Enteric bacterial proteases in inflammatory bowel diseasepathophysiology and clinical implications

Numerous reports have identified a dysbiosis in the intestinal microbiota in patients suffering from inflammatory bowel diseases(IBD),yet the mechanism(s)in which this complex microbial community initiates or perpetuates inflammation remains unclear.The purpose of this review is to present evidence for one such mechanism that implicates enteric microbial derived proteases in the pathogenesis of IBD.We highlight and discuss studies demonstrating that proteases and protease receptors are abundant in the digestive system.Additionally,we investigate studies demonstrating an association between increased luminal protease activity and activation of protease receptors,ultimately resulting in increased intestinal permeability and exacerbation of colitis in animal models as well as in human IBD.Proteases are essential for the normal functioning of bacteria and in some cases can serve as virulence factors for pathogenic bacteria.Although not classified as traditional virulence factors,proteases originating from commensal enteric bacteria also have a potential association with intestinal inflammation via increased enteric permeability.Reports of increased protease activity in stools from IBD patients support a possible mechanism for a dysbiotic enteric microbiota in IBD.A better understanding of these pathways and characterization of the enteric bacteria involved,their proteases,and protease receptors may pave the way for new therapeutic approaches for these diseases.     

Size distribution of leukocyte aggregates differentiate between stress‐ and infection/inflammation‐related leukocytosis

We evaluated the state of leukocyte adhesiveness/aggregation in the peripheral blood of 33 patients with stress and 33 patients with infection/inflammation. Both groups had a similar white blood cell count (9542±3067 and 10,512±2758 cells per cmm, respectively). It was found that the percentage of aggregated leukocytes in the peripheral blood of patients with infection/inflammation was significantly higher than in the patients with stress (24.7±11 per cent versus 15.8±6 per cent; p<0.0001). When we analyzed the size distribution of the aggregated cells we also found a significant difference between the number of couplets (2.7±1.9 versus 1.6±0.9; p=0.006), triplets (0.6±1.3 versus 0.2±0.2; p=0.05), quadruplets (0.14±0.2 versus 0.03±0.07; p=0.005) or quintets (0.04±0.1 versus 0.003±0.002; p=0.05) between these two groups. Thus, by using a simple slide test to reveal the state of leukocyte adhesiveness/aggregation in the peripheral blood one could favor the diagnosis of infection/inflammation induced leukocytosis as opposed to a stress‐related one. Copyright © 2000 John Wiley & Sons, Ltd.     

Effects of diets high in simple sugars on urinary chromium losses

Thirty-seven subjects, 19 men and 18 women, consumed reference diets for 12 weeks formulated by nutritionists to contain optimal levels of protein, fat, carbohydrate, and other nutrients; the following 6 weeks, subjects consumed high sugar diets. The reference diets contained 35% of total calories from complex carbohydrates and 15% from simple sugars while the high sugar diets contained 15% complex carbohydrates and 35% simple sugars. Chromium contents of the reference and high sugar diets were both approximately 16 micrograms per 1000 calories. Compared to the reference diets, consumption of the high sugar diets increased urinary Cr losses from 10% to 300% for 27 of 37 subjects. Urinary Cr excretion of males and females was similar, and there was no significant difference in Cr absorption (calculated from urinary excretion divided by intake times 100) between sexes when adjusted for the increased caloric intake of males. These data demonstrate that consumption of diets high in simple sugars stimulates Cr losses; this coupled with marginal intake of dietary Cr may lead to marginal Cr deficiency, which is associated with impaired glucose and lipid metabolism.     

The synthesis in vivo of proteins in various tissues in chickens adapted to intermittent feeding

1. Protein synthesis was estimated in vivo in breast (superficial pectoral) and tibia (gastrocnemius) muscles, liver, kidney, pancreas, crop, duodenum, jejunum and ileum, using L-[U-14C]lysine injection. The effect on incorporation of [14C]lysine 1 and 2 h after injection was examined in five chickens adapted or not adapted to intermittent feeding. 2. Incorporation of [14C]lysine into tissue decreased in magnitude in the following descending order: pancreas greater than jejunum, duodenum greater than ileum, crop, liver greater than kidney greater than tibia, breast muscle and blood plasma. 3. The incorporation of [14C]lysine into muscle protein was higher in chicks after 24 h of refeeding than after 24 h of food deprivation. These differences were higher in adapted than in non-adapted birds. On days of refeeding the rate of incorporation exceeded that found in chickens fed ad lib. 4. Bound 14C from lysine in the intestinal segments was less than in control birds after food deprivation and greater after refeeding in non-adapted chicks only. 5. A negative relation was observed between bound and free 14C in muscles and in other tissues. 6. Short- and long-term adaptations to feeding regimens are discussed.     

The "chewing wheel" device: plaque-removing efficiency and use in oral hygiene programs

Control of bacterial plaque on tooth surfaces is the most important method of controlling dental disease. The patient's ability to achieve good plaque control is of utmost importance in preventing the occurrence of periodontal disease and in maintaining periodontal health. The search for better methods that enable easier and more effective plaque control has led to the development of the "chewing wheel." A clinical trial was conducted to compare the plaque-removing efficiency of the chewing wheel to that of a manual toothbrush. The tested device removed 18% to 37% of the accumulated dental deposits. In spite of its limited efficiency, the wheel can be used as part of an oral hygiene program for individuals with perceptomotor dysfunctions.     

Cryosurgical depigmentation of the gingiva

Gingival melanin pigmentation (GMP) occurs in all races of man. Although clinical melanin pigmentation does not present a medical problem, demand for cosmetic therapy is commonly made by fair-skinned people with moderate GMP. The present study was undertaken to test the effectiveness of cryosurgical destruction of the gingival epithelium in the removal of gingival melanin pigmentation. The patient was a fair-skinned Ashkenazi Jew with moderate GMP who demanded any possible "cosmetic therapy" which would convert her "black gums" to "normal". Gingival cryosurgery was carried out by segments. A gas expansion cryoprobe cooled to -81 degrees C was applied to the gingiva for 10 s. Frozen sites thawed spontaneously within 1 min. Superficial necrosis became apparent within a week. Treated sites were covered by epithelium within 2 weeks following freezing and keratinization was completed after 3-4 weeks. The treated gingiva appeared normal and remained depigmented until the present time, 20 months following freezing. It is concluded that cryosurgery may prove to be the treatment of choice when gingival depigmentation is indicated.     

The APC I1307K allele conveys a significant increased risk for cancer

This study is the first attempt to evaluate the association between the APC I1307K variant and overall cancer risk. It is unique in both its large sample size and in the reliability of data in the control group. The findings described in this article have major implications in terms of identifying asymptomatic individuals who are at increased risk to harbor cancer and therefore targeted to be enrolled in specific early detection and prevention programs. The prevalence of the APC I1307K missense mutation among Ashkenazi Jews is ～6%. Carriers are at an increased risk for colorectal neoplasia. In this study, we examined the association of this variant with non‐colorectal cancers. Consecutive 13,013 healthy subjects who underwent screening at the Integrated Cancer Prevention Center between 2006 and 2014 were enrolled. This population was supplemented with 1,611 cancer patients from the same institution. Demographics, medical history, and pathological data were recorded. Mortality data were obtained from the Ministry of Health's registry. The prevalence of APC I1307K in cancer patients and healthy subjects was compared. The APC I1307K variant was detected in 189 (11.8%) cancer patients compared to 614 (4.7%) healthy subjects, reflecting an adjusted age and sex odds ratio (OR) of 2.53 (p < 0.0001). History of two or more cancer types was associated with a positive carrier prevalence (OR = 4.38 p < 0.0001). Males had significantly increased carrier prevalence in lung, urologic, pancreatic, and skin cancers. The carrier prevalence among females was significantly higher only in breast and skin cancers. Female carriers developed cancer at a significantly older age compared to non‐carriers (average 62.7 years vs. 57.8, respectively, p = 0.027), had better survival rates (HR = 0.58, p = 0.022) and overall increased longevity (average age of death 78.8 vs. 70.4 years, respectively, p = 0.003). In conclusion, the APC I1307K variant is a reliable marker for overall cancer risk (OR 2.53). Further studies are needed to evaluate its use for specific cancer types—particularly in males. Female carriers have better prognosis and increased lifespan.     

Peripheral giant cell granuloma associated with dental implants

BACKGROUND: Peripheral giant cell granuloma (PGCG) is a well-circumscribed lesion confined to the alveolar and gingival mucosa. PGCG is considered a reactive lesion caused by local irritation or trauma. The objectives of the present study were to evaluate the incidence of PGCG in peri-implant lesions submitted for histologic examination, to establish its correlation with implant failure, and to discuss its pathogenesis. METHODS: The study was conducted on 25 periimplant biopsy specimens submitted for histological examination between 1999 and 2001. Sections (5 microm) of paraffin embedded tissues were cut and stained with hematoxylin and eosin. RESULTS: From the 25 specimens, three (two males and one female, ranging in age from 31 to 69 years) were identified as peripheral giant cell granuloma. The posterior mandible was affected in two cases and the anterior maxilla in one. The clinical appearance was an exophytic mass with a bleeding surface. The time interval between implantation and lesion development was from several months to 6 years. Recurrence following curettage was found in all cases. The implants were stable; however, two were removed either because of bone loss around the implant or because of several recurrences. In all cases healing was uneventful. CONCLUSIONS: Peripheral giant cell granuloma can develop in association with dental implants. Clinically, the lesions are similar to the classical PGCG. In the present study, the precise incidence could not be concluded because of the small number of selected cases. Due to the aggressive nature of the lesion and the high recurrence rate, implants can fail unless the lesion is detected early and proper surgical removal is performed. Tissue removed from the peri-implant area should always be submitted for histologic examination for accurate diagnosis.     

A multicenter comparative study of two root coverage procedures: coronally advanced flap with addition of enamel matrix proteins and subpedicle connective tissue graft

BACKGROUND: Free grafts, pedicle flaps, and barrier membranes have been used to cover exposed root surfaces. The aim of the present study was to evaluate the clinical efficacy of a coronally advanced flap procedure with the additional use of enamel matrix protein derivative (EMD) to treat gingival recession and to compare it to the subpedicle connective tissue graft procedure (CTG). METHODS: The study was conducted in six different periodontal clinics. Miller Class I or II buccal recession type defects in the anterior or premolar teeth were treated in 70 consecutive patients, 30 with EMD and 40 with CTG. At baseline and 6 and 12 months post-surgical treatment, vertical recession defect, defined as the distance from cemento-enamel junction to gingival margin; width of keratinized tissue; and probing depth were recorded and the percentage of coverage of the original defect was calculated. Statistical analyses consisted of t-test, analysis of variance, and analysis of covariance. RESULTS: At 6 months, percent of root coverage was 77.4% +/- 11.92% in EMD and 84.1% +/- 11.97% in CTG (statistically significant at P = 0.024). At 12 months, percent of root coverage in EMD was 71.7% +/- 16.14% and 87.0% +/- 12.22% in CTG; again, differences between groups were statistically significant (P < 0.001). Differences between the 6- and 12-month vertical recession defect and percent of root coverage recordings within each group were also statistically significant. CONCLUSIONS: The connective tissue graft procedure was superior to the coronally positioned flap with the addition of enamel matrix proteins derivative in percentage of coverage and increase in width of keratinized tissue. The EMD procedure is a predictable treatment for root coverage that is relatively easy to perform and presents low patient morbidity, and is appropriate especially where a substantial increase in the width of keratinized tissue is not of prime importance.