylpyrazine on large-conductance Ca²⁺-activated potassium channels in porcine coronary artery smooth muscle cells].

The aim of the present study was to examine the effects of tetramethylpyrazine (TMP) on large-conductance Ca(2+)-activated potassium channels (BK(Ca) channels) in porcine coronary artery smooth muscle cells, in order to provide the experimental evidence for expounding the mechanism of TMP in dilating coronary artery. Cell-attached and inside-out single channel recording techniques were used to observe the effects of TMP on BK(Ca) channels as well as the effects after the cells were treated by protein kinase A (PKA) inhibitor or protein kinase G (PKG) inhibitor. In inside-out patch, TMP activated BK(Ca) channels by increasing open-state probability (N(Po)) and decreasing close time (Tc) in a concentration-dependent manner. TMP (0.73~8.07 mmol/L) in the bath solution increased N(Po) from (0.01+/-0.003) to (0.03+/-0.01)~(1.21+/-0.18) (P<0.01, n=10), and decreased Tc from (732.33+/-90.67) ms to (359.67+/-41.30) ~ (2.96+/-0.52) ms (P<0.01, n=10). These actions of TMP occurred even when the free Ca(2+) concentration in the bath was reduced to ~ 0 mmol/L. The specific inhibitors of PKA (H-89, 3 mumol/L) and PKG (KT-5823, 1 mumol/L) had no influence on the activation of TMP on BK(Ca) channels. These findings suggest that TMP can directly activate BK(Ca) channels in coronary artery smooth muscle, which probably is an important mechanism in dilating coronary artery.

Animals↗

Dose-dependant hypothyroidism in mice induced by commercial trimethoprim-sulfamethoxazole rodent feed.

Trimethoprim-sulfamethoxazole (TMP-SMX) medication in the feed or water is commonly administered to immunocompro mised mice to prevent the occurrence of Pneumocystis murina (formerly P. carinii) pneumonia. Therapeutic doses of SMX can cause decreased total and free thyroxine (T4) levels in dogs and thyroid hypertrophy and hyperplasia in mice, rats, and dogs. Our primary objective was to determine whether SMX at doses present in commercially available rodent TMP-SMX feed would pro duce hypothyroidism in mice. Plasma T4 levels were determined prior to and after placement of Brand A TMP-SMX feed (daily SMX dose, 240 mg/kg), Brand B TMP-SMX feed (daily SMX dose, 2400 mg/kg), and their respective controls (doses calculated for a 25-g mouse according to vendor's information). T4 levels in the mice fed Brand B TMP-SMX feed were significantly decreased by 2 wk after feed placement. Levels of thyroid stimulating hormone in male and female mice given Brand B TMP-SMX feed were significantly elevated compared with those of control groups at 6 wk after feed placement, when only these mice showed evidence of thyroid hypertrophy and hyperplasia. No significant change in T4 levels occurred over the course of 11 wk in mice given the Brand A TMP-SMX chow or either control feed. In light of the significant clinical hypothyroidism that occurred in our mice while receiving Brand B TMP-SMX diet, we recommend SMX levels more similar to that of Brand A to avoid such unwanted effects which could confound research data.

Animal Feed↗

Solubilities of trimethoprim and sulfamethoxazole at various pH values and crystallization of trimethoprim from infusion fluids.

Solubilities of sulfamethoxazole (SMX) and trimethoprim (TMP) have been measured in the absence and presence of various concentrations of hydroxypropyl beta-cyclodextrin (HPCD) in buffers over a range of pH values. The solubilities of TMP increased linearly in the presence of HPCD at pH values of 7.0, 7.5, 8.9, and 9.9 indicating the formation of 1 to 1 complexes, whose association values increase as pH does and as the ionization of TMP decreases. For SMX at pH 7.0, a 1:1 complex is formed, but at pH 7.5 HPCD has little effect on the solubility of the highly ionized SMX, presumably since only un-ionized molecules can form inclusion complexes with the HPCD. At pH 7.0 when solubilities of TMP and SMX are measured in the same system containing buffer and HPCD, a massive decrease in the solubility of TMP is found, while that of SMX decreases slightly. A slightly soluble complex of TMP/SMX may be formed. When TMP/SMX injection is diluted 1;10 with phosphate buffer (pH 7.8), an immediate massive precipitation which is mostly TMP is observed. The presence of 10% w/v HPCD in the buffer delays and modifies the precipitation of TMP and SMX but does not prevent it. Mixing the injection (1 to 10) with normal saline (pH 9.5) gives a steadily increasing precipitation of TMP with time, but no discernible change in the concentration of SMX. However, in normal saline containing 10% w/v HPCD there is no crystallization of either drug over a 5 day period.

Buffers↗

Trimethoprim in pediatric urinary tract infection.

The efficacy of trimethoprim (TMP) as a single therapeutic agent in the treatment of urinary tract infection (UTI) in children was studied in 112 children prospectively comparing TMP against trimethoprim-sulfamethoxazole (TMP/Sulfa), sulfamethoxazole and ampicillin. Children with repeated colony counts of greater than 100,000 CFU/ml of the same organism grown in 2-3 consecutive clean catch specimens were successively assigned to each treatment group for 10 days' therapy. TMP achieved a cure rate of 100% compared to TMP/Sulfa 100% (p greater than 0.05), sulfamethoxazole 93% (p less than 0.05) and ampicillin 63% (p less than 0.01). TMP and TMP/Sulfa groups had no failures while sulfamethoxazole and ampicillin groups had 7% (p less than 0.05) and 37% (p less than 0.01), respectively. Relapses occurred in 4% of the TMP group whereas TMP/Sulfa had 7% (p greater than 0.05); sulfamethoxazole and ampicillin groups had none. TMP group had 7% recurrence compared to 6% TMP/Sulfa, 4% sulfamethoxazole and 7% ampicillin (p greater than 0.05). Gastrointestinal side effects and skin rashes were not encountered in the TMP group; depression of WBC was the lowest in this group. As a single therapeutic agent, TMP appears to be safe and efficacious for treatment of acute UTI in children.

Ampicillin↗

Refined crystal structures of Escherichia coli and chicken liver dihydrofolate reductase containing bound trimethoprim.

Refined crystal structures are reported for complexes of Escherichia coli and chicken dihydrofolate reductase containing the antibiotic trimethoprim (TMP). Structural comparison of these two complexes reveals major geometrical differences in TMP binding that may be important in understanding the stereo-chemical basis of this inhibitor's selectivity for bacterial dihydrofolate reductases. For TMP bound to chicken dihydrofolate reductase we observe an altered binding geometry in which the 2,4-diaminopyrimidine occupies a position in closer proximity (by approximately 1 A) to helix alpha B compared to the pyrimidine position for TMP or methotrexate bound to E. coli dihydrofolate reductase. One important consequence of this deeper insertion of the pyrimidine into the active site of chicken dihydrofolate reductase is the loss of a potential hydrogen bond that would otherwise form between the carbonyl oxygen of Val-115 and the inhibitor's 4-amino group. In addition, for TMP bound to E. coli dihydrofolate reductase, the inhibitor's benzyl side chain is positioned low in the active-site pocket pointing down toward the nicotinamide-binding site, whereas, in chicken dihydrofolate reductase, the benzyl group is accommodated in a side channel running upward and away from the cofactor. As a result, the torsion angles about the C5-C7 and C7-C1' bonds for TMP bound to the bacterial reductase (177 degrees, 76 degrees) differ significantly from the corresponding angles for TMP bound to chicken dihydrofolate reductase (-85 degrees, 102 degrees). Finally, when TMP binds to the chicken holoenzyme, the Tyr-31 side chain undergoes a large conformational change (average movement is 5.4 A for all atoms beyond C beta), rotating down into a new position where it hydrogen bonds via an intervening water molecule to the backbone carbonyl oxygen of Trp-24.

Animals↗

Trimethoprim-sulfamethoxazole pharmacokinetics during continuous ambulatory peritoneal dialysis.

Eight adult patients without peritonitis maintained on chronic ambulatory peritoneal dialysis (CAPD) were administered a single oral dose of 320 mg trimethoprim (TMP) and 1600 mg sulfamethoxazole (SMX) to characterize the pharmacokinetics of TMP and SMX. Ten blood samples were drawn following the dose. TMP and SMX-active (SMXA) concentrations were quantified in serum and dialysate. The half-life of TMP and SMXA determined by model independent methods were 33.7 +/- 10.5 h (mean +/- SD) and 13.8 +/- 2.2 h respectively. Total body clearance of TMP was 32.8 +/- 10.1 ml/min and SMXA was 21.9 +/- 6.4 ml/min. CAPD clearance of TMP was 2.27 +/- 0.81 ml/min and SMXA was 1.72 +/- 0.93 ml/min. The average peritoneal dialysate concentrations over the 72-hour collection period of TMP and SMXA were 0.9 +/- 0.1 mg/l and 5.3 +/- 0.8 mg/l respectively. A dose of 320 mg TMP and 1600 mg SMX every 48 hours is recommended for CAPD patients with mild to moderate systemic infections.

Administration, Oral↗

[Thiamphenicol versus trimethoprim-sulfamethoxazole in bacterial exacerbations of chronic unspecific respiratory tract diseases. A controlled study].

To document the efficacy of trimethoprim-sulfamethoxazole (TMP-SMZ) in treating bacterial exacerbations of chronic bronchitis, and to evaluate the efficacy of thiamphenicol (TAP), 29 patients with chronic bronchial disease were treated for two separate bacterial exacerbations, once with 0.48 g of TMP and 2.4 g SMZ daily, and once with 1.5 g of TAP daily, for 14 days. Patients were evaluated weekly and different measurements, including graded clinical observations, ventilatory tests, sputum measurements, quantitative bacterial counts and blood studies were performed. Side effects were closely monitored. Of the 29 patients entered, 20 finished the trial and hence 40 exacerbations were evaluated. All graded clinical observations were improved by the antimicrobials, whereas no marked change in the ventilatory tests was seen. Of the sputum measurements the daily volume, purulence, numbers of neutrophils and bronchial epithelial cells decreased, as did the numbers of Haemophilus influenzae and pneumococci. Of the blood studies the red blood cell count fell by more than 20% of the pretreatment value in 2 patients on TAP and 2 on TMP-SMZ. Using the same criterion, the hemoglobin level fell in 4 patients on TAP and in the hemoglobin level fell in 4 patients on TAP and in 2 patients on TAP-SMZ, while the hematocrit fell in 4 patients on TAP and in 1 on TMP-SMZ. However, all these changes were completely reversible. Minor gastrointestinal side effects were observed in 11 patients receiving TAP, compared to 3 patients on TMP-SMZ. 1 patient on the latter drug experienced a rash at the end of therapy. From the viewpoint of overall clinical assessment, 16 patients improved and 4 remained unchanged during therapy with TAP. The corresponding figures for TMP-SMZ were 17 patients improved, 2 the same and 1 worse at the end of therapy. The average relapse time after TAP was 184 days and after TMP-SMZ 180 days. In conclusion, 80% or more of exacerbations were improved by the two drugs. For all the variables measured, no significant differences were statistically detectable between the two antimicrobials, whether given in the sequence TAP first and TMP-SMZ second, or vice versa.

Adult↗

[Successful prevention of Pneumocystis carinii infection with 1,920 mg of trimethoprim-sulfamethoxazole daily in patients with malignant hematopoietic diseases].

During 1991-94 we treated 51 patients with acute myeloid leukaemias and 3 patients with a myelodysplastic syndrome of refractory anaemia with excess of blasts in transformation. The patients received trimethoprim-sulphamethoxazole (TMP-SMX) 1,920 mg daily as a prophylaxis of Pneumocystis carinii infections and selective decontamination of gastrointestinal tract. The majority of patients received TMP-SMX in their first course of chemotherapy with daunorubicin and cytosine arabinoside. Only one of the 18 patients without TMP-SMX prophylaxis during the first course of chemotherapy developed Pneumocystis carinii pneumonia. That pneumonia was successfully treated by intravenous administration of TMP-SMX 1920 mg four times a day. No other Pneumocystis carinii infection was encountered in all other patients during their clinical follow up or in autopsy material of expired patients. TMP-SMX prophylaxis had to be interrupted in 11 patients due to their suspicious allergic skin reactions, however, TMP-SMX was readministered in all without any skin changes attributable to TMP-SMX during next cycles of chemotherapy. TMP-SMX in a given daily dose of 1,920 mg seems to be a successful prophylaxis of Pneumocystis carinii infections in patients with malignant diseases of hematopoiesis.

Acute Disease↗

Molecular modelling of trimethoprim complexes of human wild-type and mutant dihydrofolate reductases: identification of two subsets of binding residues in the antifolate binding site.

Computer-assisted molecular modelling was used to generate structures for the trimethoprim (TMP):NADPH:dihydrofolate reductase (DHFR) ternary complexes for human wild-type DHFR and for five DHFR mutants (L22R, L22F, F31S, F31W and Q35P). The mutants correspond to DHFR proteins that have been isolated from tissues exposed to chronic or high dose methotrexate (MTX) and show decreased sensitivity to antifolate inhibition. Analysis of the TMP:DHFR interactions suggest the presence of two subsets of TMP binding residues in the DHFR antifolate binding site. One subset of these residues (GLU30, PHE34, ILE60 and VAL115) are common to each DHFR complex studied and are referred to as core residues. The other TMP binding residues vary among the DHFR complexes studied and are referred to as noncore residues. The core residues exhibit a greater number of TMP contacts/residue and form more stable TMP interactions than noncore residues. Additionally, the core and noncore residues make contact with different regions of the TMP structure. Information presented here provides additional insight into the design of new agents for the improved inhibition of wild-type DHFR and the simultaneous inhibition of both wild-type and mutant DHFR molecules.

Binding Sites↗

Pharmacokinetics of sulphadiazine, sulphamethoxazole and trimethoprim in patients with varying renal function.

The pharmacokinetics of tablets containing combinations of sulphadiazine (SDZ) and trimethoprim (TMP) (cotrimazine) and tablets with sulphamethoxazole (SMZ) and TMP (co-trimoxazole) were compared in patients with different renal functions. In normal renal function, SMZ is more similar to TMP than in renal impairment. In renal impairment although the serum half-life (t1/2) of both active and total SDZ remains similar to that of TMP, the t1/2 of total SMZ becomes several times higher than the t1/2 of TMP. The unchanged SMZ maintains approximately the same elimination velocity in reduced as in normal renal function. Consequently, for co-trimoxazole there is a buildup of SMZ metabolites which can only contribute to toxicity for co-trimoxazole, whereas the co-trimazine components have t1/2 values of the same order, also in renal dysfunction. The distribution volumes of SDZ, SMZ or TMP are the same regardless of renal function. However, the distribution volume of SDZ is closer to that of TMP, i.e. higher than the SMZ values. More active SDZ is excreted in the urine than SMZ both in normal and in reduced renal function. Thus co-trimazine, in addition to having some advantages in the normal individual, is in many respects distinctly more suitable in patients with renal functional impairment. On the basis of the patients with renal functional impairment. On the basis of the pharmacokinetic properties, dosage schedules are suggested that will give approximately the same plasma levels regardless of renal function.

Drug Combinations↗

A direct involvement of the central nervous system in hypophagia and inhibition of respiratory rate in rats after treatment with O,O,S-trimethyl phosphorothioate.

O,O,S-Trimethyl phosphorothioate (OOS-TMP) is known to induce unique symptoms, which are characterized by hypophagia, progressive weight loss, and hypothermia. To determine whether there is the possibility of a causal relationship between these toxic symptoms and a direct action of OOS-TMP on the central nervous system, we investigated the development of these symptoms in Fischer 344 female rats after oral or intracerebral treatment with OOS-TMP. Oral administration of OOS-TMP at 20 mg/kg induced marked hypophagia, progressive weight loss and hypothermia. Moreover, inhibition of respiratory rate was observed immediately after treatment. It lasts during the entire experimental period. Profound hypothermia below 34 degrees C was observed more frequently in the rats, which became hypercapnic (PaCO2 > or = 50 mmHg). In contrast, administration of OOS-TMP at 20 mg/kg (as much as the oral dose) into the cerebral lateral ventricle succeeded in inducing hypophagia, progressive weight loss and lowered respiratory rates. On the other hand, by this route of administration, OOS-TMP at 20 mg/kg failed to induce hypothermia, hypercapnia and lung injury. The present results suggest that hypophagia and inhibitions of respiratory rate are attributable to the direct action of OOS-TMP on the central nervous system, while other symptoms are associated with lung injury.

Administration, Oral↗

High performance liquid chromatographic determination of trimethoprim residues in egg yolk and albumen in a feeding experiment.

In a feeding experiment, the residues of trimethoprim (TMP) in egg yolk and albumen were determined by high performance liquid chromatography (HPLC). Laying hens were divided into four groups. The first group was designated as control and fed with TMP free diet during the experimental period. The second, third and fourth groups were administered with the feeds containing 4 p.p.m., 16 p.p.m. and 56 p.p.m. TMP, respectively, for 19 days and, thereafter, fed with TMP free diet. TMP was mainly found in yolk in all the three administered levels. In the medication period, the average concentration of TMP in the yolk of the second, third and fourth groups was 0.05, 0.25, and 0.90 p.p.m., respectively. After withdrawal of medication, the residues of TMP in yolk in the second, third and fourth groups decreased below the detection limit at 0.02 p.p.m. on days 4, 9, and 11, respectively.

Animals↗