The mechanism of ginger and its processed products in the treatment of estradiol valerate coupled with oxytocin-induced dysmenorrhea in mice via regulating the TRP ion channel-mediated ERK1/2/NF-κB signaling pathway.

Ginger (Rhizoma zingiberis, RZ) has been used as a food, spice, supplement, flavoring agent, and as an edible herbal medicine. It is characterized by its pungency and aroma, and is rich in nutrients with remarkable pharmacological effects. It is used in traditional medicine clinics to treat diseases and symptoms, such as colds, headache, and primary dysmenorrhea (PD). In China, a variety of processed products of RZ are used as herbal medicines, such as baked ginger (BG) or ginger charcoal (GC) to treat different diseases and symptoms. However, the molecular mechanism of the therapeutic effect of RZ and its processed products (RZPPs, including BG or GC) against PD has not been well characterized. Moreover, whether the transient receptor potential (TRP) ion channels are involved in this process is not clear. In the present study, UHPLC-Q-TOF MS was adopted to analyse the differential quality markers (DQMs) between RZ and RZPPs. In addition, differential metabolomics (DMs) was acquired between RZ- and RZPPs-treated estradiol valerate coupled with an oxytocin-induced PD mouse uterus using untargeted metabolomics (UM). A correlation analysis between DQMs and DMs was also conducted. Benzenoids, lipids, and lipid-like molecules were the main DQMs between RZ and RZPPs. RZ and RZPPs were found to improve the pathological status of the uterus of a PD mouse, with significantly decreased serum levels of E2, PGF2α, TXB2 and remarkably increased levels of PROG and 6-keto-PGF1α. Moreover, RZ and RZPPs alleviated PD in mice via regulating the TRP ion channel-mediated ERK1/2/NF-κB signaling pathway. Our results indicate that the therapeutic effect of RZ and RZPPs against PD may be mediated by regulating the TRP ion channel-mediated ERK1/2/NF-κB signaling pathway, and provide a reference for the development of new dietary supplements or medicines.

[Anti-inflammatory and hemostatic effects of total extract, saponins, and flavonoids of Clinopodium chinense in female rats with abnormal uterine bleeding and mechanism].

This study aims to explore the anti-inflammatory and hemostatic effects of the total extract of Clinopodium chinense(TEC), total saponins of C. chinense(TSC), and total flavonoids of C. chinense(TFC) in female rats with abnormal uterine bleeding(AUB), and the possible mechanism. Mifepristone(i.g., 12.4 mg·kg~(-1)) and misoprostol(i.g., 130 µg·kg~(-1)) were used to induce AUB in SD female rats conceiving on the same day. Then the AUB rats were randomized into model group, TEC group, TSC group, TFC group, Yimucao Granules(LG) group, and estradiol valerate(EV) group, with 8 rats in each group. Another 8 non-pregnant female rats were selected as normal group. During the experiment, each group was given the corresponding drug by gavage once a day for 7 days. After the administration, blood and uterine tissue were collected. The uterine bleeding volume was measured by ultraviolet spectrophotometry and the pathological changes of endometrium were observed based on hematoxylin-eosin(HE) staining. In addition, the microvessel density of endometrium was determined by immunohistochemistry, and the content of thromboxane B2(TXB2), 6-keto-PGF_(1α), interleukin-6(IL-6), and tumor necrosis factor-α(TNF-α) in plasma and levels of lutenizing hormone(LH), follicle stimulating hormone(FSH), estradiol(E_2), and progesterone in serum were detected by enzyme-linked immunosorbent assay(ELISA). The mRNA and protein expression of estrogenreceptor α(ERα), progesterone receptor(PR), matrix metalloproteinase(MMP)-2, MMP-9, and vascular endothelial growth factor(VEGF) in uterine tissue was determined by Western blot. Compared with the model group, TEC, TSC, and TFC can reduce uterine bleeding volume, alleviate the pathological damage of endometrium, and increase the microvessel density in endometrium. Moreover, TEC and TSC can significantly raise plasma TXB2 level and ratio of TXB2 to 6-keto-PGF_(1α), and TEC and TFC can significantly reduce the levels of IL-6 and TNF-α. In addition, TEC significantly elevated serum progesterone level and TFC significantly increased serum levels of E_2, FSH, and LH. TSC can significantly raise serum progesterone and FSH levels. In addition, TEC can significantly down-regulate the protein expression of PR, MMP-2, and VEGF and TSC significantly reduced the expression of MMP-9. TFC significantly decreased the expression of PR, MMP-9, and VEGF, and up-regulated the expression of ERα. In conclusion, TEC, TSC, and TFC all show therapeutic effects on AUB, particularly TEC. TSC exerts the effects by enhancing the coagulation function and promoting endometrial repair, and TFC by regulating estrogen levels and reducing inflammatory response. This study reveals the mechanism of C. chinense against AUB and also explains the holistic characteristics of Chinese medicine.

Effects of 0.0015% preservative-free tafluprost on the equine eye.

OBJECTIVE: The purpose of this study was to determine the effects and potential side effects of topical preservative-free (PF) tafluprost 0.0015% in ophthalmologically normal horses. ANIMALS: Five adult grade horses. PROCEDURES: One of the eyes of each horse was randomly chosen as the "treatment" eye, and consequently, the contralateral eye served as the "control." A single dose of PF tafluprost 0.0015% (0.2 mL) was instilled in the treated eye of each horse. Intraocular pressure (IOP), Schirmer's tear test (STT) levels of each eye, and an ophthalmic examination were performed at T0 (baseline), T30, T120, T24 h, and T48 h. RESULTS: The mean IOP values of the treated eyes at baseline (T0), T30, T120, T24 h, and T48 h were 25.4 ± 4.8 mmHg, 21.2 ± 1.92 mmHg, 15.20 ± 2.48 mmHg, 18.40 ± 1.51 mmHg, and 24.60 ± 1.94 mmHg, respectively. Significant differences were observed between the mean baseline IOP level and the T120 and T24 h time points (p = .001 and p = .009). The mean STT levels at each time point showed insignificant fluctuations during the study (p = .140). Adverse effects such as chemosis and episcleral injection were observed 30 min after the instillation of tafluprost 0.0015% (T30). Blepharospasm and conjunctival hyperemia were observed 120 min (T120) after the administration of the medication. CONCLUSION AND CLINICAL RELEVANCE: Tafluprost 0.0015% showed potential in reducing IOP, but due to its local side effects, it is not a good candidate for management of glaucoma in horses. Tafluprost did not notably affect STT.

Progesterone-responsive vaginal leiomyoma and hyperprogesteronemia due to ovarian luteoma in an older bitch.

BACKGROUND: This is the first report about a vaginal leiomyoma concomitant with an ovarian luteoma in a bitch. CASE PRESENTATION: A 11-year-old intact female Labrador retriever was referred because of anuria, constipation and protrusion of a vaginal mass through the vulvar commissure. The bitch had high serum progesterone concentration (4.94 ng/ml). Because of the possibility of progesterone responsiveness causing further increase of the vaginal mass and since the bitch was a poor surgical candidate a 10 mg/kg aglepristone treatment was started SC on referral day 1. A computerized tomography showed a 12.7 × 6.5 × 8.3 cm mass causing urethral and rectal compression, ureteral dilation and hydronephrosis. A vaginal leiomyoma was diagnosed on histology. As serum progesterone concentration kept increasing despite aglepristone treatment, a 0.02 ng/mL twice daily IM alfaprostol treatment was started on day 18. As neither treatment showed remission of clinical signs or luteolysis, ovariohysterectomy was performed on referral day 35. Multiple corpora lutea were found on both ovaries. On histology a luteoma was diagnosed on the left ovary. P4 levels were undetectable 7 days after surgery. Recovery was uneventful and 12 weeks after surgery tomography showed a reduction of 86.7% of the vaginal mass. The bitch has been in good health and able to urinate without any complication ever since. CONCLUSIONS: This case demonstrates the importance of identifying progesterone related conditions as well as the importance of judiciously using a combined medical and surgical approach.

Effectiveness of Blepharoptosis Surgery in Patients With Deepening of the Upper Eyelid Sulcus.

The purpose of this retrospective study was to evaluate the effectiveness of blepharoptosis surgery in patients with deepening of the upper eyelid sulcus (DUES). This case series included 10 consecutive patients (19 eyes) with DUES associated with use of a prostaglandin analog for glaucoma. Patients who had used bimatoprost and developed DUES were changed to an alternative prostaglandin analog and observed for ≥3 months. If there was no improvement, they underwent levator resection for blepharoptosis and were followed up for ≥6 months postoperatively. Improvement in margin reflex distance-1 and surgical complications was evaluated. After discontinuation of bimatoprost in 3 cases (6 eyes), mild subjective and objective improvement in DUES was seen in 2 cases (4 eyes) but without improvement in blepharoptosis. The prostaglandin analog used before surgery was travoprost in 4 eyes (21.0%), tafluprost in 7 eyes (36.9%; including 4 eyes switched from bimatoprost), and latanoprost in 8 eyes (42.1%; including 2 eyes switched from bimatoprost). The mean margin reflex distance-1 value was 1.11 ±â€Š0.96 mm before surgery and 3.72 ±â€Š0.81 mm at the final postoperative follow-up; the difference was significant (P = 3.32 × -10). There were no intraoperative or postoperative complications. Levator resection is a useful and safe procedure for blepharoptosis with DUES.

Circulating progesterone dynamics after intravaginal instillation of prostaglandin-F2α to lactating dairy cows.

Our objectives were to evaluate circulating progesterone (P4) concentration dynamics and test the feasibility of inducing luteal regression after intravaginal (IVG) instillation of the PGF2α analogue dinoprost (PGF) in lactating dairy cows. In two experiments, cows were synchronized using the Ovsynch protocol to induce the formation of a corpus luteum (CL). Cows with at least one functional (P4 ≥1 ng/mL) CL ≥15 mm 7.5 days after Ovsynch remained in the studies. In experiment 1, cows (n = 31) were stratified by parity group and received 5 mL of saline IVG (SAL-IVG, n = 6), 25 mg of PGF intramuscular (IM) (PGF25-IM, n = 7), 25 mg of PGF IVG (PGF25-IVG, n = 6), 50 mg of PGF IVG (PGF50-IVG, n = 6), and 125 mg of PGF IVG (PGF125-IVG, n = 6). Experiment 2 was conducted to test the hypothesis that IVG instillation of two 25 mg doses of PGF 12 hours apart would be more effective than a 25- or 50-mg dose in a single application. Cows (n = 32) were stratified by parity and received SAL-IVG (n = 7), PGF25-IM (n = 7), PGF25-IVG (n = 6), and PGF50-IVG (n = 6) as in experiment 1, whereas another group received two IVG instillations of 25 mg of PGF 12 hours apart (PGF25-2X-IVG, n = 6). Blood was collected at -1 hour, every 6 hours from 0 hour to 24 hours, and every 12 hours up to 96 hours after treatment (trt). In experiment 1, there was an effect of trt (P < 0.01), time (P < 0.001), and an interaction between trt and time on P4 concentrations (P < 0.001). All PGF-treated groups had lower (P < 0.05) concentrations of P4 than cows in the SAL-IVG group from 12 to 96 hours after trt. Although an initial decline in P4 concentrations was induced in all PGF-treated cows, some cows in the IVG-treated groups presented a rebound in plasma P4, indicating CL recovery. More cows in the PGF25-IVG and PGF125-IVG groups than in the PGF50-IVG and PGF25-IM groups presented CL recovery, suggesting that greater doses of PGF may not necessarily improve CL regression. In experiment 2, there was an effect of trt (P < 0.001), time (P < 0.001), and an interaction between trt and time on P4 concentrations (P < 0.001). All PGF-treated groups had lower (P < 0.05) P4 than the SAL-IVG group from 12 to 96 hours after trt. Cows in the PGF25-2X-IVG group had a P4 profile that was similar to that of cows in the PGF25-IM group and the lowest P4 concentrations after treatment among the IVG-treated groups, and all cows presented complete CL regression (defined as P4 <0.4 ng/mL). We conclude that CL regression can be induced through IVG instillation of PGF in lactating dairy cows and that instillation of two IVG doses of 25 mg of PGF 12 hours apart was the most effective strategy.

Urrets- Zavalia Syndrome after glaucoma filtration device implantation.

We report a case of Urrets-Zavalia Syndrome after a glaucoma filtration device (g.f.d.) implantation. A 74-year-old woman with bilateral advanced glaucoma has been planned for surgery. The patient underwent to g.f.d. implantation in the right eye. On postoperative day 1, the patient had an edematous cornea with a dilated and non reactive pupil. In this article we describe the clinical history of this patient. To our knowledge, this is the first case of Urrets-Zavalia Syndrome after a g.f.d. implantation.

New drug update: 2012.

Five new drugs that are used for medical problems often experienced by the elderly have been selected for consideration in this review. The uses and most important properties of these agents are considered, and a rating for each new drug is determined. The rating is based on a comparison of the new drug with related drugs already marketed. Advantages, disadvantages, and other important information regarding the new drug are identified and used as the basis for determining the rating.

New fluoroprostaglandin F(2alpha) derivatives with prostanoid FP-receptor agonistic activity as potent ocular-hypotensive agents.

To find new prostanoid FP-receptor agonists possessing potent ocular-hypotensive effects with minimal side effects, we evaluated the agonistic activities of newly synthesized prostaglandin F(2alpha) derivatives for the prostanoid FP-receptor both in vitro and in vivo. The iris constrictions induced by the derivatives and their effects on melanin content were examined using cat isolated iris sphincters and cultured B16 melanoma cells, respectively. The effects of derivative ester forms on miosis and intraocular pressure (IOP) were evaluated in cats and cynomolgus monkeys, respectively. Of these derivatives, 6 out of 12 compounds were more potent iris constrictors, with EC(50) values of 0.6 to 9.4 nM, than a carboxylic acid of latanoprost (EC(50)=13.6 nM). A carboxylic acid of latanoprost (100 microM) significantly increased the melanin content of cultured B16 melanoma cells, but some 15,15-difluoro derivatives, such as AFP-157 and AFP-172, did not. Topically applied AFP-168, AFP-169 and AFP-175 (isopropyl ester, methyl ester and ethyl ester forms, respectively, of AFP-172) induced miosis in cats more potently than latanoprost. AFP-168 (0.0005%) reduced IOP to the same extent as 0.005% latanoprost (for at least 8 h). These findings indicate that 15,15-difluoroprostaglandin F(2alpha) derivatives, especially AFP-168, have more potent prostanoid FP-receptor agonistic activities than latanoprost. Hence, AFP-168 may be worthy of further evaluation as an ocular-hypotensive agent.

An ultrasonographic study of bovine cystic ovarian disease and its treatment.

This study assessed the value of ultrasonography in characterising bovine cystic ovaries and monitoring their responses to different treatments. Thirteen cows were diagnosed by ultrasonography as having luteinised ovarian cysts and seven were diagnosed as having follicular ovarian cysts. Six of the former were treated with prostaglandin, four with a progesterone intravaginal device (PRID) and three with gonadotrophin-releasing hormone (Gn-RH); five of the latter were treated with Gn-RH and two with a PRID. All the animals were re-examined by ultrasound and blood was collected for the measurement of plasma progesterone concentration at intervals until oestrus. The treatment of the luteinised cysts with prostaglandin caused marked decreases in size and plasma progesterone concentration and altered their echotexture within two to four days; oestrus occurred within three to four days. In two of the cows treated with a PRID the cysts regressed within one to two weeks but the other two cows required supplementary treatment with prostaglandin; oestrus and ovulation were observed only after the cysts collapsed. Gn-RH stimulated oestrus and ovulation within three to four days but the cysts did not collapse until much later. The treatment of the follicular cysts with Gn-RH or a PRID caused fresh ovulation and the formation of a corpus luteum but had little immediate effect upon the cyst. The plasma progesterone concentrations in some of the cows with either follicular or luteal cysts were similar on the day of treatment and were therefore of little value in differentiating the types of cyst.(ABSTRACT TRUNCATED AT 250 WORDS)

Prostaglandina F2 alfa comparada con placebo en reflujo gastroensofágico: evaluación clínica y manométrica / Prostaglandin F2 alpha compared with placebo in gastroesophageal reflux: clinical and manometric assesment

Los factores que controlan la competencia de la unión gastroesofágica, han sido estudiados cuidadosamente en la última década. Aunque no se ha identificado la presencia anatómica de un enfínter gastroesofágico inferior en el hombre, existe una zona manométricamente definida de alta presión en el esófago distal. La magnitud de la presión de este esfínter, tiene una buena correlación con la incidencia de reflujo gastroesofágico patológico. Las acciones de prostaglandina F2 alfa sobre la contracción de la musculatura lisa son bien conocidas. Más importantes, sin embargo son las pocas publicaciones que enfocan la acción de prostaglandina F2 alfa sobre la contracción del esfínter esofágico inferior. Hemos desarrollado este trabajo, para investigar los efectos de esta sustancia sobre síntomas y los cambios en la manometría esofágica, en dos grupos de pacientes, que ingresan a un estudio aleatorio y dobre ciego con prostaglandina F2 alfa o placebo. La ingestión oral de prostaglandina F2 alfa, no muestra ningún cambio en la presión del esfínter esofágico inferior en comparación con el placebo. Los hallazgos clínicos, sin embargo sugieren que esta sustancia podría ser un agente útil en el alivio sintomático de esta patología. El mecanismo responsable de esta acción es desconocido. Sugerimos que puediera estar involucrada una acción citoprotectora, pero se requiere mayor investigación para dilucidarlo

[Radiomodifying properties of the synthetic analog of prostaglandin F2 alpha-estrofan]. / Radiomodifitsiruiushchie svoistva sinteticheskogo analoga prostaglandina F2 al'fa-éstrofana.

Estrofan (0.1 to 5 mg/kg) administered to rats and mice 5 min prior to gamma irradiation with doses of 8.5 to 9.5 Gy (LD90/30) increases the survival rate up to 30-40 per cent. The drug is ineffective when administered 30 and 60 min before irradiation.

[Stress reactions in clinically healthy sows at the time of birth and their relationship to the CK test]. / Belastungsreaktionen bei klinisch gesunden Sauen zur Zeit der Geburt und ihre Beziehung zum CK-Test.

Concentrations of the enzymes creatine kinase (CK) and aspartate aminotransferase (ASAT/GOT) were determined in plasma of 100 gilts and 175 sows at the 112. day of pregnancy and one day after parturition. Gilts and sows were divided into a stress resistant (n = 146) and a stress susceptible group (n = 129) following the creatine-kinase-test carried out after the performance test period at a body weight of 90 kg (CK-90). Stress susceptible gilts and sows showed higher CK-values before and especially after parturition than stress resistant ones. Significant correlations were demonstrable between CK-90 and the CK values before and after parturition (r = 0.5). Regarding body temperature, respiration rate and heart frequency as well as the percentage of stillborn piglets, the two groups of sows did not differ from each other. The increase of enzyme activities after parturition was not influenced by prophylactic treatment with prostaglandin-F2-alpha or beta receptor blocking agent. The beta blocking agent Carazolol, however, caused a transient depression of heart rate after parturition.

Intravesical prostaglandin F2 for promoting bladder emptying after surgery for female stress incontinence.

Prostaglandin F2 alpha 10 mg was administered intravesically in a double-blind placebo-controlled study to promote micturition in cases of urinary retention after operative treatment of urinary stress incontinence in women. Fifteen of 18 patients (83%) succeeded in voiding after treatment with prostaglandin F2 alpha, but the placebo was ineffective in all 18 patients (P less than 0.001). Although the effect of prostaglandin F2 alpha on bladder muscle contraction was short-lived, it seemed to enhance the restoration of bladder motor function with no serious side effects, and thus to be clinically useful in the treatment of post-operative urinary retention.

Prostaglandin F2-alpha bladder irrigation for control of intractable cyclophosphamide-induced hemorrhagic cystitis.

We report a case of intractable cyclophosphamide-induced hemorrhagic cystitis. Conservative therapy, including suprapubic cystostomy with through-and-through bladder irrigation, failed to slow the bleeding. We then instilled 200 cc of a 0.7 mg. per cent solution of prostaglandin F2-alpha into the bladder for 4 hours daily. The bleeding ceased completely by the end of treatment 5 and the patient remains free of hematuria. There were no side effects noted during the 5 days of treatment. This form of therapy offers an effective, safe and easy alternative to more caustic bladder irrigants and methods of treatment.

Hormone therapy for control of reproduction in mares and stallions.

Because the reproductive performance of mares is lower than that of any other domesticated species, hormone therapy is important in ensuring fertility and proper management of pregnancy. Current techniques of hormone therapy are discussed.

The characteristic pattern of aspartate aminotransferase and alanine aminotransferase in the bitch with the cystic hyperplasia-pyometra complex: effect of medical or surgical treatment.

In 75 clinically normal unspayed female control dogs between two and eleven years old the average plasma level of aspartate aminotransferase (AST) was 21.6 +/- 5.7 (+/- SD) IU/l, of alanine aminotransferase (ALT) 40.4 +/- 13.0 IU/l and of the AST/ALT ratio 0.6 +/- 0.2. These values showed only minor changes over years. In 96 bitches with the cystic hyperplasia-pyometra complex there was a very significant increase of the AST, decrease of the ALT and increase of the AST/ALT ratio. The changes were more pronounced in 62 clinically ill bitches with typical endometritis post oestrum, in 18 dogs with gram negative organisms in the uterus and in 53 bitches with white blood cell (WBC) levels higher than 40 X 10(9)/1. Renal failure had no influence on the specific changed values. The changed values returned either temporarily to normal after prostaglandin (PGF2 alpha)-treatment or definitely after ovariohysterectomy.

Carbohydrate metabolism and the temporal occurrence of a serotonin-like indole in the male and female reproductive tract and its relationship with PGF and infertility: a review.

Both in the male and in the female reproductive tract glucose can be converted via either the pentose pathway or the sorbitol pathway. It is shown that a disturbed carbohydrate metabolism can lead to infertility, i.e. in the cow and in the bull semen. Evidence is provided that the serotonin-like indole which occurs in the protein-complex and is liberated, can exert effects on the uterine endometrium comparable to those caused by serotonin. It is suggested that the indole liberated can cause ischaemia, followed by regression of the endometrium. When this occurs in repeat breeder cows, exogenous PGF given in mid-cycle on a suitable day, may restore the endometrium so that the cow can again become pregnant. The possibility is mentioned that in humans the free indole might cause regression of the endometrium and some distress symptoms, but thereafter endogenous PGF does increase the vascular permeability resulting finally in bleeding.

Non-fertility in cows: treatment with PGF and investigation of uterine biopsies.

Experiments with seventeen 'repeat breeders' confirmed that the carbohydrate composition, the hormonal pattern, the cholesterol content and the occurrence of indole metabolites, such as blue fluorescing protein, in cervical mucus can be used as parameters for the fertilizing capacity of these cows. After careful rectal examination 25 mg PGF2 alpha was administered to thirteen 'repeat breeders' on that day of the luteal phase when next to the corpus luteum no follicle was palpable; ten of them became pregnant or were fertilized. Uterine biopsies were taken from eight 'normal' cows and from eight 'repeat breeders', simultaneously with cervical mucus samples. The biochemical composition of the biopsies was comparable to that of the mucus samples. The taking of two biopsies produced injurious consequences for the animals, perceptible in oestrous behaviour. Investigation of cervical mucus samples is therefore preferred to uterine biopsies for the examination of sterility in cows.