Altered functional activity patterns of fibroblasts related to periodontitis by systemic plasminogen deficiency (ligneous periodontitis).

We report one case of ligneous periodontitis, which is a clinical sign of hypoplasmino-genemia. It appears as massive, painless ulcerated gingival enlargements and alveolar bone destruction in the affected area. The course of the disease is progressive and typically ends with early loss of teeth. At present, no efficient treatment option seems to be available. To investigate the cause of the rapid bone destruction in this disease, gingival tissue specimens were taken from one patient and a healthy control patient to compare the function of fibroblastic cells. Our results showed that diseased fibroblasts (1) reorganized collagen lattices more rapidly than normal cells, (2) demonstrated a greater overall production of pro and active matrix metalloproteinase-2 (MMP-2) and increased activation of this protease, and (3) showed a more active phenotype than healthy fibroblastic cells. From these preliminary results, there seems to be increased MMP-2 production and activation, which might be one compensatory (but insufficient) mechanism for the decreased (plasmin-dependent) pericellular fibrinolysis in plasminogen-deficient patients. Further studies on this subject should evaluate the exact pathomechanism of plasminogen on this enzymatic bone and connective tissue destruction.

Identification of three novel plasminogen (PLG) gene mutations in a series of 23 patients with low PLG activity.

Inherited severe hypoplasminogenaemia is a multisystemic disorder leading to deficient extravascular fibrinolysis. As a clinical consequence wound healing capacity of mucous membranes is markedly impaired leading to ligneous conjunctivitis and several other manifestations. Here we report the molecular genetic and clinical findings on 23 new cases with severe hypoplasminogenaemia. Homozygous or compound-heterozygous mutations in the plasminogen (PLG) gene were found in 16 of 23 patients (70%), three of which were novel mutations reported here for the first time (C166Y, Y264S, IVS10-7T/G). Compared to 79 previously published cases, clinical manifestations of the current group of patients showed higher percentages of ligneous periodontitis, congenital hydrocephalus, and involvement of the female genital tract. In contrast, involvement of the gastrointestinal or urogenital tract was not observed in any of the cases. Patients originated to a large extent (61%) from Turkey and the Middle East, and showed a comparably frequent occurrence of consanguinity of affected families and a greater female to male ratio than was derived from previous reports in the literature. Individual treatment of ligneous conjunctivitis included topical plasminogen or heparin eye drops, topical or systemic fresh frozen plasma, and surgical removal of ligneous pseudomembranes, mostly with modest or transient efficacy. In conclusion, the present study underscores the broad range of clinical manifestations in PLG-deficient patients with a trend to regional differences. Transmission of genetic and clinical data to the recently established Plasminogen Deficiency Registry should help to determine the prevalence of the disease and to develop more efficient treatment strategies.

Oral health and inflammation in patients with end-stage renal failure.

BACKGROUND/AIMS: End-stage renal disease (ESRD) patients have an increased risk of atherosclerotic complications. In both hemodialysis (HD) patients and the general population, it has become evident that inflammation plays an important role in the pathogenesis of atherosclerotic complications. Oral and dental problems in ESRD patients could be an important source of inflammation, thus treatment of these problems is important to protect these patients from potential infections. The decayed, missing, and filled teeth (DMFT) index is an indicator of oral and dental health status. Our aim was to analyze and compare salivary flow rate (SFR), salivary pH (SpH), salivary buffering capacity (SBC), and DMFT index and plaque index (PI) values in PD patients to HD patients and healthy controls (C) and establish the relationship between these parameters and C-reactive protein (CRP). METHODS: 76 PD patients, 100 HD patients, and 111 Cs were included in the study. SFR (milliliters/minute) was measured in stimulated whole saliva, SpH was measured using the Merck indicator, and SBC was measured according to the method of Ericsson: 1 mL whole saliva was added to 3 mL 0.005 N HCl and a stream of air was passed through this mixture for 20 minutes. Finally, DMFT index and PI values were calculated. RESULTS: No statistically significant differences were found in age or gender distribution among PD, HD, and C groups. There was also no significant difference in time on dialysis between PD and HD groups. SFR was significantly lower in the PD and HD groups than in the C group (1.30 +/- 0.83 and 0.70 +/- 0.32 vs 1.64 +/- 0.45 mL/min) and lower in the HD than in the PD group (p < 0.001). SpH (8.35 +/- 0.43 and 8.12 +/- 0.74 vs 7.16 +/- 0.76) and SBC (7.39 +/- 0.47 and 6.82 +/- 0.70 vs 5.08 +/- 0.73) were significantly higher in the PD and HD groups than in the C group and higher in the PD than in the HD group (p < 0.05 and p < 0.001 respectively). The numbers of filled teeth were significantly higher in the PD than in the HD and C groups (p < 0.001). DMFT index was significantly higher in the PD than in the HD group (p < 0.001). Finally, PI values were significantly higher in the PD and HD groups than in the C group (p < 0.001) and higher in the HD than in the PD group, although this was not statistically significant. In the present study, we also found higher CRP values in HD than in PD patients and a positive correlation between CRP and PI values in PD patients. CONCLUSIONS: PD patients have higher SFR, SpH, and SBC values than HD patients; however, higher DMFT index and higher numbers of filled teeth were observed in PD patients. Compared to healthy controls, patients on dialysis had worse dental and periodontal findings, which might have a role in microinflammation in this group of patients.

Effect of educational level on oral health in peritoneal and hemodialysis patients.

Background. In previous studies, the oral and dental health statuses were compared in hemodialysis (HD) and peritoneal dialysis (PD) patients without taking into account the effect of educational levels on oral health. Hence we aimed to make a comparison of these parameters based upon the subjects educational levels. Patients and Methods. 76 PD (33 males, 43 females-mean age: 44 +/- 12 years) and 100 HD (56 males, 44 females-mean age: 46 +/- 14 years) patients were included. The number of decayed, missing and filled teeth were detected, DMFT index was calculated and plaque index (PI) values were assessed. Results. Significantly higher numbers of filled teeth (P < .001) and lower PI values (P < .01) in the PD group were detected with higher educational levels, whereas no significance was detected in the HD group. Higher DMFT index values were assessed in the lower educated and high school levels in PD than HD patients (P < .05). Higher numbers of filled teeth (P < .05) were detected in the secondary school level in PD patients. This difference was even more significant in the high school level (P < .001). Conclusion. We assume that PD patients, who were found to be in a higher educational level, are more caring for their oral health as compared to HD patients.

Hypoplasminogenemia with ligneous periodontitis: a failed local therapeutic approach.

BACKGROUND: Hypoplasminogenemia is a rare condition that is associated with ligneous conjunctivitis, a form of chronic conjunctivitis characterized by firm, fibrin-rich, pseudomembranous lesions on the tarsal conjunctivae and oral lesions. Pseudomembranes may develop on the gingivae, and there may be periodontal involvement. METHODS: Several therapeutic approaches have been developed to treat such patients, but they have had limited effect. We used gingivectomies, topical heparin, and corticosteroids to treat periodontal lesions in an 18-year-old girl. RESULTS: This approach had no benefit. CONCLUSION: The question remains about how best to manage patients with hypoplasminogenemia.

Molecular and clinical spectrum of type I plasminogen deficiency: A series of 50 patients.

Severe type I plasminogen (PLG) deficiency has been causally linked to a rare chronic inflammatory disease of the mucous membranes that may be life threatening. Here we report clinical manifestations, PLG plasma levels, and molecular genetic status of the PLG gene of 50 patients. The most common clinical manifestations among these patients were ligneous conjunctivitis (80%) and ligneous gingivitis (34%), followed by less common manifestations such as ligneous vaginitis (8%), and involvement of the respiratory tract (16%), the ears (14%), or the gastrointestinal tract (2%). Four patients showed congenital occlusive hydrocephalus, 2 with Dandy-Walker malformation of cerebellum. Venous thrombosis was not observed. In all patients, plasma PLG levels were markedly reduced. In 38 patients, distinct mutations in the PLG gene were identified. The most common genetic alteration was a K19E mutation found in 34% of patients. Transient in vitro expression of PLG mutants R134K, delK212, R216H, P285T, P285A, T319_N320insN, and R776H in transfected COS-7 cells revealed significantly impaired secretion and increased degradation of PLG. These results demonstrate impaired secretion of mutant PLG proteins as a common molecular pathomechanism in type I PLG deficiency.