Alternative Therapeutic Treatments Research Articles

“Straight from the Horse’s Mouth”: Equine-Assisted Services Curriculum Development Using Industry-Based Survey Assessment of Horse Welfare and Healthcare Management Practices

Equine-assisted services (EAS) is a relatively new area of study within higher education requiring the development of a curriculum that best prepares the undergraduate student for the demands of the industry. Further, coursework targeting the specific management challenges for ensuring the welfare of horses utilized within EAS is limited. Therefore, the objective of this study was to apply an industry-based survey assessment utilizing EAS professionals within the United States to document management practices associated with healthcare and pain management challenges in the EAS horse. Suggested curriculum for undergraduate students targeting a career in EAS is given, utilizing data collected from the survey. Participant responses (n = 30) indicated that all of the surveyed facilities cared for more than three geriatric horses within their program, with the majority (60% responding “definitely yes”) utilizing regularly functionally lame horses, although the prevalence of lameness was not correlated with number of geriatric horses within a program (0.20, p = 0.22). While lameness is a common healthcare challenge within EAS, gastrointestinal conditions (73%) were one of the other leading health concerns for these facilities. The most common equine pain detection method for EAS facilities was behavior assessment (93%), in which this method was positively correlated with years of horse experience (0.51, p = 0.01). Horse pain was primarily managed through annual alternative therapeutic interventions (76%), daily prescriptions (73%), and nutritional supplements (73%). As such, the curriculum for undergraduate EAS degree programs should cover healthcare practices targeting geriatric horse management and associated health issues such as gastrointestinal conditions and lameness, including early detection and pharmaceutical, nutritional, and alternative therapeutic treatments.

Unveiling therapeutic prospects: targeting MDM-2 in non-muscle invasive bladder cancer

Non-muscle invasive bladder cancer (NMIBC) is considered one of the most costly malignancies, requiring significant surgical and therapeutic measures. However, progression and non-responsiveness to immunotherapy are common outcomes of treatment. In this study, we conducted comparative transcriptomic analysis of non-responders from two distinct populations (Asian and American) and identified six common genes associated with disease prognosis. Among these genes, MDM-2 is a major oncogenic protein linked to seven different types of cancers, as it is involved in the degradation of the tumor suppressor protein p53. To address this, we explored novel therapeutic drugs to block the binding of p53 and MDM-2 using a targeted molecular docking approach. High-throughput screening of 2500 drugs from the FDA-approved drug database led to the identification of three drug compounds: Mol-126, Mol-679, and Mol-768. Subsequently, we evaluated the structural stability and binding of these drugs for the targeted inhibition of the MDM-2 active site (hydrophobic cleft) using molecular dynamics simulations. Analysis of five trajectories, including RMSD, RMSF, hydrogen bond, radius of gyration, coulomb short-range electrostatic spectra, and free binding energy, confirmed that Mol-126 exhibited the highest structural stability compared to the reference drug (Alrizomadlin). Notably, Mol-126 is a derivative of 3-phenoxypropionic acid, which shows promise for the development of alternative therapeutic treatments for non-responsive bladder cancer patients. Communicated by Ramaswamy H. Sarma

Plant-inspired adhesive and injectable natural hydrogels: invitroand invivo studies.

The development of alternative therapeutic treatments based on the use of medicinal and aromatic plants, such as Juniper communis L., has aroused interest in the medical field to find new alternatives to conventional therapeutic treatments, which have shown problems related to bacterial resistance, high costs, or sustainability in their production. The present work describes the use of hydrogels based on sodium alginate and carboxymethyl cellulose, with combinations of juniperus leaves and berry extracts, in order to characterize their chemical characteristics, antibacterial activity, tissue adhesion test, cytotoxicity in the L929 cell line, and their effects on an in vivo model in mice to maximize the use of these materials in the healthcare field. Overall, an adequate antibacterial potential against S. aureus, E. coli and P. vulgaris was obtained with doses above 100mg.mL-1 of hydrogels. Likewise, low cytotoxicity in hydrogels combined with extracts has been identified according to the IC50 value at 17.32µg.mL-1, compared to the higher cytotoxic activity expressed by the use of control hydrogels with a value at 11.05µg.mL-1. Moreover, in general, the observed adhesion was high to different tissues, showing its adequate capacity to be used in different tissue typologies. Furthermore, the invivo results have not shown erythema, edema, or other complications related to the use of the proposed hydrogels. These results suggest the feasibility of using these hydrogels in biomedical applications given the observed safety.

Beneficial Effects of a Blended Fibroin/Aloe Gel Extract Film on the Biomolecular Mechanism(s) via the MAPK/ERK Pathway Relating to Diabetic Wound Healing.

In diabetic patients, the process of wound healing is usually delayed or impaired. A diabetic environment could be associated with dermal fibroblast dysfunction, reduced angiogenesis, the release of excessive proinflammatory cytokines, and senescence features. Alternative therapeutic treatments using natural products are highly demanded for their high potential of bioactive activity in skin repair. Two natural extracts were combined to develop fibroin/aloe gel wound dressing. Our previous studies revealed that the prepared film enhances the healing rate of diabetic foot ulcers (DFUs). Moreover, we aimed to explore its biological effects and underlying biomolecular mechanisms on normal dermal, diabetic dermal, and diabetic wound fibroblasts. Cell culture experiments showed that the γ-irradiated blended fibroin/aloe gel extract film promotes skin wound healing by enhancing cell proliferation and migration, vascular epidermal growth factor (VEGF) secretion, and cell senescence prevention. Its action was mainly linked to the activation of the mitogen-activated protein kinases/extracellular signal-regulated kinase (MAPK/ERK) signaling pathway known to regulate various cellular activities, including proliferation. Therefore, the findings of this study confirm and support our previous data. The blended fibroin/aloe gel extract film displays a biological behavior with favorable properties for delayed wound healing and can be considered as a promising therapeutic approach in the treatment of diabetic nonhealing ulcers.

Autophagic and apoptotic cell death induced by the quinoline derivative 2‐(6‐methoxynaphthalen‐2‐yl)quinolin‐4‐amine in pancreatic cancer cells is via ER stress and inhibition of Akt/mTOR signaling pathway

AbstractPancreatic cancer (PC) is among the most lethal cancers and is resistant to existing therapies, which highlights the need for new and alternative therapeutic treatments. Autophagy is emerging as one of the alternative cell death mechanisms and is well known to cross‐talk with apoptosis. Autophagy can act as a viable option to treat highly resistant PC. The current study investigates and provides insight into the autophagic and apoptotic cell death induced by quinoline derivative 2‐(6‐methoxynaphthalen‐2‐yl)quinolin‐4‐amine (6MN‐4‐AQ) in PC cell lines PANC‐1 and MIA PaCa‐2. Treatment with 6MN‐4‐AQ reduced cell viability in concentration dependent manner (2–16 μM) and inhibited the clonogenic potential of PC cells at a concentration of 4 μM for 24 h. Further, we found that 6MN‐4‐AQ induced both apoptosis and autophagic cell death simultaneously. We identified that 6MN‐4‐AQ induced autophagic cell death by forming cytoplasmic vacuoles, the elevation of autophagy flux, increase in LC3‐II, Beclin‐1 protein expression, and degradation of p62. Moreover, 6MN‐4‐AQ induced apoptosis via Caspase‐3 activation and cleavage of PARP in PC cells. Upon investigating the underlying mechanism associated with 6MN‐4‐AQ induced cell death, it was observed that 6MN‐4‐AQ treatment is able to suppress the Akt/mTOR pathway and induced ER stress leading to the induction of autophagy. Also, 6MN‐4‐AQ treatment suppressed epithelial to mesenchymal transition by reducing the protein expression of SLUG, snail, and vimentin. Subsequently, 6MN‐4‐AQ inhibited cell migration and invasion by down regulating MMP‐7 and MMP‐9 protein expression, suggesting that 6MN‐4‐AQ may serve as a plausible therapeutic agent for PC.

Evaluation of preventive homeopathic treatment against Colibacillosis in swine production

Escherichia coli is the most important etiologic agent implied in neonatal diarrhea in swine; colibacillosis is the disease with highest impact in production of swine. The demands of consumers for meat without chemical residues and the ban on the use of antibiotics and chemotherapics in production of swine compelled to find alternative therapeutic and preventive treatments. Aims: to assess homeopathic treatment as preventive against colibacillosis in swine. Methods: the study was conducted in a farm in Mato Grosso, Brazil; stools of 4 piglets with diarrhea were collected to establish the presence of E. coli; concomitantly it was performed a clinical exam to identify the symptoms leading to the choice of a homeopathy remedy. Newborn piglets were divided into 4 groups (n= 11 or 12): 1) control, subjected to antibiotic treatment against diarrhea; 2) homeopathic treatment, performed with Phosphorus 30cH according to the symptoms collected; 3) biotherapic treatment, performed with Escherichia coli 30cH prepared from the locally obtained bacteria; 4) homeopathic + biotherapics treatment. Results: all 3 groups treated with homeopathy/isotherapy presented a significant reduction of diarrhea compared to the control group (p=0.02); the group treated with Phosphorus 30cH + Escherichia coli 30cH presented the highest weight gain which was significant by comparison to all other groups (p=0.001). Conclusion: homeopathic and biotherapics treatment were more effective than antibiotics in the control of diarrhea in newborn piglets; combination of homeopathic and isopathic treatment resulted in the highest weight gain. These results suggest that homeopathy and isopathy are effective alternatives for the treatment of diarrhea by E. coli in newborn swine.

Limosilactobacillus reuteri Strains as Adjuvants in the Management of Helicobacter pylori Infection.

Helicobacter pylori (HP) is a Gram-negative bacterium which finds its suitable habitat in the stomach. The infection affects about half of the global population with high variability in prevalence among regions and for age. HP is the main causative agent of chronic active gastritis, peptic and duodenal ulcers, and may be the primary cause of gastric cancer or MALT lymphoma. Due to the high rate of failure of eradication therapy in various countries and the increase in antibiotic resistance reported in the literature, there is an ever wider need to seek alternative therapeutic treatments. Probiotics seem to be a promising solution. In particular, the Limosilactobacillus reuteri (L. reuteri) species is a Gram-positive bacterium and is commonly found in the microbiota of mammals. L. reuteri is able to survive the gastric acid environment and bile and to colonize the gastric mucosa. This species is able to inhibit the growth of several pathogenic bacteria through different mechanisms, keeping the homeostasis of the microbiota. In particular, it is able to secrete reuterin and reutericycline, substances that exhibit antimicrobial properties, among other molecules. Through the secretion of these and the formation of the biofilm, it has been found to strongly inhibit the growth of HP and, at higher concentrations, to kill it. Moreover, it reduces the expression of HP virulence factors. In clinical trials, L. reuteri has been shown to decrease HP load when used as a single treatment, but has not achieved statistical significance in curing infected patients. As an adjuvant of standard regimens with antibiotics and pump inhibitors, L. reuteri can be used not only to improve cure rates, but especially to decrease gastrointestinal symptoms, which are a common cause of lack of compliance and interruption of therapy, leading to new antibiotic resistance.

Effects of Cell-Derived Microparticles on Immune Cells and Potential Implications in Clinical Medicine.

In the past few years, interest has increased in cell-derived microparticles (MPs), which are defined by their size of from 0.1 to 1 μm, and can be derived from various cell types, including endothelial cells, leukocytes, red blood cells (RBCs), and platelets. These MPs carry negatively charged phosphatidylserine (PS) on their surfaces and proteins packaged from numerous cellular components. MPs that have been shed by the body can play important roles in the pathophysiology of diseases and can affect various biological systems. Among these systems, the immune components have been shown to be modulated by MPs. Therefore, understanding the roles of MPs in the immune system is crucial to developing alternative therapeutic treatments for diseases. This review describes the effects of MPs on various immune cells and provides plausible potential applications of the immune-modulating properties of MPs in clinical medicine.

Paecilomyces tenuipes extracts affect lipid and glucose metabolic parameters similarly to Cordyceps militaris extracts

Abstract Ascocarps of some species of the genus Cordyceps have long been used as a traditional medicine and food source for promoting human health. The compound cordycepin, isolated from C. militaris ascocarps (CE), show similar health effects to CE. In this study, we investigated and compared the anti-obesity and antidiabetic effects of dietary CE and Paecilomyces tenuipes ascocarps (PE) in mice. In addition, we investigated their effects on the expression of genes related to the regulation of obesity and diabetes. We found that dietary CE and PE suppressed body weight gain and fat accumulation in the liver and adipocyte tissues of mice fed a high-fat diet (HFD). Enzyme and lipid profiles induced by HFD returned to normal with CE or PE treatment. Dietary CE or PE reduced fasting blood glucose and serum insulin levels in HFD-fed mice. Finally, we show that CE and PE treatment restored to normal the hyperlipidemia- and hyperglycemia-related gene expressions in HFD-fed mice. These results indicate that dietary CE or PE exert their anti-obesity and antidiabetic effects by regulating adipogenesis and insulin signaling pathways. Finally, we show that dietary CE or PE have similar anti-obesity and antidiabetic effects even when included in a normal mouse diet. Although cordycepin is not found in PE, PE treatment improves lipid and glucose metabolic parameters in a manner similar to CE. We find that PE provides alternative potential therapeutic treatments for obesity and diabetes.

Ethnopharmacological documentation of medicinal plants used in the traditional treatment of diabetes in Tar faya province (Morocco)

Moroccan people have a rich tradition of phytotherapy. Studies have been carried in different areas in order to describe local pharmacopoeia. However, very little information is available on the traditional medicine of Tarfaya province. An ethnobotanical survey was conducted to document medicinal plants used for diabetes treatment by the inhabitants of this province. A 150 respondents were interviewed through semi-structured surveys. A total of 68 medical plants belonging to 35 families were identif ied in the region. The most encountered medicinal plant families were Lamiaceae, Fabaceae and Apiaceae. Citrullus colocynthis, Ajuga iva, Allium sativum, Foeniculum vulgare, Ammodaucus leucotrichus and Searsia tripartita were reported as major medicinal plants to treat diabetes in Morocco. The present ethnobotanical study will extend the list of plants already mentioned in use for diabetes treatment in Morocco. However, further studies on their conservation strategies, phytochemical characterization and pharmacological validations are required to serve as a source for alternative therapeutic treatments.

Natural Products from Mediterranean Diet: From Anti-hyperlipidemic Agents to Dietary Epigenetic Modulators.

Cardiovascular Diseases (CVD) are, currently, the major contributor to global mortality and will continue to dominate mortality rates in the future. Hyperlipidemia refers to the elevated levels of lipids and cholesterol in the blood, and is also identified as dyslipidemia, manifesting in the form of different disorders of lipoprotein metabolism. These abnormalities may lead to the development of atherosclerosis, which can lead to coronary artery disease and stroke. In recent years, there is a growing interest in the quest for alternative therapeutic treatments based on natural products, offering better recovery and the avoidance of side effects. Recent technological advances have further improved our understanding of the role of epigenetic mechanisms in hyperlipidemic disorders and dietary prevention strategies. This is a comprehensive overview of the anti-hyperlipidemic effects of plant extracts, vegetables, fruits and isolated compounds thereof, with a focus on natural products from the Mediterranean region as well as the possible epigenetic changes in gene expression or cardiometabolic signaling pathways. For the purpose of this study, we searched the PubMed, Scopus and Google Scholar databases for eligible articles and publications over the last five years. The keywords included: "hyperlipidemia", "plant extract", "herbs", "natural products", "vegetables", "cholesterol" and others. We initially included all relevant articles referring to in vitro studies, animal studies, Randomized Controlled Trials (RCTs) and previous reviews. Many natural products found in the Mediterranean diet have been studied for the treatment of hyperlipidemia. The antihyperlipidemic effect seems to be dose and/or consumption frequency related, which highlights the fact that a healthy diet can only be effective in reversing disease markers if it is consistent and within the framework of a healthy lifestyle. Finally, epigenetic biomarkers are increasingly recognized as new lifestyle management tools to monitor a healthy dietary lifestyle for the prevention of hyperlipidaemic disorders and comorbidities to promote a healthy life.

The Blood-Brain Barrier and the EphR/Ephrin System: Perspectives on a Link Between Neurovascular and Neuropsychiatric Disorders.

Interactions among endothelial cells (EC) forming blood vessels and their surrounding cell types are essential to establish the blood-brain barrier (BBB), an integral part of the neurovascular unit (NVU). Research on the NVU has recently seen a renaissance to especially understand the neurobiology of vascular and brain pathologies and their frequently occurring comorbidities. Diverse signaling molecules activated in the near proximity of blood vessels trigger paracellular pathways which regulate the formation and stabilization of tight junctions (TJ) between EC and thereby influence BBB permeability. Among regulatory molecules, the erythropoietin-producing-hepatocellular carcinoma receptors (EphR) and their Eph receptor-interacting signals (ephrins) play a pivotal role in EC differentiation, angiogenesis and BBB integrity. Multiple EphR-ligand interactions between EC and other cell types influence different aspects of angiogenesis and BBB formation. Such interactions additionally control BBB sealing properties and thus the penetration of substances into the brain parenchyma. Thus, they play critical roles in the healthy brain and during the pathogenesis of brain disorders. In this mini-review article, we aim at integrating the constantly growing literature about the functional roles of the EphR/ephrin system for the development of the vascular system and the BBB and in the pathogenesis of neurovascular and neuropsychiatric disorders. We suggest the hypothesis that a disrupted EphR/ephrin signaling at the BBB might represent an underappreciated molecular hub of disease comorbidity. Finally, we propose the possibility that the EphR/ephrin system bears the potential of becoming a novel target for the development of alternative therapeutic treatments, focusing on such comorbidities.

Natural Substances in the Treatment of Cystic Fibrosis

The research on the biological activity of natural products and biomaterials is becoming year by year more competitive and complex, and involves experts in different research fields, including chemists, biochemists, molecular biologists, immunologists and bioinformatics. While unfractionated natural products exhibit “per se” biological properties relevant for alternative therapeutic treatments of human diseases, the identification of lead compounds within these products, the characterization of molecular targets and studies of structurally-related molecules are key processes to develop novel therapeutic strategies. Cystic fibrosis is a genetic disease caused by mutations of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene. It is well established that three major fields of therapeutic intervention should be considered, targeting CFTR, bacterial infection and inflammation. In this review, we describe natural products reported to be very useful tools for correction of pathological conditions related to cystic fibrosis. The main topics are (a) CFTR potentiation and correction using natural products, (b) natural products as antibacterial agents and (c) natural products exhibiting anti-inflammatory activity. The recent issues of waste utilization and drug repurposing are also discussed in the context of the development of possible therapeutic approaches for cystic fibrosis. Keywords: Cystic fibrosis, CFTR potentiation, CFTR correction, inflammation, antibacterial agents, drug repurposing.

Cnbp ameliorates Treacher Collins Syndrome craniofacial anomalies through a pathway that involves redox-responsive genes.

Treacher Collins Syndrome (TCS) is a rare congenital disease (1:50 000 live births) characterized by craniofacial defects, including hypoplasia of facial bones, cleft palate and palpebral fissures. Over 90% of the cases are due to mutations in the TCOF1 gene, which codifies the nucleolar protein Treacle. Here we report a novel TCS-like zebrafish model displaying features that fully recapitulate the spectrum of craniofacial abnormalities observed in patients. As it was reported for a Tcof1+/− mouse model, Treacle depletion in zebrafish caused reduced rRNA transcription, stabilization of Tp53 and increased cell death in the cephalic region. An increase of ROS along with the overexpression of redox-responsive genes was detected; furthermore, treatment with antioxidants ameliorated the phenotypic defects of craniofacial anomalies in TCS-like larvae. On the other hand, Treacle depletion led to a lowering in the abundance of Cnbp, a protein required for proper craniofacial development. Tcof1 knockdown in transgenic zebrafish overexpressing cnbp resulted in barely affected craniofacial cartilage development, reinforcing the notion that Cnbp has a role in the pathogenesis of TCS. The cnbp overexpression rescued the TCS phenotype in a dose-dependent manner by a ROS-cytoprotective action that prevented the redox-responsive genes' upregulation but did not normalize the synthesis of rRNAs. Finally, a positive correlation between the expression of CNBP and TCOF1 in mesenchymal cells from both control and TCS subjects was found. Based on this, we suggest CNBP as an additional target for new alternative therapeutic treatments to reduce craniofacial defects not only in TCS but also in other neurocristopathies.

Feasibility study for the introduction of a new treatment method for benign thyroid nodules in a teaching and research hospital.

Numerous scientific publications have confirmed that percutaneous laser thermal ablation (LTA) represents a possible therapeutic option in selected patients with benign thyroid nodules. A study was carried out to evaluate the feasibility of adopting the LTA technique to treat benign thyroid nodules in a teaching and research hospital in northern Italy. A cost analysis from a company's perspective determined the impact of adoption of the new technique on the overall Hospital budget, considering currently available equipment, infrastructure and personnel, equipment costs and treatment tariffs. The cost analysis shows that, strictly from an economic point of view, any provision of the LTA technique will result as a loss on the Hospital's balance sheet. However, it does not estimate the extent of the impact on the overall budget because it did not evaluate the savings that such a technique would make with respect to alternative therapeutic treatments. Therefore, the Hospital policy management decided to extend the current agreement with a private authorized health care structure that already carries out LTA. Also, although difficult to express in economic terms, this new technique would undoubtedly raise the profile and enhance the reputation of the Hospital. Using the new technique in these patients could cut costs for the entire regional health care system, widen the experience of the Hospital's endocrinology team and offer the potential for the procedure also to be provided by operators on a freelance basis within the Hospital.

Survey-based analysis of risk factors for injury among dogs participating in agility training and competition events

To identify potential risk factors for agility-related injuries among dogs. Internet-based, retrospective, cross-sectional survey. 3,801 privately owned dogs participating in agility training or trials. A retrospective electronic survey was used to investigate potential risk factors for injury among dogs participating in agility-related activities. Respondents were handlers recruited through member lists of large canine agility associations in Canada and the United Kingdom and through promotion on an agility blog site. Variables evaluated included demographic information for handlers and dogs, exposure variables (eg, frequency of agility practice and competition in the past year), and use of preventive measures intended to keep dogs fit for agility (warmup, cooldown, or conditioning exercises; alternative therapeutic treatments [eg, acupuncture, massage, or chiropractic care]; or dietary supplement products). Data were collected from 1,669 handlers of 3,801 agility dogs internationally; 1,209 (32%) dogs incurred ≥ 1 injury. Previous injury (OR, 100.5), ≤ 4 years of agility experience for dogs (OR, 1.5), use of alternative therapeutic treatments (OR, 1.5), and Border Collie breed (OR, 1.7) were associated with increased odds of injury. Handlers having 5 to 10 or > 10 years of experience (OR, 0.8 and 0.6, respectively) and dogs having > 4 years of experience in the sport (OR, 0.6) were associated with decreased odds of injury. Specific factors were associated with agility-related injuries in dogs. Educational prevention strategies should target at-risk populations in an effort to reduce potential injuries. Future research should focus on the biomechanical factors associated with agility-related injuries.

Encapsulation of Phaseolus lunatus Protein Hydrolysate with Angiotensin-Converting Enzyme Inhibitory Activity.

The objective of recent research has been to seek alternative therapeutic treatments; for this reason, the use of protein hydrolysates from diverse sources has been studied. A way to guarantee that these treatments reach the site of action is through protection with covers, such as microcapsules. Therefore, proteins from the legume Phaseolus lunatus were hydrolyzed and encapsulated with a blend of Delonix regia carboxymethylated gum/sodium alginate (50 : 50 w/w). Hydrolysis release conditions in a simulated gastrointestinal system were obtained using CaCl2 concentrations as the main factor, indicating that lower CaCl2 concentrations lead to an increased hydrolysis release. Beads obtained with 1.0 mM of CaCl2 exhibited a better hydrolysate release rate under intestinal simulated conditions and the proteins maintained an IC50 of 2.9 mg/mL. Capsules obtained with the blend of Delonix regia carboxymethylated gum/sodium alginate would be used for the controlled delivery of hydrolysates with potential use as nutraceutical or therapeutic agents.

Marine bacteria: potential sources for compounds to overcome antibiotic resistance

Methicillin-resistant Staphylococcus aureus (MRSA) is the most problematic Gram-positive bacterium in the context of public health due to its resistance against almost all available antibiotics except vancomycin and teicoplanin. Moreover, glycopeptide-resistant S. aureus have been emerging with the increasing use of glycopeptides. Recently, resistant strains against linezolid and daptomycin, which are alternative drugs to treat MRSA infection, have also been reported. Thus, the development of new drugs or alternative therapies is clearly a matter of urgency. In response to the antibiotic resistance, many researchers have studied for alternative antibiotics and therapies. In this review, anti-MRSA substances isolated from marine bacteria, with their potential antibacterial effect against MRSA as potential anti-MRSA agents, are discussed and several strategies for overcoming the antibiotic resistance are also introduced. Our objective was to highlight marine bacteria that have potential to lead in developing novel antibiotics or clinically useful alternative therapeutic treatments.

High-throughput small molecule screening reveals structurally diverse compounds that inhibit the growth of Escherichia coli O157:H7 in vitro.

Escherichia coli O157:H7 colonizes the gastrointestinal tract of ruminants asymptomatically and may enter the human food supply through fecal contamination. A fraction of individuals infected by E. coli O157:H7 develop hemolytic uremic syndrome, a life-threatening condition. When individuals infected by E. coli O157:H7 are treated with certain antibiotics, an increased incidence of hemolytic uremic syndrome may result. This finding supports the need to identify novel compounds that can either reduce the load of E. coli O157:H7 entering the human food supply or serve as alternative therapeutic treatments for infected individuals. We developed a high-throughput turbidometric assay to identify novel compounds that inhibit E. coli O157:H7 growth. Pin transfers were performed to introduce small molecule libraries into 384-well plates, where each well contained approximately 5.0 log CFU of E. coli O157:H7. Plates were incubated at 37°C for 18 h, and the optical density was measured to determine the effect of each small molecule. A total of 64,562 compounds were screened in duplicate, and 43 unique compounds inhibited E. coli O157:H7 growth. Thirty-eight of the 43 inhibitory compounds belonged to known bioactive libraries, and the other 5 compounds were from commercial libraries derived from splitting and pooling. Inhibitory compounds from known bioactive libraries were most frequently therapeutic antibiotics (n = 34) but also included an antiviral compound, a compound that disrupts the citric acid cycle, and two biguanide compounds, which have been used for various nonclinical applications. We identified two novel compounds (i.e., biguanides) that should be studied further for their ability to reduce pathogen populations in foods.

Oral l-cysteine ethyl ester (LCEE) reduces amoebic gill disease (AGD) in Atlantic salmon Salmo salar

There is a need for the development of alternative therapeutic treatments for amoebic gill disease (AGD) in Atlantic salmon Salmo salar L. to maintain the sustainability of the Tasmanian Atlantic salmon aquaculture industry. This study aimed to assess the effects of the mucolytic drug L-cysteine ethyl ester (LCEE) on marine Atlantic salmon mucus and whether or not it may have a therapeutic advantage for the alleviation of AGD when administered orally. We also aimed to document any physiological consequences of LCEE. Results showed that LCEE significantly decreased the viscosity of marine Atlantic salmon mucus both in vitro, where LCEE concentration showed a negative relationship to mucus viscosity (R2 = 0.95 at 11.5 s(-1)), and in vivo. Oral administration of LCEE at 52.7 mg LCEE kg(-1) fish d(-1) over 2 wk significantly delayed the progression of AGD-associated pathology during an aggressive, cohabitation induced, laboratory infection. Medicated fish had approximately 50% less gill filaments affected by AGD than control fed fish at 3 d post-infection when assessed using histology. Palatability of medicated feed was shown to be approximately 65% of control feed. No osmoregulatory disturbance was seen in medicated fish, although blood and whole body flux data indicated a slight acidosis coinciding with an increased plasma total ammonia concentration. However, both variables were within a tolerable physiological range and returned to control levels 3 d post-cessation of medicated feed. LCEE holds potential as an in-feed additive when administered over 2 wk prior to infection to delay the progression of AGD associated pathology. From the parameters measured, LCEE seems to have minimal physiological consequences after 2 wk of administration.