Luteal tissue blood flow and side effects of horse-recommended luteolytic doses of dinoprost and cloprostenol in donkeys.

This study assessed luteolysis and side effects in jennies receiving standard horse-recommended doses of cloprostenol and dinoprost. Sixteen cycles of eight jennies were randomly assigned in a sequential crossover design to receive dinoprost (5 mg, i.m.) and cloprostenol (0.25 mg, i.m.) at 5-d post-ovulation. B-mode and Doppler ultrasonography were employed to assess luteal tissue size and blood flow before (-15 min and 0h) and after (0.5, 1, 2, 3, 4, 5, 6, 7, 8, 12, 24, and 48h) administering PGF2α. Immunoreactive progesterone concentrations were assayed at similar timepoints via RIA. Side effects such as sweating, abdominal discomfort, and diarrhea were scored at 15-min-intervals for 1h after PGF2α. Data normality was assessed with the Shapiro-Wilk's test. Luteal tissue size and blood flow were analyzed using PROC-MIXED and post-hoc by Tukey. Non-parametric tests analyzed side effect variables. The luteal blood flow increased overtime by 27% at 45 min and peaked by 49% at 3 h for dinoprost, and conversely, it increased by 14% at 30 min and peaked at 39% at 5h for cloprostenol (P<0.05). Luteal blood flow was reduced by 50%, 25%, and 10% on both groups at 8, 12, and 24h (P<0.05). Immunoreactive progesterone concentrations decreased in 0.5h for dinoprost and 1h for cloprostenol and gradually decreased by 48h (P<0.05). Dinoprost induced greater sudoresis scores, while cloprostenol resulted in greater abdominal discomfort and diarrhea scores (P<0.05). In conclusion, dinoprost and cloprostenol effectively induced luteolysis with distinct side effects; this could guide practitioners' case selection to use one or another PGF2α.

Aspirin resistance mediated by oxidative stress-induced 8-Isoprostaglandin F2.

WHAT IS KNOWN AND OBJECTIVE: Aspirin resistance refers to a patient's poor response to aspirin. There are many factors that can contribute to aspirin resistance, including single-nucleotide polymorphisms, medication compliance, drug-drug interactions and inflammation. COMMENT: Recently, oxidative stress-induced 8-isoprostaglandin F2α has attracted considerable attention because it is considered as a mechanism of aspirin resistance in many diseases, including coronary artery disease, neurology system disease, metabolic syndrome, cancer, chronic obstructive pulmonary disease and chronic kidney disease. In these diseases, increased oxidative stress may promote platelet activation and reduce the efficacy of aspirin by producing excessive amounts of 8-isoprostaglandin F2α. WHAT IS NEW AND CONCLUSION: Given the wide clinical use of aspirin, it is essential to understand why some patients do not response to it. This article reviews current research on aspirin resistance mediated by oxidative stress-induced 8-isoprostaglandin F2α.

Prostaglandin F2-Alpha Eye Drops (Bimatoprost) in Graves' Orbitopathy: A Randomized Controlled Double-Masked Crossover Trial (BIMA Trial).

BACKGROUND: Previous in vitro experiments have demonstrated that prostaglandin F2-alpha (PF2α) reduced proliferation and adipogenesis in a murine cell line and human orbital fibroblasts derived from subjects with inactive Graves' orbitopathy (GO). The objective of this study was to determine if the PGF2α analogue bimatoprost is effective at reducing proptosis in this population. METHODS: A randomized controlled double-masked crossover trial was conducted in a single tertiary care academic medical center. Patients with long-standing, inactive GO but persistent proptosis (>20 mm in at least one eye) were recruited. Allowing for a 15% dropout rate, 31 patients (26 females) were randomized in order to identify a treatment effect of 2.0 mm (p = 0.05; power 0.88). Following informed consent, participants were randomized to receive bimatoprost or placebo for three months, after which they underwent a two-month washout before switching to the opposite treatment. The primary outcome was the change in exophthalmometry readings over the two three-month treatment periods. RESULTS: The mean exophthalmometer at baseline was 23.6 mm (range 20.0-30.5 mm), and the mean age of the patients was 55 years (range 28-74 years). The median duration of GO was 7.6 years (interquartile range 3.6-12.3 years). The majority were still suffering from diplopia (61.3%) with bilateral involvement (61.3%). Using multi-level modeling adjusted for baseline, period, and carry-over, bimatoprost resulted in a -0.17 mm (reduction) exophthalmometry change ([confidence interval -0.67 to +0.32]; p = 0.490). There was a mean change in intraocular pressure of -2.7 mmHg ([confidence interval -4.0 to -1.4]; p = 0.0070). One patient showed periorbital fat atrophy on treatment, which resolved on stopping treatment. Independent analysis of proptosis by photographic images (all subjects) and subgroup analysis on monocular disease (n = 12) did not show any apparent benefit. CONCLUSIONS: In inactive GO, bimatoprost treatment over a three-month period does not result in an improvement in proptosis.

[Evaluation of the Association between Topical Prostaglandin F2α Analogs and Asthma Using the JADER Database: Comparison with ß-Blockers].

　Prostaglandin F2α (PGF2α) analog formulations are the most commonly used drugs for glaucoma treatment. They are known to be superior to ß-blockers for reducing intraocular pressure and can be effective all through the day. Because of the action, topical ß-blockers are contraindicated for patients with bronchial asthma. PGF2α is also known to act as a constrictor of the respiratory tract. The present study aims to analyze the relationship between PGF2α analogs and asthma. In addition, we utilized ß-blockers and combined formulations of both contents to evaluate for comparison with PGF2α analogs. Data from Japanese adverse drug event reports (JADERs) from April 2004 to January 2016 were used for analysis. The drugs of interest were 4 PGF2α analogs, 4 ß-blockers, and 2 combined formulations of both. For quantitative signal detection, the reporting odds ratios (RORs) with Haldane-Anscombe 1/2 correction were calculated. The corrected RORs (95%CI) were detected to be 4.73 (2.30-9.75) for PGF2α analogs, 4.61 (1.82-11.7) for ß-blockers, and 28.7 (12.1-68.1) for combined formulations. Our results suggest that not only topical ß-blockers but also PGF2α analogs are associated with asthma, and the combined formulations have stronger associations with asthma than when administered alone. Therefore, further clinical research will be necessary, and careful attention should be paid to any glaucoma patient using PGF2α analogs for asthma symptoms.

Blood Pressure Elevation Associated with Topical Prostaglandin F2α Analogs: An Analysis of the Different Spontaneous Adverse Event Report Databases.

Topical prostaglandin F2α (PGF2α) analogs are widely used as the first line of therapy for glaucoma. Systemic PGF2α is suggested to increase blood pressure. Some ophthalmic formulations with ß-receptor blocking or α-receptor stimulating actions are reported to cause systemic adverse events such as a decrease in heart rate and blood pressure. The objective of this study was to evaluate the association between topical PGF2α analogs and blood pressure elevation. We analyzed the reports obtained from the Food and Drug Administration Adverse Event Reporting System (FAERS) database from the first quarter of 2004 until the end of 2015 and the Japanese Adverse Drug Event Report (JADER) database from April 2004 to January 2016 for signal detection using reporting odds ratio (ROR), a method of disproportionality analyses. Signals are considered significant if the ROR estimates and lower bound of the 95% confidence interval (CI) exceed 1. Preferred terms in the Medical Dictionary for Regulatory Activities were utilized to define blood pressure elevation. A total of 6156081 reports from the FAERS and 351226 reports from the JADER were analyzed. The significant RORs with 95% CI were calculated to be 1.82 (95% CI: 1.55-2.13) for bimatoprost, 1.69 (95% CI: 1.53-1.85) for latanoprost, and 2.17 (95% CI: 1.82-2.59) for travoprost from the FAERS. From the JADER, 5.01 (95% CI: 1.59-15.8) was calculated for bimatoprost and 8.02 (95% CI: 2.94-21.9) for tafluprost. The resulting data suggest the necessity for further clinical research on blood pressure elevation associated with topical PGF2α analogs and close monitoring.

Effect of topical isopropyl unoprostone on macular atrophy progression in eyes with exudative age-related macular degeneration.

BACKGROUND: To evaluate the efficacy and safety of topical isopropyl unoprostone (IU) in treating macular atrophy in age-related macular degeneration (AMD) patients. METHODS: Fifty-two AMD patients with macular atrophy were included and randomly assigned (1:1) to the treatment (topical 0.15% IU) or placebo group. Subjects used study eye drops 3 times a day for 54 weeks. The macular atrophy was documented on fundus autofluorescence photographs and measured using RegionFinder. The enlargement rate of macular atrophy and the changes in visual acuity were examined statistically between baseline and 54 weeks. RESULTS: Forty-eight subjects were included in the analyses because 4 subjects withdrew from the study. The differences between the IU and placebo groups in mean and median area of macular atrophy were not statistically significant at baseline. The baseline median lesion size of macular atrophy was 2.33 mm in the IU group and 1.63 mm in the placebo group (P = 0.51). The intergroup difference in the enlargement ratio of macular atrophy (21 ±â€Š15% in the IU group and 111 ±â€Š96% in the placebo group) was statistically significant (P < 0.001). Additionally, visual acuity tended to improve over baseline in the IU group. No serious adverse events were observed. CONCLUSIONS: Topical IU therapy is safe and effective for treating macular atrophy in AMD patients.

Prenatal phthalate exposure and 8-isoprostane among Mexican-American children with high prevalence of obesity.

Oxidative stress has been linked to many obesity-related conditions among children including cardiovascular disease, diabetes mellitus and hypertension. Exposure to environmental chemicals such as phthalates, ubiquitously found in humans, may also generate reactive oxygen species and subsequent oxidative stress. We examined longitudinal changes of 8-isoprostane urinary concentrations, a validated biomarker of oxidative stress, and associations with maternal prenatal urinary concentrations of phthalate metabolites for 258 children at 5, 9 and 14 years of age participating in a birth cohort residing in an agricultural area in California. Phthalates are endocrine disruptors, and in utero exposure has been also linked to altered lipid metabolism, as well as adverse birth and neurodevelopmental outcomes. We found that median creatinine-corrected 8-isoprostane concentrations remained constant across all age groups and did not differ by sex. Total cholesterol, systolic and diastolic blood pressure were positively associated with 8-isoprostane in 14-year-old children. No associations were observed between 8-isoprostane and body mass index (BMI), BMI Z-score or waist circumference at any age. Concentrations of three metabolites of high molecular weight phthalates measured at 13 weeks of gestation (monobenzyl, monocarboxyoctyl and monocarboxynonyl phthalates) were negatively associated with 8-isoprostane concentrations among 9-year olds. However, at 14 years of age, isoprostane concentrations were positively associated with two other metabolites (mono(2-ethylhexyl) and mono(2-ethyl-5-carboxypentyl) phthalates) measured in early pregnancy. Longitudinal data on 8-isoprostane in this pediatric population with a high prevalence of obesity provides new insight on certain potential cardiometabolic risks of prenatal exposure to phthalates.

Comparison of pregnancy rates in beef cattle after a fixed-time AI with once- or twice-used controlled internal drug release devices.

The use of fixed-time artificial insemination (FTAI) provides producers with numerous benefits including the use of superior genetics, shorter breeding and calving seasons, and a more uniform calf crop. However, the cost of implementing FTAI protocols is one of the several drawbacks hindering their use in the beef industry. Potential injection-site lesions from intramuscular injections of the hormones necessary for estrus synchronization are also a cause of concern for carcass quality. The objectives of this experiment were to (1) determine whether or not a twice-used controlled internal drug release (CIDR) device would be effective in an FTAI protocol without adversely affecting pregnancy rate and (2) whether or not the subcutaneous administration of PGF2α affects pregnancy rate. Nulliparous females (n = 99) between 13 and 27 months of age and multiparous cows (n = 43) between 48 and 74 months of age were synchronized for estrus using the 7-day CO-Synch + CIDR protocol. The females were randomly assigned to one of the two treatments: (1) a once-used CIDR (control) or (2) a twice-used CIDR device (treatment) incorporated into their synchronization protocol. The females were also randomly assigned to have their injection of PGF2α administered either intramuscularly or subcutaneously. Blood was taken in a random subset of nulliparous females (n = 52) just before device removal and assayed for concentration of progesterone. The concentration of progesterone was higher (P = 0.01) in the animals that received once-used CIDR devices than that in those received twice-used CIDR devices (3.4 ± 0.5 and 1.4 ± 0.5 ng/mL, respectively). There was no significant effect of parity (P = 0.82), artificial insemination technician (P = 0.60), PGF2α administration (P = 0.83), or treatment (P = 0.67) on pregnancy rates to artificial insemination which were 75.4 ± 6.0% and 71.7 ± 6.4%, for animals that received once- and twice-used CIDR devices, respectively. This study provides evidence that although concentration of progesterone is decreased in animals treated with a twice-used CIDR device, there is still a sufficient release of progesterone from the device to effectively synchronize estrus without adversely affecting the fertility of a herd.

Influence of repeated dinoprost treatment on ovarian activity in cycling dairy cows.

To study the ovarian response to the long-term effect of PGF2α, 16 cows were treated with 25 mg tromethamine dinoprost (Pronalgon F; Pfizer, Tokyo, Japan) for 21 days after natural ovulation. Five control cows were treated with sterile physiological saline. The follicle and corpus luteum (CL) development were monitored using a real-time ultrasound instrument. In addition, the plasma concentration of progesterone (P4) was determined. In nine of the 16 Pronalgon-treated cows, the first dominant follicle (1st DF), second dominant follicle (2nd DF), and third dominant follicle ovulated consecutively (group A). In five cows, the 1st and 2nd DFs ovulated consecutively (group B). The developing CL started to regress approximately 5 days after each ovulation without maturation in groups A and B. In the two remaining Pronalgon-treated cows, there was no further ovulation after natural ovulation (group C). In one cow in group C, the 1st DF became atretic and the 2nd DF became cystic with the diameter of the cystic follicle reaching 31.2 mm on Day 30. In another cow, the 1st DF became cystic with a diameter of 30.9 mm on Day 18. Although P4 began to increase after each ovulation in all of the Pronalgon-treated cows, it decreased immediately after each ovulation without a large increase, peaking at approximately 1 ng/mL. Furthermore, the number of days when P4 was >1 ng/mL from natural ovulation to Day 21 was 2.6 ± 0.7 days, which was significantly less than that in the control cows (16.0 ± 0.6 days). These results indicate that the long-term effect of PGF2α has an important role in ovulation of all dominant follicles and might induce cystic ovaries in cows.

[Pleiotropic effects in local drug treatment for glaucoma]. / Pleiotrope Effekte in der lokalen medikamentösen Glaukomtherapie.

In glaucoma treatment, beside the traditional reduction of intraocular pressure, additional therapeutic strategies have come into consideration. Therefore pleiotropic effects of medications, defined as positively acting effects independent of the main mechanism of action, represent a new research sub-field in medical therapy and play an increasingly important role in internal medicine. Using the example of local beta-blockers, alpha-2-agonists, carbonic anhydrase inhibitors and prostaglandin analogues, their pleiotropic spectra will be shown and discussed.

Evaluation of reproductive and economic outcomes of dairy heifers inseminated at induced estrus or at fixed time after a 5-day or 7-day progesterone insert-based ovulation synchronization protocol.

The objectives of the current experiment were to evaluate the reproductive performance and economic outcome of 3 synchronization strategies for first artificial insemination (AI) of dairy heifers. Holstein heifers from 2 herds (site A, California, n=415; site B, Idaho, n=425) were assigned to 1 of 3 treatments. Heifers assigned to the AI on estrus (AIE) treatment received an injection of 25mg of PGF(2α) at enrollment (d 0) and every 11 d thereafter until AI occurred. Heifers assigned to the CIDR5 treatment received a controlled internal drug release insert (CIDR) containing 1.38 g of progesterone, which was removed 5 d later concomitantly with an injection of 25mg of PGF(2α), and received fixed-time AI (TAI) concomitantly with an injection of 100 µg of GnRH 53 to 60 h later. Heifers assigned to the CIDR7 treatment received a CIDR insert, which was removed 7 d later concomitantly with an injection of 25mg of PGF(2α), and received TAI concomitantly with an injection of 100 µg of GnRH 53 to 60 h later. Heifers were observed for estrus and inseminated up to 98 and 73 d after enrollment in sites A and B, respectively. Thereafter, heifers were moved to pens with bulls and considered failure to conceive to AI if still not pregnant at the end of the observation period. Economic outcomes were based on cost of synchronization protocol (CIDR treatment=$11, PGF(2α) or GnRH treatments=$2.5/treatment, estrous detection=$0.80/heifer per day), rearing cost ($2.75/heifer per day), and economic loss if a heifer did not conceive to first AI ($150). Input cost of the reproductive programs=synchronization protocol cost + semen cost + rearing cost + replacement cost. Pregnancy per AI (P/AI) 38 ± 3 d after first AI was greatest for AIE heifers (61.1%) followed by CIDR5 (44.8%) and CIDR7 (35.7%) heifers. Furthermore, P/AI 73 ± 7 d after first AI was greatest for AIE (58.8%) and tended to be greater for CIDR5 (42%) than for CIDR7 (34.1%) heifers. The percentage of heifers that had spontaneous luteolysis from CIDR insertion to CIDR removal was reduced for CIDR5 compared with CIDR7 (13.8 vs 31.8%). Pregnancy rate was greatest for AIE heifers but did not differ between CIDR5 [adjusted hazard ratio (95% confidence interval)=0.75 (0.63, 0.90)] and CIDR7 [adjusted hazard ratio (95% confidence interval)=0.65 (0.54, 0.77)] heifers. Consequently, rearing cost and input cost of AIE heifers ($67.1 ± 4.4 and -$107.1 ± 7.0, respectively) were reduced compared with CIDR5 ($86.9 ± 5.1 and -$143.4 ± 8.1, respectively) and CIDR7 ($98.3 ± 5.1 and -$156.5 ± 8.2, respectively) heifers, but no differences were observed between CIDR5 and CIDR7 heifers.

Deepening of the upper eyelid sulcus caused by 5 types of prostaglandin analogs.

PURPOSE: Upper eyelid sulcus deepening has recently been reported as an adverse effect of prostaglandin (PG) eye drop use. However, no data are available regarding the frequency of upper eyelid sulcus deepening caused by different types of PG eye drops. We used 5 types of PG eye drops in Japanese subjects and examined the frequency of appearance of upper eyelid sulcus deepening in these subjects. PATIENTS AND METHODS: The study included 250 patients (250 eyes) diagnosed with primary open-angle glaucoma or ocular hypertension. Five healthy patients were included as controls. One eye of each patient was treated with one of the following PG eye drops for >3 months: latanoprost, travoprost, tafluprost, bimatoprost, and isopropyl unoprostone. A single-lens reflex camera was used to photograph the open eyelids. Three ophthalmologists independently judged the appearance of the deepened upper eyelid sulcus in the photographs of the 250 patients and 5 controls by comparing the right and left eyes. A subjective self-reported symptom questionnaire was also administered. RESULTS: Upper eyelid sulcus deepening was objectively (photograph) and subjectively (questionnaire) noted in 24.0% and 12.0%, 50.0% and 24.0%, 18.0% and 10.0%, 60.0% and 40.0%, and 8.0% and 10.0% of the patients in the latanoprost, travoprost, tafluprost, bimatoprost, and unoprostone groups, respectively. It occurred more frequently (objectively and subjectively) in the bimatoprost group than in the latanoprost, the tafluprost, and the unoprostone groups (P<0.001). CONCLUSION: Upper eyelid sulcus deepening frequently occurred with bimatoprost usage, and this effect should be sufficiently elucidated before starting bimatoprost treatment.

Adverse periocular reactions to five types of prostaglandin analogs.

PURPOSE: We investigated the appearance frequency of eyelid pigmentation and eyelash bristles after the use of five types of prostaglandin (PG) analogs. METHODS: This study included 250 eyes from 250 patients diagnosed with primary open-angle glaucoma or ocular hypertension who were treated with either latanoprost, travoprost, tafluprost, bimatoprost, or isopropyl unoprostone for >3 months in only one eye. Photographs of both eyes were obtained, and the images were assessed by three ophthalmologists who were masked to treatment type. The existence of eyelid pigmentation and eyelash bristles was judged, and images of the left and right eyes were compared. Subjective symptoms regarding the existence of eyelid pigmentation and eyelash bristles were investigated through a questionnaire. RESULTS: There was no significant difference between the five types of medications with regard to eyelid pigmentation (P=0.537). Use of isopropyl unoprostone resulted in a significantly lower incidence of eyelash bristles (P<0.0001). The questionnaire investigation showed that eyelid pigmentation and eyelash bristles were significantly more frequent with travoprost (42.0% and 42.0%, respectively) and bimatoprost (58.0% and 60.0%, respectively) than with other three medications (P<0.0001). CONCLUSION: The appearance frequency of eyelid pigmentation was similar among the five types of PG analogs studied, and eyelash bristles appeared less frequently with isopropyl unoprostone use. Patients are conscious of eyelash bristles; therefore, these adverse effects should be sufficiently explained to patients before PG administration.

In vitro study of antiadipogenic profile of latanoprost, travoprost, bimatoprost, and tafluprost in human orbital preadiopocytes.

PURPOSE: To investigate the effect of prostaglandin F2α (PGF2α), latanoprost, travoprost, bimatoprost, and tafluprost on human orbital preadipocyte differentiation and intracellular lipid storage, and to reveal the potential mechanisms by which topical prostaglandin analogs induce orbital fat volume reduction and cause deep superior sulcus syndrome. METHODS: Human orbital adipose precursors were treated in vitro for 24 h (day 1) with PGF2α, latanoprost, travoprost, bimatoprost, and tafluprost in their commercial formulations (1:100 dilution). Expressions of adipogenic transcription factor, peroxisome proliferator-activated receptor-gamma (PPARγ), and CCAAT-enhancer-binding protein α (C/EBPα) were determined by real-time reverse transcription-polymerase chain reaction (RT-PCR) at day 7. At 14 days, cells were stained with oil red O, intracellular lipid accumulation was evaluated by lipid absorbance, and adipocyte expression marker [Lipoprotein lipase (LPL)] was determined by real-time RT-PCR. RESULTS: Our results showed that PGF2α and topical prostaglandin analogs down-regulated the expression of PPARγ and C/EBPα, and inhibited accumulation of intra-cytoplasmic lipid droplets and expression of LPL compared with the untreated control. Comparison between the 4 drugs showed that latanoprost had the weakest antiadipogenic effect, and bimatoprost induced the most significant reduction of adipogenesis. CONCLUSION: Latanoprost, travoprost, bimatoprost, and tafluprost inhibited human preadipocyte differentiation and intracellular lipid accumulation. Morphologic and metabolic changes in orbital adipocytes caused by PGF2α analogs are a possible pathophysiologic explanation of superior eyelid deepening in patients with glaucoma.

Second trimester abortion in women with and without previous uterine scar: Eleven years experience from a developing country.

OBJECTIVES: To study the safety of second trimester abortion in women with previous uterine scar. METHODS: We screened the records of 518 women who underwent an abortion between 12 and 20 weeks' gestation at the Postgraduate Institute of Medical Education and Research, Chandigarh, India, from January 2000 to December 2010. Methods used for abortion were: (i) vaginal misoprostol with or without pre-treatment with mifepristone, and (ii) intracervical dinoprostol gel or vaginal misoprostol ± extra-amniotic saline ± oxytocin infusion. Seventeen women, aborted by means of a hysterotomy, were excluded from further analysis. RESULTS: Of the remaining 501 women, 44 had a uterine scar (Group 1) and 457 had none (Group 2). In Group 1, 40/44 (91%) and in Group 2, 452/457 (99%) women aborted successfully. The mean induction-abortion interval (IAI) was similar in the two groups (15.03 ± 10.69 hours and 12.52 ± 9.0 hours in Groups 1 and 2, respectively; p = 0.083). There were three uterine ruptures, 1/44 (2%) in group 1 and 2/457 (0.4%) in group 2 (p = 0.132, NS); all three women had received mifepristone followed by vaginal misoprostol. CONCLUSION: In women with a scarred uterus, midtrimester abortion may be successfully achieved using any of the aforementioned regimens.

The effect of intramuscular injection of dinoprost or gonadotropin-releasing hormone in dairy cows on beef quality.

Intramuscular injections of drugs and vaccines cause tissue damage and subsequent effects on tenderness and consumer acceptability of beef. In the 2007 National Market Cow and Bull Beef Quality Audit, 100% of plants reported fabricating subprimal cuts such as rib eyes and tenderloins from cow and bull carcasses. Dairy beef quality should therefore be a consideration when injections are given to dairy animals. The discussion about injection site reactions and tenderness has focused on vaccines and antimicrobial drugs with little concern for the effects of reproductive hormones. The objective of this study was to quantify antemortem the effects of semimembranosis/semitendinosis muscle injection of dinoprost and GnRH in lactating dairy cows by estimating the weight of tissue damaged and comparing that with a drug known to cause extensive tissue damage, flunixin meglumine. Tissue damage was estimated from previously reported equations for grams of muscle tissue damage based on area under the curve of serum concentrations of the muscle enzyme creatine kinase over time. Dinoprost and flunixin injection both caused a significantly increased estimate of muscle tissue damaged compared with needle only (P = 0.0351 and 0.0355, respectively). Dinoprost and flunixin caused a marginally significant increased muscle tissue damage compared with GnRH (P = 0.1394 and 0.1475, respectively). No statistically significant difference was found between the estimated weight of muscle tissue damaged by flunixin compared with dinoprost (P = 1.0000), or by saline compared with GnRH (P = 0.7736) or needle only (P = 0.4902). The assumption that reproductive hormones are less damaging than vaccines and antimicrobial drugs should be examined more closely, including postmortem evaluation of injection site lesions and effects on tenderness.

Do uterotrophic drugs increase the risk of fatal hemorrhagic brain stroke?

OBJECTIVE: To evaluate whether uterotrophic agents increase the risk of fatal hemorrhagic brain stroke. METHODS: Between 1991 and 1992, there were 230 maternal deaths among 2,420,000 pregnant women in Japan and the causes of these deaths was investigated in 1994. Using information provided in this report, we identified 35 women who died from or were assumed to die from hemorrhagic brain stroke. We assumed that 93% of women would have tried vaginal delivery. The risk of fatal hemorrhagic brain stroke after uterotrophic agent use was calculated according to the assumption that 5.0-40% of women received uterotrophic agents. RESULTS: Use of uterotrophic agents for induction/augmentation of labor was confirmed in five (14.3%) of the 35 women who died from hemorrhagic brain stroke. The incidence of fatal brain stroke after the use of uterotrophic agents was only significantly higher than that for spontaneous hemorrhagic brain stroke if these agents were administered in ≤ 6.0% of women. CONCLUSIONS: Because more than 6.0% of women received uterotrophic agents, these agents are unlikely to increase the risk of fatal hemorrhagic brain stroke.

Human health hazards of veterinary medications: information for emergency departments.

BACKGROUND: There are over 5000 approved prescription and over-the-counter medications, as well as vaccines, with labeled indications for veterinary patients. Of these, there are several products that have significant human health hazards upon accidental or intentional exposure or ingestion in humans: carfentanil, clenbuterol (Ventipulmin), ketamine, tilmicosin (Micotil), testosterone/estradiol (Component E-H and Synovex H), dinoprost (Lutalyse/Prostamate), and cloprostenol (Estromate/EstroPlan). The hazards range from mild to life-threatening in terms of severity, and include bronchospasm, central nervous system stimulation, induction of miscarriage, and sudden death. OBJECTIVE: To report medication descriptions, human toxicity information, and medical management for the emergent care of patients who may have had exposure to veterinary medications when they present to an emergency department (ED). DISCUSSION: The intended use of this article is to inform and support ED personnel, drug information centers, and poison control centers on veterinary medication hazards. CONCLUSION: There is a need for increased awareness of the potential hazards of veterinary medications within human medicine circles. Timely reporting of veterinary medication hazards and their medical management may help to prepare the human medical community to deal with such exposures or abuses when time is of the essence.

[Compare of misoprostol and dinoprost effectivity by induced second-trimester abortion]. / Srovnání efektivity misoprostolu a dinoprostu pri indukci druhotrimestrálního abortu.

OBJECTIVES: To compare the effectivity and safety of second-trimester abortion induced by two different types of prostaglandins. TYPE OF STUDY: Retrospective study. SETTING: Department of Obstetrics and Gynecology, University Hospital Ostrava and Department of Obstetrics and Gynecology, University Hospital Olomouc. METHODS: Retrospective analysis of 128 second trimester abortions induced by misoprostol and 82 second trimester abortions induced by dinoprost. Total length of abortion, failure of the method, need for instrumental revision of the uterine cavity, request for epidural analgesia and length of hospital stay were compared. RESULTS: In total 210 women were included. Misoprostol was used in 128 cases and dinoprost in 82 cases. The average gestational age was 18+1 in misoprostol group and 20+2 in dinoprost group. Ninety two percent of women with misoprostol aborted within 24 hours while in the dinoprost group it was 68%, withing 16 hours the number of completed abortions was 62% (misoprostol) versus 48% (dinoprost). The method failed in 2% of cases with misoprostol and 7% of cases with dinoprost. CONCLUSION: We conclude that induction of second-trimester abortion with the use of misoprostol is safe, quick, non-invasive and comfortable method with low frequency of complications and side effects.

[Comparison of dinoprostone (ovules and gel) to achieve cervical ripening in patients with term pregnancy that occurs with premature membranes rupture]. / Comparación de dinoprostona (óvulos y gel) en la maduración cervical en embarazo de término con rotura prematura de membranas.

BACKGROUND: Premature rupture of membranes is a normal occurrence of labor and can occur before or after the onset of contractions. The clinical factors associated with premature rupture of membranes include: low socioeconomic status, low body mass index, prior preterm pregnancies, smoking, sexually transmitted infections and urinary tract, conization, cervical cerclage and amniocentesis. OBJECTIVE: To evaluate whether prolonged release of the vaginal insert of PGE2 is superior to dinoprostone gel to achieve cervical ripening in patients with term pregnancy that occur with premature rupture of membranes. MATERIAL AND METHOD: Randomized clinical trial in the surgical unit of play in a period of 6 months, with an estimated sample of 50 patients was randomized by block table. After assessment confirming rupture of membranes, Bishop Score and meeting inclusion criteria, group A was applied PGE2 intracervical gel 0.5 mg with a maximum of 3 doses, every 6 hours. Group B was administered at vaginal insert of PGE2 single dose for 24 hours, the patient was left to sleep 30 minutes cardio toco-monitoring chart for at least 2 hours after application. RESULTS: The average time to maturity was 310.59 minutes with a standard deviation of 198.7 and concluded that there was no significant difference between the onset of uterine activity and the onset of labor among the prolonged release dinoprostone and alternatives such as the gel cervical for cervical ripening. CONCLUSIONS: Either this is a good choice to ripen the cervix in patients with term pregnancy and premature rupture of membranes.