Gut microbiota imbalance and chaperoning system malfunction are central to ulcerative colitis pathogenesis and can be counteracted with specifically designed probiotics: a working hypothesis.

In this work, we propose that for further studies of the physiopathology and treatment for inflammatory bowel diseases, an integral view of the conditions, including the triad of microbiota-heat shock proteins (HSPs)-probiotics, ought to be considered. Microbiota is the complex microbial flora that resides in the gut, affecting not only gut functions but also the health status of the whole body. Alteration in the microbiota's composition has been implicated in a variety of pathological conditions (e.g., ulcerative colitis, UC), involving both gut and extra-intestinal tissues and organs. Some of these pathologies are also associated with an altered expression of HSPs (chaperones) and this is the reason why they may be considered chaperonopathies. Probiotics, which are live microorganisms able to restore the correct, healthy equilibrium of microbiota composition, can ameliorate symptoms in patients suffering from UC and modulate expression levels of HSPs. However, currently probiotic therapy follows ex-adiuvantibus criteria, i.e., treatments with beneficial effects but whose mechanism of action is unknown, which should be changed so the probiotics needed in each case are predetermined on the basis of the patient's microbiota. Consequently, efforts are necessary to develop diagnostic tools for elucidating levels and distribution of HSPs and the microbiota composition (microbiota fingerprint) of each subject and, thus, guide specific probiotic therapy, tailored to meet the needs of the patient. Microbiota fingerprinting ought to include molecular biology techniques for sequencing highly conserved DNA, e.g., genes encoding 16S RNA, for species identification and, in addition, quantification of each relevant microbe.

From gut microflora imbalance to mycobacteria infection: is there a relationship with chronic intestinal inflammatory diseases?

The gut of a healthy adult harbours a myriad of different microbial species. It is estimated that approximately 10 14 are present in total bacterial colony forming units (CFU). Each colony colonizes a specific intestinal tract. In healthy adult, the main control of intestinal bacterial colonization occurs through gastric acidity but also other factors can influence the intestinal microenvironment such as pH, temperature, competition among different bacterial strains, peristalsis, drugs, radiotherapy and much more. Impaired microbial homeostasis leads to an alteration of the permeability of tissue, together with the activation of the intestinal immune system MALT (mucosal associated lymphoid tissue). In this regard we discuss the increasing experimental evidences of the role of commensal microbiota in the activation of specific intestinal immunocompetent cells. The aforementioned micro-environmental changes provide the substrate for the etiopathogenetic outbreak of numerous pathologies of gastro-intestinal tract, such as intestinal chronic inflammation (Crohn's disease and Ulcerative Colitis), together with a miscellany of extra intestinal disorders. This article is an overview of the latest scientific findings about the close causal relationship between intestinal microbial flora and inflammatory bowel diseases or other extra-intestinal diseases; it is also mentioned the possible relationship between mycobacteria and Chron's disease. Finally we analyse the beneficial role of probiotics.

Bleeding in orthopaedic surgery: the role of blood transfusion and erythropoietin alpha.

High energy trauma is often responsible for acute bleeding. Long bone and pelvis fractures are correlated with increased blood loss. Hypovolaemia could become a life threatening complication especially in elderly patients because of the reduced physiological response. Furthermore it could compromise the course of associated morbidities. Haemorrage is also associated in both comminuted fractures and osteoporosis. An increased intraoperative bleeding often occurs when a prolonged surgical time is required to obtain an appropriate ostheosynthesis. The final consequence of a mayor bleeding is hypovolaemic shock. The reduced oxygen tension of the tissue may be responsible for heart attack, arrhythmia, stroke, multi organ deficiency. For these reasons, it is important to immediately recognize and correct all potential bleeding in order to avoid complications.

Intestinal dysbiosis and hormonal neuroendocrine secretion in the fibromyalgic patient: Relationship and correlations.

Fibromyalgia is a rheumatic syndrome and its pathogenesis is controversial. The recent literature has placed considerable attention on the link between alteration of the intestinal microbiota and fibromyalgia, emphasizing the close connection between the neuroenteric system and the CNS. This study aims to evaluate the probable relationship between intestinal dysbiosis and altered secretion of hormones and vitamins such as cortisol, serotonin, Vitamin D and thyroid hormones in a patient with fibromyalgia.

Posture and posturology, anatomical and physiological profiles: overview and current state of art.

BACKGROUND AND AIM OF WORK: posture is the position of the body in the space, and is controlled by a set of anatomical structures. The maintenance and the control of posture are a set of interactions between muscle-skeletal, visual, vestibular, and skin system. Lately there are numerous studies that correlate the muscle-skeletal and the maintenance of posture. In particular, the correction of defects and obstruction of temporomandibular disorders, seem to have an impact on posture. The aim of this work is to collect information in literature on posture and the influence of the stomatognathic system on postural system. METHODS: Comparison of the literature on posture and posturology by consulting books and scientific sites. RESULTS: the results obtained from the comparison of the literature show a discrepancy between the thesis. Some studies support the correlation between stomatognathic system and posture, while others deny such a correlation. CONCLUSIONS: further studies are necessary to be able to confirm one or the other argument.

Colorectal Carcinogenesis: Role of Oxidative Stress and Antioxidants.

One of the contributory causes of colon cancer is the negative effect of reactive oxygen species on DNA repair mechanisms. Currently, there is a growing support for the concept that oxidative stress may be an important etiological factor for carcinogenesis. The purpose of this review is to elucidate the role of oxidative stress in promoting colorectal carcinogenesis and to highlight the potential protective role of antioxidants. Several studies have documented the importance of antioxidants in countering oxidative stress and preventing colorectal carcinogenesis. However, there are conflicting data in the literature concerning its proper use in humans, since these studies did not yield definitive results and were performed mostly in vitro on cell populations, or in vivo in experimental animal models.

The long-term effects of probiotics in the therapy of ulcerative colitis: A clinical study.

AIM: Intestinal dysbiosis seems to be the leading cause of inflammatory bowel diseases, and probiotics seems to represent the proper support against their occurrence. Actually, probiotic blends and anti-inflammatory drugs represent a weapon against inflammatory bowel diseases. The present study evaluates the long-term (2 years) effects of combination therapy (mesalazine plus a probiotic blend of Lactobacillus salivarius, Lactobacillus acidophilus and Bifidobacterium bifidus strain BGN4) on ulcerative colitis activity. METHOD: Sixty patients with moderate-to-severe ulcerative colitis were enrolled: 30 of them were treated with a single daily oral administration of mesalazine 1200 mg; 30 patients received a single daily oral administration of mesalazine 1200 mg and a double daily administration of a probiotic blend of Lactobacillus salivarius, Lactobacillus acidophilus and Bifidobacterium bifidus strain BGN4. The treatment was carried out for two years and the clinical response evaluated according to the Modified Mayo Disease Activity Index. RESULTS: All patients treated with combination therapy showed better improvement compared to the controls. In particular, the beneficial effects of probiotics were evident even after two years of treatment. CONCLUSIONS: A long-term treatment modality of anti-inflammatory drugs and probiotics is viable and could be an alternative to corticosteroids in mild-to moderate ulcerative colitis.

Simple and fast orotracheal intubation procedure in rats.

INTRODUCTION: Endotracheal intubation in the rat is difficult because of the extremely small size of anatomical structures (oral cavity, epiglottis and vocal cords), small inlet for an endotracheal tube and the lack of proper technical instruments. MATERIAL AND METHODS: In this study we used seventy rats weighting 400-500 g. The equipment needed for the intubation was an operating table, a longish of cotton, a cotton tip, orotracheal tube, neonatal laryngoscope blades, KTR4 small animal ventilator and isoflurane for inhalation anaesthesia. Premedication was carried out by medetomidine hydrochloride 1 mg/mL; then, thanks to a closed glass chamber, a mixture of oxygen and isoflurane was administered. By means of a neonatal laryngoscope the orotracheal tube was advanced into the oral cavity until the wire guide was visualized trough the vocal cords; then it was passed through them. The tube was introduced directly into the larynx over the wire guide; successively, the guide was removed and the tube placed into the trachea. Breathing was confirmed using a glove, cut at the end of a finger, simulating a small balloon. RESULTS: We achieved a fast and simple orotracheal intubation in all animals employed. CONCLUSIONS: We believe that our procedure is easier and faster than those previously reported in scientific literature.

Nutrition, oxidative stress and intestinal dysbiosis: Influence of diet on gut microbiota in inflammatory bowel diseases.

BACKGROUND: Microbiota refers to the population of microorganisms (bacteria, viruses and fungi) that inhabit the entire gastrointestinal tract, more particularly the colon whose role is to maintain the integrity of the intestinal mucosa and control the proliferation of pathogenic bacteria. Alteration in the composition of the gut microbiota is called dysbiosis. Dysbiosis redisposes to inflammatory bowel diseases such as ulcerative colitis, Crohn disease and indeterminate colitis. METHODS: The purpose of this literature review is to elucidate the influence of diet on the composition of the gastrointestinal microbiota in the healthy gut and the role of diet in the development of dysbiosis. CONCLUSION: The "Western diet", in particular a low - fiber high fat/high carbohydrate diet is one factor that can lead to severe dysbiosis. In contrast, "mediterranean" and vegetarian diets that includes abundant fruits, vegetables, olive oil and oily fish are known for their anti-inflammatory effects and could prevent dysbiosis and subsequent inflammatory bowel disease.

Validation of a modified model of TNBS-induced colitis in rats. How to induce a chemical colitis in rats.

BACKGROUND: There is no standard practice in the induction of colitis by 2,4,6-trinitrobenzene sulfonic (TNBS) acid. Usually, the repeated administration of TNBS is preferred, because it will result in a local Th1 response that has the characteristics of Crohn`s disease. MATERIALS AND METHODS: A total of 30 rats were randomized into two groups, consisting of a saline control group of ten rats and a TNBS groups of 20 rats. After the animals were anesthetized, 0.5 ml of either 0.9% saline (controls) or TNBS 50 mg/kg dissolved in 50% ethanol were instilled into the colon through a rubber catheter. The experiment was repeated weekly for four weeks, then, the rats were killed at day 40, and the distal colon removed. RESULTS: At day 40, the bowel wall was basically normal in the control group. In the TNBS group, the bowel lumen became narrow with thickened wall, and the mucosal surface presented adherent membrane with brown black, linear ulcers, proliferous lymphocyte tissue, inflammatory granulomas and submucosal neutrophil infiltration. The median score of the severity of the colonic damage was 0 in the control group, and 4,75 (range 4-5) in the TNBS group; the mean weight of the rats was 180+35 g in the TNBS group, while it was 215+25 in the control group. CONCLUSIONS: The presented experiment is a cost-effective and safe method to induce Crohn-like colonic damage using a lower dose of TNBS, thus avoiding the risk of a massive loss of rats. This model is rather suitable for the assessment of the effects of potential therapeutic agents. (www.actabiomedica.it).

Serum ionized magnesium in diabetic older persons.

OBJECTIVE: Several alterations of magnesium metabolism have been associated with type 2 diabetes pathophysiology, a condition particularly frequent in older persons. We aimed to evaluate serum total (Mg-tot) and serum ionized magnesium (Mg-ion) in older persons with type 2 diabetes in order to explore clinically applicable methods for the detection of magnesium deficit. MATERIAL/METHODS: Mg-tot and Mg-ion were measured in 105 fasting subjects with type 2 diabetes (mean age: 71.1±0.8 years; M/F: 45/60) and in 100 age-matched non-diabetic control persons (mean age: 72.2±0.8 years; M/F: 42/58). RESULTS: Mg-ion concentrations were significantly lower in diabetic persons compared with controls (0.49±0.05 mmol/L vs. 0.55±0.05 mmol/L; p<0.001). Mg-tot was also slightly but significantly lower in diabetic patients (0.82±0.007 mmol/L vs. 0.84±0.006 mmol/L; p<0.05). There was an almost complete overlap in the values of Mg-tot in older diabetic patients and controls; conversely, 44.8% of diabetic patients had Mg-ion values below 0.47 mmol/L, while none of the controls did. After adjustment for age, sex, BMI, and triglycerides, Mg-tot was significantly associated with FBG in all the participants (p<0.05) and Mg-ion was significantly associated with FBG in all the participants (p<0.01) and with HbA1c in diabetic participants (p<0.001). CONCLUSIONS: Alterations of magnesium serum concentrations are common in type 2 diabetic older adults; Mg-ion evaluation may help to identify subclinical magnesium depletion (i.e. in patients with normal Mg-tot); the close independent associations of Mg-tot and Mg-ion with FBG and with HbA1c reinforce the possible link between magnesium homeostasis and altered glucose metabolism.

Dismicrobism in inflammatory bowel disease and colorectal cancer: changes in response of colocytes.

Patients with inflammatory bowel disease (IBD) have an increased risk of 10%-15% developing colorectal cancer (CRC) that is a common disease of high economic costs in developed countries. The CRC has been increasing in recent years and its mortality rates are very high. Multiple biological and biochemical factors are responsible for the onset and progression of this pathology. Moreover, it appears absolutely necessary to investigate the environmental factors favoring the onset of CRC and the promotion of colonic health. The gut microflora, or microbiota, has an extensive diversity both quantitatively and qualitatively. In utero, the intestine of the mammalian fetus is sterile. At birth, the intestinal microbiota is acquired by ingesting maternal anal or vaginal organisms, ultimately developing into a stable community, with marked variations in microbial composition between individuals. The development of IBD is often associated with qualitative and quantitative disorders of the intestinal microbial flora (dysbiosis). The healthy human gut harbours about 10 different bacterial species distributed in colony forming units which colonize the gastrointestinal tract. The intestinal microbiota plays a fundamental role in health and in the progression of diseases such as IBD and CRC. In healthy subjects, the main control of intestinal bacterial colonization occurs through gastric acidity but other factors such as endoluminal temperature, competition between different bacterial strains, peristalsis and drugs can influence the intestinal microenvironment. The microbiota exerts diverse physiological functions to include: growth inhibition of pathogenic microorganisms, synthesis of compounds useful for the trophism of colonic mucosa, regulation of intestinal lymphoid tissue and synthesis of amino acids. Furthermore, mucus seems to play an important role in protecting the intestinal mucosa and maintaining its integrity. Changes in the microbiota composition are mainly influenced by diet and age, as well as genetic factors. Increasing evidence indicates that dysbiosis favors the production of genotoxins and metabolites associated with carcinogenesis and induces dysregulation of the immune response which promotes and sustains inflammation in IBD leading to carcinogenesis. A disequilibrium in gut microflora composition leads to the specific activation of gut associated lymphoid tissue. The associated chronic inflammatory process associated increases the risk of developing CRC. Ulcerative colitis and Crohn's disease are the two major IBDs characterized by an early onset and extraintestinal manifestations, such as rheumatoid arthritis. The pathogenesis of both diseases is complex and not yet fully known. However, it is widely accepted that an inappropriate immune response to microbial flora can play a pivotal role in IBD pathogenesis.

HSP-molecular chaperones in cancer biogenesis and tumor therapy: an overview.

Molecular chaperones, many of which are heat-shock proteins (HSPs), are an important class of molecules with various functions. Pathological conditions in which chaperones become etiological and/or pathogenic factors are called chaperonopathies, and are classified into by defect, by excess, and by 'mistake'. In the latter case, the chaperone is structurally and functionally normal but participates in pathways that favor disease, although in some cases the chaperone may have post-translational modifications that may lead it to change its location and function and, thus, to become pathogenic. For example, HSP-chaperones are involved in carcinogenesis in various ways, so that some forms of cancer may be considered 'chaperonopathies by mistake'. This concept suggests new strategies for anticancer therapy (chaperonotherapy), in which the primary targets or therapeutic agents are chaperones. Chaperonotherapy consists of the utilization of HSP-chaperones for treating chaperonopathies, including cancer. Negative chaperonotherapy is aimed at eliminating or blocking the action of chaperones that favor carcinogenesis or other diseases, whereas positive chaperonotherapy uses chaperones, genes or proteins, to fight against diseases, such as cancer, by stimulating the immune system or the cellular defenses against stress.

Argentum-quarz solution in the treatment of anorectal fistulas: is it possible a conservative approach?

Patients suffering from chronic intestinal diseases (Crohn's disease, Ulcerative Colitis, Indeterminate Colitis) are prone to the development of pyogenic complications. These complications are most commonly in the form of perianal or intraabdominal abscesses and/or fistulas. The treatment of these complications are managed differently but, after an initial treatment based on medical or minimally invasive management, the solution of the pathological condition is always achieved by a surgical procedure. In the last few years prospective studies have proposed an alternative conservative therapeutic approach based on application of fibrin glue in the healing of patients with fistulas-in-ano. In this paper we suggest and discuss the therapeutic potential of silver and quarz in the conservative treatment of anorectal fistulas pointing out their role in modulating particular steps of the pathogenetic process which characterizes this pathological condition.

Changes in immunohistochemical levels and subcellular localization after therapy and correlation and colocalization with CD68 suggest a pathogenetic role of Hsp60 in ulcerative colitis.

In an earlier work, the role of heat shock protein (Hsp60) in the pathogenesis of ulcerative colitis (UC) was suggested by its significant increase in the pathological mucosa parallel with an increase in inflammatory cells. More data in this direction are reported in this work. We analyzed by immunohistochemistry biopsies of colon tissue from 2 groups of patients with UC and treated with either 5-aminosalicylic acid (5-ASA) alone or in combination with a probiotic. We looked for inflammatory markers and Hsp60. Both the treatments were effective in reducing symptoms but the group treated with both 5-ASA and probiotics showed better clinical results. Amelioration of symptoms was associated with reduction of both inflammation and Hsp60, a reduction that was most marked in the group treated with 5-ASA and probiotics. The levels of Hsp60 positively correlated with those of CD68-positive cells, and double immunofluorescence showed a high index of colocalization of the chaperonin and CD68 in lamina propria. Immunoelectron microscopy showed that Hsp60-classically a mitochondrial protein-was abundantly also present in cytosol in biopsies taken at the time of diagnosis, but not after the treatment. Our data suggest that Hsp60 is an active player in pathogenesis of UC and it can be hypothesized that the chaperonin is responsible, at least in part, for initiation and maintenance of disease.

Hsp60 and Hsp10 increase in colon mucosa of Crohn's disease and ulcerative colitis.

The purpose of this work was to determine in colon mucosa of Crohn's disease (CD) and ulcerative colitis (UC) in relapse: a) the levels of the chaperonins Hsp60 and Hsp10; b) the quantity of inflammatory cells; and c) if the levels of chaperonins parallel those of inflammation cells. Twenty cases of CD and UC and twenty normal controls (NC) were studied using immunohistochemistry, Western blotting and immunofluorescence. Immunohistochemically, Hsp60 and Hsp10 were increased in both inflammatory bowel diseases (IBD) compared to NC. These results were confirmed by Western blotting. Hsp60 and Hsp10 occurred in the cytoplasm of epithelial cells in CD and UC but not in NC. Hsp60 and Hsp10 co-localised to epithelial cells of mucosal glands but not always in connective tissue cells of lamina propria, where only Hsp60 or, less often, Hsp10 was found. Cells typical of inflammation were significantly more abundant in CD and UC than in NC. Since chaperonins are key factors in the activation of the immune system leading to inflammation, we propose that they play a central role in the pathogenesis of the two diseases, which, consequently, ought to be studied as chaperonopathies.