EFFECTIVENESS OF ANHYDROUS AMMONIA AS A PRESERVATIVE FOR HIGH-MOISTURE HAY

1984 ◽  
Vol 64 (4) ◽  
pp. 867-880 ◽  
Author(s):  
S. O. THORLACIUS ◽  
J. A. ROBERTSON
Keyword(s):  
Treatment Period ◽  
Day Treatment ◽  
Application Rate ◽  
Mold Growth ◽  
High Moisture ◽  
Moisture Control ◽  
Anhydrous Ammonia ◽  
Alfalfa Hay ◽  
Voluntary Intake

Two experiments were conducted to determine the effectiveness of anhydrous ammonia as a preservative for high-moisture hays. In the first experiment, alfalfa hay, containing approximately 35% moisture was baled, stacked, sealed in polyethylene and treated with 1 and 2% (wt/wt) anhydrous ammonia. The plastic was removed at either 4 or 21 days after ammoniation and the bales were sampled following 4 mo in storage. The effects of ammoniation on heating, spoilage, chemical composition and in vitro organic matter digestibility (IVDOM) relative to untreated high- and low-moisture control stacks were determined. In the second experiment, ammonia was injected at the same rates into stacks of baled bromegrass hay containing approximately 30% moisture. The treated stacks were sealed for periods of 1 and 4 mo. In addition to the parameters measured in the first experiment, the bromegrass hays were fed to wethers to measure voluntary intake and digestibility in vivo. Injection of 2% anhydrous ammonia was completely effective in preventing heating and mold growth in the legume and grass hays during both the treatment period and following removal of the polyethylene cover. The 1% ammonia treatment reduced but did not prevent heat damage and mold growth. Ammoniation increased the crude protein content of all treated hays, the 2% application rate being more effective than 1%. Retention of the added N varied from 26.5 to 72% depending on application rate and duration of the treatment period. Applying 2% anhydrous ammonia to alfalfa hay prevented the decrease in IVDOM which occurred during storage in all other treatments and limited the increases in the proportion of NDF and ADF relative to the changes in these components which occurred in the high moisture control and 1% ammoniation treatments. Ammoniation of bromegrass hay did not affect voluntary intake (P > 0.05). The treated hays were readily consumed by the wethers and no toxic or other deleterious effects were observed. Ammoniation of bromegrass hay increased in vivo digestibility of all components measured except protein. In general, the increases in digestibility were greater following application of 2% than 1% ammonia and for the 119 vs. the 29 day treatment period. Key words: Anhydrous ammonia, preservative, hay, sheep, digestibility

EFFECTIVENESS OF ANHYDROUS AMMONIA AS A PRESERVATIVE FOR HIGH-MOISTURE ALFALFA HAY IN LARGE ROUND BALES

1986 ◽  
Vol 66 (3) ◽  
pp. 743-753 ◽  
Author(s):  
A. S. ATWAL ◽  
L. C. HESLOP ◽  
K. LIEVERS
Keyword(s):  
Ambient Temperature ◽  
Insoluble Fraction ◽  
Reference Points ◽  
Control Treatment ◽  
High Moisture ◽  
Total N ◽  
Heat Damage ◽  
Anhydrous Ammonia ◽  
Alfalfa Hay ◽  
Large Round

Two experiments were conducted in sequence to determine the effectiveness of anhydrous ammonia (AA) as a preservative of alfalfa hay stored as large round bales (LRB). In the the first experiment application of 3% AA (wt/wt) to alfalfa hay baled at about 23% moisture-content (MC) increased the temperature markedly above the control treatment and resulted in a significantly (P < 0.05) higher acid-detergent-insoluble nitrogen and acid-detergent lignin. In the second experiment application of about 1% AA slowly (over 48 h) to LRB of alfalfa hay packaged at about 30% and > 35% MC, significantly (P < 0.05) reduced the cumulative degree-days above all reference points from 35 to 65 °C. Ammoniation completely eliminated dry matter losses in storage which were highest (8.3%) for 33% MC control hay. High moisture control hay (33% MC) suffered severe heat damage with 33% of total N being in the acid-detergent-insoluble fraction as compared to less than 10% for medium-moisture (26% MC) control and even lower values for ammoniated hay. Digestibility of crude protein and energy was significantly (P < 0.05) improved by ammoniation of medium-moisture (about 30% in-to-storage) alfalfa hay. When the ammonia-treated hay was uncovered in spring, coarsely ground and stored in a hay wagon the high-moisture-ammoniated hay (> 35% MC) became moldy within 4 wk, even when the ambient temperature was about 6 °C, whereas medium-moisture-ammoniated hay (about 30% MC) showed some deterioration after 7 wk as the ambient temperature increased to about 12 °C. Key words: Ammonia, alfalfa hay, digestibility, heat damage, high-moisture hay, large bales

Enhancement of FSH bioactivity in vivo using site-specific antisera

1997 ◽  
Vol 152 (3) ◽  
pp. 355-363 ◽  
Author(s):  
L Ferasin ◽  
G Gabai ◽  
J Beattie ◽  
G Bono ◽  
A T Holder
Keyword(s):  
Biological Activity ◽  
Treatment Period ◽  
Ovarian Function ◽  
Day Treatment ◽  
Site Specific ◽  
Dose Dependent Fashion ◽  
Snell Dwarf ◽  
Fsh Bioactivity ◽  
Dose Dependent

The ability of site-specific antipeptide antisera to enhance the biological activity of ovine FSH (oFSH) in vivo was investigated using hypopituitary Snell dwarf mice. These animals were shown to respond to increasing doses of oFSH (3·3–90 μg/day), administered in two daily injections over a 5-day treatment period, in a highly significant dose-dependent fashion. The responses measured were increases in uterine weight, ovarian weight and the index of keratinisation in vaginal smears. The dose-dependent response to oFSH confirmed the suitability of this animal model for these investigations and suggested the suboptimal dose of oFSH (20 μg/day) for use in enhancement studies. Five peptides derived from the β subunit of bovine FSH (bFSH) (A, residues 33–47; B, 40–51; C, 69–80; D, 83–94; E, 27–39) were used to generate polyclonal antipeptide antisera. Of these peptides, only A and B produced an antiserum (raised in sheep) capable of recognising 125I-bFSH in a liquid phase RIA. Antisera prepared against peptide A or peptide B were found to significantly enhance the biological activity of 20 μg oFSH/day over a 5-day treatment period. The response to antipeptide antisera alone did not differ significantly from that observed in PBS-injected control animals, neither did the response to FSH alone differ from that observed in animals treated with FSH plus preimmune serum. Thus the enhanced responses are dependent upon the presence of FSH plus antipeptide antiserum. Peptides A and B are located in a region thought to be involved in receptor recognition, this may have implications for the mechanism underlying this phenomenon and/or the structure/function relationships of FSH. That FSH-enhancing antisera can be generated by immunisation of animals with peptides A and B suggests that it may be possible to develop these peptides as vaccines capable of increasing reproductive performance, such as ovulation rate. The high degree of sequence homology between ovine, bovine and porcine (and to a lesser extent human and equine) FSH in the region covered by peptides A and B suggests that these peptides could also be used to promote and regulate ovarian function in all of these species. Journal of Endocrinology (1997) 152, 355–363

Adaptation of a Xenograft AML Model to Evaluate Chemotherapeutic Efficacy In Vivo

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3304-3304 ◽  
Author(s):  
Mark Wunderlich ◽  
Fu-Sheng Chou ◽  
Mahesh Shrestha ◽  
Benjamin Mizukawa ◽  
James C. Mulloy
Keyword(s):  
Blood Cell ◽  
Treatment Period ◽  
Conflicts Of Interest ◽  
Residual Disease ◽  
Synergistic Effects ◽  
Day Treatment ◽  
Chemotherapeutic Agents ◽  
Mouse Strains

Abstract Abstract 3304 Although significant progress has been made in the treatment of leukemia, relapse continues to be a major problem, particularly in acute myeloid leukemia (AML). The prognosis for relapsed leukemia is poor, indicating an area for potential improvements. However, animal models to study the response of human AML to chemotherapeutics and subsequent relapse are lacking. Recently we developed an improved NOD/SCID mouse with IL2RG knockout and transgenic expression of myelo-supportive cytokines SCF, GM-CSF, and IL-3 (the NSGS mouse). This mouse is remarkable in its ability to accept human AML grafts more efficiently than all other available strains. When coupled with in vitro derived AML cells, the NSGS mouse allows for a more predictable AML model with shorter latency and smaller range of death than in other mouse strains, including NSG mice. Importantly, very low numbers of cells reliably generate fatal AML in roughly 40 days, even in non-irradiated NSGS mice, allowing for rapid experimental conclusions and reduced toxicity. With the benefits of these unique tools, we sought to develop a model system to evaluate the efficacy of chemotherapeutic agents on human AML cells in vivo. Engrafted mice received a chemotherapy regimen over a 5-day treatment period consisting of a daily dose of cytarabine with simultaneous injection of doxorubicin during the first three days. Treated mice experienced striking weight loss during the treatment period with a nadir at days 8–10 post-treatment. Mice recovered body weight within 3 weeks. Serial complete blood counts indicated a rapid transient drop in total white blood cell and neutrophil counts and a delayed transient drop in red blood cell and platelet numbers, reminiscent of the effects observed in patients undergoing chemotherapy. The drugs successfully targeted the cells of the bone marrow, as evidenced by a profound loss of cellularity in treated mice relative to controls. When mice harboring N-Ras(G12D) positive AML cells were treated at early time points post-transplant, a significant reduction of tumor burden was observed in the BM and PB, with the grafts of treated mice essentially undetectable for weeks after treatment cessation. Nevertheless, treated mice inevitably succumbed to disease, although with a significantly prolonged latency compared to mock treated mice. However, when AML cells containing the FLT3-ITD mutation were used, a shift in disease latency was not reproducibly seen. This data correlates well with patient data showing that FLT3-ITD mutant AML has a worse prognosis than AML samples with N-Ras mutations. Importantly, the reappearance of AML within weeks of treatment affords the opportunity to model drug resistance and relapse, as well as the potential synergistic effects of experimental compounds used in combination with traditional chemotherapy. Additionally, the period following treatment may allow for studies of minimal residual disease as well as the testing of potential maintenance therapies. Finally, this approach permits a detailed analysis of the critical few cancer stem cells that remain after induction therapy with the goal of identifying novel compounds capable of targeting these cells. Disclosures: No relevant conflicts of interest to declare.

Effect of inducing HR deficiency using AVB500, a receptor tyrosine kinase AXL inhibitor, on response to olaparib in uterine serous cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e18108-e18108
Author(s):  
Michael Driscoll Toboni ◽  
Barbara Blachut ◽  
Mary M Mullen ◽  
Jo'an Tankou ◽  
Hollie M Noia ◽  
...  
Keyword(s):  
Treatment Period ◽  
Cell Lines ◽  
Day Treatment ◽  
Parp Inhibitor ◽  
Tumor Burden ◽  
Scid Mice ◽  
In Vivo Studies ◽  
Treatment Groups

e18108 Background: Evidence suggests DNA repair is a therapeutic target in endometrial cancer (EC). Given this, we determined whether combination therapy with AVB500, an AXL inhibitor, could improve response in a uterine serous cancer (USC) model. Methods: Two USC cell lines (ARK1 & ARK4) were treated with AVB500 (Aravive Biologics, Houston, TX) in combination with the poly ADP ribose polymerase (PARP) inhibitor, olaparib. Colony forming assays were assessed after 4 days of treatment with either AVB500 alone, olaparib alone or combination treatment (olaparib + AVB500); colonies were stained and absorbance was obtained to calculate relative cell viability using Graph Pad Prism. Baseline homologous recombination (HR) status was determined after radiating cells with 10Gy and identifying RAD51 foci by immunofluorescence (IF). Cell lines were considered to be HR proficient if over 30% of the cells expressed RAD51 ( > 5 foci per cell). IF was conducted using a Leica confocal microscope and foci were quantified using FociCounter. In vivo studies were performed using NOD-SCID mice injected with 1 x 107 ARK1 cells intraperitoneally followed by treatment q3 days for a 14 and 21 day treatment period. Treatment groups were vehicle control, AVB500 alone, olaparib alone and olaparib with AVB500. Results: The absorbance for olaparib + AVB500 was significantly less than the olaparib only group in two assays involving ARK1s (0.417nm vs 0.756nm, p = 0.001; 0.320nm vs 0.620nm, p = 0.008) as well as in ARK4s (0.186nm vs 0.641nm, p = 0.003). The HR assay indicated both cell lines were HR proficient. After baseline HR proficiency was established, the cell lines were pretreated with AVB500 prior to radiation. When compared to cells without treatment with AVB500, IF showed a decrease in RAD51 foci per cell in ARK1 (2.7 vs 7.3, p = 0.0003) and ARK4 (6.3 vs 13.0, p = 0.0054). The proportion of ARK1 cells expressing RAD51 decreased to 21%, indicating HR deficiency. Lastly, NOD-SCID mice receiving olaparib + AVB500 had less tumor weight than those treated with olaparib alone (0.008g vs 0.138g, p = 0.002) and AVB500 alone (0.008g vs 0.145g, p = 0.0006) in a 14 day and a 21 day treatment period (0.212g vs 0.586g, p = 0.027 and 0.212 vs 0.494g, p = 0.005, respectively). Conclusions: HR proficient USC cell lines treated in vitro and in vivo with the combination of AVB500 and olaparib demonstrate an improved response to olaparib or AVB500 alone with a greater decrease in tumor burden. AVB500 appears to induce HR deficiency. Additional therapeutic and mechanistic experiments are ongoing.

181 Effect of Application Rate of Sodium Lignosulfonate and Propionic Acid on DM Losses, Nutritional Composition, and Fungal Counts of High Moisture Alfalfa Hay Mini Bales

2021 ◽  
Vol 99 (Supplement_3) ◽  
pp. 98-98
Author(s):  
Marjorie A Killerby ◽  
Godloves M Oppong ◽  
Saulo T Almeida ◽  
Colt W Knight ◽  
Anna Robinson ◽  
...  
Keyword(s):  
Propionic Acid ◽  
Block Design ◽  
Application Rate ◽  
Nutritional Composition ◽  
High Moisture ◽  
Sodium Lignosulfonate ◽  
Alfalfa Hay ◽  
Randomized Complete Block Design

Abstract Our objective was to evaluate the effects of application rate (AR) of sodium lignosulfonate and propionic acid on high moisture alfalfa hay spoilage during storage. Treatments (TRT) were sodium lignosulfonate (NaL) and Propionic Acid (PRP), which were applied at four AR: 0 (CON), 0.25, 0.5 and 1% (w/w fresh basis) to 20% bloom alfalfa hay (second cut) at 68.5% DM and packed into mini bales (10.3x10.8x13cm; 346kg fresh/m3). The treated bales were stored for 33 days in open-top insulation boxes in a room kept at 22°C. Data were analyzed as a randomized complete block design (5 blocks) with a 2 (TRT) x 4 (AR) factorial arrangement, and differences were declared at P ≤ 0.05. At day 0, no differences were observed for DM (68.5 ± 0.61 %), CP (23.2 ± 0.31% DM), and NDF (42.6 ± 0.66% DM), but NaL had more sugars than PRP (0.99 vs. 0.87 ± 0.66% DM) and PRP at 1% reduced mold counts vs. CON (4.71 vs. 4.97 ± 0.05 log cfu/fresh g). At day 33, DM losses were decreased by PRP at 0.5 and 1% (0.9), relative to CON (6.92) and to NaL (6.63 ± 1.13%). Both TRT decreased NDF at 0.25% (46.3) and furthermore at 1% (44.2) relative to CON (49.4), but overall PRP had lower NDF (45.2) than NaL (47.2± 0.81% DM). No differences were observed for sugars and CP. Visual moldiness (0–10) and mold counts were also decreased by PRP at 0.5% (2.4 and 5.30) and 1% (0 and 2.7) relative to CON (6.0 and 7.13) and NaL (5.85 ± 0.67 and 7.21 ± 0.31 log cfu/fresh g, respectively). In conclusion, NaL failed to prevent spoilage of high moisture hay while PRP was effective at doses &gt;0.5%.

Effects of ammoniation of brome-alfalfa and alfalfa hay, stored as large round bales on preservation and feed quality

1991 ◽  
Vol 71 (3) ◽  
pp. 755-765 ◽  
Author(s):  
Z. Mir ◽  
J. A. Robertson ◽  
P. S. Mir ◽  
E. Z. Jan ◽  
D. H. McCartney
Keyword(s):  
Dry Matter ◽  
Rumen Fluid ◽  
Average Daily Gain ◽  
Neutral Detergent Fiber ◽  
High Moisture ◽  
Total N ◽  
Anhydrous Ammonia ◽  
Alfalfa Hay ◽  
Respective Field ◽  
Large Round

Feeding trials with growing steers and digestibility trials with sheep were conducted during each of 3 yr in a split-split plot design, to compare the effects of anhydrous ammonia (2% wt wt−1, in plastic-covered stacks of large round bales) on preservation of brome-alfalfa and alfalfa hay harvested at < 20 and at 30% moisture with respective field cured (< 20% moisture) nonammoniated hays. Even after 14 wk of storage, the ammoniated high-moisture hays were free of visible molds. Dry matter (DM) recovery varied from 93.9 to 98.7% but was not affected by either moisture content or ammoniation. Ammoniation increased (P < 0.05) acid detergent insoluble nitrogen (ADIN, % total N) in high-moisture brome-alfalfa hay to 16.8 from 9.7% in nonammoniated hay. Within each type of hay, dry matter intake and average daily gain of growing steers were not affected by treatment. Feed efficiency was reduced (P < 0.05) in animals fed ammoniated high-moisture brome-alfalfa (11.2) but was improved (P < 0.05) in those fed ammoniated high-moisture alfalfa (9.8) when compared with the respective field cured hay (10.1 and 11.4). Compared to nonammoniated hay, ammoniating high-moisture brome-alfalfa hay had no effect on digestibilities of DM and acid detergent fiber (ADF) but decreased and increased (P < 0.05) digestibility of nitrogen (N) and neutral detergent fiber (NDF), respectively. With alfalfa, ammoniation did not affect digestibilities of either low- or high-moisture hay. Rumen volatile fatty acid profiles were not influenced but rumen fluid pH was elevated in sheep fed ammoniated hays. Results indicate that anhydrous ammonia treatment effectively preserved high-moisture alfalfa without adversely affecting nutritional quality parameters. Key words: Ammonia, brome-alfalfa, alfalfa, cattle, sheep, digestibility

PSXI-12 Effect of application rate of sodium lignosulfonate and propionic acid on in vitro digestibility and gas production kinetics of high moisture alfalfa hay mini bales

2021 ◽  
Vol 99 (Supplement_3) ◽  
pp. 344-344
Author(s):  
Marjorie A Killerby ◽  
Diego Zamudio ◽  
Kaycee Ames ◽  
Darren D Henry ◽  
Godloves M Oppong ◽  
...  
Keyword(s):  
Propionic Acid ◽  
Block Design ◽  
Application Rate ◽  
Gas Production ◽  
In Vitro Digestibility ◽  
High Moisture ◽  
Sodium Lignosulfonate ◽  
In Vitro Fermentation ◽  
Alfalfa Hay

Abstract Our objective was to evaluate the effects of application rate (AR) of sodium lignosulfonate and propionic acid on the in vitro fermentation measures of high moisture alfalfa hay. Treatments (TRT) were sodium lignosulfonate (NaL) and Propionic Acid (PRP), which were applied at four AR: 0 (CON), 0.25, 0.5 and 1% (w/w fresh basis) to 20% bloom alfalfa hay (second cut) at 68.5% DM and packed into mini bales (10.3×10.8×13cm; 346 kg fresh/m3). The treated bales were stored for 33 days in open-top insulation boxes in a room kept at 22°C, after which they were dried, ground to 1 mm and incubated in vitro for 48hr with ruminal fluid from two ruminally cannulated Holstein cows in lactation. Gas kinetics were recorded using the Ankom RF Gas Production System. Data were analyzed as a randomized complete block design (5 blocks) with a 2 (TRT) x 4 (AR) factorial arrangement, and differences were declared at P ≤ 0.05. Both TRT increased apparent in vitro DM digestibility (DMD) at all AR relative to CON (54.3 vs 50.1 ± 1.20%, respectively). PRP increased asymptotic maximal (188.4) and rate of gas production (9.46) compared to NaL (179.7 ± 4.82 ml/g of incubated DM and 8.72 ± 0.45%/h, respectively). Total VFA were higher for PRP (117.5) vs NaL (114.8), and for both TRT at 1% relative to CON (118.9 vs. 113.8 ± 1.68mM). Acetate (A) was increased by both TRT at 1% (~73.5) and propionate (P) was increased by PRP at 1% (26.1) relative to CON (69.9 ± 1.10 and 24.2 ± 0.29mM, respectively), but the A:P ratio was higher for NaL at 1% (3.02) vs. CON (2.89 ± 0.04). In conclusion, NaL and PRP at 1% improved the rumen in vitro fermentation measures of high moisture alfalfa hay but PRP did so to a greater extent.

scholarly journals Feeding Dairy Cows High Moisture Alfalfa Hay Preserved with Anhydrous Ammonia

1982 ◽  
Vol 65 (7) ◽  
pp. 1212-1218 ◽  
Author(s):  
W.P. Weiss ◽  
V.F. Colenbrander ◽  
V.L. Lechtenberg
Keyword(s):  
Dairy Cows ◽  
High Moisture ◽  
Anhydrous Ammonia ◽  
Alfalfa Hay

In Vivo Studies on the Inhibition of Coagulation by Fractionated Heparin and by a Heparin Analogue I. Effects of Heparin Fractions

1981 ◽  
Vol 46 (03) ◽  
pp. 612-616 ◽  
Author(s):  
U Schmitz-Huebner ◽  
L Balleisen ◽  
F Asbeck ◽  
J van de Loo
Keyword(s):  
Molecular Weight ◽  
Day Treatment ◽  
Gel Filtration ◽  
Weight Fraction ◽  
In Vivo Studies ◽  
Low Molecular Weight ◽  
High Molecular Weight Fraction ◽  
Platelet Factor ◽  
Heparin Fractions

SummaryHigh and low molecular weight heparin fractions obtained by gel filtration chromatography of sodium mucosal heparin were injected subcutaneously into six healthy volunteers and compared with the unfractionated substance in a cross-over trial. Equal doses of 5,000 U were administered twice daily over a period of three days and heparin activity was repeatedly controlled before and 2, 4, 8 hrs after injection by means of the APTT, the anti-Xa clotting test and a chromogenic substrate assay. In addition, the in vivo effect of subcutaneously administered fractionated heparin on platelet function was examined on three of the volunteers. The results show that s.c. injections of the low molecular weight fraction induced markedly higher anti-Xa activity than injections of the other preparations. At the same time, APTT results did not significantly differ. Unfractionated heparin and the high molecular weight fraction enhanced ADP-induced platelet aggregation and collagen-mediated MDA production, while the low molecular weight fraction hardly affected these assays, but potently inhibited thrombin-induced MDA production. All heparin preparations stimulated the release of platelet Factor 4 in plasma. During the three-day treatment periods, no side-effects and no significant changes in the response to heparin injections were detected.

Neurotrophic Properties of Silexan, an Essential Oil from the Flowers of Lavender-Preclinical Evidence for Antidepressant-Like Properties

2020 ◽  
Vol 54 (01) ◽  
pp. 37-46
Author(s):  
Kristina Friedland ◽  
Giacomo Silani ◽  
Anita Schuwald ◽  
Carola Stockburger ◽  
Egon Koch ◽  
...  
Keyword(s):  
Essential Oil ◽  
Hippocampal Neurons ◽  
Day Treatment ◽  
Neuronal Cell ◽  
Antidepressant Activity ◽  
In Vivo Models ◽  
Antidepressant Effects ◽  
Primary Hippocampal Neurons

Abstract Background Silexan, a special essential oil from flowering tops of lavandula angustifolia, is used to treat subsyndromal anxiety disorders. In a recent clinical trial, Silexan also showed antidepressant effects in patients suffering from mixed anxiety-depression (ICD-10 F41.2). Since preclinical data explaining antidepressant properties of Silexan are missing, we decided to investigate if Silexan also shows antidepressant-like effects in vitro as well as in vivo models. Methods We used the forced swimming test (FST) in rats as a simple behavioral test indicative of antidepressant activity in vivo. As environmental events and other risk factors contribute to depression through converging molecular and cellular mechanisms that disrupt neuronal function and morphology—resulting in dysfunction of the circuitry that is essential for mood regulation and cognitive function—we investigated the neurotrophic properties of Silexan in neuronal cell lines and primary hippocampal neurons. Results The antidepressant activity of Silexan (30 mg/kg BW) in the FST was comparable to the tricyclic antidepressant imipramine (20 mg/kg BW) after 9-day treatment. Silexan triggered neurite outgrowth and synaptogenesis in 2 different neuronal cell models and led to a significant increase in synaptogenesis in primary hippocampal neurons. Silexan led to a significant phosphorylation of protein kinase A and subsequent CREB phosphorylation. Conclusion Taken together, Silexan demonstrates antidepressant-like effects in cellular as well as animal models for antidepressant activity. Therefore, our data provides preclinical evidence for the clinical antidepressant effects of Silexan in patients with mixed depression and anxiety.

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