Medicinal plants - prophylactic and therapeutic options for gastrointestinal and respiratory diseases in calves and piglets? A systematic review.

BACKGROUND Gastrointestinal and respiratory diseases in calves and piglets lead to significant economic losses in livestock husbandry. A high morbidity has been reported for diarrhea (calves ≤ 35 %; piglets ≤ 50 %) and for respiratory diseases (calves ≤ 80 %; piglets ≤ 40 %). Despite a highly diverse etiology and pathophysiology of these diseases, treatment with antimicrobials is often the first-line therapy. Multi-antimicrobial resistance in pathogens results in international accordance to strengthen the research in novel treatment options. Medicinal plants bear a potential as alternative or additional treatment. Based on the versatile effects of their plant specific multi-component-compositions, medicinal plants can potentially act as 'multi-target drugs'. Regarding the plurality of medicinal plants, the aim of this systematic review was to identify potential medicinal plant species for prevention and treatment of gastrointestinal and respiratory diseases and for modulation of the immune system and inflammation in calves and piglets. RESULTS Based on nine initial sources including standard textbooks and European ethnoveterinary studies, a total of 223 medicinal plant species related to the treatment of gastrointestinal and respiratory diseases was identified. A defined search strategy was established using the PRISMA statement to evaluate 30 medicinal plant species starting from 20'000 peer-reviewed articles published in the last 20 years (1994-2014). This strategy led to 418 references (257 in vitro, 84 in vivo and 77 clinical trials, thereof 48 clinical trials in veterinary medicine) to evaluate effects of medicinal plants and their efficacy in detail. The findings indicate that the most promising candidates for gastrointestinal diseases are Allium sativum L., Mentha x piperita L. and Salvia officinalis L.; for diseases of the respiratory tract Echinacea purpurea (L.) MOENCH, Thymus vulgaris L. and Althea officinalis L. were found most promising, and Echinacea purpurea (L.) MOENCH, Camellia sinensis (L.) KUNTZE, Glycyrrhiza glabra L. and Origanum vulgare L. were identified as best candidates for modulation of the immune system and inflammation. CONCLUSIONS Several medicinal plants bear a potential for novel treatment strategies for young livestock. There is a need for further research focused on gastrointestinal and respiratory diseases in calves and piglets, and the findings of this review provide a basis on plant selection for future studies.

Resistance to colistin : what is the fate for this antibiotic in pig production?

Colistin, a cationic polypeptide antibiotic, has reappeared in human medicine as a last-line treatment option for multidrug-resistant Gram-negative bacteria (MDR-GNB). Colistin is widely used in veterinary medicine for the treatment of gastrointestinal infections caused by Enterobacteriaceae. GNB resistant to colistin owing to chromosomal mutations have already been reported both in human and veterinary medicine, however several recent studies have just identified a plasmid-mediated mcr-1 gene encoding for colistin resistance in Escherichia coli colistin resistance. The discovery of a non-chromosomal mechanism of colistin resistance in E. coli has led to strong reactions in the scientific community and to concern among physicians and veterinarians. Colistin use in food animals and particularly in pig production has been singled out as responsible for the emergence of colistin resistance. The present review will focus mainly on the possible link between colistin use in pigs and the spread of colistin resistance in Enterobacteriaceae. First we demonstrate a possible link between Enterobacteriaceae resistance emergence and oral colistin pharmacokinetics/pharmacodynamics and its administration modalities in pigs. We then discuss the potential impact of colistin use in pigs on public health with respect to resistance. We believe that colistin use in pig production should be re-evaluated and its dosing and usage optimised. Moreover, the search for competitive alternatives to using colistin with swine is of paramount importance to preserve the effectiveness of this antibiotic for the treatment of MDR-GNB infections in human medicine.

Resistance to colistin : what is the fate for this antibiotic in pig production?

Colistin, a cationic polypeptide antibiotic, has reappeared in human medicine as a last-line treatment option for multidrug-resistant Gram-negative bacteria (MDR-GNB). Colistin is widely used in veterinary medicine for the treatment of gastrointestinal infections caused by Enterobacteriaceae. GNB resistant to colistin owing to chromosomal mutations have already been reported both in human and veterinary medicine, however several recent studies have just identified a plasmid-mediated mcr-1 gene encoding for colistin resistance in Escherichia coli colistin resistance. The discovery of a non-chromosomal mechanism of colistin resistance in E. coli has led to strong reactions in the scientific community and to concern among physicians and veterinarians. Colistin use in food animals and particularly in pig production has been singled out as responsible for the emergence of colistin resistance. The present review will focus mainly on the possible link between colistin use in pigs and the spread of colistin resistance in Enterobacteriaceae. First we demonstrate a possible link between Enterobacteriaceae resistance emergence and oral colistin pharmacokinetics/pharmacodynamics and its administration modalities in pigs. We then discuss the potential impact of colistin use in pigs on public health with respect to resistance. We believe that colistin use in pig production should be re-evaluated and its dosing and usage optimised. Moreover, the search for competitive alternatives to using colistin with swine is of paramount importance to preserve the effectiveness of this antibiotic for the treatment of MDR-GNB infections in human medicine.

In vitro efficacy of selected medicinal plants from Cholistan desert, Pakistan, against gastrointestinal helminths of sheep and goats

Gastrointestinal helminths are a major constraint to small ruminants in extensive husbandry systems of tropical regions. Yet, unavailability, high prices, side effects, and development of parasite resistance often limit the use of synthetic anthelmintics. Traditional medicinal plants might be an effective low-cost alternative. Therefore the in vitro anthelmintic activity of leaf extracts of the ligneous plants Capparis decidua, Salsola foetida, Suaeda fruticosa, Haloxylon salicornicum, and Haloxylon recurvum from Cholistan, Pakistan, was investigated against adult worms of Haemonchus contortus, Trichuris ovis, and Paramphistomum cervi. Various concentrations (from 7.8 to 500 mg dry matter ml^(−1)) of three extracts (aqueous, methanol, and aqueous-methanol) of each plant were tested at different time intervals for their anthelmintic activity via adult motility assay. Plant species (p<=0.01), extract type (p<=0.001), parasite species (p<=0.001), extract concentration (p<=0.001), time of exposure (p<=0.001) and their interactions (p<=0.001) affected the number of immobile or dead helminths. The 50% lethal concentration (LC_(50)) values indicated that the methanol and aqueous-methanol extracts of C. decidua, H. recurvum, and H. salicornicum as well as the methanol extract of S. fruticosa have the potential to be developed into plant-based remedies against the studied helminths. Further studies are needed to investigate the in vivo anthelmintic activity of these extracts, in order to develop effective, cheap and locally available anthelmintics for pastoralists in Cholistan and neighbouring desert regions.

Primary Antibiotic Resistance to Helicobacter pylori Strains Isolated From Children in Northern Iran: A Single Center Study

Background: Initial resistance to antibiotics is the main reason for the failure of Helicobacter pylori (H. pylori) eradication in children. Objectives: As we commonly face high antibiotic resistance rates in children, we aimed to determine the susceptibility of H. pylori to common antibiotics. Patients and Methods: In this cross-sectional in vitro study, 169 children younger than 14 years with clinical diagnosis of peptic ulcer underwent upper gastrointestinal endoscopy. Biopsy specimens from stomach and duodenum were cultured. In isolated colonies, tests of catalase, urease, and oxidase as well as gram staining were performed. After confirming the colonies as H. pylori, the antibiogram was obtained using disk diffusion method. Results: Culture for H. pylori was positive in 12.3% of the specimens, urease test in 21.3%, serological test in 18.9% and stool antigen test was positive in 21.9%. We could show high specificity but moderate sensitivity of both histological and H. pylori stool antigen tests to detect H. pylori. The overall susceptibility to metronidazole was 42.9%, amoxicillin 95.2%, clarithromycin 85.7%, furazolidone 61.9%, azithromycin 81.0%, and tetracycline 76.2% with the highest resistance to metronidazole and the lowest to clarithromycin. Conclusions: In our region, there is high resistance of H. pylori to some antibiotics including metronidazole and furazolidone among affected children. To reduce the prevalence of this antibiotic resistance, more controlled use of antibiotics should be considered in children.

Fiber, a component for health gastrointestinal endocrine system

Dietary fiber was classified according to its solubility in an attempt to relate physiological effects to chemical types of fiber. Soluble fibers (B-glucans, gums, wheat dextrin, psyllium, pectin, inulin) were considered to have benefits on serum lipids, while insoluble fibers (cellulose, lignin, pectins, hemicelluloses) were linked with laxation benefits. More important characteristics of fiber in terms of physiological benefits are viscosity and fermentability. Viscous fibers (pectins, B-glucans, gums, psyllium) are those that have gel-forming properties in the intestinal tract, and fermentable fibers (wheat dextrin, pectins, B-glucans, gum, inulin) are those that can be metabolized by colonic bacteria. Objective: To summarize the beneficial effects of dietary fiber, as nutraceuticals, in order to maintain a healthy gastrointestinal system. Methods: Our study is a systematic review. Electronic databases, including PubMed, Medline, with supplement of relevant websites, were searched. We included randomized and non-randomized clinical trials, epidemiological studies (cohort and case-control). We excluded case series, case reports, in vitro and animal studies. Results: The WHO, the U.S. Food and Drug Administration (FDA), the Heart Foundation and the Romanian Dietary Guidelines recommends that adults should aim to consume approximately 25–30 g fiber daily. Dietary fiber is found in the indigestible parts of cereals, fruits and vegetables. There are countries where people don’t eat enough food fibers, these people need to take some kind of fiber supplement. Evidence has been found that dietary fiber from whole foods or supplements may (1) reduce the risk of cardiovascular disease by improving serum lipids and reducing serum total and low-density lipoprotein (LDL) cholesterol concentrations, (2) decreases the glycaemic index of foods, which leads to an improvement in glycemic response, positive impact on diabetes, (3) protect against development of obesity by increasing satiety hormone leptin concentrations, (4) reduced risk of developing colorectal cancer by normalizes bowel movements, improve the integrity of the epithelial layer of the intestines, increase the resistance against pathogenic colonization, have favorable effects on the gut microbiome, wich is the second genomes of the microorganisms, (5) have a positive impact on the endocrine system by gastrointestinal polypeptide hormonal regulation of digestion, (6) have prebiotic effect by short-chain fatty acids (SCFA) production; butyrate acid is the preferred energy source for colonic epithelial cells, promotes normal cell differentiation and proliferation, and also help regulate sodium and water absorption, and can enhance absorption of calcium and other minerals. Although all prebiotics are fiber, not all fiber is prebiotic. This generally refers to the ability of a fiber to increase the growth of bifidobacteria and lactobacilli, which are beneficial to human health, and (7) play a role in improving immune function via production of SCFAs by increases T helper cells, macrophages, neutrophils, and increased cytotoxic activity of natural killer cells. Conclusion: Fiber consumption is associated with high nutritional value and antioxidant status of the diet, enhancing the effects on human health. Fibers with prebiotic properties can also be recommended as part of fiber intake. Due to the variability of fiber’s effects in the body, it is important to consume fiber from a variety of sources. Increasing fiber consumption for health promotion and disease prevention is a critical public health goal.

Role of bioactive compounds in the gastrointestinal host-pathogen interaction of poultry and swine

The better understanding of mechanisms at the basis of host-pathogen interaction can represent a valid tool to increase productivity and contain economic losses in animal production through the maintenance of intestinal homeostasis. With this project, three preliminary in vitro studies were conducted with the aim of investigating how bioactive compounds could influence mechanisms of host-pathogen interaction in poultry and swine. Different panels of nature identical compounds, medium chain fatty acids, and plant extracts were employed against strains of Salmonella Typhimurium, Brachyspira hyodysenteriae, and Salmonella Enteritidis, respectively. When bacterial field strains were tested, the comparison between natural compounds and antibiotics was examined, with the aim of evaluating the role of the substances in the antibiotic-resistance context. Results demonstrate that bioactive compounds have positive effects on the host, the pathogen, or both in different experimental conditions. Additionally, when compared to antibiotics, bioactive compounds have proven to be valid alternatives to address the phenomenon of antibiotic resistance.

Gastrointestinal stromal tumors: Arbutus unedo L. as a source of novel chemotherapeutics & mechanisms behind metastasis

Gastrointestinal stromal tumors (GIST) are mesenchymal neoplasms frequently caused by a gain of function mutation in KIT or PDGFRα, two tyrosine kinase receptors (TKR). For this reason, they are successfully treated with imatinib, a tyrosine kinase inhibitor (TKI). However, the therapy is typically long-term ineffective due to imatinib resistance, which represents the main issue in the clinic of GISTs. Although numerous efforts have been made in the last two decades to develop novel therapies for imatinib-resistant GISTs, the approvals of multi-target TKIs have only improved the clinical outcomes modestly. Emblematic is the recent failure of ripretinib in the phase III INTRIGUE trial, decisively marking the end of the paradigm only based on the central role of KIT secondary mutations in imatinib resistance, and the consequent seeking of multi-target TKIs as the solution. Consistent with this clinical result, preclinical studies have revealed numerous mechanisms of resistance that are not targetable with multi-target TKIs, indicating that imatinib resistance is more multifaceted than initially hypothesized and explaining the modest efficacy of these latter. In this scenario, the absence of drugs capable of long-term counteracting the rise of imatinib-resistant subclones unavoidably leads to progressive disease and metastasis. In particular, the onset of metastases remarkably impacts the median overall survival and determines the most GIST-related deaths. Therefore, new therapy proposals are needed. Here, we present two project lines investigating novel strategies to counteract imatinib-resistant GISTs.

Ikkε Is Key To Induction Of Insulin Resistance In The Hypothalamus, And Its Inhibition Reverses Obesity.

IKK epsilon (IKKε) is induced by the activation of nuclear factor-κB (NF-κB). Whole-body IKKε knockout mice on a high-fat diet (HFD) were protected from insulin resistance and showed altered energy balance. We demonstrate that IKKε is expressed in neurons and is upregulated in the hypothalamus of obese mice, contributing to insulin and leptin resistance. Blocking IKKε in the hypothalamus of obese mice with CAYMAN10576 or small interfering RNA decreased NF-κB activation in this tissue, relieving the inflammatory environment. Inhibition of IKKε activity, but not TBK1, reduced IRS-1(Ser307) phosphorylation and insulin and leptin resistance by an improvement of the IR/IRS-1/Akt and JAK2/STAT3 pathways in the hypothalamus. These improvements were independent of body weight and food intake. Increased insulin and leptin action/signaling in the hypothalamus may contribute to a decrease in adiposity and hypophagia and an enhancement of energy expenditure accompanied by lower NPY and increased POMC mRNA levels. Improvement of hypothalamic insulin action decreases fasting glycemia, glycemia after pyruvate injection, and PEPCK protein expression in the liver of HFD-fed and db/db mice, suggesting a reduction in hepatic glucose production. We suggest that IKKε may be a key inflammatory mediator in the hypothalamus of obese mice, and its hypothalamic inhibition improves energy and glucose metabolism.

Gastrointestinal Involvement In Lipoid Proteinosis: A Ten-year Follow-up Of A Brazilian Female Patient.

Lipoid proteinosis is a rare autosomal recessive disease characterized by the deposition of hyaline material in the skin and internal organs. The main clinical features are hoarseness and typical skin lesions. In this report we describe the endoscopic and radiologic findings in a Brazilian female patient presenting extensive gastrointestinal involvement and the evolution of the detected lesions in ten years of follow-up. Initial upper endoscopy and colonoscopy showed a similar pattern of multiple yellowish nodules throughout the esophagus, stomach, duodenum, and colons. Histological analysis confirmed the diagnosis of lipoid proteinosis. In addition, small bowel follow through demonstrated numerous well defined, round, small filling defects throughout the jejunum. Ten years later, the esophageal lesions remained the same, but none of the previous alterations were detected in the stomach, duodenum, and colons. In conclusion, lipoid proteinosis may affect all gastrointestinal organs with the same pattern of macroscopic and microscopic lesions. Some lesions may regress with increasing age.

Neck Circumference As A New Anthropometric Indicator For Prediction Of Insulin Resistance And Components Of Metabolic Syndrome In Adolescents: Brazilian Metabolic Syndrome Study.

To evaluate the correlation between neck circumference and insulin resistance and components of metabolic syndrome in adolescents with different adiposity levels and pubertal stages, as well as to determine the usefulness of neck circumference to predict insulin resistance in adolescents. Cross-sectional study with 388 adolescents of both genders from ten to 19 years old. The adolescents underwent anthropometric and body composition assessment, including neck and waist circumferences, and biochemical evaluation. The pubertal stage was obtained by self-assessment, and the blood pressure, by auscultation. Insulin resistance was evaluated by the Homeostasis Model Assessment-Insulin Resistance. The correlation between two variables was evaluated by partial correlation coefficient adjusted for the percentage of body fat and pubertal stage. The performance of neck circumference to identify insulin resistance was tested by Receiver Operating Characteristic Curve. After the adjustment for percentage body fat and pubertal stage, neck circumference correlated with waist circumference, blood pressure, triglycerides and markers of insulin resistance in both genders. The results showed that the neck circumference is a useful tool for the detection of insulin resistance and changes in the indicators of metabolic syndrome in adolescents. The easiness of application and low cost of this measure may allow its use in Public Health services.

Undulatory Physical Resistance Training Program Increases Maximal Strength In Elderly Type 2 Diabetics.

To investigate the effects of a specific protocol of undulatory physical resistance training on maximal strength gains in elderly type 2 diabetics. The study included 48 subjects, aged between 60 and 85 years, of both genders. They were divided into two groups: Untrained Diabetic Elderly (n=19) with those who were not subjected to physical training and Trained Diabetic Elderly (n=29), with those who were subjected to undulatory physical resistance training. The participants were evaluated with several types of resistance training's equipment before and after training protocol, by test of one maximal repetition. The subjects were trained on undulatory resistance three times per week for a period of 16 weeks. The overload used in undulatory resistance training was equivalent to 50% of one maximal repetition and 70% of one maximal repetition, alternating weekly. Statistical analysis revealed significant differences (p<0.05) between pre-test and post-test over a period of 16 weeks. The average gains in strength were 43.20% (knee extension), 65.00% (knee flexion), 27.80% (supine sitting machine), 31.00% (rowing sitting), 43.90% (biceps pulley), and 21.10% (triceps pulley). Undulatory resistance training used with weekly different overloads was effective to provide significant gains in maximum strength in elderly type 2 diabetic individuals.

Urothelial Carcinogen Resistance Driven By Stronger Toll-like Receptor 2 (tlr2) And Uroplakin Iii (up Iii) Defense Mechanisms: A New Model.

The objective of the study was to illustrate the applicability and significance of the novel Lewis urothelial cancer model compared to the classic Fisher 344. Fischer 344 and Lewis females rats, 7 weeks old, were intravesical instilled N-methyl-N-nitrosourea 1.5 mg/kg every other week for a total of four doses. After 15 weeks, animals were sacrificed and bladders analyzed: histopathology (tumor grade and stage), immunohistochemistry (apoptotic and proliferative indices) and blotting (Toll-like receptor 2-TLR2, Uroplakin III-UP III and C-Myc). Control groups received placebo. There were macroscopic neoplastic lesions in 20 % of Lewis strain and 70 % of Fischer 344 strain. Lewis showed hyperplasia in 50 % of animals, normal bladders in 50 %. All Fischer 344 had lesions, 20 % papillary hyperplasia, 30 % dysplasia, 40 % neoplasia and 10 % squamous metaplasia. Proliferative and apoptotic indices were significantly lower in the Lewis strain (p < 0.01). The TLR2 and UP III protein levels were significantly higher in Lewis compared to Fischer 344 strain (70.8 and 46.5 % vs. 49.5 and 16.9 %, respectively). In contrast, C-Myc protein levels were significantly higher in Fischer 344 (22.5 %) compared to Lewis strain (13.7 %). The innovative Lewis carcinogen resistance urothelial model represents a new strategy for translational research. Preservation of TLR2 and UP III defense mechanisms might drive diverse urothelial phenotypes during carcinogenesis in differently susceptible individuals.

Mechanisms Of Insulin Resistance In The Amygdala: Influences On Food Intake.

Obesity is increasing worldwide and is triggered, at least in part, by enhanced caloric intake. Food intake is regulated by a complex mechanism involving the hypothalamus and hindbrain circuitries. However, evidences have showing that reward systems are also important in regulating feeding behavior. In this context, amygdala is considered a key extra-hypothalamic area regulating feeding behavior in human beings and rodents. This review focuses on the regulation of food intake by amygdala and the mechanisms of insulin resistance in this brain area. Similar to the hypothalamus the anorexigenic effect of insulin is mediated via PI3K (phosphoinositide 3-kinase)/Akt (protein kinase B) pathway in the amygdala. Insulin decreases NPY (neuropeptide Y) and increases oxytocin mRNA levels in the amygdala. High fat diet and saturated fatty acids induce inflammation, ER (endoplasmic reticulum) stress and the activation of serine kinases such as PKCθ (protein kinase C theta), JNK (c-Jun N-terminal kinase) and IKKβ (inhibitor of nuclear factor kappa-B kinase beta) in the amygdala, which have an important role in insulin resistance in this brain region. Overexpressed PKCθ in the CeA (central nucleus of amygdala) of rats increases weight gain, food intake, insulin resistance and hepatic triglycerides content. The inhibition of ER stress ameliorates insulin action/signaling, increases oxytocin and decreases NPY gene expression in the amygdala of high fat feeding rodents. Those data suggest that PKCθ and ER stress are main mechanisms of insulin resistance in the amygdala of obese rats and play an important role regulating feeding behavior.

Two Novel Mutations In The Thyroid Hormone Receptor β In Patients With Resistance To Thyroid Hormone (rth β): Clinical, Biochemical, And Molecular Data.

The syndrome of resistance to thyroid hormone (RTH β) is an inherited disorder characterized by variable tissue hyposensitivity to 3,5,30-l-triiodothyronine (T3), with persistent elevation of free-circulating T3 (FT3) and free thyroxine (FT4) levels in association with nonsuppressed serum thyrotropin (TSH). Clinical presentation is variable and the molecular analysis of THRB gene provides a short cut diagnosis. Here, we describe 2 cases in which RTH β was suspected on the basis of laboratory findings. The diagnosis was confirmed by direct THRB sequencing that revealed 2 novel mutations: the heterozygous p.Ala317Ser in subject 1 and the heterozygous p.Arg438Pro in subject 2. Both mutations were shown to be deleterious by SIFT, PolyPhen, and Align GV-GD predictive methods.