Comment on "Which Patients with Obesity Are at Risk for Renal Disease?"

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DISMICROBISM IN INFLAMMATORY BOWEL DISESE 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 nad progression of this pathology. moreover, it appears absolutely necessary to investigate the environmental factors favoring the onset of CRC and the production of colonic healt. the gut microflora, or microbiota, has an extensive diversity both quantitatively and qualitatively. in utero, the intestine of the mammalian fetus is sterile. Al birth, the intestinal microbiota in acquired by ingestion 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 arbours about 10 different bacterial species distributed in colony forming units which colonize the gastrointestinal tract. The intestinal microbiota plays a fundamental role in helath and the progeression 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 microrganisms, synthesis of compounds useful for the trophysm of colonic mucosa, regulation of the intestinal lymphoid tissue and synthesis of amino acids. furthermopre, 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 metabolities associated with carcinogeneasis and induces dysregulation of the immune response wich 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 diasease are the two major IBDs characterized by an early onset and extraintestinal manifestations, such as rheumatoid arthtritis. 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

EFFICACY OF ARGENTUM-QUARTZ SOLUTION IN THE TREATMENT OF PERIANAL FISTULAS: A PRELIMINARY STUDY

Objective: Nowadays, an optional and effective medical surgery remains the gold standard for perianal fistulas. Hereby we reported preliminary rsults in favor of using Argentum-Quartz solution for both primary and recurrent perianal fisrtulas. Methods: Three patients with intersphimncter and extrasphinteric fistulas were enrolled. Argentum-Quartz solution was administrated twice a week for sa period of 4 weeks, followed by a pause of 8 days and then another 4 weeks of treatment, totally 16 administrations. After treatment, all patients were monitored for 4-months follow-up. Results: Complete closures of 2 extrasphinteric fistulas and a partial closure with absence of inflammation and superative phenomena in the intraspinteric fistula were both manifested. Conclusions: Selective treatment of perianal fistulas with argentum-quartz solution is safe and effective. and may represent a reliable alternative

THE ROLE OF BUTYRIC ACID AS A OPROTECTIVE AGENT AGAINST INFLAMMATORY BOWEL DISEASE

Inflammatory Bowel disease (IBD), such as Crohn's disease and ulcerative colitis, are pathologies characterized by a chronic inflammation of the gastrointestinal tract. Their etiopathogenesis is not yet fully understood. Immune system and heat shock proteins (HSPs) dysfunctions are considered to be among the most likely causes of these diseases. Butyrate is a short-chain fatty acid produced by intestinal microflora. It has a trophic, benefical and protective role in the colonic mucosa, and it also induces changes in Hsp levels and localization. It may therefore be a valuable complementary therapeutic agent when used alongside trraditional drugs (mesalazine and corticosteroids) to treat the production of butyrate in the endoluminal environment may promote clinical remission in IBD patients. Due to these characteristics, there has been keen interest in the use of butyrate as a novel therapeutic supplement in the recent years. The current findings need to be validated through further clinical trials to better define the bbiomolecular dynamics of butyrate in the colonocytes of IBD patients

Acute kidney injury in a patient with metabolic syndrome

Introduction: The metabolic syndrome (MS) encompasses many metabolic abnormalities and the insulin resistance is considered as one of the most significant denominators. The chronic kidney disease (CKD) is an emerging health problem but only few patients would reach the end stage renal disease. There exists an increasing strong association between MS and CKD, but up until now the link between MS and CKD is unclear and there are few studies regarding the renal histology in MS. Methods: We describe an acute tubulointerstitial nephritis case, due to both infective and pharmacological aetiology, overlapping relevant histological changes (focal segmental glomerulosclerosis [FSG], hyaline arteriosclerosis) in a patient with MS and previously normal renal function. Despite the severe vascular finding (elevated renal arterial resistive index), the patient recovered a normal renal function. Results: We reviewed the kidney pathological studies in MS and analyzed the principal renal histological images of glomerulomegaly, segmental glomerulosclerosis, and obesity-related glomerulopathy. Conclusion: Despite the strong association, the renal involvement in MS has not been proven. A greater knowledge of the combination of histological renal changes in MS can help to understand the pathophysiological mechanism(s) of MS

Targeted Therapies for Inflammatory Bowel Disease and Colorectal Cancer: An Increasing Need for Microbiota-Intestine Mutualism

The involvement of intestinal microbiota and dysbiosis in the pathogenesis of inflammatory bowel disease (IBD) and colorectal cancer (CRC) is a well-established fact to be taken into real consideration when developing tartgeted therapies. This review aimed to depict what advances in our understanding of the role of intestinal flora in the pathogenesis of IBD and CRC is shaping up the therapeutic protocols of their management. It was demonstrated that there is a circadian regulation of colocytes gene expression in response to microbiota. In addition, dysbiosis leading to a decrease in microbiome biodiversity was also described in IBD patients whereby thick layers of adherent mucosa associated bacteria exist both in ulcerative colitis (UC) and Crohn's disease (CD). Probiotics based approaches using lactobacilli and Bibidobacteria improved clinical symptoms of IBD's through the GALT immune modulation. In addition, fecal microbiota transplantation (FMT) has also been used for IBD treatment. It consists of transferring gastrointestinal microbiota from a healthy donor to an IBD patient by duodenal infusion of liquid stool suspension to establish microbial homeostasis. The passage of bacteria in the injured mucosal zone triggers chronic inflammation and eventually CRC development by creating a carcinogenic environment. Actually, high level of Fusobacterium nucleatun and other bacteria are prevalent in CRC patients, thus suggesting a potential role of these organisms in the initiation and progression processes due to the production of genotoxic metabolites causing a direct damage to DNA integrity. Moreover, regular probiotics intake was shown to actively prevent the whole process. In conclusion, the mutualistic relationship between microbiota and colonic mucosa proved useful in depicting some of the dynamics of the initiation and development of IBD and CRC. Therapies oriented towards establishing equilibrium of intestinal microbiota may represent the key strategy to switch off chronic inflammatory processes hitting colonic mucosa, thus preventing the onset of CRC

Modulation of MMP-2 and MMP-9 in Churg-Strauss syndrome respiratory mucosa: potential monitoring parameters

Churg-Strauss (CSS) syndrome is rare and of unknown etiology. It is associated with vasculitis, blood eosinophilia and granulomatosis, and affects multiple organs and systems at various stages of the disease. Specific diagnostic and monitoring tests are not yet available. This study aims to assess the changes in MMP-2 and MMP-9 along with the histopathological alterations in two cases of CSS, as possible potential diagnostic and monitoring criteria. Two adult male patients were diagnosed with CSS in the otorhinolaryngology clinic in the University of Palermo, based on multiple clinical and histopathologic criteria. Biopsies of respiratory mucosa were taken after the consent of the patients, processed for routine histopathology and immunohistochemistry as well as quantitative polymerase chain reaction (qPCR). Similar biopsies were also taken from a non- CSS patient. The Assessment of MMP-2 and MMP-9 was performed using both immunohistochemistry and qPCR techniques. Histopathological alterations in the respiratory mucosa were consistent with vasculitis and granulomatous tissue formation, in addition to inflammatory cell infiltration with abundance of eosinophils. Immunohistochemistry assay performed on the samples derived from the two CSS patients showed a relative and remarkable increase of both MMP-2 and MMP-9 compared to controls. Such an increase was consistent with the qPCR results which depicted a significant increase between 20 and 30% for both MMP-2 and MMP-9, respectively. Since the secretion of MMPs is an essential step in angiogenesis, could these enzymatic factors be used as parameters to diagnose or monitor the evolution of CSS? The small number of samples analyzed in this study does not allow us to suggest a general statement correlating the increase in expression of MMP-2 and MMP-9 to the appearance or evolution of vasculitis; it is only speculative

Efficacy of Argentum-Quartz Solution in the Treatment of Perianal Fistulas: A Preliminary Study

Abstract Background: Nowadays, an optimal and effective medical surgery remains the gold standard for perianal fistulas. Hereby we reported preliminary results in favor of using Argentum-quartz solution for both primary and recurrent perianal fistulas. Methods: Three patients with intersphincteric and extrasphincteric fistulas were enrolled. Argentum-quartz solution was administrated twice a week for a period of 4 weeks, followed by a pause of 8 days and then another 4 weeks of treatment, totally 16 administrations. After treatment, all patients were monitored for a 4-month follow-up. Results: Complete closures of 2 extrasphincteric fistulas and a partial closure with absence of inflammation and superative phenomena in the intrasphincteric fistula were both manifested. Conclusion: Selective treatment of perianal fistulas with an argentum-quartz solution is safe and effective, and may represent a reliable alternative

Metabolomic analysis of plasma from Alzheimer disease patients

Alzheimer Disease is a degenerative disease characterized by progressive impairment of cognitive function. The main feature of AD the generation of an abnormal peptide, beta amyloid 42 (Ab42) from Amyloid Precursor Protein (APP). Ab42 is the main constituent of neurotangles and amyloid plaques, microscopic lesions found in AD patients brain. Ab42 triggers an inflammatory response that is responsible for most of the observed tissue damage. The diagnosis of AD is a complex task, mostly based on imaging techniques and clinical evaluation of the patient’s neurological and cognitive functions. The search for plasma biomarkers able to detect early mild cognitive impairment is one of the recent attempt the supply the clinician with new diagnostic tools. In this study we focused on a gas-chromatography mass-spectrometry (GC-MS) analysis coupled to chemometric automated metabolomic analysis of AD plasma samples compared with plasma of healthy subjects of comparable age and gender. Sera from twenty AD and twenty controls have been subjects to a procedure optimized to extract short chain organic acids, sugars and some fatty acids that can be detected by GC coupled to ion trap/MS detection. The method allowed the detection of over five thousands of individual ions that have been collected and measured by the XCMS software. After automated peak detection and alignment by XCMS, peaks have been normalized by a set of internal standards (C13 Leucine, C13 palmitic acid) and clustered into putative compounds by a homemade software. About 80 compounds were differentially expressed between AD and controls. After manual verification of the automated data, most of the compounds have been excluded since they represent column leakage or method artifacts, but some compounds represent true plasma constituents that are under investigation. Current findings will be presented after putative compound identification by the AMDIS/NIST software