Pharmacodynamic study of a long-acting parenteral formulation of omeprazole in horses.
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Biomedical subjects
Publications and source records attributed to L Ocampo.
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The major metabolite from the use of furazolidone (FZD) in mammals, birds and fish is 2,3-dihydro-3-cyanomethyl-2-hydroxy-5-nitro-1alpha, 2-di(2-oxo-oxazolidin-3-yl)iminomethyl-furo[2,3-beta]furan, also called 3-amine-2-oxazolidone (AOZ). A minor metabolite was identified as N-(5-amine-2-furfuryliden)-3-amine-2-oxazolidone (FOZ). To assess the potential carcinogenicity of FZD and the metabolic mixture of AOZ/FOZ, 11 mg FZD/kg feed/day was fed for 12 weeks to mollies (Poecilia formosa), an ornamental fish species prone to develop tumors. The rate of tumors was quantified and defined both in mollies and their offspring. Then, some fish was made into fishmeal and incorporated into fish food at 500 g of meal/kg of food and fed to other mollies for 12 weeks. The rate of tumors was assessed. A similar trial design was carried out in tilapia fish (Oreochromis niloticus) by adding 50 mg FZD/kg to the feed for 90 days. All animals were placed in glass fishponds under controlled laboratory conditions. Each week, a significant biomass was collected from both groups to assess the macroscopic and histopathological changes. All mollies developed melanohistiocytomic tumors in the liver and other organs. Offspring from surviving mollie females stimulated to breed showed no changes compared to control animals. None of the mollies fed with the mollie-meal food contaminated with AOZ/FOZ developed tumors. Neither tilapia medicated with FZD nor tilapia fed with tilapia-meal contaminated with AOZ/FOZ developed tumors. These results do not support the established viewpoint that FZD must be banned from trophic chains based on its potential carcinogenic properties.
Considering the already known pharmacological features of cefotaxime, a study with two approaches of pharmacokinetics and clinical efficacy in septicaemic dogs was carried out. Pharmacokinetic variables were defined for doses of 10 mg/kg, and 20 mg/kg, utilising a quantitative bacteriological analysis. Values for half-life (T1/2 beta) at 10 mg/kg were 0.8, 1.48 and 1.52 h for the i.v., s.c. and i.m. routes, respectively. Corresponding values for the 20 mg/kg dose for the same routes were 0.8, 1.49 and 1.53 h, respectively. Relatively fast clearance (ranging from 0.58 to 0.64 L/kg/h) allowed a maximum dose interval of 12 h. The above-stated doses of cefotaxime were administered i.v. to 40 cases of septicaemia, clinically divided into 20 moderately severe cases treated with 10 mg/kg i.v., of cefotaxime bid, and 20 severe ones, treated with 20 mg/kg i.v. of cefotaxime bid. Injections continued until a previously defined criterion of 'clinically recovered' was obtained. Thereafter, a follow-up treatment was established using the same dose and dose-interval but through the s.c. route. Due to the apparent volumes of distribution obtained (ranging from 0.48 to 0.51 L/kg), considering the overall clinical efficacy obtained (90% for the 10 mg/kg dose and 75% for the 20 mg/kg dose), and due to the rapid improvement observed after a few doses of the drug (1.8 to 2.5 doses to 'clinical improvement'), it is safe to postulate such doses of cefotaxime as excellent choices for the treatment of septicaemia in dogs.
We investigated expression of the alpha(3)-integrin subunit by rat alveolar epithelial cells (AECs) grown in primary culture as well as the effects of monoclonal antibodies with blocking activity against the alpha(3)-integrin subunit on AEC monolayer formation. alpha(3)-Integrin subunit mRNA and protein were detectable in AECs on day 1 and increased with time in culture. alpha(3)- and beta(1)-integrin subunits coprecipitated in immunoprecipitation experiments with alpha(3)- and beta(1)-subunit-specific antibodies, consistent with their association as the alpha(3)beta(1)-integrin receptor at the cell membrane. Treatment with blocking anti-alpha(3) monoclonal antibody from day 0 delayed development of transepithelial resistance, reduced transepithelial resistance through day 5 compared with that in untreated AECs, and resulted in large subconfluent patches in monolayers viewed by scanning electron microscopy on day 3. These data indicate that alpha(3)- and beta(1)-integrin subunits are expressed in AEC monolayers where they form the heterodimeric alpha(3)beta(1)-integrin receptor at the cell membrane. Blockade of the alpha(3)-integrin subunit inhibits formation of confluent AEC monolayers. We conclude that the alpha(3)-integrin subunit modulates formation of AEC monolayers by virtue of the key role of the alpha(3)beta(1)-integrin receptor in AEC adhesion.
Beta-adrenergic agonists have been shown to be capable of improving growth performance in poultry when added to the feed at 1.0 ppm. However, no reference has been made concerning the cardiovascular responses when one of these agents is added to the feed at a lower concentration during the whole production cycle. The aim of this paper was to assess the effects on the ascites syndrome of 0.25 ppm clenbuterol in the feed, throughout 52 d, in broiler chicks. Results showed a lack of difference in growth and feed conversion rate between the untreated control groups and the experimental group. There were differences in mortality due to the ascites syndrome, abdominal fat:body weight ratio, and ventricular index. A statistically significant positive correlation was also found between ventricular index and mortality rate (r = 0.98). If adequate withdrawal times are ensured, the use of clenbuterol at 0.25 ppm is suggested to reduce mortality due to the ascites syndrome in broilers.
INTRODUCTION: Chronic idiopathic spastic paraparesis (CHISPA) have been associated to HTLV-I virus infection, and unknown environmental factors have been suggested to play a role in its pathogenesis. METHOD: Based in our previous studies we wanted to know if the lack of refrigerators and the mycotoxin contamination of food might have any relationship with the presence of CHISPA in patients living at southeastern Colombia. RESULTS: Interestingly only four out of 15 patients with CHISPA had some method of refrigeration, in, 14 out of these 15 patients at least a metabolite of Fusarium was detected. CONCLUSIONS: The fact that mycotoxins found in the urine samples of these patients are immunosuppressors and demyelinating allow us to suggest that these toxins could be the most important environmental cofactors leading to the susceptible people to the clinically established disease.
This study compares the frequency of telomeric associations in the peripheral blood of women suffering breast and cervix uterine cancer with a healthy control group. Two kinds of cultures were developed for each individual: with and without aphidicolin. In the normal cultures, the number of telomeric associations observed was 95.5 times higher in individuals affected by breast cancer and 41.3 times higher in those affected by cervix uterine cancer when compared to the control group (p < 0.001). In the cultures with aphidicolin, higher numbers of altered metaphases were observed in both groups as compared to the control groups (p < 0.001). Statistically significant differences (p < 0.001) could also be observed when comparing telomeric associations between the two types of cancer in both cultures. When we compared individuals affected by breast cancer in both types of cultures statistical differences were found (p < 0.05), and similar results were found in individuals affected by uterine cervix cancer (p < 0.001). The findings suggest that telomeric associations may be reflecting chromosome instability observed in cancer and that this instability behaves differently for various types of cancer.
Blood samples were obtained from 80 women: Twenty of these samples were from women affected by ductal infiltrating breast carcinoma, twenty from women affected by cervix uterine cancer, and forty individuals were screened for a control group. The search for chromosome instability that is known to affect individuals with cancer was performed through chromosome analysis in nontumor cells, intending to establish frequency and different types of numerical and structural aberrations. The results, in regard to spontaneous and aphidicolin induced chromosome aberrations, showed a significantly greater frequency (p < 0.001) of chromosome fragility, as well as other numerical and structural aberrations in breast cancer patients when compared to the control group. Similar results were obtained from cervix uterine cancer patients with the exception of certain numerical aberrations in which no significant differences were found. This suggests the existence of a certain degree of chromosomal instability affecting individuals with both types of cancer. The increase in fragility may play an important role in the biologic behavior and progression of cancer.
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Lack of consistency in clinical effectiveness of various commercial preparations of enrofloxacin prompted a compositional analysis surveillance of 11 trade marks of this fluoroquinolone using various physicochemical properties and high performance liquid chromatography (HPLC). Only one preparation resembled Baytril (Bayer of Mexico), the original brand of enrofloxacin. Variations in the concentration of enrofloxacin, use of different vehicles, substitution of this fluoroquinolone by ciprofloxacin and variations in pH were found. The use of ciprofloxacin in veterinary medicine is discussed.
We studied 30 women with cervical lesions that showed human papillomavirus infection (HPV). Cervical HPV infection was diagnosed by cytology, histology, immunohistochemistry, and electron microscopy, as well as by DNA viral hybridization in situ with 6, 11, 16, and 18 HPV types. Three groups of patients were studied: 15 women infected by HPV of 6 and 11 types with koilocytic lesions and benign evolution, 15 women infected by HPV of 16 and 18 types with koilocytic lesions and malignant evolution, and 15 normal women without cervical lesions who served as controls. For each group, chromosome fragility was studied in peripheral blood lymphocytes. Aphidicolin (AP) was used as a clastogenic agent at a concentration of 0.12 microM. There were significant differences (p less than 0.001) between the control population and the patients affected by HPV. There were also significant differences (p less than 0.001) between the two groups infected with HPV. Our findings support the concept that chromosome fragility could serve as a cytogenetic marker to measure evolution, prognosis, and treatment of cervical lesion associated with HPV.
1. The pharmacokinetic and residue elimination patterns of sulphachloropyridazine appear to be modified by disease, even without affecting key organs essential for drug metabolism. 2. Drug kinetics and residue elimination data of a sulphachloropyridazine-trimethoprim preparation were compared using infectious coryza-affected (IC) fowl and healthy chickens. 3. The plasma concentrations of sulphachloropyridazine and trimethoprim were higher in affected animals, hence a reduced volume of distribution was obtained. 4. The half-life of sulphachloropyridazine and trimethoprim was reduced in IC-affected fowl and body clearance values were decreased. 5. The rate of drug residue elimination was noticeably slower in the IC-affected group. 6. These results indicate that drug elimination patterns in healthy and diseased animals are not the same.
The effects of albendazole, fenbendazole and oxfendazole on the fermentation ability of the rumen were assessed in 12 Dorset sheep, using as parameters volatile fatty acid concentration, percentage digestibility of cellulose in vitro and pH. Although the digestibility of cellulose was affected only at high concentrations, volatile fatty acid concentrations were markedly reduced after treatment. Correlation coefficient analysis revealed a significant correlation between digestibility of cellulose and volatile fatty acids, as well as between volatile fatty acids and pH. Despite an evident decrease in volatile fatty acids and digestibility of cellulose, it is suggested that this does not outweigh the advantages derived from the use of these benzimidazoles.
The uptake, distribution, and excretion of hexachlorobenzene (HCB) was studied in young male (castrated) lambs. Lambs were exposed for 90 days at a dietary concentration of 0, 0.01, 0.1 and 1.0 ppm. Tissue concentration of HCB were monitored by periodic omental biopsy and by post-slaughter collection of tissues at 90 and at 300 days. Blood samples were collected by venipuncture each time that biopsies or sacrifice occurred. Findings of the 300 days duration study were: (1) the growth rate of the exposed lambs was unaffected by the exposure to the dietary HCB, (2) adipose tissue concentrations reached a level approximately ten times that in the diet at the end of the 90-day exposure period, (3) HCB concentration was higher in the omental fat than in the perirenal fat at 90 days but not at 300 days, (4) a good portion of the apparent decresae in HCB in the fat following cessation of exposure is due to dilution (by increasing carcass fat), (5) the apparent half-life of HCB was approximately 90 days and was not dose-dependent at the exposure rates studied, and (6) the highest HCB concentrations in other tissues were in the brain and liver. The study demonstrated that the omental biopsy provides an excellent means of estimating body fat burden of this lipid soluble pesticide, although it tends to provide an overestimate during actual dietary exposure. The finding that the bioconcentration of and the depletion from the adipose tissues were independent of dose enables prediction of the degree to which food animals might become contaminated if allowed to feed on HCB-contaminated pastures or feed stuffs, and of the time which will be required for such residues to decrease to negligible levels. This predictive ability is of obvious benefit to both the food animal producer and the consumer. Since the HCB is apparently much more stable in the body than is indicated by the depletion half-life of 90 days in these growing lambs, it follows that environmental contamination of grazing lands or animal feeds is of far greater consequence for adult animals which would not be likely to experience the growth dilution of carcass residues.
Fifty growing male (castrated) lambs were exposed to hexachlorobenzene in the diet at levels of 0, 0.01, 0.1 and 1.0 ppm for 90 days. They were then moved to clean quarters and the study continued for an additional 210 days. Growth rates, certain plasma enzyme activities and hepatic microsomal enzyme activities were studied to detect subclinical effects related to the exposure. A 19-day acute exposure at 100 ppm was done and the same parameters except for growth rate, measured. Hematocrit and plasma protein concentrations were also monitored. No significant changes were seen in the growth rates (90 days exposure), in the plasma enzymes alkaline phosphatase, glutamic oxaloacetic transaminase, glucose 6-phosphate dehydrogenase or succinic dehydrogenase, or in the hematocrit or plasma protein concentrations after either the 90-day or 19-day exposures. However, in vivo metabolism of antipyrine was increased in both the 1.0 ppm (90-day) and the 100 ppm (19-day), but was significantly increased (p less than 0.01) in only the 100-ppm exposure. Additionally, hepatic microsomal N-demethylase was increased significantly by the 90-day exposure at 1.0 ppm and the 19-day exposure at 100 ppm, but the hepatic microsomal O-demethylase was significantly increased only after the 1.0-ppm exposure. Histopathologic examination of tissues (brain, lung, myocardium, large and small intestines, liver, kidneys, adrenals, mesenteric lymph nodes) collected from animals sacrificed at 90 days and at the termination of the study (300 days) revealed no lesions suggestive of harmful HCB exposure.