Current Understanding of the Gut Microflora in Subjects with Nutrition-Associated Metabolic Disorder Such as Obesity and/or Diabetes : Is There Any Relevance with Oral Microflora?

Purpose of review: The oral cavity is one of the main gateways to the whole body and leads to the gastrointestinal tract. Both oral cavity and gastrointestinal tract have complex ecosystems of microorganisms called microbiota. Recent studies have showed that altered local microbiome in human, such as gut microflora, is associated with various systemic diseases. This review focuses on the association between the microbiota at local sites, such as gut and oral cavity, and the systemic diseases, especially nutrition-associated metabolic disorder, such as obesity and/or diabetes. Recent findings: The gut microbiota has a potential for regulation in host immune system and metabolisms, such as energy, glucose and lipid, and is therefore an additional contributing environmental factor to the pathophysiology of obesity and diabetes as well as gut infectious inflammatory diseases. In addition, oral microorganisms play important roles as reservoirs for exacerbation of gut diseases and altered oral microbial profiles causing periodontal diseases, one of common oral infectious diseases, has been also associated with several systemic diseases including diabetes. Summary: It is necessary to consider that impaired oral microbiota, called oral dysbiosis, may affect the metabolic disorders leading to obesity and diabetes in addition to the gut inflammatory diseases via alteration of gut microflora. The relevance of oral microflora to gut dysbiosis leading to nutrition-associated metabolic disorder should be addressed as future investigations

Progressive renal fibrosis in murine polycystic kidney disease: An immunohistochemical observation

Progressive renal fibrosis in murine polycystic kidney disease: An immunohistochemical observation.BackgroundThe appearance of interstitial fibrosis in polycystic kidneys is emblematic of progressive disease. Matrix forming this scar tissue is derived from local renal cells in response to cystogenesis. We investigated the phenotype of collagen-producing cells in the cystic kidneys of DBA/2-pcy mice to better characterize the spectrum of interstitial cells associated with renal fibrogenesis.MethodsThe extent of interstitial fibrosis and the number of fibroblasts in cystic kidneys were first quantitated over time using computer-assisted image analysis. Subsequently, antisera to four cell protein markers were studied by coexpression immunohistochemistry during progression of fibrosis using confocal microscopy. The antisera included fibroblast-specific protein 1 (FSP1) for fibroblast phenotype, α-smooth muscle actin (α-SMA) for contractile phenotype, vimentin (VIM) for mesenchymal phenotype, and heat shock protein 47 (HSP47) for interstitial collagen-producing phenotype.ResultsInterstitial fibrosis in cystic kidneys gradually increased throughout the 30-week observation period of our study. With progression of cystogenesis, most of the tubules in pcy mice either dilated or disappeared with time. FSP1+ fibroblasts were distributed sparsely throughout the renal interstitium of young pcy and wild-type mice. Their number increased in the widening fibrotic septa by 18 weeks of age and persisted through 30 weeks of the study interval. Some epithelia among remnant tubules trapped within fibrotic septa around adjacent cysts also acquired the phenotype of FSP1+, HSP47+ collagen-producing fibroblasts, suggesting a possible role for epithelial-mesenchymal transformation (EMT) in this process. Most FSP1+ fibroblasts were α-SMA-, but HSP47+, suggesting they were producing collagen proteins for the extracellular matrix. α-SMA+, FSP1-, HSP47+ or HSP47- cells were also observed, and the latter tended to distribute independently in a linear pattern, reminiscent of vasculature adjacent to forming cysts. VIM+ expression was not observed in α-SMA+ cells.ConclusionsMany nonoverlapping as well as fewer overlapping populations of FSP1+ and α-SMA+ cells shared in the collagen expression associated with progressive fibrogenesis in pcy mice undergoing cystogenesis. Some FSP1+ fibroblasts are likely derived from tubular epithelium undergoing EMT, while αSMA+, VIM- cells probably represent vascular smooth muscle cells or pericytes surviving vessel attenuation during the chaos of fibrogenesis. Importantly, not all interstitial cells producing collagens are α-SMA+

Very-Low-Dose Pegylated Interferon a2a Plus Ribavirin Therapy for Advanced Liver Cirrhosis Type C: A Possible Therapeutic Alternative without Splenic Intervention

Despite the recent progress in interferon (IFN) therapies for chronic hepatitis C, liver cirrhosis remains refractory. One of the major obstacles to successful IFN therapy is low platelet count. Currently, splenic interventions, such as partial splenic embolization (PSE) or surgical splenectomy, have been applied effectively and make standard IFN therapy possible. However, there may be a group of patients with low platelet counts who can be treated without splenic intervention. We here report two patients with advanced type C liver cirrhosis who were successfully treated using very-low-dose pegylated interferon a2a plus ribavirin. One patient had a very low platelet count (2.5 × 104/μl) due to splenomegaly before treatment. However, pretreatment serum HCV titers were low in both patients and early viral responses were obtained in both. Because PSE or splenectomy may still have some safety concerns, this attenuated IFN treatment protocol can be an alternative therapeutic option for patients with advanced type C liver disease, but good virological factors for sustained virological response

Arrhythmogenic Right Ventricular Cardiomyopathy Diagnosed during Hospitalization for Cardiac Arrest

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetically mediated cardiomyopathy charac-terized by progressive myocardial loss of the right ventricle and its replacement by fibrofatty tissue, causing dyskinesia, aneurysm, and/or arrhythmia. The prevalence of ARVC is estimated to be 1 in 2,000-5,000, with the condition accounting for up to 20% of sudden cardiac deaths in individuals < 35 years old. This report describes the case of 61-year-old Japanese who was diagnosed with ARVC after cardiac arrest (CA) and successful resusci-tation. After the sudden CA, the restoration of spontaneous circulation was achieved with appropriate resusci-tation, followed by the introduction of target temperature management in the intensive care unit. He was diag-nosed with ARVC based on angiography and histology results. An ICD (implantable cardioverter-defibrillator) was implanted, and he was discharged without neurological sequelae 1 month post-CA. ARVC is an important cause of sudden CA, and successfully resuscitated patients with right ventricular dilation should undergo testing to rule out ARVC

Successful Treatment of Staphylococcus schleiferi Infection after Aortic Arch Repair: In Situ Aortic Arch Replacement and Domino Reconstruction of the Debranching Graft using Autologous Iliac Artery

A 62-year-old Japanese male presented with graft infection by Staphylococcus schleiferi 50 days after debranching of the left subclavian artery and frozen elephant trunk repair for the entry closure of a Stanford type B aortic dissection. The graft was removed, and the patient was successfully treated using in situ reconstruction of the arch with omental flap coverage, removal of the debranching graft, autologous iliac artery grafting, and longterm antibiotics. Domino reconstruction of the infected debranching graft using autologous external iliac artery and a Dacron graft can thus be a good option in similar cases

Generation of mouse models for type 1 diabetes by selective depletion of pancreatic beta cells using toxin receptor-mediated cell knockout

AbstractBy using the toxin receptor-mediated cell knockout (TRECK) method, we have generated two transgenic (Tg) murine lines that model type 1 (insulin-dependent) diabetes. The first strain, C.B-17/Icr-Prkdcscid/Prkdcscid-INS-TRECK-Tg, carries the diphtheria toxin receptor (hDTR) driven by the human insulin gene promoter, while the other strain, C57BL/6-ins2(BAC)-TRECK-Tg, expresses hDTR cDNA under the control of the mouse insulin II gene promoter. With regard to the C.B-17/Icr-Prkdcscid/Prkdcscid-INS-TRECK-Tg strain, only one of three Tg strains exhibited proper expression of hDTR in pancreatic β cells. By contrast, hDTR was expressed in the pancreatic β cells of all four of the generated C57BL/6-ins2(BAC)-TRECK-Tg strains. Hyperglycemia, severe ablation of pancreatic β cells and depletion of serum insulin were observed within 3days after the administration of diphtheria toxin (DT) in these Tg mice. Subcutaneous injection of a suitable dosage of insulin was sufficient for recovery from hyperglycemia in all of the examined strains. Using the C.B-17/Icr-Prkdcscid/Prkdcscid-INS-TRECK-Tg model, we tried to perform regenerative therapeutic approaches: allogeneic transplantation of pancreatic islet cells from C57BL/6 and xenogeneic transplantation of CD34+ human umbilical cord blood cells. Both approaches successfully rescued C.B-17/Icr-Prkdcscid/Prkdcscid-INS-TRECK-Tg mice from hyperglycemia caused by DT administration. The high specificity with which DT causes depletion in pancreatic β cells of these Tg mice is highly useful for diabetogenic research

Gingival bleeding and pocket depth among smokers and the related changes after short-term smoking cessation

Background: Smoking is associated with the deteriorating health of the gingiva and periodontium. The long-term beneficial effects of smoking cessation on oral health are well known. However, the effects of short-term smoking cessation on gingival bleeding and periodontal pocket depth are unknown. The purpose of the present study was to determine the effects of short-term smoking cessation on gingival bleeding and periodontal pocket depth. Methods: Dentate smokers with a mean age of 56.9 ± 14.4 years at an outpatient smoking cessation clinic participated in this study. A professional dentist checked the periodontal pocket depth and gingival bleeding. Patients visited the smoking cessation clinic on their first visit and 2, 4, 8, and 12 weeks (three months). The gingival assessment was re-performed in those who succeeded in smoking cessation 3 months after the baseline. Results: The baseline data of 83 patients showed that an increase in pocket depth was associated with increasing age and the amount of smoking. A significant increase in gingival bleeding (p = .031) and increase in pocket depth (p = .046) were observed 3 months after the baseline in patients who successfully quit smoking (n = 14). Conclusion: Short-term smoking cessation increased periodontal pocket depth and gingival bleeding. These findings may reflect healing processes that occur in the healthy gingiva. Implications: Study findings will be useful to advise patients during smoking cessation programs. Dentists can inform patients that an initial increase in gingival bleeding and pocket depth could be associated with smoking cessation. Such advice will prevent patients from any apprehension that may cause them to recommence smoking

Indirect Calorimetry Measurement of Energy Expenditure Related to Body Position Changes in Healthy Adults

Early mobilization is advocated to prevent intensive care unit-acquired physical weakness, but the patient's workload and its changes in response to body position changes have not been established. We used indirect calorimetry to determine the energy expenditure (EE) in response to body position changes, and we assessed EE's correlation with respiratory parameters in healthy volunteers: 8 males and 8 females, mean age 23.4±1.3 years. The subjects started in the resting supine position followed by a 30° head-up position, a 60° head-up position, an upright sitting position, a standing position, and the resting supine position. EE was determined in real time by indirect calorimetry monitoring the subject’s respiratory rate, tidal volume (VT), and minute volume (MV). The highest values were observed immediately after the subjects transitioned from standing to supine, and this was significantly higher compared to the original supine position (1,450±285 vs. 2,004±519 kcal/day, p<0.01). Moderate correlations were observed between VT and EE (r=0.609, p<0.001) and between MV and EE (r=0.576, p<0.001). Increasing VT or MV indicates an increasing patient workload during mobilization. Monitoring these parameters may contribute to safe rehabilitation. Further studies should assess EE in critically ill patients