Importance of Animals in Agricultural Sustainability and Food Security.

A conservative projection shows the world's population growing by 32% (to 9.5 billion) by 2050 and 53% (to 11 billion) by 2100 compared with its current level of 7.2 billion. Because most arable land worldwide is already in use, and water and energy also are limiting, increased production of food will require a substantial increase in efficiency. In this article, we highlight the importance of animals to achieving food security in terms of their valuable contributions to agricultural sustainability, especially in developing countries, and the high nutritional value of animal products in the diet.

Duloxetine versus placebo for the treatment of women with stress predominant urinary incontinence in Taiwan: a double-blind, randomized, placebo-controlled trial.

BACKGROUND: This manuscript compares the efficacy and safety of duloxetine with placebo in Taiwanese women with SUI. METHODS: Taiwanese women with SUI were were randomly assigned to placebo (n = 61) or duloxetine 80 mg/day (n = 60) in this double-blind, 8-week, placebo-controlled study. Outcome variables included: incontinence episode frequency (IEF), Incontinence Quality of Life questionnaire (I-QOL) scores, and Patient Global Impression of Improvement rating (PGI-I). RESULTS: Decrease in IEF was significantly greater in duloxetine-treated than placebo-treated women (69.98% vs 42.56%, P < .001). No treatment differences in I-QOL scores were significant. There were significant differences in PGI-I rating. Treatment-emergent adverse events (TEAEs) were experienced by more duloxetine-treated than placebo-treated women (80.0% vs 44.3%; P < .001). Discontinuations due to adverse events were significantly greater for duloxetine-treated than placebo-treated women (26.7% vs 6.6%; P = .003). CONCLUSION: Data provide evidence for the safety and efficacy of duloxetine for the treatment for Taiwanese women with SUI. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00475358.

A retrospective pooled analysis of duloxetine safety in 23,983 subjects.

OBJECTIVE: The safety and tolerability of duloxetine for major depressive disorder (MDD), generalized anxiety disorder (GAD), diabetic peripheral neuropathic pain (DPNP), fibromyalgia, and lower urinary tract disorders (LUTD) (including female stress urinary incontinence [SUI] and other LUTDs) has been established in individual clinical studies. The objective of this manuscript is to characterize the overall safety profile of duloxetine, regardless of indication, based on data from the duloxetine exposures integrated safety database. RESEARCH DESIGN AND METHODS: The duloxetine exposures integrated safety database was examined using pooled data from 23,983 patients randomized to receive duloxetine in 64 studies for MDD, GAD, DPNP, fibromyalgia, or LUTDs. Evaluated aspects of drug safety included treatment-emergent adverse events (TEAEs), adverse events leading to discontinuation, serious adverse events (SAEs), clinical laboratory tests, vital signs, and electrocardiograms. RESULTS: Common TEAEs included nausea, headache, dry mouth, insomnia, constipation, dizziness, fatigue, somnolence, diarrhea, and hyperhidrosis. Most TEAEs emerged early; the majority were mild to moderate in severity, and did not worsen. Overall, discontinuation rates due to AEs were 20.0%. SAEs occurred at a rate of 3.5% and no single event was predominant. Mean pulse increased by < 2 beats per minute. Mean increases in systolic and diastolic blood pressure were < 1 mmHg. Mean alanine transaminase and aspartate transaminase values increased by < 2 U/L. CONCLUSIONS: The safety profile for the molecule from the overall duloxetine exposures integrated safety database suggests that benign and common pharmacologic side effects occur with duloxetine treatment. Because these pooled analyses do not allow for statistical comparison to placebo or active comparator, and include data from five different studied indications, these data do not suggest causality for AEs, nor are they necessarily generalizable to each disease stated studied.

Prostaglandin F2alpha upregulates uterine immune defenses in the presence of the immunosuppressive steroid progesterone.

PROBLEM: Uterine infections often develop in some livestock species during the first luteal phase postpartum. Exogenous prostaglandin F(2alpha) (PGF(2alpha)) induces luteolysis, reduces progesterone, and enables the uterus to resolve infections. However, the effects of PGF(2alpha) on luteal function and on immune functions are confounded. These effects must be disentangled to determine whether alternatives to antibiotic treatments can be successfully developed. METHOD OF STUDY: Treatments were in a 2 x 2 x 2 factorial arrangement. Main effects were ovariectomy or sham on day 0 (i.e. estrus), exogenous progesterone or sesame oil from day 0 to 11, and exogenous PGF(2alpha) or saline on day 9. Intrauterine inoculations with Arcanobacterium pyogenes and Escherichia coli were administered on day 6. RESULTS: Ewes treated with exogenous PGF(2alpha) either did not have uterine infections, infections were less severe, or infections were resolving when uteri were examined on day 12, despite increased progesterone. CONCLUSIONS: Exogenous PGF(2alpha) has effects on the resolution of uterine infections that are independent of its effects on luteal progesterone production.

Safety and adverse event profile of duloxetine.

Duloxetine is the first relatively balanced serotonin and noradrenaline re-uptake inhibitor to be widely available for three indications including: major depressive disorder, peripheral diabetic neuropathic pain and female stress urinary incontinence, although it is not currently approved for all indications in all countries. Generally, duloxetine is safe and well-tolerated across indications, with few reported serious side effects. Common adverse events are consistent with the pharmacology of the molecule and are mainly referable to the gastrointestinal and the nervous systems. The studied dose range is up to 400 mg/day (administered 200 mg b.i.d) but the maximum dose approved for marketing is 120 mg/day (administered 60 mg b.i.d). Duloxetine is eliminated (half-life = 12.1 hours) primarily in the urine after extensive hepatic metabolism by multiple oxidative pathways, methylation and conjugation. Duloxetine would not be expected to cause clinically significant inhibition of the metabolic clearance of drugs metabolised by P450 (CYP)3A, (CYP)1A2, (CYP)2C9, or (CYP)2C19, but would be expected to cause some inhibition of CYP 2D6. Duloxetine should not be used in combination CYP 1A2 inhibitors or nonselective, irreversible monoamine oxidase inhibitors. The purpose of this review is to provide an overview of some of the most important information related to safety and tolerability of duloxetine.

Uterine response to multiple inoculations with Arcanobacterium pyogenes and Escherichia coli in nulliparous ewes.

PROBLEM: Uterine infections seem more severe in nulliparous animals. Our objective was to determine whether intrauterine inoculation of nulliparous ewes with Arcanobacterium pyogenes and Escherichia coli would produce an antibody response and reduce the severity of subsequent infections. METHOD OF STUDY: Nulliparous ewes (n = 9/treatment) received (i) 'primary intrauterine inoculation' with phosphate-buffered saline (PBS) and 'secondary intrauterine inoculation' with PBS; (ii) primary PBS-secondary 75 x 10(7) cfu of A. pyogenes and 35 x 10(7) cfu of E. coli (PBS-Bacteria); (iii) primary bacteria-secondary PBS; or (iv) primary bacteria-secondary bacteria (Bacteria-Bacteria). RESULTS: Inoculations evoked an antibody response. Postmortem examinations 6 days after the secondary inoculation indicated that PBS-treated ewes did not develop uterine infections, but all bacteria-treated ewes did. Infections were either less severe or closer to resolution in Bacteria-Bacteria than they were in PBS-Bacteria ewes. CONCLUSIONS: Intrauterine inoculation of nulliparous ewes with A. pyogenes and E. coli evokes an antibody response that may help the uterus reduce the severity of subsequent infections.

Stress urinary incontinence in women: diagnosis and medical management.

Stress urinary incontinence (SUI) is the most common form of urinary incontinence in women and is associated with high financial, social, and emotional costs. The history and physical examination can identify most patients with a significant stress incontinence component without the need for urodynamic testing. A variety of pharmacologic agents have been used off-label, but an evidence-based pharmacologic treatment has not been readily available. The development of a selective serotonin and norepinephrine reuptake inhibitor will add a potentially useful drug to the primary care physician's practice for treating female patients with SUI. In August 2004, a selective serotonin and norepinephrine reuptake inhibitor, duloxetine, became the first medication approved for the treatment of women with moderate to severe SUI throughout the European Union. As of November 2005, however, duloxetine has not been approved for the treatment of SUI in the United States.

A hemoglobin based oxygen carrier, bovine polymerized hemoglobin (HBOC-201) versus Hetastarch (HEX) in an uncontrolled liver injury hemorrhagic shock swine model with delayed evacuation.

BACKGROUND: As HBOC-201 improves outcome in animals with hemorrhagic shock (HS), we compared HBOC-201 and HEX (used by U.S. military special operations forces) in a swine model of delayed evacuation and uncontrolled HS. METHODS: Twenty-four Yucatan pigs underwent a grade III liver injury and were resuscitated with HBOC-201, HEX, or no fluid (NON). Additional infusions were given for hypotension or tachycardia. After 4 hours, the liver was repaired; IV fluids and blood transfusions were administered. Pigs were monitored for 72 hours. RESULTS: Survival was 7/8, 1/8, and 1/8 in HBOC-201-, HEX-, and NON-resuscitated pigs, respectively. Compared with HEX, HBOC-201 pigs had higher systemic and pulmonary artery pressures and had comparable cardiac outputs, but were less tachycardic. Transcutaneous tissue oxygenation was restored more rapidly in HBOC-201 pigs, there was a trend to lower lactic acid, and base deficit was less. HBOC-201 pigs had lower fluid requirements, higher urine output, and lower blood loss than HEX pigs. CONCLUSIONS: Despite evidence of vasoactivity, HBOC-201 more effectively stabilized tissue oxygenation, reversed anaerobic metabolism, decreased bleeding, and increased survival in comparison with HEX. If confirmed in clinical trials, these data suggest that for the resuscitation of combat casualties with delayed evacuation and uncontrolled HS due to solid organ injury, HBOC-201 is a superior low-volume resuscitative fluid.

Transcervical artificial insemination in sheep: effects of a new transcervical artificial insemination instrument and traversing the cervix on pregnancy and lambing rates.

Cervical anatomy limits the use of transcervical intrauterine artificial insemination (TC AI) in sheep. We have developed an instrument to cope atraumatically with the cervix; although this instrument has not affected fertilization rate or pregnancy rate through Day 3, the effects on sperm transport and pregnancy after Day 3 are not known. The objective of the present study was to determine whether our TC AI instrument affected sperm transport, pregnancy rates, or lambing rate. In Experiment 1, ewes were assigned to two treatments: TC AI using the new TC AI instrument (n=10) or AI via laparotomy using a laparoscopic AI instrument (n=10). Twenty hours after artificial insemination, the uterine horns and oviducts were recovered and flushed to collect spermatozoa. Sperm transport did not differ (P>0.05) between the two treatments. In Experiment 2, ewes were assigned to three treatments: TC AI using the new TC AI instrument+sham intrauterine AI via laparotomy (n=29); sham TC AI+intrauterine AI via laparotomy using a laparoscopic AI instrument (n=29); and sham TC AI+intrauterine AI via laparotomy using the new TC AI instrument (n=30). On Day 14 after AI, uteri were collected and flushed to recover blastocysts. Transcervical deposition of semen reduced (P<0.05) Day 14 pregnancy rate (17.2% versus 61%), but intrauterine deposition of semen using the TC AI instrument via midventral laparotomy increased (P<0.05) Day 14 pregnancy rate (76.6% versus 44.8%). In Experiment 3, ewes were assigned to two treatments: sham cervical manipulation (n=40) or cervical manipulation to mimic TC AI (n=40). Immediately after treatment, each ewe was mated with a ram and watched until the ram mounted and ejaculated into the ewe. Treatment did not affect Day 30 or 50 pregnancy rate (67.5 and 66.2%, respectively), determined ultrasonically, or lambing rate (62.5%). The differences between Days 30 and 50 pregnancy rates and lambing rate were not significant. In Experiment 4, ewes were assigned to two treatments: TC AI (n=99) or laparoscopic AI (n=99). Transcervical AI reduced (P<0.01) Day 30 (TC AI versus laparoscopic AI; 5.0% versus 46.0%) and Day 50 pregnancy rates (4.0% versus 41.0%), determined ultrasonically, and lambing rate (4.0% versus 41.0%). Although the TC AI procedure significantly reduced pregnancy and lambing rates, large numbers of spermatozoa deposited at natural insemination seemed to compensate. Because our TC AI procedure has all but eliminated any visual evidence of trauma, and because the procedure does not seem to affect sperm transport or embryonal survival until Day 3, we speculate that cervical manipulation associated with TC AI may activate pathways that interrupt pregnancy between Days 3 and 14.

Adiponectin differentially regulates cytokines in porcine macrophages.

Adiponectin, an adipocyte-derived hormone, attenuates the production of TNFalpha by activated human macrophages. In the present study, we used porcine blood-derived macrophages to test the hypothesis that the anti-inflammatory action of adiponectin includes suppression of IL6 and an induction of IL10. Adiponectin suppressed both TNFalpha and IL6 production in macrophages activated with lipopolysaccharide (P<0.01). In contrast, adiponectin increased IL10 expression (P<0.05) and augmented (P<0.05) the induction of this cytokine by lipopolysaccharide (LPS). Mechanistically, the attenuation of proinflammatory cytokine production by adiponectin was associated with an attenuation of the translocation of NFkappaB to the nucleus. Either adiponectin or inhibition of ERK1/2 with U0126 diminished the induction of IL6 by LPS (P<0.05), but the combination of adiponectin and the inhibitor did not further reduce IL6 production. In contrast, the inhibitory actions of adiponectin and a p38 MAPK inhibitor (SB203580) were additive (P<0.05). These data indicate that the anti-inflammatory actions of adiponectin include suppression of IL6 and induction of IL10. In addition, we provide evidence that some of the anti-inflammatory actions of adiponectin are mediated in part by suppression of NFkappaB signaling and ERK1/2 activity.

Uterine response to infectious bacteria in estrous cyclic ewes.

PROBLEM: Luteal-phase uteri are susceptible to infections, and PGE2 and exogenous progesterone can down-regulate, whereas PGF2alpha can up-regulate, uterine immune functions. METHOD OF STUDY: Uteri of follicular- or luteal-phase ewes were inoculated with either saline or bacteria (Arcanobacterium pyogenes and Escherichia colt). Vena caval blood was collected for the next 3 days, and progesterone, PGE2, and PGF2alpha were measured. The effects of 10(-7) M PGE2 (Experiment 1), 10(-7) M PGF2alpha (Experiment 2), 10(-7) M indomethacin (INDO), and diluent on proliferation of lymphocytes from the vena caval blood in response to mitogens was quantified. RESULTS: Experiment 1: Progesterone was greater (P < 0.01) in luteal than in follicular ewes (3.4 versus 0.4 ng/mL), and only luteal ewes inoculated with bacteria developed infections.Lymphocyte proliferation was least (P = 0.08) in follicular ewes (2.6 versus 4.5 pmol for follicular and luteal, respectively). Concanavalin A (Con A)-stimulated proliferation was less (P < 0.05) for ewes inoculated with bacteria and for cells cultured with diluent (5.9 versus 3.1 pmol for saline and bacteria, respectively) or with INDO (6.6 versus 2.8 pmol for saline and bacteria, respectively). Also, Con A-stimulated lymphocytes from ewes inoculated with bacteria tended to proliferate less (P < 0.1) when cultured with PGE2 (4.9 versus 3.7 pmol for saline and bacteria, respectively) or PGE2 + INDO (5.5 versus 3.8 pmol for saline and bacteria, respectively). Experiment 2: Progesterone was greater (P < 0.01) in luteal than in follicular ewes (6.5 versus 1.2 ng/mL), and only luteal ewes inoculated with bacteria developed infections. Con A-stimulated lymphocyte proliferation was greater (P < 0.001) for follicular ewes (4.1 versus 3.1 pmol for follicular and luteal, respectively). Proliferation of lymphocytes collected from follicular ewes was greater (P < 0.01) when cells were cultured with PGF2alpha (3.5 versus 2.7 pmol for follicular and luteal, respectively), but INDO did not affect unstimulated or mitogen-stimulated proliferation. CONCLUSIONS: Prostaglandin F2alpha enhanced lymphocyte proliferation, whereas bacterial inoculation and in vitro treatment with PGE2 suppressed lymphocyte proliferation. This may signify the involvement of bacterial products and prostaglandins in regulation of uterine immunity.

Field evaluation of moxidectin/praziquantel oral gel in horses.

The safety and efficacy of 2% moxidectin/12.5% praziquantel oral gel administered at a rate of 0.4 mg moxidectin and 2.5 mg praziquantel/kg was studied in client-owned horses under field use conditions. Four hundred horses (300 treated with moxidectin/praziquantel oral gel and 100 treated with vehicle) were enrolled, feces were collected, and eggs were counted. Investigators as well as horse owners were masked to treatment assignment. No adverse reactions to treatment were observed in any horses. Moxidectin/praziquantel gel reduced Anoplocephala spp by more than 99% and provided a significant (P <.05) reduction (> 98%) in the strongyle egg count of treated horses.

Development of a new transcervical artificial insemination method for sheep: effects of a new transcervical artificial insemination catheter and traversing the cervix on semen quality and fertility.

The difficulty of traversing the cervix severely limits transcervical artificial insemination (TC AI) in sheep. Cervical trauma and poorly designed instruments can reduce fertility after AI. To overcome problems associated with TC AI, we developed a new TC AI catheter. Three bench experiments were conducted to determine the effects of the new TC AI catheter on semen quality independent of the effects of moving the catheter through the cervix. In each of the three bench experiments, the standard laparoscopic instrument for intrauterine AI in sheep was used as the control for the TC AI catheter. In Experiment 1, the total volume of semen extender expelled and void volumes for both types of AI instrument (TC versus laparoscopic) were determined. In Experiment 2, the effects of each type of AI instrument (TC versus laparoscopic) on semen quality, estimated as percentage motility and percentage forward progressive motility, of frozen-thawed semen was determined. In Experiment 3, the effects of both types of AI instrument (TC versus laparoscopic) on number of spermatozoa expelled was determined. The type of AI instrument affected neither semen quality nor the number of spermatozoa expelled. However, void volume differed (P < 0.01) between the two instruments. After differences in void volume were taken into account, an in vivo experiment was conducted to determine whether using our new TC AI catheter for TC or surgical intrauterine AI affected fertilization and pregnancy rates. For this, ewes were assigned to one of three treatments: (1) TC AI using the new TC AI catheter + sham AI via laparotomy (n = 9); (2) sham TC AI + AI via laparotomy using a laparoscopic AI instrument (n = 8); and (3) sham TC AI + AI via laparotomy using the new TC Al catheter (n = 10). To synchronize estrus, progestogenated pessaries were inserted and left in place for 12 days. On Day 5 after pessary insertion, PGF2alpha (15 mg) was given i.m. At pessary removal, 400 IU of eCG were administered i.m. Ewes were inseminated 48-52 h after pessary removal using fresh diluted semen (200 x 10(6) to 350 x 10(6) spermatozoa per 0.2 ml) pooled from the same four rams each day during the experiment. At 72 h after AI, uteri were collected postmortem and flushed. Oocytes and embryos were recovered and evaluated. Treatments did not affect (P > 0.01) ovum and embryo recovery rate (mean = 87.3%), fertilization rate (59.3%), or Day 3 pregnancy rate (mean = 66.6%). We conclude from these data that the use of our new TC AI catheter for TC AI or intrauterine AI should not impair the success of AI in sheep.

Modulation of the uterine response to infectious bacteria in postpartum ewes.

PROBLEM: Exogenous progesterone and prostaglandin E2 (PGE2) can downregulate uterine immune functions and render the uterus susceptible to bacterial infection. METHOD OF STUDY: Ewes were sham-ovariectomized (SHAM) or ovariectomized (OVEX) 9 days after parturition (day 0), and their uteri were inoculated with Arcanobacterium pyogenes and Escherichia coli on day 15. Vena caval blood was collected on day 14 and days 16-19, and uteri were collected on day 20. Ewes began receiving either canola oil (OIL) or progesterone in oil (PROG) on day 10. Lymphocytes from each blood sample were assigned to a 2 x 2 factorial array of in vitro treatments; 10(-7) M PGE2 and 10(-7) M indomethacin (INDO) were main effects. [3H]Thymidine incorporation (expressed in picomoles) was used to quantify proliferation. RESULTS: Progesterone was greater (P = 0.001) in PROG than in OIL ewes (3.6 versus 0.7 ng/mL), and only PROG ewes developed infections. Lymphocyte proliferation was least (P = 0.02) in PROG-OVEX ewes (4.1 versus 5.4, 5.7, and 5.8 pmol for OIL-SHAM, PROG-SHAM, and OIL-OVEX, respectively). Concanavalin A (Con-A)-stimulated proliferation was less (P < 0.01) for PGE2- and PGE2 + INDO-treated lymphocytes (7.5 and 8.3 pmol, respectively) than for control or INDO-treated cells (12.9 and 14.7 pmol, respectively). CONCLUSIONS: Progesterone treatment of postpartum ewes suppressed uterine immunity. In vitro PGE, treatment suppressed lymphocyte proliferation, regardless of PROG, and highlights a progesterone-independent level of regulation of uterine immune function.