Biomedical subjects

A Saran

Publications and source records attributed to A Saran.

At least 55 records · Page 3Linked to original sources

PubMed1998

Comparative conformational studies on cyclic hexapeptides corresponding to message sequence His-Phe-Arg-Trp of alpha-melanotropin by NMR.

Solution conformation of cyclo(Gly1-His2-Phe3-Arg4-Trp5-Gly6) and its D-Phe analog corresponding to the message sequence [Gly-alpha-MSH5-10] of alpha-MSH has been studied by 1D and 2D proton magnetic resonance spectroscopy in dimethyl sulfoxide (DMSO)-d6 solution and in a DMSO-d6/H2O cryoprotective mixture. The NMR data for both the analogs in solution at 300 K cannot be interpreted based on a single ordered conformation, as evidenced by the broadening of only -NH resonances as well as the temperature coefficients of the amide protons. An analysis of the nuclear Overhauser effect (NOE) cross-peaks in conjunction with temperature coefficient data indicates an equilibrium of multiple conformers with a substantial population of particular conformational states at least in the D-analog. The molecular dynamics simulations without and with NOE constraints also reveal numerous low-energy conformers with two gamma-turns, a gamma-turn and a beta-turn, two beta-turns, etc. for both the analogs. The observed NMR spectra can be rationalized by a dynamic equilibrium of conformers characterized by a gamma-bend at Gly6, two gamma-bends at Phe3 and Gly6 and a conformer with a single beta-turn and a gamma-bend for the L-Phe analog. On the other hand, a conformation with two fused beta-turns around the two tetrads His2-D-Phe3-Arg4-Trp5 and Trp5-Gly6-Gly1-His2 dominates the equilibrium mixture for the D-Phe analog. For the D-Phe analog, the experimentally observed average conformation is corroborated by molecular dynamics simulations as well as by studies in cryoprotective solvent.

Magnetic Resonance Spectroscopy↗

PubMed1998

An investigation of the conformation of peptide-T and its D-Ala analog by NMR and molecular dynamics simulations.

Peptide-T (ASTTTNYT) and its D-Ala analog (D-ASTTTNYT-NH2) have been designed to block the adsorption of HIV to CD4 receptors on T-cell lymphocytes, thus inhibiting viral infectivity. The conformation of these important peptides has been investigated by 2D-NMR and molecular dynamics simulations. The NMR studies in DMSO show that the peptides exist in solution as a mixture of conformations. beta-Turns and non-specific folded conformations are present in a small proportion in the ensemble of conformations, which is largely dominated by more or less extended structures. This result is in line with molecular dynamics simulations where beta-turns were found to occur with a low frequency and with energies 10 to 17 kcal/mole higher than the global minimum structure. Our findings differ from previous reports on the conformation of peptide-T determined by NMR.

Antiviral Agents↗

PubMed1997

Pharmacokinetics and penetration of marbofloxacin from blood into the milk of cows and ewes.

The single-dose disposition kinetics of marbofloxacin were determined in lactating cows and ewes after intravenous (i.v.) and intramuscular (i.m.) administration of 2, 2.5 and 4 mg/kg. Drug concentrations in blood and milk were determined by microbiological assay and the data were subjected to compartmental and non-compartmental kinetic analyses. In cows, the i.v. serum elimination half-life (t1/2 beta) was approximately 2 h and the i.m. serum elimination half-life (t1/2el) was approximately 3 h. The mean steady-state volume of distribution (Vss) was 1.5 l/kg for the cows and 0.6 l/kg for the ewes. The i.m. availability was nearly 100% for both cows and ewes. Drug penetration into the milk was rapid and extensive with milk marbofloxacin concentrations exceeding those in serum 2 h after administration. Milk drug concentrations equal to or greater than the minimal inhibitory concentrations for the majority of gram-negative udder pathogens were maintained for approximately 12 h after i.v. and i.m. treatment of 2-4 mg/kg. The drug was not detected in milk 24 h after treatment (sensitivity limit of assay = 0.05 microgram/ml).

Animals↗

PubMed1997

Efficacy of cefquinome for treatment of cows with mastitis experimentally induced using Escherichia coli.

The efficacy of intramuscularly and intramammarily administered cefquinome was evaluated in experimental Escherichia coli mastitis in dairy cows. Forty-seven multiparous, Israeli Holstein cows in early lactation that produced at least 25 L/d of milk were used, and 400 to 750 cfu of E. coli were infused into two healthy quarters of each cow. Cows were randomly assigned to one of the following treatment groups: 1) 75 mg of cefquinome administered intramammarily three times at 12-h intervals, 2) 75 mg of cefquinome administered intramammarily three times at 12-h intervals and 1 mg/kg of cefquinome administered intramuscularly two times at a 24-h interval, 3) 1 mg/kg of cefquinome administered intramuscularly two times at a 24-h interval, and 4) 75 mg of ampicillin and 200 mg of cloxacillin administered intramammarily three times at 12-h intervals. All cows developed typical signs of acute clinical mastitis by 12 to 16 h postinoculation. Parenteral cefquinome therapy, with or without intramammary cefquinome (groups 2 and 3), significantly improved clinical recovery and return to milk production. The bacteriological cure rates were considerably and significantly higher for cows in the groups treated with cefquinome than for cows in the group treated with ampicillin and cloxacillin. This study supported the efficacy of cefquinome in the treatment of clinical coliform mastitis in dairy cows.

Animals↗

PubMed1997

NMR and molecular dynamics studies of tachykinins: conformation of the C-terminal pentapeptide of substance P(SP7-11).

Substance P belongs to the tachykinin family of neuropeptides which exhibit diverse pharmacological activity. The conformation of Phe1-Phe2-Gly3-Leu4-Met5-NH2 the C-terminal pentapeptide of substance P (SP7-11) has been studied by NMR and molecular dynamics (MD) methods. NMR studies were carried out both in DMSO-d6 and 95% H2O. Based on the observed chemical shifts, 3JNH alpha coupling constants, temperature coefficients of chemical shifts of NH resonances and the pattern of inter- and intraresidue NOE's, a predominantly extended backbone conformation has been deduced for the peptide in both DMSO and H2O. MD calculations carried out in vacuo indicate that the global minimum energy conformation of the molecule is folded with an intramolecular hydrogen bond between the protonated N-terminal and the C-terminal CONH2 group. The simulation shows that beta-turns are energetically unfavourable, while alpha-helices are seen to be unstable for the peptide. gamma-Bends at either Gly3 or Leu4 are the most preferred ones. Simulations carried out in DMSO as well as in water show a preference for a nearly extended conformation.

Magnetic Resonance Spectroscopy↗

PubMed1996

Mastitis in dairy cattle caused by Corynebacterium pseudotuberculosis and the feasibility of transmission by houseflies. I.

Morbidity due to Corynebacterium pseudotuberculosis infection occurred in 29 dairy herds. The disease appeared basically in three clinical forms: cutaneous, mastitic, and visceral. The appearance of the disease showed a marked seasonality: in 23 herds it occurred during the spring and summer months (dry season) (March-October). The mastitic form occurred in only 10 herds and the causative bacterium was isolated from 33 cows (5.8%). All the strains of C. pseudotuberculosis isolated from the milk samples were found not to be nitrate reducers. The bacterium was excreted in the milk of six cows from herd B during a period of 11 months. In the mastitic cows, a decrease in milk production and considerable increases in the somatic cell count were noted. C. pseudotuberculosis was isolated from houseflies collected over a cow lesion. Laboratory-reared houseflies were successfully infected with C. pseudotuberculosis-contaminated milk, broth and sugar cubes. Flies infected with the bacterium from contaminated milk excreted the bacterium in their droppings for up to 4 h and from their saliva for up to 3 h post infection. The bacterium survived on the external organs of houseflies for no longer than 10 min post infection, after the flies had been dipped in contaminated broth.

Animals↗

PubMed1996

Sensitivity of C3H 10T1/2 cells to radiation-induced killing and neoplastic transformation as a function of cell cycle.

Cell-age sensitivity to both cell killing and neoplastic transformation induced by radiation was investigated using synchronized populations of C3H10T1/2 cells. Mitotic-cell suspensions, collected using a mitotic shake-off procedure, were irradiated with 4Gy 250 kVp X-rays or 0.5 Gy fission neutrons from the RSV-TAPIRO reactor at CR-Casaccia. For study of cell killing the mitotic-cell suspensions were either irradiated immediately after collection, or plated for subsequent irradiation, which was performed every hour, covering an interval of 17 h. The response pattern observed was similar after X-rays and neutron irradiation, but the magnitude of the variation through the cell cycle was smaller in the case of neutrons (1.3- compared with 5-fold). For study of neoplastic transformation induction the irradiation was performed immediately after collection, i.e. in M phase, or at later times corresponding to mid-G1, G1/S and G2 phases. The sensitivity of the G2/M phase was examined by irradiating the cells with 4Gy X-rays while still attached to the flask bottom, and dislodging them after 25 min. SimilarLy to cell survival, the transformation frequency showed a small variation after neutron irradiation (1.4- compared with 3.1-fold) for the phases examined.

Animals↗

PubMed1996

Genetics of chemical carcinogenesis--III. Tissue-specificity of the genes controlling susceptibility and resistance to skin carcinogenesis in the mouse.

Carcinogenesis-resistant (Car-R) and carcinogenesis-susceptible (Car-S) mice have been obtained by the method of bi-directional selective breeding. After 10 generations of selection Car-R and Car-S mice show a remarkable difference in their response to chemical carcinogenesis. Car-R and Car-S mice, initiated and promoted by skin application of 9,10-dimethyl-1,2-benzanthracene (DMBA) and 12-O-tetradecanoylphorbol-13-acetate (TPA) reach a tumour multiplicity of 0.05 and 6.2, respectively, after 49 days of promotion. When benzo[a]pyrene (B[a]P) is topically applied for initiation, followed by TPA promotion, Car-R and Car-S mice maintain a large difference in sensitivity to skin tumour induction. Car-S mice are also more susceptible than Car-R mice to complete carcinogenesis produced by single or repeated applications of DMBA only. On the contrary, when DMBA or B[a]P are administered by subcutaneous injection rather than by topical application, no significant difference in tumour incidence is observed between the two lines. All tumours induced by topical administration of carcinogens on the skin are of epithelial origin, whereas the tumours produced by subcutaneous injection are of connectival origin. These observations suggest a tissue-specific effect of the selected genes, probably restricted at the skin level.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1996

The anti-inflammatory drugs phenylbutazone and dipyrone in the treatment of field cases of bovine mastitis.

The efficacy of phenylbutazone vs. dipyrone for the treatment of acute clinical mastitis were compared in a clinical trial. All cows were treated with 20 g sulfadiazine and 4 g trimethoprim i.m. upon diagnosis and half dosage once daily thereafter. In addition, the NSAIDs treated cows received once daily either 4 g phenylbutazone or 20 g dipyrone i.m. for the duration of the antimicrobial therapy. In all treatment groups the major causative organisms were coliforms. Recovery rates for the controls, the phenylbutazone and dipyrone treatment groups were 81.8%, 89.4% and 86.6%, respectively. Recovery was evaluated by the logistic regression analysis, the odds ratios (OR) and their 95% confidence interval (CI) of treatment success for phenylbutazone and dipyrone treatments relative to the control treatment were calculated. Odds ratio of recovery was high for phenylbutazone (OR = 2.42; CI = 0.98-5.96; P = 0.054) as well as for dipyrone (OR = 1.71; CI = 0.98-3.00; P = 0.060), demonstrating a strong trend towards improved recovery in NSAID groups. The odds of treatment failure for the phenylbutazone group relative to the dipyrone group was 0.71 with 95% CI of 0.28-1.78. Clearly no significant difference could be demonstrated between phenylbutazone and dipyrone in this field trial.

Animals↗

PubMed1996

Siberian hamsters free run or become arrhythmic after a phase delay of the photocycle.

Body temperature (Tb) and locomotor activity were recorded telemetrically from male Siberian hamsters (Phodopus sungorus sungorus) that were 3 or 12 mo of age and maintained in a light-dark (LD) cycle of 16 h light/day for 2-4 mo. After 3 wk of Tb recording, the LD cycle was phase delayed by extending the light phase by 5 h for 1 day; animals remained on a 16:8-h LD cycle for the remainder of the experiment. Tb and activity rhythms of all animals were stably entrained to the LD cycle before the phase shift. After the phase shift, > or = 80% of the animals in each age group failed to reentrain and expressed free-running Tb rhythms with stable periods that ranged from 24.33 to 26.33 h; one hamster in each age group reentrained within several days. Tb became arrhythmic in 10% of all animals immediately after, and in 28% of free running animals several weeks after, the phase shift. Changes in tau and phase of activity rhythms closely paralleled Tb rhythms in individual hamsters. Daily mean Tb was unchanged, but Tb rhythm amplitude decreased by 25-50% in individual animals after the phase shift. We believe this to be the first report of neurologically intact animals failing to reentrain to a phase shift of the LD cycle. These phenomena are not readily explained by current knowledge of circadian systems and suggest that the entrainment process in Siberian hamsters differs markedly from that in other rodent species.

Animals↗

PubMed1996

The influence of sex on life shortening and tumor induction in CBA/Cne mice exposed to X rays or fission neutrons.

An experimental study of male and female CBA/Cne mice was set up at Casaccia primarily to investigate the influence of sex on long-term survival and tumor induction after exposure to high- and low-LET radiation. Mice were whole-body-irradiated at 3 months of age with fission-neutron doses of 0.1, 0.2, 0.4, 0.8, 1.2 and 1.8 Gy at the RSV-TAPIRO reactor (mean neutron energy 0.4 MeV, in terms of kerma, y(D) = 51.5 keV/micron), or with 250 kVp X-ray doses of 1, 3, 5 and 7 Gy. Control and irradiated animals were then followed for their entire life span. As a general finding, male CBA/Cne mice appear more susceptible to tumorigenesis than females. In particular, the incidences of induced acute myeloid leukemia and malignant lymphomas are significant only in male mice. Benign and malignant solid tumors of many types are observed in mice of both sexes, the most frequent being in the lung, liver and ovary. However, evidence for a radiation response is limited to the case of Harderian gland neoplasms. In addition, a comparison of the observed frequency of all irradiated compared to unirradiated animals bearing solid tumors shows that the total tumor occurrence is not altered markedly by radiation exposure. A decrease in survival time is observed for both sexes and radiation types and correlates well with increasing dose. Moreover, both sex and radiation quality appear to influence the life shortening. A similar dose dependence of survival time is found when tumor-free animals alone are considered, suggesting a non-specific component of life-shortening.

Animals↗

PubMed1995

Feed contamination with Candida krusei as a probable source of mycotic mastitis in dairy cows.

Over 3 months, yeasts were isolated in pure culture from milk samples obtained from 8 lactating cows with acute mastitis and from 1 cow with subacute mastitis. Eight of the isolates were identified as Candida krusei; 1 isolate was not submitted for identification. The affected cows were assigned to separate milking groups and had not been treated by intramammary administration of antibiotic before the outbreak. Remission of disease without treatment was observed, followed by shedding of the yeast in milk for 2 to 5 weeks. Median somatic cell counts in the affected cows before, during, and 2 months after the onset of clinical signs were 93,000; 1,793,000; and 135,000 cells/ml, respectively. Wheat silage was found to be the probable source of the infecting microorganism, whereas inadequate milking hygiene resulted in its persistence in the herd. Following replacement of the silage and improvement of the milking hygiene, the outbreak ceased. Candida krusei thus may cause mastitis in cattle not only following intramammary antibiotic treatment, but also in conditions of heavy environmental contamination, in conjunction with inadequate milking hygiene.

Animal Feed↗

PubMed1995

Tilmicosin antibacterial activity and pharmacokinetics in cows.

The minimal inhibitory concentration (MIC) of tilmicosin for 90% of 112 Staphylococcus aureus isolates from the bovine udder was 0.78 microgram/mL and 149 of 164 (90.8%) other gram-positive udder pathogens were inhibited by tilmicosin concentrations < 3.12 micrograms/mL. The MIC of the drug for 19 of 22 S. aureus isolates was < 0.78 microgram/mL when the test was conducted using Mueller-Hinton (MH) agar or MH agar containing 7.5% skimmed milk. Acute cardiac toxicity followed intravenous (i.v.) injection of the drug at 10 mg/kg to 3 cows, but animals appeared clinically normal within 30 min after treatment. The pharmacokinetics of i.v.-administered tilmicosin is typical for the macrolide class of antibiotics, i.e. low serum drug concentrations and a large volume of distribution (> 2.0 L/kg). The elimination half-life (t1/2 beta) values for 3 cows were 46.4, 56.0 and 72.8 min. The drug was administered subcutaneously (s.c.) to 5 cows at 10 mg/kg; the elimination half-life (t1/2el) was 4.18 +/- 0.55 h and the mean s.c. bioavailability was 22%. Rapid and extensive penetration of tilmicosin from blood into milk, and slow elimination from the milk were among the characteristic kinetic features of the drug after i.v. and s.c. administration. Tilmicosin was injected s.c. at 10 mg/kg once to 9 cows after the last milking of lactation; dry udder secretion samples were collected daily for 11 consecutive days and assayed microbiologically. Concentrations of drug > 0.78 microgram/mL were found in the secretion for 8-9 days after dosing. Systemic side-effects were not observed after s.c. drug administration.

Animals↗

PubMed1995

Disinfection in the dairy parlour.

The dairy farmer has the responsibility of producing milk under clean and hygienic conditions, employing appropriate techniques to clean and disinfect the milking equipment and the milking parlour. The ability of raw milk to retain its quality under storage, and the safety of the product for the consumer, can both be directly related to the bacterial content of the milk. In most countries, bacterial content is one of the factors considered in determining the level of payment for milk. Cleaning and disinfection are complementary processes: neither process alone will achieve the desired end result. Milk with low bacterial and somatic cell counts cannot be produced unless milking equipment is effectively cleaned and disinfected between milkings and the cows are kept healthy. The author considers the various sources of bacterial contamination and increased somatic cell counts in raw milk, and describes the cleaning and disinfection practices recommended for the production of milk of good microbiological quality.

Animals↗

PubMed1995

1H NMR investigation of the interaction of berberine and sanguinarine with DNA.

Interaction of the alkaloids, berberine and sanguinarine with calf thymus DNA has been studied by 1H NMR. All proton resonances of the two compounds have been assigned using 2D-COSY, NOESY and ROESY spectra. Berberine has been found to partially intercalate into DNA, while sanguinarine shows normal intercalation and also binds more firmly to DNA. The NMR experiments indicate that sanguinarine is more potent than berberine in its activity.

Alkaloids↗

PubMed1994

Comparison of 7,12-dimethylbenz(a)anthracene-DNA adduction in the epidermis of two lines of mice selected for resistance (CAR-R) or susceptibility (CAR-S) to skin carcinogenesis.

Two lines of mice were produced by bidirectional selective breeding: one resistant (CAR-R) and one susceptible (CAR-S) to two-stage skin carcinogenesis by dimethylbenz(a)anthracene and 12-O-tetradecanoyl-phorbol-13-acetate. The dimethylbenz(a)anthracene-DNA adduct formation was compared in the two lines by a postlabeling procedure so as to determine whether the striking interline difference observed as to tumor incidence could (in part) be due to differences in the formation of DNA-reactive metabolites. Results show that qualitatively, adduct profiles in CAR-R and CAR-S epidermis are similar. Quantitatively, the total binding level is slightly higher in CAR-S versus CAR-R mice during the 30-day follow-up. However, these minor differences do not increase in function of the response to selection observed through three consecutive generations. A 2- or 4-week promotion with 12-O-tetradecanoylphorbol-13-acetate enhances the decrease of adduct level in the two lines. This effect is somewhat more pronounced in CAR-S mice. Results strongly suggest that the expression of the genes responsible for CAR-R/CAR-S phenotypic difference affects mainly the postinitiation stages.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1994

Anti-inflammatory ketoprofen in the treatment of field cases of bovine mastitis.

The efficacy of ketoprofen in the treatment of acute clinical mastitis was evaluated in a clinical trial comprising a non-blind controlled study and a blind, placebo-controlled study. All the cows were treated with 20 g sulphadiazine and 4 g trimethoprim intramuscularly upon diagnosis, and half the dosage was given once daily thereafter. In addition, the ketoprofen treatment groups received 2 g ketoprofen intramuscularly once daily for the duration of the antimicrobial therapy. Recovery rates for the non-blind contemporary controls and the blind placebo-controls were 83.7 per cent and 70.7 per cent, respectively. In the non-blind controlled ketoprofen and the placebo-controlled ketoprofen treatment groups, recovery rates were 94.7 per cent and 92.3 per cent, respectively. The odds ratio (OR) of recovery was significantly (P < or = 0.01) high in the placebo-controlled study (OR = 6.75, confidence interval [CI] = 1.45 to 31.4), and high but not significant in the non-blind controlled study (OR = 2.64, CI = 0.53 to 13.10). It was concluded that ketoprofen significantly improved recovery in clinical mastitis in dairy cows.

Animals↗

PubMed1994

Genetics of chemical carcinogenesis--II. Papilloma induction and malignant conversion in susceptible (Car-s) and resistant (Car-R) lines of mice produced by bidirectional selective breeding and in their (Car-S X Car-R) F1 hybrids.

Susceptible (Car-S) and resistant (Car-R) lines of mice separated by 10 consecutive generations of bidirectional selective breeding present a very large difference in responsiveness to two-stage skin carcinogenesis. Car-S mice initiated with 0.5 micrograms 9,10-dimethyl-1,2-benzanthracene (DMBA) and promoted with 0.25 micrograms 12-O-tetradecanoyl-phorbol-13-acetate (TPA) for 77 days showed a papilloma incidence of 88% and a tumour multiplicity of 3.2 +/- 0.4 (mean +/- SE), with a tumour induction rate of 0.415. Car-R mice initiated with larger DMBA and TPA doses (50 micrograms and 20 micrograms respectively) and promoted for 111 days gave a comparable papilloma response: incidence 65%, tumour multiplicity 3.2 +/- 0.6 and tumour induction rate 0.288. The difference in papilloma response between the two lines is due to the interaction of genetic and environmental factors. In order to overcome the genetic effect with environmental factors and induce in Car-R a papilloma response comparable to that of Car-S, the DMBA dose had to be increased up to 100 times, that of TPA 40 times and the promotion time augmented by 44%. Papilloma to carcinoma conversion 112 days after the end of promotion depends on the DMBA and TPA doses applied. The number of carcinomas induced in Car-S mice and in (Car-S X Car-R) F1 hybrids was larger than that induced in Car-R mice, but the ratio of carcinoma conversion was lower, therefore a larger proportion of the small number of papillomas induced in the Car-R mice progressed to malignancy. The dominance effect measured in (Car-S X Car-R) F1 hybrids demonstrated that the susceptibility to papilloma induction was an incomplete dominant character (d/a = 0.38), whereas for carcinoma conversion the resistance was incompletely dominant (d/a = -0.49).

9,10-Dimethyl-1,2-benzanthracene↗