Experimental tooth pain elevates substance P and matrix metalloproteinase-8 levels in human gingival crevice fluid

Objective. Tooth pain can induce a neurogenic inflammatory reaction in gingiva in association with local elevations of matrix metalloproteinase (MMP)-8, which is considered the major tissue destructive protease in gingival crevice fluid (GCF). The pro-inflammatory neuropeptides released by sensory nerves coordinate the activities of the immuno-effector cells and may influence the secretion of MMP-8. With this background, we studied whether experimental tooth pain can trigger changes in GCF levels of the neuropeptide substance P (SP) and MMP-8. Material and methods. The GCF SP levels of stimulated and non-stimulated teeth were analyzed for SP using a competitive enzyme immunoassay (EIA). The GCF MMP-8 levels were determined by quantitative immunofluorometric assay (IFMA). Results. Painful stimulation of the upper central incisor caused significant elevations in GCF SP and MMP-8 levels of the stimulated tooth. At the same time, the GCF SP and MMP-8 levels of non-stimulated control teeth were unchanged. Conclusions. These data indicate that experimental tooth pain can induce local elevations of SP and MMP-8 levels in GCF simultaneously. This supports the possibility of a local neurogenic spread of inflammatory reactions from intrapulpal to surrounding periodontal tissues.     

Subjective reactions to intervention with artificial interferences in subjects with and without a history of temporomandibular disorders

In a previous double-blind randomized controlled study, subjects with a history of temporomandibular disorder (TMD) reacted to artificial interference with more signs of TMD than did subjects with no TMD history. In the present study, we analysed the subjective reactions of these individuals on several symptom scales. Every day during the 2-week follow-up period, the subjects rated the intensity of their symptoms on 9 VAS scales (occlusal discomfort, chewing difficulties, tender teeth, fatigue in the jaws, headache, facial pain, opening difficulty, bruxism, ear symptoms). Subjects with a history of TMD and true interferences reported stronger symptoms than subjects with no TMD history and placebo interferences. The most prominent symptoms were occlusal discomfort and chewing difficulties. The difference in outcome between the groups with and without a TMD history suggests that there are individual differences in vulnerability to occlusal interferences. It is likely that the etiological role of occlusal interferences in TMD has not been correctly addressed in previous studies on artificial interferences.     

Amyloid precursor protein (APP) A673T mutation in the elderly Finnish population

Pathogenic mutations of the APP gene, leading to early-onset Alzheimer's disease (AD) have been known for more than 20 years. Recently, it was discovered that APP mutations might also be protective. A rare variant A673T reportedly protects against AD and age-related cognitive impairment and might functionally inhibit proteolytic cleavage at the β-secretase site of APP. We sequenced APP exon 16 in a population-based sample of 515 Finnish subjects aged 85 or older. Neuropathologic data were available in 274. We found the A673T variant in 1 subject (0.2%), who lived until age 104.8 years (second highest age-at-death in the cohort). Neuropathologic analysis showed little beta-amyloid pathology (Consortium to Establish a Registry for Alzheimer's Disease score 0). Some vascular amyloid was detected in meningeal arteries suggesting that vascular β-amyloid accumulation might be less inhibited than the parenchymal. She was demented at the age of 104, most likely because of hippocampal sclerosis. The low amount of parenchymal β-amyloid pathology at the age of 104.8 years supports the concept that the A673T variant protects the brain against β-amyloid pathology and AD.     

Detection of Group A Streptococcus from Pharyngeal Swab Samples by Bacterial Culture Is Challenged by a Novel mariPOC Point-of-Care Test

mariPOC is a novel point-of-care test system for rapid detection of respiratory tract infections. We compared the performance of the mariPOC test to that of bacterial culture for detecting group A streptococcus (GAS) in 219 pharyngitis patients (ages 1–64 years) and 109 healthy asymptomatic controls (ages 19–69 years). In addition, 42 patient samples were analyzed by quantitative PCR (qPCR). Of the 219 pharyngeal patient samples, 32 were positive in a GAS bacterial culture (prevalence 15%) and 65 (30%) in the mariPOC test. The amount of GAS in samples reported positive by the mariPOC test and negative by culture was, on average, 10-fold less than that of those positive in both methods. This indicated that the negative results in bacterial cultures were due to lower sensitivity. The qPCR results were positive and in line with the mariPOC results in 43% of the discordant samples studied. Two GAS culture-positive samples were negative by the mariPOC test. The prevalences of GAS in the control subjects were 2% and 6% by culture and mariPOC results, respectively. We conclude that the mariPOC antigen detection test is more sensitive than the conventional bacterial culture for the detection of GAS among symptomatic pharyngitis patients. The higher prevalence of GAS by the mariPOC test among symptomatic patients was probably not due to carriership, since among the control patients, the difference in the prevalence of GAS by the mariPOC test and culture was not nearly as high, 15% versus 4%, respectively. Clinical trials are needed to show the clinical importance of our findings.     

Rectovesical ligament and fusion defect of the uterus with or without obstructed hemivagina and ipsilateral renal agenesis

Objective

The rectovesical ligament is a peritoneal band in women with failure of fusion of the two Müllerian ducts. The aim was to evaluate existence of this abnormal structure in women with dysfused uterus and its possible relations to concomitant vaginal and renal anomalies.

Study design

The study group comprised 47 women with uterine fusion defect (37 didelphic and 10 bicornuate uterus). They had undergone laparoscopy or laparotomy to visualize the pelvic cavity, and imaging for renal evaluation. The rectovesical ligament was present if inspection of the pelvic cavity revealed a broad peritoneal band between the two hemiuteri, attached anteriorly to the bladder and posteriorly to the sigmoid. Presence or absence of the ligament was reported, and concomitant renal and vaginal anomalies were evaluated.

Results

The rectovesical ligament was not visualized in 14 patients with didelphic or complete bicornuate uterus associated with unilateral renal agenesis: of these 13 had a previously treated obstructive longitudinal vaginal septum. A peritoneal band was found in 27 women with didelphic uterus with longitudinal vaginal septum with no obstruction and normal bilateral kidneys. Six women with bicornuate uterus had normal kidneys and an identified rectovesical ligament between the uterine hemicorpora, except for one with partial bicornuate uterus.

Conclusion

The rectovesical ligament is not merely a consequence of the failed fusion of two Müllerian ducts, but its relation to uterine malformation with or without vaginal and renal anomalies indicates some share of this structure in the early development of the urogenital system.     

Elevated globotriaosylsphingosine is a hallmark of Fabry disease

Fabry disease is an X-linked lysosomal storage disease caused by deficiency of alpha-galactosidase A that affects males and shows disease expression in heterozygotes. The characteristic progressive renal insufficiency, cardiac involvement, and neuropathology usually are ascribed to globotriaosylceramide accumulation in the endothelium. However, no direct correlation exists between lipid storage and clinical manifestations, and treatment of patients with recombinant enzymes does not reverse several key signs despite clearance of lipid from the endothelium. We therefore investigated the possibility that globotriaosylceramide metabolites are a missing link in the pathogenesis. We report that deacylated globotriaosylceramide, globotriaosylsphingosine, and a minor additional metabolite are dramatically increased in plasma of classically affected male Fabry patients and plasma and tissues of Fabry mice. Plasma globotriaosylceramide levels are reduced by therapy. We show that globotriaosylsphingosine is an inhibitor of alpha-galactosidase A activity. Furthermore, exposure of smooth muscle cells, but not fibroblasts, to globotriaosylsphingosine at concentrations observed in plasma of patients promotes proliferation. The increased intima-media thickness in Fabry patients therefore may be related to the presence of this metabolite. Our findings suggest that measurement of circulating globotriaosylsphingosine will be useful to monitor Fabry disease and may contribute to a better understanding of the disorder.