Correlation of dose-antimicrobial effect in modeling in vitro pharmacokinetic profiles of normal and impaired elimination of antibiotics

Relationships between concentration and antimicrobial effect (AME) of sisomicin (SMN) and cefotaxime (CTX) were established by simulating their pharmacokinetic profiles in an in vitro dynamic model. The AME duration (TE, time shift between the curves of bacteria heat output in the presence and absence of the antibiotics) or intensity (IE, area between the above curves) for both the antibiotics depended in the same way on the area under the concentration/time curve (AUC, mimicing of intravenous administration of the antibiotics in various doses). At low and moderate values of the AUC the dependences of IE or TE vs the AUC (the bacteriostatic phase of the AME development) were of the sigmoid shape while at high values of the AUC there was a marked increase in IE or TE (the bactericidal phase). The patterns of the IE or TE vs AUC curves in impaired antibiotic elimination were analogous. At the same time the IE or TE vs AUC curves for both the antibiotics under simulation of normal elimination (T 1/2, SMN-2.1 h, T 1/2, CTX-1.2 h) and impaired one (T 1/2, SMN-8.3 h, T 1/2, CTX-4.6 h) did not match. In the first case the AMESMN was on the whole higher and the AMECTX was lower than in the second case. Therefore, in patients with renal failure the efficient concentration of the aminoglycoside in blood can be higher and that of the cephalosporin on the contrary can be lower than the normal.     

Kinetics of the antibacterial effect of ampicillin and sulbactam combinations in dynamic and static conditions

Kinetics of antimicrobial effect (AME) of ampicillin/sulbactam combinations (ratios of 4:1 to 1:2) on ampicillin resistant bacterial strains producing beta-lactamases of types II, III, IV and V according to Richmond classification was studied with using the computerized system MS-2 (turbidimetric recording) and an in vitro dynamic model (microcalorimetric recording). The concentrations of the drugs in system MS-2 (static conditions) corresponded to the maximum ones observed in serum of humans after bolus intravenous administration of ampicillin in a dose of 0.5 g and sulbactam in doses of 0.125 to 0.5 g. The pharmacokinetic profiles of the drugs observed in the human serum after their oral and intravenous administration and in the tissue-chamber fluid after intravenous administration of ampicillin (0.5 g) and sulbactam (0.125 g) were simulated in the dynamic model. The combination efficacy was estimated with using the parameter of AME duration (TE) reflecting shifts in the curves of the microbial regrowth in the presence of the drugs against the curve of the control growth (in the absence of the drugs) and the parameter of the AME intensity (IE) evaluated by the area between the curves. It was noted that increasing of the ampicillin/sulbactam ratio from 1:4 to 1:1 was accompanied by an increase in the AME. Further increasing of the sulbactam content in the combination did not result in higher AME. For combined ampicillin/sulbactam dosage forms the ratios of 1:1 to 2:1 should be recommended.(ABSTRACT TRUNCATED AT 250 WORDS)     

Human serum paraoxonase-1 (hPON1): in vitro inhibition effects of moxifloxacin hydrochloride,levofloxacin hemihidrate,cefepime hydrochloride,cefotaxime sodium and ceftizoxime sodium

Abstract

In this study, we investigated the effects of antibacterial drugs (moxifloxacin hydrochloride, levofloxacin hemihidrate, cefepime hydrochloride, cefotaxime sodium and ceftizoxime sodium) on human serum paraoxonase-1 (hPON1) enzyme activity from human serum in vitro conditions. For this purpose, hPON1 enzyme was purified from human serum using simple chromatographic methods. The antibacterial drugs exhibited inhibitory effects on hPON1 at low concentrations. K_i constants were calculated to be 2.641?±?0.040?mM, 5.525?±?0.817?mM, 35.092?±?1.093?mM, 252.762?±?5.749?mM and 499.244?±?10.149?mM, respectively. The inhibition mechanism of moxifloxacin hydrochloride was competitive, whereas levofloxacin hemihidrate, cefepime hydrochloride, cefotaxime sodium and ceftizoxime sodium were noncompetitive inhibitors.     

Evaluation of the effectiveness of antibacterial substances in treating an experimental form of bubonic plague in monkeys]

The modelling of glandular plague and selection of the conditions for estimating the efficacy of new antibacterials for the treatment of the infection were performed on hamadryads (baboons). The experiments showed that the average LD50 of the culture of a highly virulent strain of Yersinia pestis on its subcutaneous administration to the animals was 2089 viable microbes. In 18 per cent of the episodes the experimental glandular plague in the animals was complicated by secondary plague pneumonia. Subcutaneous administration of 2 x 10(7) viable microbial cell of the plague pathogen caused acute sepsis and the animal death. The treatment of the experimental glandular plague in the hamadryads demonstrated that new antibacterials such as amikacin, netilmicin, ceftriaxone, cefotaxime, ceftizoxime, doxycycline, rifampicin, ofloxacin and ciprofloxacin were not inferior in their efficacy to streptomycin and tetracycline successfully used in the therapy of patients with plague.     

Synergistic effect on anti-methicillin-resistant Staphylococcus aureus among combinations of α-mangostin-rich extract,lawsone methyl ether and ampicillin

α-Mangostin-rich extract (AME) exhibited satisfactory inhibitory activities against all tested MRSA strains, with minimum inhibitory concentrations (MICs) of 7·8–31·25 µg ml⁻¹, whereas lawsone methyl ether (LME) and ampicillin revealed weak antibacterial activity with MICs of 62·5–125 µg ml⁻¹. However, the combination of AME and LME showed synergistic effects against all tested MRSA strains with fractional inhibitory concentration index (FICI) values of 0·008–0·009, while the combination of AME and ampicillin, as well as LME and ampicillin produced synergistic effects with FICIs of 0·016–0·257. A time-kill assay against MRSA (DMST 20654 strain) revealed a 6-log reduction in CFU per ml, which completely inhibited bacterial growth for the combinations of AME and LME, AME and ampicillin, and LME and ampicillin at a 8-h incubation, while those against MRSA (2468 strain) were at 10-h incubation. The combination of α-mangostin and LME as well as the combinations of each compound with ampicillin synergized the alteration of membrane permeability. In addition, α-mangostin, LME and ampicillin inhibited the biofilm formation of MRSA. These findings indicated that the combinations of AME and LME or each of them in combination with ampicillin had enhanced antibacterial activity against MRSA. Therefore, these compounds might be used as the antibacterial cocktails for treatment of MRSA.     

Multidrug resistance to antibacterial drugs of Salmonella enterica subsp. enterica strains isolated in Poland in the 1998-1999 period]

A total of 510 Salmonella enterica subsp. enterica strains representing 56 serotypes, isolated from human stool specimens during 1998-2000 in sanitary-epidemiological units in Poland were tested for their susceptibility by a standard disk diffusion method for: ampicillin, cefotaxime, chloramphenicol, tetracycline, streptomycin, gentamicin, kanamycin, nalidixic acid, ciprofloxacin, furazolidone, cotrimoxazole, sulfonamides and trimethoprim. For 201 of the investigated strains, belonging to 5 most common isolated serotypes (S. Enteritidis, S. Typhimurium, S. Hadar, S. Infantis and S. Virchow) the minimal inhibitory concentrations (MICs) for the aforementioned antibiotics, as well as for amoxicillin with clavulanian were determined. Selected strains were screened for production extended spectrum b-lactamases (ESBLs). It was observed that 42.9% of Salmonella enterica subsp. enterica strains were resistant to 2 or more antibiotics, with the highest prevalence of MDR strains among serotypes Typhimurium, Hadar and Virchow. Resistance to ampicillin, streptomycin, tetracycline, nalidixic acid, furazolidone and sulphonamides was observed most frequently. Over 93% of S. Virchow strains were resistant to furazolidone. No strains resistant to ciprofloxacin were detected according to the NCCLS guidelines, but 31.3% of isolates exhibiting reduced ciprofloxacin susceptibility (MICs ranging between 0.125 and 0.5 mg/l). Two strains S. Mbandaka and Salmonella group D (variant motility--) were resistant to cefotaxime and probably produced ESBL.     

Tissue distribution of cocaine in the pregnant rat

Cocaine hydrochloride was administered by single intraperitoneal (IP) doses to pregnant rats at day 18 or 19 of gestation. Plasma and tissue cocaine and norcocaine concentrations were measured by high-pressure liquid chromatography. Pharmacokinetic analysis of concentration versus time data showed rapid distribution of cocaine and its metabolite to maternal and fetal tissues. The area under the cocaine concentration versus time curve (AUC) in fetus compared to maternal plasma was 3.33. The half-life of cocaine in the maternal plasma and fetus was 46 and 55 minutes, respectively, similar to values reported for cocaine elimination half-life in human plasma. The order of cocaine concentrations was placenta greater than fetal liver greater than maternal heart greater than whole fetus greater than fetal brain greater than maternal brain = maternal plasma. Norcocaine concentrations were usually less than 20% of cocaine concentrations in plasma and tissues. These results support extensive fetal exposure to cocaine following administration to pregnant rodents. Pharmacodynamic studies of cocaine in pregnancy should consider the effects of the drug on the developing fetus.     

Influence of subinhibitory concentrations of cefotaxime, imipenem and ciprofloxacin on adhesion of Escherichia coli strains to polystyrene

The present study investigated the ability of sub MICs of cefotaxime, imipenem and ciprofloxacin to interfere with adhesion of E. coli strains to polystyrene (selected polymer used in studies on microorganisms' adhesion). It was observed that cefotaxime and imipenem at 1/2 and 1/4 MICs decreased the adherence of E. coli strains to polystyrene significantly. 1/2, 1/4 and 1/8 MICs of ciprofloxacin generally decreased the adhesive properties of E. coli strains, but two E. coli strains showed a noticeable enhancement of adhesion after incubation at sub MICs of this antibiotic.     

Antimicrobial activity of new beta-lactams and aminoglycosides in vitro under conditions of anaerobiosis

Sensitivity of 135 strains of aerobic, facultative anaerobic and anaerobic asporogenous bacteria was tested in vitro with respect to 7 beta-lactam antibiotics and 4 aminoglycosides. It was shown that anaerobiosis influenced the MICs of the drugs for the majority of the strains. Under such conditions sensitivity of the aerobic and facultative anaerobic organisms to the beta-lactams increased 2-8 times. On the contrary, the MICs of the aminoglycosides for 74.6-85.1 per cent of the strains increased 2-16 times. The asporogenous anaerobic bacteria of clinical origin were highly sensitive to the beta-lactam antibiotics such as cefoxitin, cefotaxime, mezlocillin and carbenicillin whose MICs did not exceed 16-31.2 micrograms/ml.     

Gly-238-Ser substitution changes the substrate specificity of the SHV class A beta-lactamases

The SHV-type beta-lactamase SHV-2A is related to SHV-1 by a Gly-238-Ser replacement. Strains carrying SHV-2A are resistant to the third generation cephems cefotaxime and ceftizoxime, whereas those that carry SHV-1 are sensitive to these drugs. We present a kinetic analysis of a SHV-1 and SHV-2A enzymes, with the goal of gaining insight into the role of residue 238 in hydrolyzing cefotaxime and ceftizoxime. SHV-2A shows altered kinetic properties for a number of other cephems that also have heterocyclic side chains at the amino position of the 7-aminocephalosporanic acid nucleus (R1 side chain), including a significantly higher kcat/Km than does SHV-1 for cephaloridine, cephalothin, and cefotiam. Two cephems with straight chain R1 substitutions, cephalosporin C and cephacetrile, are not hydrolyzed more efficiently by SHV-2A. These results indicate that the Ser-238-Gly substitution increases the affinity toward cephems with a heterocyclic ring in the R1 side chain. In addition, the data for ampicillin and benzylpenicillin show that addition of a nitrogen to the second carbon of the R1 side chain of a penem results in a lower kcat/Km for SHV-2A relative to SHV-1. These data strongly suggest that the previously proposed hydrogen bond formation between Ser-238 and the second carbon nitrogen of cefotaxime is not an important factor in hydrolysis by SHV-2A. We propose that the Gly-238 to Ser-238 replacement in SHV-2A has altered the hydrophobic pocket so that it can better accommodate cephems with bulky R1 side chains.     

Toxicity of the Alternaria metabolites alternariol, alternariol methyl ether, altenuene, and tenuazonic acid in the chicken embryo assay.

The effects in the chicken embryo assay of four Alternaria metabolites (alternariol [AOH], alternariol methyl ether [AME], altenuene [ALT], and tenuazonic acid [TA]) were investigated. Administered to 7-day-old chicken embryos by yolk sac injection, AOH, AME, and ALT caused no mortality or teratogenic effect at doses up to 1,000, 500, and 1,000 micrograms per egg, respectively. TA exhibited a calculated 50% lethal dose of 548 micrograms per egg, with no teratogenic effect observed at either lethal or sublethal doses.     

Toxicity of the Alternaria metabolites alternariol, alternariol methyl ether, altenuene, and tenuazonic acid in the chicken embryo assay

The effects in the chicken embryo assay of four Alternaria metabolites (alternariol [AOH], alternariol methyl ether [AME], altenuene [ALT], and tenuazonic acid [TA]) were investigated. Administered to 7-day-old chicken embryos by yolk sac injection, AOH, AME, and ALT caused no mortality or teratogenic effect at doses up to 1,000, 500, and 1,000 micrograms per egg, respectively. TA exhibited a calculated 50% lethal dose of 548 micrograms per egg, with no teratogenic effect observed at either lethal or sublethal doses.     

Probing voltage sensing domain of KCNQ2 channel as a potential target to combat epilepsy: a comparative study

Multidrug resistance along with side-effects of available anti-epileptic drugs and unavailability of potent and effective agents in submicromolar quantities presents the biggest therapeutic challenges in anti-epileptic drug discovery. The molecular modeling techniques allow us to identify agents with novel structures to match the continuous urge for its discovery. KCNQ2 channel represents one of the validated targets for its therapy. The present study involves identification of newer anti-epileptic agents by means of a computer-aided drug design adaptive protocol involving both structure-based virtual screening of Asinex library using homology model of KCNQ2 and 3D-QSAR based virtual screening with docking analysis, followed by dG bind and ligand efficiency calculations with ADMET studies, of which 20 hits qualified all the criterions. The best ligands of both screenings with least potential for toxicity predicted computationally were then taken for molecular dynamic simulations. All the crucial amino acid interactions were observed in hits of both screenings such as Glu130, Arg207, Arg210 and Phe137. Robustness of docking protocol was analyzed through Receiver operating characteristic (ROC) curve values 0.88 (Area under curve AUC?=?0.87) in Standard Precision and 0.84 (AUC?=?0.82) in Extra Precision modes. Novelty analysis indicates that these compounds have not been reported previously as anti-epileptic agents.     

Pharmacokinetics of pralidoxime chloride in the rat

The pharmacokinetics of pralidoxime chloride (2-PAM) was studied in rats. Different groups of rats were given an intramuscular injection of 2-PAM at one of three doses (20, 40, or 80 mg/kg). This range of doses is used commonly in studies concerned with the efficacy of 2-PAM against poisoning by potent organophosphorus inhibitors of cholinesterase enzyme. Individual, sequential blood samples were collected during the course of the experiment. From these blood samples the plasma concentrations of 2-PAM were determined over time for each animal. Next the relationship of plasma concentration to time was expressed in terms of a standard pharmacokinetic model. Estimates of various pharmacokinetic parameters were calculated using an open, one-compartment model: volume of distribution (Vd), maximal plasma concentration (Cmax), elimination rate constant (k10), absorption rate constant (k01), area under the curve (AUC) and clearance (CL). Of the pharmacokinetic estimates, only Cmax and AUC were found to be statistically significant (p less than 0.0001) when compared across all the doses; these pharmacokinetic estimates were highly correlated with doses with r = 0.998 and r = 0.997, respectively. However, when AUC and Cmax were normalized by dividing through by dose, no significant differences were found in the transformed data. The results of this study in rat indicate that the pharmacokinetics of 2-PAM is linearly related to dose in a range employed in therapeutic studies of 2-PAM.     

A rapid method for determination of in vitro susceptibility to antibiotics with a bulk acoustic wave bacterial growth biosensor

A novel bulk acoustic wave (BAW) bacterial growth biosensor was developed to study in vitro susceptibility by continuous monitoring of disturbances of bacterial growth at low antibiotic concentrations, followed by the accurate and rapid estimation of growth kinetic parameters and minimum inhibitory concentrations (MICs). The susceptibilities of bacteria, e.g. Escherichia coli, Staphylococcus aureus, Proteus vulgaris, Pr. morganii and Pr. mirabilis , to various antibiotics, e.g. penicillin, streptomycin, gentamicin and cefotaxime, were investigated, respectively, and the MICs were rapidly determined with a higher reproducibility than the conventional broth micro-dilution technique (BMDT). The effects of cell constant of conductivity electrode, pH and temperature on bacterial growth and biosensor signals were discussed in detail. The proposed method offers an effective alternative to the conventional methods.     

Effects of sex and dietary phosphorus level on the apparent metabolizable energy and nutrient digestibility in broiler chickens

The influence of sex of broilers and dietary phosphorus (P) level on energy utilization and apparent ileal digestibility of N, P and phytate-P were investigated. The AME(N) was determined using 3- and 6-week old broilers, while the apparent ileal digestibility were determined only with 6-week old birds. Sex of broilers had no effect on the AME(N) values determined during week 3. During week 6, the AME(N) values for male broilers were higher (P < 0.01) than those for the females. An interaction (P < 0.05) between sex and dietary P level was also observed. AME(N) values determined with male broilers were lower in the adequate-P diet compared to those in the low-P diet, whereas no effect of P level was observed in females. Female broilers tended (P < 0.10) to have a higher ileal N digestibility than the males, but a significant (P < 0.01) sex x P level interaction was observed. Males receiving the adequate-P diet had a lower N digestibility than those receiving the low-P diet, whereas the opposite was true in the females. Ileal phytate P degradation in males was higher than in females (0.282 vs. 0.234), but the differences were not significant. Increasing dietary P level increased ileal P digestibility in both the males and females, but the improvements were greater in the females, as indicated by a significant sex x P level interaction.     

Comparison of cefoxitin and ceftizoxime in a hospital therapeutic interchange program.

OBJECTIVE: To determine whether (a) ceftizoxime can replace cefoxitin in the prevention and treatment of various infections in a major teaching hospital, (b) a previously applied two-stage intervention program is an effective method of instituting a therapeutic interchange of ceftizoxime for cefoxitin and (c) the replacement of cefoxitin with ceftizoxime results in a more cost-effective therapy. DESIGN: Two-phase, open, sequential study. SETTING: Tertiary care teaching hospital. PATIENTS: One hundred patients who received cefoxitin during the 6 months immediately before the start of the interchange program (phase 1) and 100 who received ceftizoxime during the 6 months immediately after the start of the program (phase 2) were randomly selected. RESULTS: The demographic characteristics of the two patient groups were similar except for sex (p < 0.05). The cefoxitin doses were usually given every 6 hours (in 33% of the cases) or every 8 hours (in 61%), whereas the ceftizoxime doses were usually given every 12 hours (in 98%). Prescriber distribution was stable throughout the study period, the Department of General Surgery being responsible for about 70% of the orders. Prophylactic indications accounted for over 60% of the treatment courses. The proportion of prophylactic treatment courses that resulted in a successful clinical outcome did not differ between the two groups (cefoxitin 92% and ceftizoxime 91%). Of the empiric or directed treatment courses clinical success or improvement was observed in 89% of the cefoxitin and 91% of the ceftizoxime recipients. Microbiologic eradication was seen in 65% of the cefoxitin and 90% of the ceftizoxime directed treatment courses. Pathogens isolated during therapy were similar in the two treatment groups. Diarrhea was the most common adverse effect, occurring in 8% of the cefoxitin and 10% of the ceftizoxime recipients; no Clostridium difficile or C.-difficile-producing toxin was identified in these patients. The ceftizoxime therapy was 36% less expensive than the cefoxitin therapy on average, and the annual savings was estimated to be $83,123. An estimated 5615 drug doses were avoided annually, for an additional savings of $24,875 in drug administration. Therefore, the total estimated annual cost savings resulting from this two-stage interchange program was $107,998. Given the cost of $4856 to implement and maintain the program, the estimated net savings for the first year was $103,142. CONCLUSION: Ceftizoxime can replace cefoxitin in the prevention and treatment of various infections. The form of evaluation described herein is valuable when any formulary modification is being considered in a hospital.     

Usefulness of Time-Point Serum Cortisol and ACTH Measurements for the Adjustment of Glucocorticoid Replacement in Adrenal Insufficiency

Background

Adjustment of daily hydrocortisone dose on clinical criteria lacks sensitivity for fine tuning. Long term hydrocortisone (HC) over-replacement may lead to increased morbidity and mortality in patients with adrenal insufficiency (AI). Biochemical criteria may help detecting over- or under-replacement but have been poorly evaluated.

Methods

Multicenter, institutional, pharmacokinetic study on ACTH and cortisol plasma profiles during HC replacement in 27 AI patients compared to 29 matched controls. All AI patients were administered HC thrice daily at doses of 6, 10 and 14 mg/m²/d. Blood samples were drawn hourly from 0800h to 1900h. The main outcome measures were: i) plasma peak cortisol and cortisol area under the curve (AUC) in AI patients compared to controls, ii) correlations between cortisol AUC vs single-point cortisol or ACTH decrease from baseline (ΔACTH) and iii) the predictive value of the two latters for obtaining AI patients’ cortisol AUC in the control range.

Results

Cortisol peaks were observed 1h after each HC intake and a dose response was demonstrated for cortisol peak and cortisol AUC. The comparison of AI patients’ cortisol AUC to controls showed that 81.5% AI patients receiving 6mg/m²/d were adequately replaced, whereas most patients receiving higher doses were over-replaced. The correlation coefficient between 1000h/1400h cortisol concentrations and 0800-1900h cortisol AUC were 0.93/0.88 respectively, whereas the 0800-1200h ΔACTH fairly correlated with 0800-1900h cortisol AUC (R = 0.57). ROC curve analysis indicated that the 1000h and 1400h cortisol concentrations best predicted over-replacement.

Conclusions

Patients receiving a 6mg/m² hydrocortisone daily dose exhibited the most physiological daytime cortisol profile. Single point plasma cortisol correlated with daytime cortisol AUC in AI patients. Although hydrocortisone dose should be currently determined on clinical grounds, our data suggest that single point plasma cortisol may be an adjunct for further hydrocortisone dose adjustment in AI patients.     

Estrous cycle characteristics, luteal function, secretion of oxytocin (OT) and plasma concentrations of 15-keto-13,14-dihydro-PGF2alpha (PGF2alpha-metabolite) after administration of low doses of prostaglandin F2alpha (PGF2alpha) in pony mares

In the present study, the kinetics of the prostaglandin F2alpha (PGF2alpha)-metabolite 15-keto-13,14-dihydro-PGF2alpha after a single intramuscular application of various doses of the natural PGF2alpha dinoprost at Day 7 of the cycle in the mare were investigated. Effects of low doses on estrous cycle length and life span of corpus luteum were examined, because release of PGF2alpha is still under discussion to have detrimental influence on success rates of transcervical transfer of equine embryos. Eight Shetland pony mares were each randomly assigned to each of four treatments: (a) 0.8 mg/100 kg (group T1), (b) 0.4 mg/100 kg (group T2), (c) 0.2 mg/100 kg BM dinoprost i.m. (group T3), and (d) 1 ml physiological saline i.m. (group CO). Treatments were administered as single doses on Day 7 of the estrous cycle. Administration of dinoprost caused dose-dependent rises of plasma concentrations of PGF2alpha-metabolite, although values of individual mares showed great variation within groups. Prostaglandin treatments resulted in a distinct decrease of plasma progesterone concentrations to values between 1.6 and 7.9 ng/ml within 24 h. Treatment groups had significantly lower progesterone area under the curve (AUC: T1 942.8+/-175.9, T2 1050+/-181.2 and T3 1117+/-179.8 ng/ml/h) when compared with controls (CO 1601.9+/-227.6; t-test, P<0.05 ). There was a small, but significant negative correlation between AUC of progesterone and of PGF2alpha-metabolite ( R=-0.4; P=0.05 ). Administration of PGF2alpha caused secretion of oxytocin in three (T1, T2) and two (T3) mares out of eight ranging from 19.3 to 63.1 pg/ml. The AUC of oxytocin was positively correlated with AUC of PGF2alpha-metabolite ( R=0.4, P<0.05) and negatively correlated with AUC of progesterone ( R=-0.4, P<0.05). Administration of dinoprost yielded significantly shorter intervals from treatment to estrus and ovulation (values in parentheses), respectively, when compared with controls: T1 3.9+/-0.7 days ( 12.1+/-0.7 days), T2 4.5+/-0.6 ( 12.3+/-0.6 ), T3 4.9+/-0.5 ( 12.3+/-0.6 ), and CO 8.9+/-0.6 days ( 16.5+/-0.8 days) (t-test, P<0.01 ) (Fig. 2). Different doses of PGF2alpha caused similar effects. Data suggest that progesterone concentrations at applications influence efficacy of treatments more than doses administered, as demonstrated by their high correlation with estrous cycle patterns. It is important to note that differences we achieved are gradual and that all mares responded to treatment by luteolysis and premature estrus, regardless of doses applied.     

Effects of some drugs on human cord blood erythrocyte carbonic anhydrases I and II: an in vitro study

In the present study, we purified hcbCA I and II from human cord blood erythrocytes using by Sepharose-4B-L tyrosine-sulfanilamide affinity gel chromatography. Also, it was checked the inhibition effects of ampicillin sulfate, ceftriaxone, ceftizoxime and ranitidine on hcbCA I and hcbCA II. IC(50) values for ceftriaxone, ceftizoxime and ranitidine were found to be 27.l, 79.4 and 55.5 μM for hcbCA I and of 21.0, 79.1 and 66.1 μM for hcbCA II, respectively. According to these results, Ampicillin sulfate inhibited only hcbCAII and IC(50) values of this antibiotic was found to be 56.8 μM. All these substances were found non-competitive inhibitors. It is important to study the inhibition effects of these drugs on hcbCA I and II izoenzymes. Because, pregnant woman is take all of these substance. For this reason, these drugs should be carefully used and the dosage should be very well ordered to minimize side effects.