Pharmacological Levels Research Articles

Effects of a botanical feed additive blend of capsicum oleoresin, clove and garlic essential oils on growth performance and fecal dry matter in nursery pigs

Abstract Two experiments were conducted to determine the effects of a botanical-derived feed additive containing capsicum oleoresin, clove and garlic essential oils (CCG; Fytera Start, Selko, Indianapolis, IN) in nursery pigs fed with or without pharmacological levels of Zn and Cu. In Exp. 1, 756 pigs (Duroc × Landrace/Large White composite (Smithfield Premium Genetics), initially 7.8 ± 0.09 kg) were used in a 40-d study to determine the effects of CCG level on growth performance of nursery pigs fed pharmacological levels of Zn and Cu. In Exp. 2, 340 barrows (DNA 200 × 400, initially 6.1 ± 0.08 kg) were used in 38-d study to determine the effect of CCG in diets with or without pharmacological levels of Zn and Cu on growth performance and fecal dry matter (DM). For both experiments, pigs were randomly allotted to pens which were allotted to 1 of 4 dietary treatments in a completely randomized design. There were 9 pigs per pen and 21 pens per treatment in Exp. 1 and 5 pigs per pen and 17 pens per treatment in Exp. 2. Dietary treatments in Exp. 1 were corn-soybean meal based with pharmacological levels of Zn and Cu and included either 0, 25, 50, or 100 mg/kg of CCG. Dietary treatments in Exp. 2 were arranged in a 2 × 2 factorial with main effects of CCG (none or 100 mg/kg) and nutritional or pharmacological levels of Zn and Cu. All Exp. 2 diets contained 110 mg/kg of Zn and 16.5 mg/kg of Cu from the trace mineral premix. For both experiments, pharmacological levels of Zn were added at 3,000 and 2,000 mg/kg in phase 1 and 2, respectively and Cu was added at 250 mg/kg in all phases. For Exp. 1, overall average daily gain (ADG) increased (linear, P < 0.05) and average daily feed intake (ADFI) tended to increase (linear, P < 0.10) as CCG increased from 0 to 100 mg/kg. For Exp. 2, there was a CCG × Zn/Cu interaction observed for overall ADG and ADFI (P < 0.05) where CCG numerically increased ADG and ADFI in pigs fed nutritional levels of Zn and Cu; but reduced ADG and ADFI in pigs fed pharmacological levels of Zn and Cu. There was a Zn/Cu × day interaction (P = 0.001) for fecal DM, in which there was no difference (P > 0.10) in fecal DM on d 10, but pigs fed pharmacological levels of Zn and Cu had lower (P < 0.001) fecal DM on d 21 compared to pigs fed nutritional levels of Zn and Cu. In summary, when included in diets with pharmacological levels of Zn and Cu, feeding increasing levels of CCG increased ADG in Exp. 1 but did not improve performance in Exp 2.

Prolactin locally mediates follicular atresia in hyperprolactinemic vizcachas (Rodentia, Chinchillidae)

Infertility in hyperprolactinemic females is attributed to the dysregulation of GnRH release, subsequently affecting gonadotropin levels, and ultimately leading to anovulation. However, in addition to the hypothalamus, prolactin receptor (PRLR) is expressed in ovaries as well, suggesting potential local effects of PRL in cases of hyperprolactinemia. We have developed an experimental model of sulpiride (SPD)-induced hyperprolactinemia using a wild rodent, the plains vizcacha, and studied the implications of pharmacological PRL levels on folliculogenesis and steroid production. Ovaries of SPD females showed a striking number of atretic follicles along with a reduction in the collective number of viable follicles leading to a higher atretic/viable follicle ratio compared to that of control females (CTL) (P < 0.05). In terms of sensitivity to the hormonal environment, SPD ovaries substantially changed their potential responsiveness to pituitary PRL, as evidenced by the three-fold increase in PRLR expression alongside heightened expression of both gonadotropic receptors in comparison to CTL ovaries (P < 0.05). Circulating estradiol (E2) values doubled post-treatment in the SPD females, which also showed higher expressions of aromatase and 17β-hydroxysteroid dehydrogenase, along with both E2 receptors, ERα and ERβ than the CTL group (P < 0.05). Our findings strongly suggest that hyperprolactinemia-dependent dysregulation of ovarian function can be explained at least partially, by PRL direct actions facilitated by the heightened expression of PRLR in follicles and corpora lutea. Possibly these PRL actions synergize with those triggered by gonadotropic hormones ultimately leading to alteration of the steroidogenic pathway, folliculogenesis disruption and increased atresia.

The potential of an integrated pharmaceutical care model with telepharmacy in adherence and knowledge about pharmacological treatment in patients with mental disorders: A clinical trial

Abstract The level of understanding about disease and treatment is an important factor to consider in achieving favorable outcomes in patients with mental disorders, and adherence to pharmacological treatment is crucial in this regard. The aim of this study was to assess to what extent patients with MD undergoing an integrated pharmaceutical care model with telepharmacy showed improvements in factors related to treatment adherence and their level of knowledge about pharmacotherapy. A parallel randomized clinical trial was conducted with a two-arm study in two Psychosocial Care Centers located in a state capital in Brazil. Participants in the intervention group received a comprehensive pharmaceutical care model that included attitudinal, technical, and educational interventions, while the control group received standard routine care. Predictive factors for adherence to pharmacological treatment and level of medication knowledge were assessed before and after the intervention. In the intervention group (33), significant improvements were found in the scores of adherence predictors (p&lt;0.001) and the level of knowledge of pharmacotherapy (p&lt;0.001) from baseline to follow-up, compared to the control group (33). The telepharmacy model demonstrated effectiveness in enhancing the scores of adherence predictors for pharmacological treatment and improving the level of knowledge of pharmacotherapy among patients with mental disorders.

Effects of low acid-binding capacity specialty soy protein sources on nursery pig performance in a commercial environment.

Two experiments were conducted to determine the effects of low acid-binding capacity (ABC) specialty soy protein sources on weanling pig performance. In experiment 1, 2,260 pigs, initially weighed 6.7kg, were used to determine the effects of low ABC soy proteins as a replacement to poultry meal (PM) or spray-dried blood plasma (SDBP). Treatments were arranged in a 2 × 2 factorial plus a control diet fed in two phases. There were 20 or 21 pigs per pen with 22 replications (pens) per treatment. The control diet contained PM (AV-E Digest, XFE Products, Des Moines, IA) and SDBP (Appetein, APC Inc., Ankeny, IA). Specialty soy protein concentrate (SSPC; AX3 Digest, Protekta, Newport Beach, CA) and microbial-enhanced soybean meal (MESBM; MEPRO; Prairie Aquatech, Brookings, SD) were used to replace PM or PM and SDBP on a standardized ileal digestible Lys basis. From d 0 to 21 and d 0 to 42, pigs fed either soy protein source replacing PM had greater (P ≤ 0.016) average daily gain (ADG) and average daily feed intake than pigs fed PM. From d 0 to 21, pigs fed SSPC had increased (P < 0.001) G:F compared with pigs fed MESBM and those fed either soy protein source replacing SDBP had increased (P = 0.044) G:F compared with pigs fed SDBP. In experiment 2, 1,057 pigs, initially weighed 6.2kg, were used to determine the effects of diet ABC at a pH of 4 (ABC-4) with specialty soy proteins with or without pharmacological levels of Zn from ZnO. Experimental diets were fed in two phases with 22 pigs per pen and 12 replications per treatment. Dietary treatments were arranged in a 2 × 2 factorial with main effects of ABC-4 (low or high) and pharmacological levels of Zn from ZnO (105 or 2,000mg/kg). The low ABC-4 diet without ZnO was formulated to 150 and 200 meq/kg using SSPC in phases 1 and 2, respectively. The high ABC-4 diet used enzymatically treated soybean meal (HP 300, Hamlet Protein, Findlay, OH) which increased the ABC-4 by 127 and 104 meq/kg in phases 1 and 2, respectively. From d 0 to 21 and d 0 to 42, there was an ABC-4 × ZnO interaction (P ≤ 0.026) observed where pigs fed low ABC-4 diets had greater (P < 0.05) ADG and G:F than pigs fed high ABC-4 diets without ZnO, but when diets contained added ZnO, there were no differences based on ABC-4. In conclusion, low ABC specialty soy proteins can be used to achieve low dietary ABC-4 levels to improve the performance of weanling pigs and provide a similar response to those fed pharmacological levels of Zn.

P228 THE PORTRAIT OF THE HYPERTENSIVE PATIENT: THE REALITY OF A NORTHERN PORTUGUESE SUBPOPULATION IN THE CONTEXT OF PRIMARY CARE

Background and Objectives: Hypertension is a chronic disease, and is one of the main cardiovascular risk factors. Knowing the local reality, regarding the comorbidities of the hypertensive population, profile of pharmacological therapy and level of blood pressure control are fundamental for the design of management and treatment strategies for hypertensive disease. In Portugal, hypertension has a estimated prevalence of 26,78% and the overwhelming majority of patients are assisted in primary care, where the health professionals have software tools such as BI-CSP, which uses Microsoft's Power-BI platform, allowing the retrieval of data about different variables. The aim of this study is to characterize a subpopulation studied at the Fânzeres Primary Care Center regarding demographic data, morbidity, blood pressure control and antihypertensive medication. Methods: This is an observational and cross-sectional descriptive study with an analytic component. The population consists of patients diagnosed with hypertension (N=3474). The retrieval of data was carried out using the MIMUF and BI-CSP. Results: In the population from which the 3474 hypertensive patients were selected, hypertension has a prevalence of 26%. The most common cardiovascular comorbidities were dyslipidemia (50%), Obesity (30%) and Diabetes (33%). 63% of patients had a systolic blood pressure (SBP) of &lt;140mmHg and 28% had a SBP &lt;130mmHg on the last measurement. Regarding the antihypertensives prescribed on a 4 month period, molecules that act on the renin-angiotensin axis are the main class used corresponding to 583K DDD (defined daily dose), followed by thiazides (300K DDD) and calcium channel blockers (250K DDD). Conclusions: There is still suboptimal control of hypertension in the population studied, which implies the adoption of more effective treatment strategies. It is important not only to involve adapting pharmacological treatment to the most recent guidelines, but also promote healthy lifestyles, control comorbidities and improve the follow-up of these patients. A multidisciplinary approach, using face-to-face and remote methods to strengthen contact with the healthcare team, can help to achieve these goals.

44. Effects of a nutritional strategy on growth performance and health in weaned piglets compared to the use of zinc oxide at pharmacological level

44. Effects of a nutritional strategy on growth performance and health in weaned piglets compared to the use of zinc oxide at pharmacological level

The bidirectional role of GABAA and GABAB receptors during the differentiation process of neural precursor cells of the subventricular zone.

The intricate process of neuronal differentiation integrates multiple signals to induce transcriptional, morphological, and electrophysiological changes that reshape the properties of neural precursor cells during their maturation and migration process. An increasing number of neurotransmitters and biomolecules have been identified as molecular signals that trigger and guide this process. In this sense, taurine, a sulfur-containing, non-essential amino acid widely expressed in the mammal brain, modulates the neuronal differentiation process. In this study, we describe the effect of taurine acting via the ionotropic GABAA receptor and the metabotropic GABAB receptor on the neuronal differentiation and electrophysiological properties of precursor cells derived from the subventricular zone of the mouse brain. Taurine stimulates the number of neurites and favors the dendritic complexity of the neural precursor cells, accompanied by changes in the somatic input resistance and the strength of inward and outward membranal currents. At the pharmacological level, the blockade of GABAA receptors inhibits these effects, whereas the stimulation of GABAB receptors has no positive effects on the taurine-mediated differentiation process. Strikingly, the blockade of the GABAB receptor with CGP533737 stimulates neurite outgrowth, dendritic complexity, and membranal current kinetics of neural precursor cells. The effects of taurine on the differentiation process involve Ca2+ mobilization and the activation of intracellular signaling cascades since chelation of intracellular calcium with BAPTA-AM, and inhibition of the CaMKII, ERK1/2, and Src kinase inhibits the neurite outgrowth of neural precursor cells of the subventricular zone.

Peripheral 5-HT Mediates Gonadotropin-Inhibitory Hormone-Induced Feeding Behavior and Energy Metabolism Disorder in Chickens via the 5-HT2C Receptor

Introduction: Since the discovery of gonadotropin-inhibitory hormone (GnIH), it has been found to play a critical role in reproduction in vertebrates. Recently, a regulatory role of GnIH in appetite and energy metabolism has emerged, although its precise physiological mechanisms remain unknown. Methods: Thus, the present study evaluated the effects of a single or long-term intraperitoneal GnIH treatment on the food intake, weight, and glucolipid metabolism of chickens, as well as investigating the possible neuroendocrinology factors and mechanisms involved in GnIH-induced obesity and glucolipid metabolism disorder. Results: Our results show that the intraperitoneal administration of GnIH to chickens resulted in a marked body mass increase, hyperlipidemia, hyperglycemia, and glucose intolerance. Subsequently, the results of metabolomics studies and the pharmacological inhibition of the 5-HT2C receptor revealed that blocking the 5-HT2C receptor reinforced the effects of GnIH on food intake, body weight, and blood glucose and lipid levels, resulting in even worse cases of GnIH-induced hyperglycemia, hyperlipidemia, and hepatic lipid deposition. This suggests that, via the 5-HT2C receptor, peripheral 5-HT may act as a negative feedback regulator to interplay with GnIH and jointly control energy balance homeostasis in chickens. Discussion: Our present study provides evidence of cross-talk between GnIH and 5-HT in food intake and energy metabolism at the in vivo pharmacological level, and it proposes a molecular basis for these interactions, suggesting that functional interactions between GnIH and 5-HT may open new avenues for understanding the mechanism of the neuroendocrine network involved in appetite and energy metabolism, as well as providing a new therapeutic strategy to prevent obesity, diabetes, and metabolic disorders.

189 Combination of organic acid and monoglyceride blend improved growth performance in nursery pigs with and without added antibiotics and ZnO

Abstract This study was to investigate the effects of supplementing a combination of organic acid and monoglyceride additives in feed with and without added antibiotics and pharmacological levels of ZnO on growth performance of nursery pigs. Pigs (n = 1,008; 21 d of age with initial body weight (BW) = 5.8] were assigned to 4 treatments (n = 12, 21 pigs/pen, mixed sex) following 2 × 2 factorial experiment design and fed for 42 d in 4 phases (d 0-8, d 9-21, d 22-35, and d 36-42, respectively). Treatments were 1) Positive control (PC), basal diet with in-feed antibiotics in phase 1-3, and 3000 ppm of Zn in phase 1, 2000 ppm of Zn in phase 2 and 125 ppm of Zn in phase 3 and 4 (i.e., pharmacological levels); 2) PC supplemented with the combination of Acitra G20C (formic acid-based acid blend on inert carrier) and Entero-Nova 410C (blend of monoglycerides of short-chain and medium-chain fatty acids on inert carrier), Acitra G20C was added at 3 kg/MT in phase 1 diet and 1.5 kg/MT in phase 2 diet, while Entero-Nova 410C was added at 3 kg/MT in phase 1 and 2 diets, and 1 kg/MT in phase 3 and 4 diets; 3) Negative control (NC), basal diet without in-feed antibiotics and pharmacological levels of ZnO; and 4) NC supplemented with the combination of Acitra G20C and Entero-Nova 410C (same supplementation rate as Treatment 2). Diets contained nutrients meeting or exceeding NRC requirements. Growth performance was measured for each phase. Data were analyzed using JMP software with pen serving as the experimental unit and differences considered significant at P ≤ 0.05. Throughout the trial, pigs fed diets without in-feed antibiotics and pharmacological levels of ZnO had ess (P &amp;lt; 0.01) BW, average daily gain (ADG) and average daily feed intake (ADFI) than pigs fed diets added with antibiotics and pharmacological levels of ZnO. During the period of phase 2 and overall phase 1 and 2 of the trial, pigs fed diets supplemented with the combination of Acitra and Entero-Nova additives had greater (P &amp;lt; 0.05) ADG and ADFI and greater (P &amp;lt; 0.05) BW on d 22 of trial. In phase 3 and 4, there was no significant improvement on growth performance of pigs fed diet only supplemented with 1 kg/MT of Entero-Nova comparing with the pigs in control groups. In conclusion, under current trial conditions, the combination of Acitra G20C and Entero-Nova 410C improved growth performance of nursery pigs in phase 1 and 2 when supplemented at tested dosage comparing with pigs in control groups without the additives.

196 Effects of zinc source and level in low ABC-4 diets on nursery pig growth performance and fecal dry matter

Abstract Incorporating pharmacological levels of Zn in nursery pig diets is a well-recognized practice for reducing post-weaning diarrhea, enhancing growth performance, and enhancing gut health. We hypnotized that the use of a specific form of ZnO (small aggregates and agglomerated particles; SAAP), which provides a greater antibacterial property than standard ZnO, could be added at reduced levels without compromising piglet performance. This study aimed to explore the effects of different levels of SAAP Zn source (HiZox, Animine, France) in low ABC-4 diets with low or high CP content. A total of 360 weanling barrows [DNA 200 × 400, initial body weight (BW) = 5.9 ± 0.4 kg] were used in a 38-d experiment. Pigs were randomly assigned to pens (5 pigs/pen) and pens assigned to 1 of 6 treatments with 12 pens/treatment. The experiment consisted of phase 1 from d 0 to 10, phase 2 from d 11 to 24, and phase 3 from d 25 to 38. Treatments consisted in a negative control (NC), which had 150 ppm of Zn (HiZox) throughout the experiment and the remaining treatments were: positive control (PC) containing 3,000 ppm (phase 1) and 2,000 ppm (phase 2) of Zn provided by ZnO; low-HiZox containing 500 ppm (phase 1) and 300 ppm (phase 2) of Zn; low-HiZox-low-CP was similar to low-HiZox but contained less CP (19.3%) than the NC, PC, low and high-HiZox diets (21.3%); high-HiZox containing 800 ppm (phase 1) and 500 ppm (phase 2) of Zn; and high-HiZox-low-CP was similar to high-HiZox but contained 19.3% CP. In phase 3, all pigs were fed a common diet containing 150 ppm of Zn (HiZox) and high CP. For the experimental period (d 0 to 24), average daily gain (ADG; quadratic, P = 0.007) and average daily feed intake (ADFI; quadratic, P = 0.018) increased as HiZox increased (Table). Pigs fed high-HiZox-low-CP had poorer gain to feed ratio (G:F; P &amp;lt; 0.05) than NC, PC, low-HiZox, and high-HiZox. Additionally, in both experimental and overall periods, pigs fed diets with low CP had decreased G:F (P = 0.043) than those fed the same Zn levels but with high CP. Overall, pigs fed high-HiZox-low-CP had decreased G:F than pigs fed high-HiZox only (732 vs. 761 g/kg, respectively; P &amp;lt; 0.05), with other treatments intermediate. For fecal dry matter (DM), pigs fed low CP diets had greater (P = 0.008) DM compared with pigs fed high CP. Thus, the inclusion of HiZox at 800 and 500 ppm in phases 1 and 2, respectively, in a low-ABC-4 diet might be a strategy to reduce the use of pharmacological levels of Zn from ZnO in nursery diets.

69 Effect evaluation of two sources of zinc at EU-authorized level on growth performance and gut health of piglets with a low or normal birth weight

Abstract This study aimed to investigate the effect of ZnSO4 or a porous form of ZnO, at EU-authorized level, on growth performance, gut health and colon microbiota in low and normal birth body weight (BBW) piglets. At birth, 64 piglets were chosen by their BBW and divided into low BBW (LBBW &amp;lt; 1 kg; 32 piglets) and normal BBW (NBBW &amp;gt; 1 kg; 32 piglets). At weaning, 25 d old (d 0), piglets were allocated into four groups (8 piglets/group, 2 pigs/replicate) and fed a standard diet plus 120 ppm of Zn from ZnSO4 or from a porous source of Zn (HZ - HiZox, Animine, France). Groups were balanced for litter of origin and category of BBW. Piglets were weighed weekly until d 21 post-weaning. The prevalence of diarrhea was determined by the fecal index (percentage of animals with fecal score &amp;gt; 3), and feed intake per pen was recorded daily. On d 9 and d 21, one piglet/replicate was slaughtered, and jejunum tissue was collected for morphology, colon content for microbiota analyzes, and distal jejunum pH was measured. Performance, pH, and morphometric parameters were analyzed using a linear mixed model, fecal index using a generalized linear mixed model with a Poisson distribution, including treatment, class of BBW and their interaction as fixed factors, and the litter as random factor. The statistical analysis on alpha, beta diversity and taxonomic composition were carried out using phyloseq, vegan and microbiomeMarker packages. Piglets in the NBBW group had greater BW throughout the study (P &amp;lt; 0.01). The treatment HZ tended to increase the average daily gain (ADG) at d 9-14 (P &amp;lt; 0.10), and significantly increased the gain to feed ratio (G:F) ratio (P &amp;lt; 0.05) at d 0-14. The HZ-fed piglets had a greater G:F in the overall period (P = 0.04). Additionally, the jejunum pH of the HZ-fed piglets was reduced (P = 0.02) at d 21. An interaction was observed between treatment and BBW for fecal index during d 0-14 and d 0-21 (P &amp;lt; 0.01), in which HZ decreased the index in LBBW. An interaction was also observed in villus height (P = 0.05) and absorptive mucosal surface (P = 0.02) on d 21, that resulted greater in NBBW piglets fed ZnSO4. For Beta diversity, using the Adonis test, BBW category tended to affect the microbial structure at d 9 (R2 = 0.04; P = 0.07) and significantly affected the bacterial structure (R2 = 0.05, P = 0.03) at d 21. At d 21, the NBBW piglets fed ZnSO4 had a greater abundance of Succinivibrio which is able to degrade complex carbohydrates, while the NBBW piglets fed HZ had a greater abundance of Ruminococcus gauvreauii which is linked to the production of short chain fatty acids (SCFAs). The use of HZ seems can be a part of the strategy to replace the pharmacological level of ZnO.

197 Effects of dietary zinc supplementation strategy on immune response, bacterial load and disease severity in growing gilts infected with Mycoplasma hyopneumoniae.

Abstract The objective of this study was to assess impacts of dietary zinc (Zn) supplementation strategy on immune response, bacterial clearance, and disease severity in growing gilts infected with Mycoplasma hyopneumoniae. Weaned gilts [n = 96; 21-d old; initial body weight (BW) = 6.94 kg], were used in a 63-d experiment which consisted of a pre- (d 0-35) and post- (d 35-63) M. hyopneumoniae challenge. On d 0 (-35 d post-inoculation; dpi), gilts were confirmed negative for M. hyopneumoniae and PRRSv and assigned randomly to 1 of 2 dietary treatments with 8 pens/treatment and 6 gilts/pen. Treatments were: 1) Control; 125 mg/kg Zn from ZnSO4, and 2) Zn-blend; 125 mg/kg Zn with 50 mg/kg Zn from Zn-amino acid complex (ZnAA) and 75 mg/kg Zn from ZnSO4. Dietary treatments were fed in 4-phases with pharmacological levels of zinc oxide included in the first 2 phases. Phase 1 (d 0) control and Zn-blend diets contained 3,121 and 3,256 mg/kg total Zn, respectively. Phase 2 (d 0-14) control and Zn-blend diets contained 3,657 and 3,593 mg/kg total Zn, respectively. Phases 3 (d 14-35) and 4 (d 35-63) control and Zn-blend diets contained 213 and 193 mg/kg and 229 and 212 mg/kg total Zn, respectively. At 0 and 1 dpi, all gilts were inoculated intratracheally with 10 mL of a lung homogenate containing 1×105 CCU/mL of M. hyopneumoniae strain 232. Blood and tracheal secretions were collected on -35, 0, 7, 14, 21, 28 dpi. Blood samples were evaluated for antibody detection, and tracheal secretions were analyzed by PCR. Number of coughs were recorded daily from 7 to 28 dpi. At 28 dpi, gilts were humanely euthanized, and bronchoalveolar lavage fluid (BALF) and macroscopic lung lesion observations were collected. Gross lung lesions were scored, and lung tissues were fixed for histopathology. Normally distributed data were analyzed in a generalized linear model with the fixed effect of diet and repeated measures for days post-inoculation. Non-normal data were analyzed using a Mann Whitney U Test using the NPAR1WAY procedure of SAS with a fixed effect of diet or a Chi-square test. Gilts consuming control diets tended (21.68 vs. 20.90 Ct, P = 0.08) to have less relative bacterial load than those consuming Zn-blend diets, over time. No differences in mean sample-to-positive ratio or proportion of gilt seroconversion (P &amp;gt; 0.05) were detected between treatments. There were no differences in mean concentrations of IL-1α, IL-1β, IL-6, IL-8, IL-10 (P &amp;gt; 0.05) in BALF for gilts consuming control or Zn-blend diets. There were no differences in mean macroscopic (P = 0.73) or microscopic (P = 0.67) lung scores, and coughing index score (P = 0.25) over the entire period between gilts consuming the different dietary Zn supplementation strategies. In conclusion, growing gilts consuming diets containing different Zn sources exhibited similar signs of infection during the acute phase of a M. hyopneumoniae infection.

201 The effects of the supplementation of a Zinc-amino acid complex in pig nursery diets with differing pharmacological levels of zinc oxide and complexity

Abstract Diet complexity (DC), which has significance in nursery pig production, generally refers to a greater number of highly digestible ingredients. Increased DC may have even greater significance in scenarios of reduction or withdrawal of zinc oxide (ZnO) in nursery diets. The objectives were to determine 1) the impact of adding Zn-amino acid complex (Zinpro ProPath Zn) to mid- (MC) and low-complexity (LC) diets on nursery pig performance and health compared with a high complexity (HC) diet, and 2) the impact of Zinpro ProPath Zn in diets with and without pharmacologic levels of ZnO. A total of 2,400 mixed-sex weanling pigs [initial body (BW) weight = 5.79 ± 0.15 kg] were assigned to 1 of 5 dietary treatments during nursery (42 d) as follows: 1) HC; MC diet with 2) MC+ZnO) or without 3) MC-ZnO) pharmacologic ZnO; and LC diet with 4) LC+ZnO) or without 5) LC-ZnO) pharmacologic ZnO. All diets except HC were supplemented with Zinpro ProPath Zn (125 mg/kg Zn) and ZnO [3,000, 2,000, and 0 mg/kg Zn during Phases I (14 d), II (14 d) and III (14 d), respectively]. Different DC were achieved by manipulating the inclusion of spray-dried plasma, soy protein concentrate, and whey protein. Growth performance, onset of feed intake, fecal dry matter, number of injectable treatments administered, and serum acute-phase response were assessed. Pigs fed HC (20.0 kg) had greater final BW (FBW) compared with pigs fed MC-ZnO (18.8 kg), which had greater FBW compared with pigs fed LC-ZnO (17.5 kg; SEM = 0.34; P &amp;lt; 0.05). Average daily feed intake (ADFI) was greater in pigs fed HC (0.46 kg/d) compared with MC-ZnO (0.43 kg/d) and LC+ZnO (0.42 kg/d), which had greater ADFI compared with LC-ZnO (0.39 kg/d; SEM = 0.01; P &amp;lt; 0.05). Similarly, average daily gain (ADG) and gain to feed ratio (G:F) were greater in pigs fed HC (0.33 kg/d, 0.72 kg/kg, respectively) compared with pigs fed LC (0.27 kg/d, 0.67 kg/kg, respectively), regardless of ZnO (SEM = 0.01; P &amp;lt; 0.05). There was no effect of dietary treatments on the fecal dry matter or on the onset of feed intake of pigs (P &amp;gt; 0.10). The number of injectable treatments administered was greatest in LC-ZnO (62.7%), followed by LC+ZnO (50.6%), MC regardless of ZnO (44.0%), and HC (36.7%; SEM = 1.04; P &amp;lt; 0.05). Serum alkaline phosphatase was less in LC-ZnO than the other groups (229.8 vs. 280.9 ± 11.9 IU/L; P &amp;lt; 0.05). Taken together, feeding HC diets during the nursery appears to be effective in improving performance and health of pigs, particularly when compared with MC and LC diets without ZnO. Moreover, the addition of Zinpro ProPath Zn may partially attenuate the negative effects of ZnO removal in MC, but not LC, diets.

PSVI-9 Effect of botanical extracts in diets with nutritional or pharmacological levels of copper and zinc on growth performance and fecal dry matter in nursery pigs

Abstract A total of 340 barrows (DNA 200 × 400, initially 6.1 kg) were used in a 38-d growth study to determine the effect of botanical extracts of capsicum oleoresin, clove essential oil, and garlic essential oil (CCG; Fytera Start, Selko, Indianapolis, IN) in diets with or without pharmacological levels of Zn and Cu on growth performance and fecal dry matter (DM) of nursery pigs. Pigs were weaned at 21 d of age, randomly allotted to pens based on initial body weight (BW), and allotted to 1 of 4 dietary treatments in a CRD with 5 pigs/pen and 17 pens/treatment. Diets were fed in three phases from d 0 to 10, d 10 to 21, and d 21 to 38 and treatments were arranged in a 2 × 2 factorial with main effects of CCG (none or 100 mg/kg) and nutritional or pharmacological levels of Zn and Cu. Zinc levels were 110 or 3,000, 2,000, and 110 mg/kg of Zn (ZnO) in phase 1, 2, and 3, respectively, and Cu levels were 16.5 or 250 mg/kg of Cu (CuSO4). On d 0, there was an unintentional minor main effect of CCG (P = 0.008) on BW. As a result, d 0 BW was used as a covariate for all other growth performance responses. From d 0 to 21 and d 0 to 38, there was a CCG × Zn/Cu interaction for average daily gain (ADG) and average daily feed intake (ADFI; P &amp;lt; 0.05; Table) where CCG numerically increased ADG and ADFI in pigs not fed pharmacological levels of Zn/Cu; but reduced ADG and ADFI when pigs were fed pharmacological levels of Zn/Cu. Overall gain to feed ratio (G:F) tended to increase (P &amp;lt; 0.10) in pigs fed diets with pharmacological levels of Zn/Cu. For fecal dry matter, there was a Zn/Cu × day interaction (P = 0.001) in which there was no difference in fecal DM on d 10 (P &amp;gt; 0.10), but pigs fed pharmacological levels of Zn/Cu had decreased fecal DM (P &amp;lt; 0.001) on d 21. Fecal DM was increased (P &amp;lt; 0.001) on d 10 compared with d 21. In summary, feeding pharmacological levels of Zn and Cu resulted in increased ADG and ADFI. CCG numerically increased ADG and ADFI in pigs fed nutritional levels of Zn/Cu and numerically decreased ADG and ADFI in pigs fed pharmacological levels of Zn/Cu. There was no impact of CCG or Zn and Cu level on fecal DM on d 10. However, feeding pharmacological levels of Zn and Cu resulted in decreased fecal DM at d 21.

75 Diet acid-binding capacity-4 influences nursery pig performance and fecal dry matter

Abstract A total of 360 pigs (initial body weight = 5.9 kg) were used to evaluate the effects of increasing acid-binding capacity-4 (ABC-4) of the diet on nursery pig performance and fecal dry matter (DM). At weaning, pigs were allotted to 1 of 6 dietary treatments. There were 5 pigs/pen and 12 replications/treatment. Pigs were fed experimental diets in two phases with phase 1 from d 0 to 10 post-weaning followed by phase 2 from d 10 to 23. Diets were formulated with increasing ABC-4 levels ranging from 150 meq/kg (diet 1, low ABC-4) to 312 meq/kg (diet 5, high ABC-4) in phase 1 and 200 meq/kg (diet 1, low ABC-4) to 343 meq/kg (diet 5, high ABC-4) in phase 2. For diet 1, low ABC-4 diets were formulated using specialty soy protein concentrate (AX3 Digest; Protekta; Newport Beach, CA) at 12.5 and 10.0% of the diet in phase 1 and 2, respectively. The low ABC-4 diet also utilized fumaric and formic acid at 0.50 and 0.48% of the diet, respectively, for both phase 1 and 2. For diets 2 (medium low), 3 (medium), 4 (medium high), and 5 (high), increasing dietary ABC-4 was achieved by progressively decreasing the level of acidifiers and replacing specialty soy protein concentrate with enzymatically treated soybean meal (HP 300; Hamlet Protein; Findlay, OH) on an SID Lys basis. Diets 1 through 5 were formulated without the addition of pharmacological levels of Zn from ZnO. For diet 6, a positive control diet was used which had the same formulation as the highest ABC-4 diet but with the addition of 3,000 and 2,000 mg/kg of Zn from ZnO in phase 1 and 2, respectively. Following phase 2, all pigs were fed a common diet until d 38 of the study. In the experimental period and overall, there was a quadratic response observed (P ≤ 0.030) where body weight (BW) and average daily gain (ADG) were greatest for pigs fed the medium low and medium ABC-4 diets (Table). During the experimental period, increasing ABC-4 decreased (linear, P = 0.002) gain to feed ratio (G:F). For overall G:F, a quadratic response was observed (P = 0.023) where G:F was most improved for pigs fed the medium low and medium ABC-4 levels. For fecal DM, increasing ABC-4 decreased (linear, P ≤ 0.036) fecal DM on d 10 and 17, with no differences on d 23. Pigs fed the diet with pharmacological levels of Zn from ZnO had increased (P ≤ 0.038) ADG compared with pigs fed diets without ZnO during the experimental period and overall. In summary, a dietary ABC-4 level of 203 and 247 meq/kg for phase 1 and 2, respectively, was most beneficial to improve both growth performance and fecal DM in weanling pigs.

135 Effects of altering diet acid-binding capacity-4 (ABC-4) with specialty soy protein sources or acidifiers on nursery pig performance and fecal dry matter

Abstract A total of 300 pigs (initial body weight = 6.0 kg) were used to evaluate the effects of altering diet acid-binding capacity-4 (ABC-4) with specialty soy protein sources or acidifiers on nursery pig performance and fecal dry matter (DM). At weaning, pigs were allotted to 1 of 5 dietary treatments. There were 5 pigs/pen and 12 replications/treatment. Pigs were fed experimental diets in two phases with phase 1 fed from d 0 to 10 post-weaning followed by phase 2 from d 10 to 24. A low ABC-4 diet was formulated to 200 and 250 meq/kg in phase 1 and 2, respectively. The low ABC-4 diet utilized 0.38% fumaric acid, 0.36% formic acid, and specialty soy protein concentrate (AX3 Digest; Protekta; Newport Beach, CA) at 9.38 and 7.50% of the diet in phase 1 and 2, respectively. For the first medium ABC-4 diet, specialty soy protein concentrate was replaced with enzymatically treated soybean meal (HP 300; Hamlet Protein; Findlay, OH) on an SID Lys-basis and resulted in an ABC-4 of 290 and 322 meq/kg for phase 1 and 2, respectively. For the second medium ABC-4 diet, acidifiers were removed resulting in an ABC-4 of 271 and 321 meq/kg for phase 1 and 2, respectively. In the high ABC-4 diet, both soy protein replacement and acidifier removal strategies were utilized resulting in ABC-4 values of 362 and 394 meq/kg for phase 1 and 2, respectively. In addition, a control diet was utilized with the same formulation as the high ABC-4 diet but with 3,000 and 2,000 mg/kg of Zn from ZnO in phase 1 and 2, respectively. Following phase 2, all pigs were fed a common diet until d 38 of the study. Increasing ABC-4 decreased (linear, P ≤ 0.043) gain to feed ratio (G:F) during the experimental period and overall (Table). Increasing ABC-4 decreased (linear, P ≤ 0.005) fecal DM on d 10 and 24, with no differences on d 17. Pigs fed the medium ABC-4 diet based on specialty soy protein replacement had increased (P = 0.003) fecal DM on d 10 compared with the medium ABC-4 diet where acidifiers were removed. Pigs fed diets containing pharmacological levels of Zn from ZnO had increased (P ≤ 0.047) body weight (BW), average daily gain (ADG), average daily feed intake (ADFI), and G:F during the experimental period but decreased (P = 0.005) ADG and G:F during the common period, with no differences overall compared with pigs fed diets not containing ZnO. In conclusion, as dietary ABC-4 increased from 200 to 362 meq/kg in phase 1 and 250 to 294 meq/kg in phase 2, growth performance and fecal DM decreased. This study suggests a dietary ABC-4 of 200 and 250 meq/kg in phase 1 and 2, respectively, can be utilized to improve growth performance and fecal dry matter of weanling pigs.

Adherence to Antihypertensive Therapy and Its Determinants: A Systematic Review.

Hypertension is a globally prevalent condition, and low adherence to antihypertensive therapy is considered one of the main causes of poor blood pressure (BP) control. Non-adherence to antihypertensive treatment is a complex issue that can arise from various factors; however, gaining an understanding of this provides key targets for intervention strategies. This study aimed to provide an overview of the current status and recent developments regarding our understanding of the determinants of patients' adherence to antihypertensives. A systematic review was performed using the electronic databases MEDLINE/PubMed, Web of Science, Scientific Electronic Library Online (SciELO), and "Índex das Revistas Médicas Portuguesas", which included studies published between 2017 and 2021 following the PICOS model: (P) Adult patients with the diagnosis of primary hypertension, using at least one antihypertensive agent; (I) all interventions on both pharmacological and non-pharmacological level; (C) patient's adherence against their non-adherence; (O) changes in adherence to the therapeutic plan; and (S) any study design (except review articles) written in English, French, Spanish or Portuguese. Articles were reviewed by two researchers and their quality was assessed. Subsequently, determinants were classified according to their consistent or inconsistent association with adherence or non-adherence. Only 45 of the 635 reports identified met the inclusion criteria. Adherence was consistently associated with patient satisfaction with communication, patient-provider relationship, their treatment, and use of eHealth and mHealth strategies; a patient's mental and physical health, including depression, cognitive impairment, frailty, and disability, previous hospitalization, occurrence of vital events; drug treatment type and appearance; and unwillingness due to health literacy, self-efficacy, and both implicit and explicit attitudes towards treatment. There were discrepancies regarding the association of other factors to adherence, but these inconsistent factors should also be taken into account. In conclusion, the barriers to adherence are varied and often interconnected between socioeconomic, patient, therapy, condition, and healthcare system levels. Healthcare teams should invest in studying patients' non-adherence motives and tailoring interventions toindividual levels, by using a multifaceted approach to assess adherence. Further research is needed to analyze the impact of implicit attitudes, the use of new technological approaches, and the influence of factors that are inconsistently associated with non-adherence, to understand their potential in implementing adherence strategies.

Factors Associated with Patient Education in Patients with Chronic Obstructive Pulmonary Disease (COPD) - A Primary Health Care Register-Based Study.

Patient education in chronic obstructive pulmonary disease (COPD) is recommended in treatment strategy documents, since it can improve the ability to cope with the disease. Our aim was to identify the extent of and factors associated with patient education in patients with COPD in a primary health care setting. In this nationwide study, we identified 29,692 COPD patients with a registration in the Swedish National Airway Register (SNAR) in 2019. Data on patient education and other clinical variables of interest were collected from SNAR. The database was linked to additional national registers to obtain data about pharmacological treatment, exacerbations and educational level. Patient education had been received by 44% of COPD patients, 72% of whom had received education on pharmacological treatment including inhalation technique. A higher proportion of patients who had received education were offered smoking cessation support, had performed spirometry and answered the COPD Assessment Test (CAT), compared with patients without patient education. In the adjusted analysis, GOLD grade 2 (OR 1.29, 95% CI 1.18-1.42), grade 3 (OR 1.41, 95% CI 1.27-1.57) and grade 4 (OR 1.79, 95% CI 1.48-2.15), as well as GOLD group E (OR 1.17, 95% CI 1.06-1.29), ex-smoking (OR 1.70, 95% CI 1.56-1.84) and current smoking (OR 1.45, 95% CI 1.33-1.58) were positively associated with having received patient education, while cardiovascular disease (OR 0.92, 95% CI 0.87-0.98) and diabetes (OR 0.93, 95% CI 0.87-1.00) were negatively associated with receipt of patient education. Fewer than half of the patients had received patient education, and the education had mostly been given to those with more severe COPD, ex- and current smokers and patients with fewer comorbidities. Our study highlights the need to enhance patient education at an earlier stage of the disease.

LSD1 inhibition circumvents glucocorticoid-induced muscle wasting of male mice

Synthetic glucocorticoids (GC), such as dexamethasone, are extensively used to treat chronic inflammation and autoimmune disorders. However, long-term treatments are limited by various side effects, including muscle atrophy. GC activities are mediated by the glucocorticoid receptor (GR), that regulates target gene expression in various tissues in association with cell-specific co-regulators. Here we show that GR and the lysine-specific demethylase 1 (LSD1) interact in myofibers of male mice, and that LSD1 connects GR-bound enhancers with NRF1-associated promoters to stimulate target gene expression. In addition, we unravel that LSD1 demethylase activity is required for triggering starvation- and dexamethasone-induced skeletal muscle proteolysis in collaboration with GR. Importantly, inhibition of LSD1 circumvents muscle wasting induced by pharmacological levels of dexamethasone, without affecting their anti-inflammatory activities. Thus, our findings provide mechanistic insights into the muscle-specific GC activities, and highlight the therapeutic potential of targeting GR co-regulators to limit corticotherapy-induced side effects.

Abstract 4258: An innovative PDX and patient-derived 3D platform for improved translatability of new medical entities

Abstract The preclinical platform landscape in oncology has radically changed in the last 15 years, mainly due to an increased ability to generate patient-derived models. Multiple 3D tumor cell cultures methods, either from established cell lines or from primary cultures, have been developed to assess the activity of therapeutic agents in vitro. These methods are strongly influenced by the experimental conditions, such as cell culture conditions, the presence of 3D supports like Matrigel, and the experimental design of the assay, such as the choice of the dose and the duration of the assay. The ability of these methods to predict drug efficacy in the patient relies not only in the optimization of the experimental settings, but also on the representativeness of the patient population, and on the prevention of model drifts due to clonal selection and/or tumor cell adaptation to culture conditions with passages. In this project, we aimed to develop an innovative 3D cell model platform that addresses all these experimental challenges. To do so, we took advantage of our low passage Tumorgraft platform, a bank of more than 1500 patient-derived xenografts (PDXs) well characterized at molecular and pharmacological level and highly representative of the patient population, to generate the Tumorgraft3D platform. We derived TumorGraft3D models from low passage PDXs, by using proprietary, indication-specific culture conditions. By keeping these models at low passage, we were able to avoid clonal drifts. Moreover, the use of indication specific media allowed the preservation of patient’s and PDX’s tumor histology, molecular traits at genetic, gene expression and proteomic level, and displayed proliferation rates that recapitulate those observed in the parental PDXs. So far, we have successfully developed over 100 models from breast, ovarian, prostate, NSCLC, colorectal and gastric indications, with success rates up to 90%. Ex-vivo testing of standard of care highlighted different response profiles in accordance with the molecular feature of these models. The tumor dissociation process and culture conditions optimized with PDXs were also used for the development of 3D cultures derived from patients’ samples. These data demonstrated that our 3D platform can integrate the complementarity of our PDX and patient-derived 3D platform, which lies in the possibility of evaluating test agent activity in the repeatable and reproducible setting provided by the patient-derived 3D models, as well as in models directly derived from patients with more heterogeneous and indication-specific establishment success rate, and throughput dependent on the amount of primary tumor material. Citation Format: Samaneh Kamali, Stefano Cairo, Fu-Ju Chou, Taylor Light, Mara Gilardi, Brandon Walling, Christine Baer, Hsiu-Wen Tsai, Abhay Andar, Karin Abarca-Heidemann, Maria Mancini. An innovative PDX and patient-derived 3D platform for improved translatability of new medical entities [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4258.