Adverse fluctuations in the distribution of the intestinal microbiome cohort has been associated with the onset of intra- and extra-intestinal inflammatory conditions, like the metabolic syndrome (MetS) and it's hepatic manifestation, non-alcoholic fatty liver disease (NAFLD). The intestinal microbial community of obese compared to lean subjects has been shown to undergo configurational shifts in various genera, including but not limited to increased abundances of Prevotella, Escherichia, Peptoniphilus, and Parabacteroides and decreased levels of Bifidobacteria, Roseburia, and Eubacteria genera. At the phylum level, decreased Bacteroidetes and increased Firmicutes have been reported. The intestinal microbiota therefore presents an important target for designing novel therapeutic modalities that target extra-intestinal inflammatory disorders, such as NAFLD. This review hypothesizes that disruption of the intestinal–mucosal macrophage interface is a key factor in intestinal-liver axis disturbances. Intestinal immune responses implicated in the manifestation, maintenance and progression of NAFLD provide insights into the dialogue between the intestinal microbiome, the epithelia and mucosal immunity. The pro-inflammatory activity and immune imbalances implicated in NAFLD pathophysiology are reported to stem from dysbiosis of the intestinal epithelia which can serve as a source of hepatoxic effects. We posit that the hepatotoxic consequences of intestinal dysbiosis are compounded through intestinal microbiota-mediated inflammation of the local mucosa that encourages mucosal immune dysfunction, thus contributing important plausible insight in NAFLD pathogenesis. The administration of probiotics and prebiotics as a cure-all remedy for all chronic diseases is not advocated, instead, the incorporation of evidence based probiotic/prebiotic formulations as adjunctive modalities may enhance lifestyle modification management strategies for the amelioration of NAFLD.
The intestinal microbiota is now recognised to play key roles in health due to its involvement in many aspects of human physiology. Disturbance in gut microbiota (dysbiosis) is thus associated with many diseases including nonalcoholic fatty liver disease (NAFLD) which includes nonalcoholic fatty liver and nonalcoholic steatohepatitis. The mechanisms for the effect of dysbiosis in NAFLD pathogenesis are not completely elucidated. Many explanations have been proposed to trigger dysbiosis, leading to NAFLD including inflammation, ethanol produced by the gut bacteria and lipotoxicity. Recently the roles of bile acids and nuclear receptors are highly regarded. It is well known that gut microbes produce enzymes that convert primary bile acids into secondary bile acids in the intestines. Several studies have demonstrated that disturbance of the intestinal microbiota leads to decreased synthesis of secondary bile acids, which in turn decreases activation of nuclear receptors such as farnesoid X receptor (FXR), pregnane X receptor, Takeda G-proteincoupled bile acid protein 5 and vitamin D receptor. These receptors are important in energy regulation and their dysregulation can cause NAFLD. Therefore, stimulation of nuclear receptors especially FXR has been extensively explored for the amelioration of NAFLD. However, paradoxical effects of nuclear receptor activation are a major problem for the clinical application of nuclear receptor stimuli. We further posit that microbiome restoration could be an alternative approach for the treatment of NAFLD. Several gut bacteria are now known to be involved in bile acid metabolism. It will be necessary to identify which one/ones is/are feasible. Careful selection of commensal bacteria for probiotics may lead to an effective therapy for NAFLD.
Background: Chemoradiotherapy-associated mucositis can manifest as pain, inflammation, dysphagia, diarrhea, weight loss, rectal bleeding, and infection. Mucositis is a major dose-limiting side effect of chemotherapy, affecting nutritional intake and oral and intestinal function. Despite several interventions being available, there is a need for safe and effective preventative and treatment options for treatment-induced mucositis. The goals of this review are to discuss interventions based on foods and natural products and present the research to date. Methods: A narrative literature review identified 60 clinical studies examining various nutritional compounds and 20 examining probiotics. 9 studies on probiotics for the prevention of diarrhea were also assessed on methodological quality and limitations identified. Results: Several compounds have been posited as useful adjuvants for cancer treatment–related mucositis. Probiotics demonstrate efficacy for the prevention and treatment of chemoradiotherapy-induced gastrointestinal toxicity without significant side effects. Glutamine and activated charcoal were reported to reduce chemotherapy-induced diarrhea but not radiation-induced intestinal mucositis. Honey has been reported to decrease treatment interruptions, weight loss, and delays the onset of oral mucositis. Zinc, glutamine, and topical vitamin E were demonstrated efficacy for oral mucositis. Conclusion: There is plausible clinical evidence for the administration of several adjunctive treatments for the prevention and treatment of mucositis. Probiotics were reported to reduce the burden of intestinal mucositis and treatment-induced diarrhea. Activated charcoal and glutamine are beneficial for chemotherapy-induced diarrhea, whereas the administration of honey, zinc, and glutamine reduce the risk of developing oral mucositis during chemotherapy or radiotherapy.
The existence of an implicit living microscopic world, composed primarily of bacteria, has been known for centuries. The exact mechanisms that govern the contribution of bacteria to human health and disease have only recently become the subject of intense research efforts. Within this very evident shift in paradigms, the rational design of probiotic formulations has led to the creation of an industry that seeks to progress the engineering of probiotic bacteria that produce metabolites that may enhance human host health and prevent disease. The promotion of probiotics is often made in the absence of quality scientific and clinically plausible data. The latest incursions into the probiotic market of claims have posited the amelioration of oxidative stress via potent antioxidant attributes or limiting the administration of probiotics to those species that do not produce D-Lactic acid (i.e., claims that D-Lactic acid acidosis is linked to chronic health conditions) or are strain-specific (shaping an industry point of difference) for appraising a therapeutic effect. Evidence-based research should guide clinical practice, as there is no place in science and medicine that supports unsubstantiated claims. Extravagant industry based notions continue to fuel the imprimatur of distrust and skepticism that is leveled by scientists and clinicians at an industry that is already rife with scientific and medical distrust and questionable views on probiotics. Ignoring scientifically discordant data, when sorting through research innovations and false leads relevant to the actions of probiotics, drives researcher discomfit and keeps the bar low, impeding the progress of knowledge. Biologically plausible posits are obligatory in any research effort; companies formulating probiotics often exhibit a lack of analytical understanding that then fuels questionable investigations failing to build on research capacity.
Two galenical formulations of an ivy herbal extract, syrup and cough drops, were tested for their efficacy and safety in the paediatric treatment of cough and bronchitis in two independent open, non-interventional studies with identical design. Two-hundred and sixty-eight children aged 0-12 yr were treated with one of the two preparations for up to 14 days. The effects on cough-related symptoms were addressed on a verbal rating scale. At the end of the study the major symptoms rhinitis, cough and viscous mucus, were found to be only mildly expressed or absent in 93, 94.2 and 97.7% of cases. The global effect was rated as 'good' or 'very good' in 96.5% of cases. Tolerability and compliance were found 'good' to 'very good' in 99% (syrup) and 100% (drops) of patients on completion of the study. A subgroup analysis according to four different age and dosing groups did not reveal differences in treatment response. Safety was confirmed and corresponded to literature findings. Five adverse events classified as mild and non-serious were reported (1.9%). In conclusion, ivy leaf extract in the form of syrup and of cough drops was confirmed as an effective and safe treatment of cough in children.
Immune defence against pathogenic agents comprises the basic premise for the administration of vaccines. Vaccinations have hence prevented millions of infectious illnesses, hospitalizations and mortality. Acquired immunity comprises antibody and cell mediated responses and is characterized by its specificity and memory. Along a similar congruent yet diverse mode of disease prevention, the human host has negotiated from in utero and at birth with the intestinal commensal bacterial cohort to maintain local homeostasis in order to achieve immunological tolerance in the new born. The advent of the Human Microbiome Project has redefined an appreciation of the interactions between the host and bacteria in the intestines from one of a collection of toxic waste to one of a symbiotic existence. Probiotics comprise bacterial genera thought to provide a health benefit to the host. The intestinal microbiota has profound effects on local and extra-intestinal end organ physiology. As such, we further posit that the adjuvant administration of dedicated probiotic formulations can encourage the intestinal commensal cohort to beneficially participate in the intestinal microbiome-intestinal epithelia-innate-cell mediated immunity axes and cell mediated cellular immunity with vaccines aimed at preventing infectious diseases whilst conserving immunological tolerance. The strength of evidence for the positive effect of probiotic administration on acquired immune responses has come from various studies with viral and bacterial vaccines. We posit that the introduction early of probiotics may provide significant beneficial immune outcomes in neonates prior to commencing a vaccination schedule or in elderly adults prior to the administration of vaccinations against influenza viruses.
We determined the feasibility of laryngoscope-guided tracheal intubation (LG-TI) in microgravity obtained during parabolic flight and tested the hypothesis that LG-TI is similarly successful in the free-floating condition, with the patient's head gripped between the anesthesiologist's knees, as in the restrained condition, with the torso strapped to the surface. Three personnel with no experience in airway management or microgravity participated in the study. LG-TI of a sophisticated full-size manikin was attempted on seven occasions in each condition by each investigator after ground-based training. The parabolic flights, which took place in an Airbus 300 over the Atlantic Ocean, provided 23 s of microgravity. During this time, the investigator opened a box with airway equipment, performed LG-TI, and attached and held onto a self-inflating bag. The efficacy of ventilation was assessed during level flight by squeezing the bag and noting whether the manikin sensors indicated a tidal volume > or =300 mL. There were no differences in ventilation success (41% versus 33%) or time to successful insertion (both 18 s) between the free-floating and the restrained conditions. More than 90% of failures were caused by the inability to insert the tracheal tube within 23 s. There were no differences in performance among investigators. We conclude that LG-TI is feasible in microgravity obtained during parabolic flight, but the success rate is infrequent because of severe time restrictions. There were no differences in success rate between the free-floating condition, with the head gripped between the knees, and the restrained condition, with the torso strapped to the surface.
Roots of Echinacea purpurea and Echinacea pallida cultivated for 4 years in a North European climate were analyzed for seasonal variations in the concentrations of lipophilic constituents (alkamides, ketoalkenes, and ketoalkynes) and phenolic acids by harvesting five times during 1 year to establish the optimal time for harvest. A total of 16 alkamides, three ketoalkenes, two ketoalkynes, and four phenolic acids (echinacoside, cichoric acid, caftaric acid, and chlorogenic acid) were identified in aqueous ethanolic (70%) extracts by liquid chromatography-mass spectrometry and quantified by reverse-phase high-performance liquid chromatography. The major alkamides in the roots of E. purpurea were at their lowest concentration in the middle of autumn and early winter, and the total concentration of lipophilic compounds in E. pallida showed the same pattern. Moreover, all of the major phenolic acids in E. purpurea were at their highest concentrations in spring. The optimal harvest time in spring is in contrast to normal growing guidelines; hence, this specific information of seasonal variations in the concentrations of lipophilic and phenolic compounds in E. purpurea and E. pallida is valuable for research, farmers, and producers of medicinal preparations.
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