DOCA-salt treatment enhances responses to endothelin-1 in murine corpus cavernosurn

The penis is kept in the flaccid state mainly via a tonic activity of norepinephrine and endothelins (ETs). ET-1 is important in salt-sensitive forms of hypertension. We hypothesized that cavernosal responses to ET-1 are enhanced in deoxycorticosterone acetate (DOCA)-salt mice and that blockade of ETA receptors prevents abnormal responses of the corpus cavernosum in DOCA-salt hypertension. Male C57BL/6 mice were unilaterally nephrectomized and treated for 5 weeks with both DOCA and water containing 1% NaCl and 0.2% KCl. Control mice were uninephrectomized and received tap water with no added salt. Animals received either the ETA antagonist atrasentan (5 mg.day(-1).kg(-1) body weight) or vehicle. DOCA-salt mice displayed increased systolic blood pressure (SBP), and treatment with atrasentan decreased SBP in DOCA-salt mice. Contractile responses in cavernosal strips from DOCA-salt mice were enhanced by ET-1, phenylephrine, and electrical field stimulation (EFS) of adrenergic nerves, whereas relaxations were not altered by IRL-1620 (an ETB agonist), acetylcholine, sodium nitroprusside, and EFS of nonadrenergic noncholinergic nerves. PD59089 (an ERK1/2 inhibitor), but not Y-27632 (a Rho-kinase inhibitor), abolished enhanced contractions to ET-1 in cavernosum from DOCA-salt mice. Treatment of DOCA-salt mice with atrasentan did not normalize cavernosal responses. In summary, DOCA-salt treatment in mice enhances cavernosal reactivity to contractile, but not to relaxant, stimuli, via ET-1/ETA receptor-independent mechanisms.

15d-prostaglandin J(2) inhibits inflammatory hypernociception: Involvement of peripheral opioid receptor

The 15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)) is an endogenous ligand of peroxisome proliferator-activated receptors gamma (PPAR-gamma) and is now recognized as a potent anti-inflammatory mediator. However, information regarding the influence of 15d-PGJ(2) on inflammatory pain is still unknown. In this study, we evaluated the effect of 15d-PGJ(2) upon inflammatory hypernociception and the mechanisms involved in this effect. We observed that intraplantar administration of 15d-PGJ(2) (30-300 ng/paw) inhibits the mechanical hypernociception induced by both carrageenan (100 mu g/paw) and the directly acting hypernociceptive mediator, prostaglandin E-2 (PGE(2)). Moreover, 15d-PGJ(2) [100 ng/temporomandibular joint (TMJ)] inhibits formalininduced TMJ hypernociception. On the other hand, the direct administration of 15d-PGJ(2) into the dorsal root ganglion was ineffective in blocking PGE(2)- induced hypernociception. In addition, the 15d-PGJ(2) antinociceptive effect was enhanced by the increase of macrophage population in paw tissue due to local injection of thioglycollate, suggesting the involvement of these cells on the 15d-PGJ(2)-antinociceptive effect. Moreover, the antinociceptive effect of 15d-PGJ(2) was also blocked by naloxone and by the PPAR-gamma antagonist 2-chloro-5-nitro-N-phenylbenzamide (GW9662), suggesting the involvement of peripheral opioids and PPAR-gamma receptor in the process. Similar to opioids, the 15d-PGJ(2) antinociceptive action depends on the nitric oxide/cGMP/protein kinase G (PKG)/K-ATP(+) channel pathway because it was prevented by the pretreatment with the inhibitors of nitric-oxide synthase (N-G-monomethyl-L-arginine acetate), guanylate cyclase] 1H-(1,2,4)-oxadiazolo(4,2-alpha) quinoxalin-1- one[, PKG [indolo[2,3-a]pyrrolo[3,4-c]carbazole aglycone (KT5823)], or with the ATP-sensitive potassium channel blocker glibenclamide. Taken together, these results demonstrate for the first time that 15d-PGJ(2) inhibits inflammatory hypernociception via PPAR-gamma activation. This effect seems to be dependent on endogenous opioids and local macrophages.

Ethinylestradiol and estradiol have different effects on oxidative stress and nitric oxide synthesis in human endothelial cell cultures

Study objective: To compare the effects of ethinylestradiol (EE) and 17 beta-estradiol (E(2)) on nitric oxide (NO) production and protection against oxidative stress in human endothelial cell cultures. Design: Experimental study. Settings: Research laboratory. Material: Human ECV304 endothelial cell cultures. Intervention(s): The NO synthesis was determined by flow cytometry, and oxidative stress was determined by a cell viability assay, after exposure to hydrogen peroxide (H(2)O(2)) and stimulation of endothelial cells with EE at concentrations similar to those of a contraceptive containing 30 mu g EE. Main Outcome Measure(s): The effects of EE were compared with those of E(2) at concentrations similar to those occurring during the follicular phase. Result(s): Ethinylestradiol did not increase NO synthesis and did not protect cells against oxidative stress. The viability of the cells incubated with E(2) in combination with H(2)O(2) was greater than the viability obtained with H(2)O(2) only or with H(2)O(2) in combination with EE. The cells stimulated with E(2) presented a significant increase in NO production compared with control. Conclusion(s): In contrast to the effects of E(2), EE did not protect human ECV304 endothelial cells against oxidative stress and did not increase their production of NO. (Fertil Steril (R) 2010; 94: 1578-82. (C) 2010 by American Society for Reproductive Medicine.)

Effect of low-dose combined oral contraceptive on aerobic capacity and anaerobic threshold level in active and sedentary young women

Background: The purpose of this study was to evaluate the effect of long-term use of oral contraceptives (DC) containing 0.20 mg of ethinylestradiol (EE) combined with 0.15 mg of gestodene (GEST) on the peak aerobic capacity and at the anaerobic threshold (AT) level in active and sedentary young women. Study Design: Eighty-eight women (23 +/- 2.1 years old) were divided into four groups active-OC (G1), active-NOC (G2), sedentary-OC (G3) and sedentary-NOC (G4) and were submitted to a continuous ergospirometric incremental test on a cycloergometer with 20 to 25 W min(-1) increments. Data were analyzed by two-way ANOVA with Tukey post hoc test. Level of significance was set at 5%. Results: The OC use effect for the variables relative and absolute oxygen uptake VO(2) mL kg(-1) min(-1); VO(2), L min(-1), respectively), carbon dioxide output (VCO(2), L min(-1)), ventilation (VE, L min(-1)), heart rate (HR, bpm), respiratory exchange ratio (RER) and power output (W) data, as well as the interaction between OC use and exercise effect on the peak of test and at the AT level did not differ significantly between the active groups (G1 and G2) and the sedentary groups (G3 and G4). As to the exercise effect, for all variables studied, it was noted that the active groups presented higher values for the variables VO(2), VCO(2), VE and power output (p<.05) than the sedentary groups. The RER and HR were similar (p>.05) at the peak and at the AT level between G1 vs. G3 and G2 vs. G4. Conclusions: Long-term use of OC containing EE 0.20 mg plus GEST 0.15 mg does not affect aerobic capacity at the peak and at the AT level of exercise tests. (C) 2010 Elsevier Inc. All rights reserved.

Effects of the levonorgestrel-releasing intrauterine system on cardiovascular risk markers in patients with endometriosis: a comparative study with the GnRH analogue

Background: The study was conducted to evaluate the cardiovascular risk markers associated with endometriosis and the influence of the levonorgestrel intrauterine system (LNG-TUS) compared with the GnRH analogue (GnRHa) leuprolide acetate on these risk markers after 6 months of treatment. Study Design: This was a randomized, prospective, open clinical Study, with 44 patients with laparoscopically and histologically confirmed endometriosis. Patients were randomized into two groups: the LNG-IUS group, composed of 22 patients who underwent LNG-IUS insertion., and the GnRHa group, composed of 22 patients who received a monthly GnRHa injection for 6 months. Body mass index systolic and diastolic arterial blood pressure; heart rate; and laboratory cardiovascular risk markers such as interlelikin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), C-reactive protein (CRP), homocysteine (HMC), lipid profile, total leukocytes and vascular cell adhesion molecule (VCAM) were measured before and 6 months after treatment. Results: After 6 months of treatment, a significant reduction in pain score occurred in both groups with no significant difference in improvement between the two medications evaluated. In the LNG-IUS group, from pretreatment to posttreatment period, there was a significant reduction in the levels (mean +/- SD) of VCAM (92.8 +/- 4.2 to 91.2 +/- 2.7 ng/mL, p=.04), CRP (0.38 +/- 0.30 to 0.28 +/- 0.21 mg/dL, p=.03), total cholesterol (247.0 +/- 85.0 to 180.0 +/- 31.0 mg/dL, p=.0002), triglycerides (118.0 +/- 76.0 to 86.5 +/- 41.5 mg/dL, p=.003), low-density lipoprotein cholesterol (160.5 +/- 66.0 to 114.5 +/- 25.5 mg/dL, p=.0005) and high-density lipoprotein cholesterol (63.0 +/- 20.5 to 48.5 +/- 10.5 mg/dL, p=.002). The GnRHa group showed an increase in HMC levels (11.5 +/- 2.9 to 13.0 +/- 2.7 mu mol/L, p=.04) and a reduction in IL-6 levels (4.3 +/- 3.9 to 2.3 +/- 0.8 pg/mL, p=.005), VCAM (94.0 +/- 3.8 to 92.0 +/- 1.6 ng/mL, p=.03) and total leukocytes (7330 +/- 2554 to 6350 +/- 1778, p=.01). In the GnRH group, the remaining variables, including lipid profile, did not show any statistical difference. Conclusions: This study shows that some cardiovascular risk markers are influenced by both GnRHa and the LNG-TUS, but the latter had a greater positive impact on the lipid profile, which could lead to a favorable effect during long-term treatment. (C) 2010 Elsevier Inc. All rights reserved.

Safety of the etonogestrel-releasing implant during the immediate postpartum period: a pilot study

Background: The effects of etonogestrel (ETG)-releasing contraceptive implant during the immediate postpartum period on maternal safety are unknown. Study design: Forty healthy women exclusively breastfeeding were randomized to receive either ETG-releasing implant 24-48 h after delivery (n=20) or depot medroxyprogesterone acetate (DMPA group; n=20) at the sixth week postpartum. We measured blood pressure, maternal and neonatal weight, body mass index (BMI; kg/m(2)), waist circumference (WC), complete blood count, C-reactive protein, interleukin-6, tumor necrosis factor (TNF-alpha), lipid profile, fasting serum glucose and maintenance of exclusive lactation up to the 12th week postpartum. Results: Decreases in mean maternal weight, BMI (kg/m(2)) and WC were significantly greater in the ETG-releasing implant group than in the MPA group during the first 6 weeks postpartum (-4.64 +/- 2.71 kg vs. -2.6 +/- 2.45 kg mean +/- SD, p=.017; -1.77 +/- 1.06 kg/m(2) vs. -0.97 +/- 0.95 kg/m(2), p=.026; -15.3 +/- 6.72 cm vs. -9.05 +/- 5.84 cm, p=.003, respectively). In addition, total cholesterol and HDL, were lower in DMPA users, and TNF-alpha and leukocytes were higher in DMPA users compared to in the implant group, between 6 and 12 weeks after delivery. The newborns of implant users showed a trend towards gaining more weight, as compared with the infants of the DMPA mothers during the first 6 weeks of life (implant group: +1460.50 +/- 621.34 g vs. DMPA group: +1035.0 +/- 562.43 g, p=.05). The remaining variables, including the duration of exclusive breastfeeding, were similar between the groups. Conclusion: The insertion of ETG-releasing contraceptive implant during the immediate postpartum period was not associated with deleterious maternal clinical effects or with significant maternal metabolic alterations or decreased infant weight gain. (C) 2009 Elsevier Inc. All rights reserved.

Tibolone in postmenopausal women with systemic lupus erythematosus: A pilot study

Objective: To determine the influence of the use of tibolone on the frequency of flares of systemic lupus erythematosus (SLE) in postmenopausal patients. Methods: Thirty patients with inactive or controlled SLE were included in the study. Patients were randomized to receive a 12-month course of either tibolona (2.5 mg/day) or placebo. The following were investigated: hypoestrogenism symptoms by Kupperman index, weight; anti-dsDNA antibodies; SLE flares (frequency) assessed by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI); and biochemical profile (total cholesterol, high-density lipoprotein cholesterol [HDL-C], triglycerides, complement components [C3/C4], alpha 1-acid glycoprotein, urea, creatinine, 24-h proteinuria, C-reactive protein and erythrocyte sedimentation rate). Results: The reduction in Kupperman index was greater in the patients using tibolone than in those using placebo. I-lie mean SLEDAI was not different between the groups during the study as well as SLE flare frequency (tibolone: 2/15 [13.3%] vs. placebo: 1/15 [6.7%]; p = 0.54). All cases of flares were considered mild to moderate. Although the groups were similar at the baseline evaluation, after 6 and 12 months of treatment lower values were found in the tibolone group for triglycerides (6 months: 161.6 +/- 30.9 mg/dl vs. 194.4 +/- 46.5: p = 0.04: 12 months 163.7 +/- 29.8 mg/dl vs. 204.1 +/- 49.9 mg/dl; p = 0.02: tibolone vs. placebo group, respectively) and for HDL-C (6 months: 40.7 +/- 10.7 mg/dl vs. 53.4 +/- 16.5; p = 0.02; 12 months: 47.2 +/- 7.9 mg/dl vs. 63.2 +/- 16.3 mg/dl; p < 0.01: tibolone vs. placebo group, respectively). There were no differences between the two groups in any of the remaining variables. Conclusion: In patients with inactive or stable SLE, the short-term use of tibolone did not significantly affect the frequency of flares. In addition, tibolone was well tolerated and effective to control hypoestrogenism related symptoms in SLE patients. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

Determination of Cyclophosphamide Enantiomers in Plasma by LC-MS/MS: Application to Pharmacokinetics in Breast Cancer and Lupus Nephritis Patients

This article describes the enantioseleclive analysis of cyclophosphamide (CPA) in human plasma using LC-MS/MS. CPA enantiomers were extracted from plasma using a mixture of ethyl acetate and chloroform (75:25, v/v). The enantiomers were separated on a Chiralcel(R) OD-R column, with the mobile phase consisting of a mixture of acetonitrile and water (75:25, v/v) plus 0.2% formic acid. The protonaled ions and their respective product ions were monitored using two functions, 261 > 141 for CPA enantiomers and 189 > 104 for the internal standard (antipyrine). Recovery rates were higher than 95% and the quantification limit was 2.5-ng/ml plasma for both enantiomers. The coefficients of variation and the relative errors obtained for the validation of intra- and interassay precision and accuracy were less than 10%. The method was applied for the investigation of the enantioselective pharmacokinetics of CPA in a lupus nephritis patient treated with 1 g CPA infused over 2 h and in a breast cancer patient treated with 0.9 g infused over 1 h. No stereoselectivity in the pharmacokinetic parameters was observed for either patient. Clearance values of 2.63 and 2.93 l/h and of 3.36 and 3.61 l/h for (-)-(S) and (+)-(R)-CPA were obtained for the breast cancer and lupus nephritis patient., respectively. Chirality 21:383-389, 2009. (C) 2008 Wiley-Liss, Inc.

UTERINE ULTRASONOGRAPHIC CHANGES DURING ENDOMETRIOSIS TREATMENT: A COMPARISON BETWEEN LEVONORGESTREL-RELEASING INTRAUTERINE DEVICES AND A GONADOTROPIN-RELEASING HORMONE AGONIST

We compared the effects of levonorgestrel-releasing intrauterine devices (LNG-IUD) and a gonadotropin-releasing hormone agonist (GnRHa) on uterine volume, uterine arteries pulsatility index (PI) and endometrial thickness before and after six months of endometriosis treatment. Sixty women aged 18-40 y were allocated randomly to one of two groups: LNG-IUDs were inserted in 30 women, and GnRHa monthly injections were performed on the other 30. All 60 women were submitted to transvaginal 2-D ultrasound scans on the day that the treatment started and then six months later. Measurements of uterine arteries PI, uterine volume and endometrial thickness were performed at both evaluations. The use of LNG-IUDs significantly decreased endometrial thickness (pre = 6.08 +/- 3.00 mm, post = 2.7 +/- 0.98 mm; mean +/- SD), as did the use of GnRHa (pre = 6.96 +/- 3.82 mm, post = 3.23 +/- 2.32 mm). The uterine volume decreased in the GnRHa group (pre = 86.67 +/- 28.38 cm(3), Post = 55.27 +/- 25.52 cm(3)), but not in the LNG-IUD group (pre = 75.77 +/- 20.88 cm(3), post = 75.97 +/- 26.62 cm(3)). Uterine arteries PI increased for both groups; however, the increase was higher in the GnRHa group (0.99 +/- 0.84 vs. 0.38 +/- 0.84, p = 0.007; PI increase in GnRHa and in LNG-IUD groups, respectively). In conclusion, levonorgestrel released directly onto the endometrium by the LNG-IUD induced smaller uterine changes than did the hypoestrogenism induced by GnRHa. Nevertheless, both promoted similar effects on endometrial thickness. (E-mail: wpmartins@gmail.com) (C) 2008 World Federation for Ultrasound in Medicine & Biology.

Low-dose transdermal hormone therapy does not interfere with the blood pressure of hypertensive menopausal women: a pilot study

Objectives To determine the effects of low-dose transdermal hormone therapy (HT) on systolic (SBP) and diastolic (DBP) blood pressure (BP) evaluated by 24-h ambulatory blood pressure monitoring (ABPM) in hypertensive postmenopausal women. Methods The study was conducted on 24 hypertensive postmenopausal women aged, on average, 54 years and under treatment with enalapril maleate (10-20 mg/day) combined or not with hydrochlorothiazide (25 mg/day). Thirteen women used a transdermal adhesive containing estradiol and norethisterone (25 and 125 mu g active substance/day, respectively) and 11 did not receive HT. ABPM, lipid profile, and climacteric symptoms were evaluated before and 3 and 6 months after treatment. Results After 3 and 6 months of follow-up, there was a statistically significant reduction of the Blatt-Kupperman menopausal index in the treated group (19.6 +/- 8.3 vs. 9.6 +/- 5.9 vs. 9.7 +/- 7.0; P=0.01). No significant difference in any of the ABPM variables (areas under the systolic and diastolic curves, mean SBP and DBP, SBP and DBP loads and wakefulness-sleep variation) or in the lipid profile was observed between or within groups at the three time points studied. Conclusion Low-dose transdermal HT administered for 6 months was effective in improving climacteric symptoms and did not change BP values or circadian pattern in postmenopausal women with mild-to-moderate arterial hypertension taking antihypertensive medications.

Toothache referred from auriculotemporal neuralgia: case report

P>Aim To present a 52-year-old male patient who complained of intense pain of short duration in the region of the left external ear and in the ipsilateral maxillary second molar that was relieved by blockade of the auriculotemporal nerve in the infratemporal fossa. Summary Extra- and intraoral physical examination revealed a trigger point that reproduced the symptoms upon finger pressure in the ipsilateral auriculotemporal nerve and in the outer auricular pavilion. The patient`s medical history was unremarkable. The maxillary left second molar tooth was not responsive to pulp sensitivity testing and there was no pain upon percussion or palpation of the buccal sulcus. Periapical radiographs revealed a satisfactory root filling in the maxillary left second molar. On the basis of the clinical signs and symptoms, the auriculotemporal was blocked with 0.5 mL 2% lidocaine and 0.5 mL of a suspension containing dexamethasone acetate (8 mg mL(-1)) and dexamethasone disodium sulfate (2 mg mL(-1)), with full remission of pain 6 months later. The diagnosis was auriculotemporal neuralgia. Key learning point Auriculotemporal neuralgia should be considered as a possible cause of nonodontogenic toothache and thus included in the differential diagnoses. The blockade of the auriculotemporal nerve in the infratemporal fossa is diagnostic and therapeutic. It can be achieved with a solution of lidocaine and dexamethasone.

Increased plasma levels of brain derived neurotrophic factor (BDNF) after multiple sclerosis relapse

Brain derived neurotrophic factor (BDNF) has been related to neuroprotection in a series of central nervous system diseases, although its role in multiple sclerosis (MS) was only partially investigated. In this work, we aimed to evaluate the plasma levels of BDNF from 29 MS patients and 24 control subjects. MS patients had decreased levels of BDNF in comparison with healthy controls. BDNF levels increased significantly after MS relapse. Our results provide some evidence for the involvement of BDNF in the pathogenesis of MS and suggest a role for this neurotrophin during the recovery of acute demyelinating inflammatory lesion. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

Anatomical description of arterial segments of the spleen of deer

The anatomosurgical segmentation of the arteries of the spleen was studied in 31 deer of the species Mazama gouazoubira and Blastocerus dichotomus by means of vascular injection with latex and vinyl acetate and radiographic examination. The arteria lienalis penetrated through the hilus lienis in 87% of the cases, whereas an extrahilar artery was present in the other cases. An extraparenchymal division of the lineal artery into two, three or four segmental arteries was observed in 74% of the cases. Anastomoses between intraparenchymal arterial branches were rare and of a reduced calibre.

Vaccinating the vampire bat Desmodus rotundus against rabies

The objective of this study was to extend the previous work of indirect oral rabies immunization of vampire bats (Desmodus rotundus) maintained in captivity, which demonstrated the immunogenicity of the V-RG vaccine (Vaccinia-Rabies Glycoprotein) and indicated that although the results had been encouraging, a new method for concentrating the vaccine should be tested in order to avoid vaccine loss and increase the survival proportion of bats after rabies challenge. In this study, three groups of seven bats each were tested with vaccine concentrated by ultrafiltration through a cellulose membrane. The vaccine was homogenized in Vaseline paste and applied to the back of one vector bat, which was then reintroduced into its group. A dose of 10(5.0) MICLD50 rabies virus was used by intramuscular route to challenge the bats postvaccination. The survival proportion in the three groups after the challenge was 71.4%, 71.4% and 100%. (c) 2008 Elsevier B.V. All rights reserved.

Effects of adding polyclonal antibody preparations on ruminal fermentation patterns and digestibility of cows fed different energy sources

Nine ruminally cannulated cows fed different energy sources were used to evaluate an avian-derived polyclonal antibody preparation (PAP-MV) against the specific ruminal bacteria Streptococcus bovis, Fusobacterium necrophorum, Clostridium aminophilum, Peptostreptococcus anaerobius, and Clostridium stick-landii and monensin (MON) on ruminal fermentation patterns and in vivo digestibility. The experimental design was three 3 x 3 Latin squares distinguished by the main energy source in the diet [dry-ground corn grain (CG), high-moisture corn silage (HMCS), or citrus pulp (CiPu)]. Inside each Latin square, animals received one of the feed additives per period [none (CON), MON, or PAP-MV]. Dry matter intake and ruminal fermentation variables such as pH, total short-chain fatty acids (tSCFA), which included acetate, propionate, and butyrate, as well as lactic acid and NH(3)-N concentration were analyzed in this trial. Total tract DM apparent digestibility and its fractions were estimated using chromic oxide as an external marker. Each experimental period lasted 21 d. Ruminal fluid sampling was carried out on the last day of the period at 0, 2, 4, 6, 8, 10, and 12 h after the morning meal. Ruminal pH was higher (P = 0.006) 4 h postfeeding in MON and PAP-MV groups when compared with CON. Acetate: propionate ratio was greater in PAP-MV compared with MON across sampling times. Polyclonal antibodies did not alter (P > 0.05) tSCFA, molar proportion of acetate and butyrate, or lactic acid and NH(3)-N concentration. Ruminal pH was higher (P = 0.01), 4 h postfeeding in CiPu diets compared with CG and HMCS. There was no interaction between feed additive and energy source (P > 0.05) for any of the digestibility coefficients analyzed. Starch digestibility was less (P = 0.008) in PAP-MV when compared with CON and MON. In relation to energy sources, NDF digestibility was greater (P = 0.007) in CG and CiPu vs. the HMCS diet. The digestibility of ADF was greater (P = 0.002) in CiPu diets followed by CG and HMCS. Feeding PAP-MV or monensin altered ruminal fermentation patterns and digestive function in cows; however, those changes were independent of the main energy source of the diet.