scholarly journals Immunology and Homeopathy. 3. Experimental Studies on Animal Models

2006 ◽  
Vol 3 (2) ◽  
pp. 171-186 ◽  
Author(s):  
Paolo Bellavite ◽  
Riccardo Ortolani ◽  
Anita Conforti
Keyword(s):  
Animal Models ◽  
Observational Studies ◽  
Experimental Studies ◽  
Ultralow Doses ◽  
Controlled Trials ◽  
Research Groups ◽  
Curative Effect ◽  
High Dilutions ◽  
Inflammatory Processes ◽  
High Doses

A search of the literature and the experiments carried out by the authors of this review show that there are a number of animal models where the effect of homeopathic dilutions or the principles of homeopathic medicine have been tested. The results relate to the immunostimulation by ultralow doses of antigens, the immunological models of the ‘simile’, the regulation of acute or chronic inflammatory processes and the use of homeopathic medicines in farming. The models utilized by different research groups are extremely etherogeneous and differ as the test medicines, the dilutions and the outcomes are concerned. Some experimental lines, particularly those utilizing mice models of immunomodulation and anti-inflammatory effects of homeopathic complex formulations, give support to a real effect of homeopathic high dilutions in animals, but often these data are of preliminary nature and have not been independently replicated. The evidence emerging from animal models is supporting the traditional ‘simile’ rule, according to which ultralow doses of compounds, that in high doses are pathogenic, may have paradoxically a protective or curative effect. Despite a few encouraging observational studies, the effectiveness of the homeopathic prevention or therapy of infections in veterinary medicine is not sufficiently supported by randomized and controlled trials.

scholarly journals Designs for research of High Dilutons in animal models: an update

2021 ◽  
Vol 10 (35) ◽  
pp. 80-80
Author(s):  
Adrian Alecu ◽  
Romeo Brezeanu
Keyword(s):  
Clinical Practice ◽  
Animal Models ◽  
Biological Effects ◽  
Experimental Studies ◽  
Experimental Models ◽  
Daily Clinical Practice ◽  
Basic Requirement ◽  
Pharmacological Studies ◽  
High Dilutions

This article discusses the series of tests on animal experimental models carried out by our group to evaluate the effect of homeopathic preparations selected according to traditional criteria of pathogenetic similarity. Our overall experience indicates that it is not difficult to carry out experimental studies assaying homeopathic medicines in randomized placebo-controlled tests returning statistically analyzable results. The basic requirement for this purpose is to select validated experimental models. The simplest and most reliable ones are the ones arising from common daily clinical practice or those taken from classical pharmacological studies modified as to fit the goals of a homeopathic assay. By proceeding in this way it will be possible to build a sound body of evidence for the biological effects of high dilutions.

A Vicious Circle of Clonal Haematopoiesis of Indeterminate Potential and Cardiovascular Disease

2021 ◽  
Vol 41 (06) ◽  
pp. 443-446
Author(s):  
Carolin A. Ehlert ◽  
Ingo Hilgendorf
Keyword(s):  
Cardiovascular Disease ◽  
Observational Studies ◽  
Experimental Studies ◽  
Vicious Circle ◽  
Driver Mutations ◽  
Cvd Risk ◽  
Genetic Studies ◽  
Increased Risk ◽  
Inflammatory Processes ◽  
Inflammatory Immune Response

AbstractClonal haematopoiesis of indeterminate potential (CHIP) represents a recently identified overlap between cancer and cardiovascular disease (CVD). CHIP develops as a result of certain acquired somatic mutations that predispose to leukaemia, but clinically even more prevalent, associate with increased risk for CVD and CVD-related death. Experimental studies suggest a causal role for CHIP aggravating inflammatory processes in CVD, and recent epidemiologic and genetic studies indicate that classical CVD risk factors may increase the risk of acquiring CHIP driver mutations, thus fuelling a vicious circle. The potential mechanism underlying the associative link between CHIP and CVD and mortality has been the focus of a few recent excellent experimental and observational studies which are summarized and discussed in this concise non-systematic review article. These data support a pathomechanistic view of a spiralling vicious circle in which CHIP aggravates the inflammatory immune response in CVD, and CVD-driven elevated haematopoietic activity promotes CHIP development.

scholarly journals Nebulized Colistin in Ventilator-Associated Pneumonia and Tracheobronchitis: Historical Background, Pharmacokinetics and Perspectives

2021 ◽  
Vol 9 (6) ◽  
pp. 1154
Author(s):  
Yinggang Zhu ◽  
Antoine Monsel ◽  
Jason Roberts ◽  
Konstantinos Pontikis ◽  
Olivier Mimoz ◽  
...  
Keyword(s):  
Randomized Controlled Trials ◽  
Experimental Studies ◽  
Multidrug Resistant ◽  
Historical Background ◽  
Future Research ◽  
Controlled Trials ◽  
Ventilator Associated Pneumonia ◽  
Randomized Controlled ◽  
High Doses ◽  
Tract Infections

Clinical evidence suggests that nebulized colistimethate sodium (CMS) has benefits for treating lower respiratory tract infections caused by multidrug-resistant Gram-negative bacteria (GNB). Colistin is positively charged, while CMS is negatively charged, and both have a high molecular mass and are hydrophilic. These physico-chemical characteristics impair crossing of the alveolo-capillary membrane but enable the disruption of the bacterial wall of GNB and the aggregation of the circulating lipopolysaccharide. Intravenous CMS is rapidly cleared by glomerular filtration and tubular excretion, and 20–25% is spontaneously hydrolyzed to colistin. Urine colistin is substantially reabsorbed by tubular cells and eliminated by biliary excretion. Colistin is a concentration-dependent antibiotic with post-antibiotic and inoculum effects. As CMS conversion to colistin is slower than its renal clearance, intravenous administration can lead to low plasma and lung colistin concentrations that risk treatment failure. Following nebulization of high doses, colistin (200,000 international units/24h) lung tissue concentrations are > five times minimum inhibitory concentration (MIC) of GNB in regions with multiple foci of bronchopneumonia and in the range of MIC breakpoints in regions with confluent pneumonia. Future research should include: (1) experimental studies using lung microdialysis to assess the PK/PD in the interstitial fluid of the lung following nebulization of high doses of colistin; (2) superiority multicenter randomized controlled trials comparing nebulized and intravenous CMS in patients with pandrug-resistant GNB ventilator-associated pneumonia and ventilator-associated tracheobronchitis; (3) non-inferiority multicenter randomized controlled trials comparing nebulized CMS to intravenous new cephalosporines/ß-lactamase inhibitors in patients with extensive drug-resistant GNB ventilator-associated pneumonia and ventilator-associated tracheobronchitis.

Vitamin D Therapy in Adults With Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis

2020 ◽  
Vol 26 (12) ◽  
pp. 1819-1830 ◽  
Author(s):  
Yuli Guzman-Prado ◽  
Ondrej Samson ◽  
Jonathan P Segal ◽  
Jimmy K Limdi ◽  
Bu’Hussain Hayee
Keyword(s):  
Inflammatory Bowel Disease ◽  
Vitamin D ◽  
Observational Studies ◽  
Meta Analysis ◽  
Vitamin D Supplementation ◽  
Controlled Trials ◽  
Randomized Controlled ◽  
Vitamin D Levels ◽  
Inflammatory Bowel ◽  
High Doses

Abstract Background Vitamin D deficiency has been implicated in the pathogenesis of inflammatory bowel disease. Emerging literature suggests that optimization of vitamin D levels may be associated with improvements in disease activity and quality of life. We conducted a meta-analysis exploring the effect of vitamin D on serum 25-hydroxyvitamin D (s-25[OH]D) levels, clinical improvement, and biomarkers. Methods MEDLINE, EMBASE, the Cochrane Library, and sources for grey literature were searched from inception until September 2019. The primary outcome was s-25(OH)D mean differences. Heterogeneity was assessed using the χ 2 test and the I2 statistic. Review Manager software v. 5.3 was used. Results Twelve randomized controlled trials (n = 611) and 4 observational studies (n = 359) were included in the meta-analysis. On average, in the randomized controlled trials, vitamin D supplementation increased s-25(OH)D levels by 15.50 ng/mL (95% confidence interval [CI], 11.08-19.92, P ≤ 0.00001, I2 = 90%) and in observational studies they increased by 18.39 ng/mL (95% CI, 8.91-27.88, P = 0.0001, I2 = 82%). Subgroup analyses between vitamin D and placebo groups revealed that vitamin D increased s-25(OH)D by 14.85 ng/mL (95% CI, 9.96-19.73, P ≤ 0.00001, I2 = 90%) and when high doses of vitamin D were compared with low doses, high doses increased s-25(OH)D by 18.27 ng/mL (95% CI, 5.44-31.10, P = 0.005, I2 = 90%). The Harvey Bradshaw Index improved by –1.47 points (95% CI, –2.47 to –0.47, P = 0.004, I2 = 0%) and the high-sensitivity C-reactive protein decreased by –1.58 mg/L (95% CI, –2.95 to –0.21, P = 0.02, I2 = 0%). Conclusions Vitamin D supplementation in patients with IBD and vitamin D deficiency is effective at correcting vitamin D levels and is associated with improvement in clinical and biochemical disease activity scores.

scholarly journals Beta-blocker therapy in patients with COPD: a systematic literature review and meta-analysis with multiple treatment comparison

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Claudia Gulea ◽  
Rosita Zakeri ◽  
Vanessa Alderman ◽  
Alexander Morgan ◽  
Jack Ross ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Beta Blocker ◽  
Observational Studies ◽  
Beta Blockers ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Life Outcomes ◽  
Blocker Therapy ◽  
Beta Blocker Therapy

Abstract Background Beta-blockers are associated with reduced mortality in patients with cardiovascular disease but are often under prescribed in those with concomitant COPD, due to concerns regarding respiratory side-effects. We investigated the effects of beta-blockers on outcomes in patients with COPD and explored within-class differences between different agents. Methods We searched the Cochrane Central Register of Controlled Trials, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL) and Medline for observational studies and randomized controlled trials (RCTs) investigating the effects of beta-blocker exposure versus no exposure or placebo, in patients with COPD, with and without cardiovascular indications. A meta-analysis was performed to assess the association of beta-blocker therapy with acute exacerbations of COPD (AECOPD), and a network meta-analysis was conducted to investigate the effects of individual beta-blockers on FEV1. Mortality, all-cause hospitalization, and quality of life outcomes were narratively synthesized. Results We included 23 observational studies and 14 RCTs. In pooled observational data, beta-blocker therapy was associated with an overall reduced risk of AECOPD versus no therapy (HR 0.77, 95%CI 0.70 to 0.85). Among individual beta-blockers, only propranolol was associated with a relative reduction in FEV1 versus placebo, among 199 patients evaluated in RCTs. Narrative syntheses on mortality, all-cause hospitalization and quality of life outcomes indicated a high degree of heterogeneity in study design and patient characteristics but suggested no detrimental effects of beta-blocker therapy on these outcomes. Conclusion The class effect of beta-blockers remains generally positive in patients with COPD. Reduced rates of AECOPD, mortality, and improved quality of life were identified in observational studies, while propranolol was the only agent associated with a deterioration of lung function in RCTs.

scholarly journals Incidence of thrombotic complications in COVID-19

2021 ◽  
Author(s):  
William J. Jenner ◽  
Diana A. Gorog
Keyword(s):  
Intensive Care Unit ◽  
Observational Studies ◽  
Severity Of Illness ◽  
Controlled Trials ◽  
Thrombotic Risk ◽  
Randomized Controlled ◽  
Hospitalised Patients ◽  
High Incidence ◽  
Thrombotic Complications ◽  
Asymptomatic Individuals

AbstractA high incidence of thrombosis in hospitalised patients with COVID-19 was identified early during the pandemic. Accurately quantifying thrombotic risk may assist prognosis and guide appropriate thromboprophylaxis. Observational studies have estimated the rate of thrombosis in both hospitalised and non-hospitalised patients with COVID-19, and how this corresponds to the severity of illness. In this review, we provide an overview of the incidence and prevalence of arterial and venous thrombotic events in patients with COVID-19 and highlight the limitations in the studies to date. Asymptomatic individuals with COVID-19 and those with mild symptoms are at very low risk of thrombotic complications. However, rates of thrombosis are substantially increased in hospitalised patients, and are strikingly high in those patients who are critically-ill requiring treatment on the intensive care unit and especially those requiring extracorporeal membrane oxygenation. Clinicians managing such patients need to be aware of these risks and take appropriate steps with respect to thromboprophylaxis and heightened clinical vigilance. Large prospective observational studies will more accurately quantify thrombotic rate, and randomized controlled trials are currently investigating optimal thromboprophylactic strategies.

The effects of aquatic therapy on mobility of individuals with neurological diseases: a systematic review

2014 ◽  
Vol 29 (8) ◽  
pp. 741-751 ◽  
Author(s):  
Andresa R Marinho-Buzelli ◽  
Alison M Bonnyman ◽  
Mary C Verrier
Keyword(s):  
Randomized Controlled Trials ◽  
Gait Speed ◽  
Neurological Diseases ◽  
Dynamic Balance ◽  
Experimental Studies ◽  
Controlled Trials ◽  
Aquatic Therapy ◽  
Randomized Controlled ◽  
Randomized Studies ◽  
Before And After

Objective:To summarize evidence on the effects of aquatic therapy on mobility in individuals with neurological diseases.Data sources:MEDLINE, EMBASE, PsycInfo, CENTRAL, CINAHL, SPORTDiscus, PEDro, PsycBITE and OT Seeker were searched from inception to 15 September 2014. Hand-searching of reference lists was performed in the selected studies.Review methods:The search included randomized controlled trials and quasi-experimental studies that investigated the use of aquatic therapy and its effect on mobility of adults with neurological diseases. One reviewer screened titles and abstracts of retrieved studies from the search strategy. Two reviewers independently examined the full texts and conducted the study selection, data extraction and quality assessment. A narrative synthesis of data was applied to summarize information from included studies. The Downs and Black Scale was used to assess methodological quality.Results:A total of 116 articles were obtained for full text eligibility. Twenty studies met the specified inclusion criteria: four Randomized Controlled Trials (RCTs), four non-randomized studies and 12 before-and-after tests. Two RCTs (30 patients with stroke in the aquatic therapy groups), three non-randomized studies and three before-and-after studies showed “fair” evidence that aquatic therapy increases dynamic balance in participants with some neurological disorders. One RCT (seven patients with stroke in the aquatic therapy group) and two before-and-after tests (20 patients with multiple sclerosis) demonstrated “fair” evidence on improvement of gait speed after aquatic therapy.Conclusion:Our synthesis showed “fair” evidence supporting the use of aquatic therapy to improve dynamic balance and gait speed in adults with certain neurological conditions.

scholarly journals Prebiotics, immune function, infection and inflammation: a review of the evidence

2008 ◽  
Vol 101 (5) ◽  
pp. 633-658 ◽  
Author(s):  
Amy R. Lomax ◽  
Philip C. Calder
Keyword(s):  
Animal Models ◽  
Immune Function ◽  
Intestinal Inflammation ◽  
Adaptive Immune System ◽  
Laboratory Animals ◽  
Beneficial Effects ◽  
Inflammatory Conditions ◽  
Intestinal Infections ◽  
Inflammatory Processes ◽  
Irritable Bowel

β2-1 Fructans are carbohydrate molecules with prebiotic properties. Through resistance to digestion in the upper gastrointestinal tract, they reach the colon intact, where they selectively stimulate the growth and/or activity of beneficial members of the gut microbiota. Through this modification of the intestinal microbiota, and by additional mechanisms, β2-1 fructans may have beneficial effects upon immune function, ability to combat infection, and inflammatory processes and conditions. In this paper, we have collated, summarised and evaluated studies investigating these areas. Twenty-one studies in laboratory animals suggest that some aspects of innate and adaptive immunity of the gut and the systemic immune systems are modified by β2-1 fructans. In man, two studies in children and nine studies in adults indicate that the adaptive immune system may be modified by β2-1 fructans. Thirteen studies in animal models of intestinal infections conclude a beneficial effect of β2-1 fructans. Ten trials involving infants and children have mostly reported benefits on infectious outcomes; in fifteen adult trials, little effect was generally seen, although in specific situations, certain β2-1 fructans may be beneficial. Ten studies in animal models show benefit of β2-1 fructans with regard to intestinal inflammation. Human studies report some benefits regarding inflammatory bowel disease (four positive studies) and atopic dermatitis (one positive study), but findings in irritable bowel syndrome are inconsistent. Therefore, overall the results indicate that β2-1 fructans are able to modulate some aspects of immune function, to improve the host's ability to respond successfully to certain intestinal infections, and to modify some inflammatory conditions.

scholarly journals Deafness-in-a-dish: modeling hereditary deafness with inner ear organoids

2021 ◽  
Author(s):  
Daniel R. Romano ◽  
Eri Hashino ◽  
Rick F. Nelson
Keyword(s):  
Animal Models ◽  
Inner Ear ◽  
Auditory System ◽  
Hearing Aids ◽  
Molecular Mechanisms ◽  
Functional Disability ◽  
Experimental Studies ◽  
Hereditary Deafness ◽  
Human Auditory System ◽  
Human Inner Ear

AbstractSensorineural hearing loss (SNHL) is a major cause of functional disability in both the developed and developing world. While hearing aids and cochlear implants provide significant benefit to many with SNHL, neither targets the cellular and molecular dysfunction that ultimately underlies SNHL. The successful development of more targeted approaches, such as growth factor, stem cell, and gene therapies, will require a yet deeper understanding of the underlying molecular mechanisms of human hearing and deafness. Unfortunately, the human inner ear cannot be biopsied without causing significant, irreversible damage to the hearing or balance organ. Thus, much of our current understanding of the cellular and molecular biology of human deafness, and of the human auditory system more broadly, has been inferred from observational and experimental studies in animal models, each of which has its own advantages and limitations. In 2013, researchers described a protocol for the generation of inner ear organoids from pluripotent stem cells (PSCs), which could serve as scalable, high-fidelity alternatives to animal models. Here, we discuss the advantages and limitations of conventional models of the human auditory system, describe the generation and characteristics of PSC-derived inner ear organoids, and discuss several strategies and recent attempts to model hereditary deafness in vitro. Finally, we suggest and discuss several focus areas for the further, intensive characterization of inner ear organoids and discuss the translational applications of these novel models of the human inner ear.

scholarly journals Associations between Nature Exposure and Health: A Review of the Evidence

2021 ◽  
Vol 18 (9) ◽  
pp. 4790
Author(s):  
Marcia P. Jimenez ◽  
Nicole V. DeVille ◽  
Elise G. Elliott ◽  
Jessica E. Schiff ◽  
Grete E. Wilt ◽  
...  
Keyword(s):  
Mental Health ◽  
Physical Activity ◽  
Cognitive Function ◽  
Observational Studies ◽  
Green Space ◽  
Current Knowledge ◽  
Experimental Studies ◽  
Empirical Literature ◽  
Protective Effects ◽  
Long Term Effects

There is extensive empirical literature on the association between exposure to nature and health. In this narrative review, we discuss the strength of evidence from recent (i.e., the last decade) experimental and observational studies on nature exposure and health, highlighting research on children and youth where possible. We found evidence for associations between nature exposure and improved cognitive function, brain activity, blood pressure, mental health, physical activity, and sleep. Results from experimental studies provide evidence of protective effects of exposure to natural environments on mental health outcomes and cognitive function. Cross-sectional observational studies provide evidence of positive associations between nature exposure and increased levels of physical activity and decreased risk of cardiovascular disease, and longitudinal observational studies are beginning to assess long-term effects of nature exposure on depression, anxiety, cognitive function, and chronic disease. Limitations of current knowledge include inconsistent measures of exposure to nature, the impacts of the type and quality of green space, and health effects of duration and frequency of exposure. Future directions include incorporation of more rigorous study designs, investigation of the underlying mechanisms of the association between green space and health, advancement of exposure assessment, and evaluation of sensitive periods in the early life-course.

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