Heparanase is expressed in adult human osteoarthritic cartilage and drives catabolic responses in primary chondrocytes.

OBJECTIVES: The chondrocytes' pericellular matrix acts as a mechanosensor by sequestering growth factors that are bound to heparan sulfate (HS) proteoglycans. Heparanase is the sole mammalian enzyme with HS degrading endoglycosidase activity. Here, we aimed to ascertain whether heparanase plays a role in modulating the anabolic or catabolic responses of human articular chondrocytes. METHODS: Primary chondrocytes were incubated with pro-heparanase and catabolic and anabolic gene expression was analyzed by quantitative polymerase chain reaction (PCR). MMP13 enzymatic activity in the culture medium was measured with a specific fluorescent assay. Extracellular regulated kinase (ERK) phosphorylation was evaluated by Western blot. Human osteoarthritis (OA) cartilage was assessed for heparanase expression by reverse-transcriptase PCR, by Western blot and by a heparanase enzymatic activity assay. RESULTS: Cultured chondrocytes rapidly associated with and activated pro-heparanase. Heparanase induced the catabolic genes MMP13 and ADAMTS4 and the secretion of active MMP13, and down-regulated the anabolic genes ACAN and COL2A1. PG545, a HS-mimetic, inhibited the effects of heparanase. Heparanase expression and enzymatic activity were demonstrated in adult human osteoarthritic cartilage. Heparanase induced ERK phosphorylation in cultured chondrocytes and this could be inhibited by PG545, by fibroblast growth factor 2 (FGF2) neutralizing antibodies and by a FGF-receptor inhibitor. CONCLUSIONS: Heparanase is active in osteoarthritic cartilage and induces catabolic responses in primary human chondrocytes. This response is due, at least in part, to the release of soluble growth factors such as FGF2.

Independent determinants of periodontitis in Yemeni adults: A case-control study.

OBJECTIVES: The relative importance of risk factors of periodontitis varies from one population to another. In this study, we sought to identify independent risk factors of periodontitis in a Yemeni population. METHODS: One hundred and fifty periodontitis cases and 150 healthy controls, all Yemeni adults 30-60 years old, were recruited. Sociodemographic data and history of oral hygiene practices and oral habits were obtained. Plaque index (PI) was measured on index teeth. Periodontal health status was assessed using Community Periodontal Index (CPI) and Clinical Attachment Loss (CAL) according to WHO. Periodontitis was defined as having one or more sextants with a CPI score ≥ 3. Multiple logistic regression modelling was employed to identify distal, intermediate and proximal determinants of periodontitis, while ordinal regression was used to identify those of CAL scores. RESULTS: In logistic regression, PI score was associated with the highest odds of periodontitis (OR = 82.9) followed by cigarette smoking (OR = 12.8), water pipe smoking (OR = 10.2), male gender (OR = 3.4) and age (OR = 1.19); on the other hand, regular visits to the dentist (OR = 0.05), higher level of education (OR = 0.37) and daily dental flossing (OR = 0.95) were associated with lower odds. Somewhat similar associations were seen for CAL scores (ordinal regression); however, qat chewing was identified as an additional determinant (OR = 4.69). CONCLUSION: Water pipe smoking is identified as a risk factor of periodontitis in this cohort in addition to globally known risk factors. Adjusted effect of qat chewing is limited to CAL scores, suggestive of association with recession.

Prevalence of oral white lesions due to qat chewing among women in Yemen.

OBJECTIVES: To investigate oral mucosal white lesions due to qat chewing among Yemeni women and their possible confounders (tobacco, water-pipe). PATIENTS AND METHODS: In a cross-sectional hospital study, 162 healthy women were divided into 109 qat chewers and 53 non-qat chewers. Inclusion criteria were as follows: ≥20 years of age, chewing qat habitually ≥5 years on one side. Women were interviewed about tobacco/water-pipe use and examined for oral mucosal lesions. RESULTS: Among chewers, white lesions were recorded in 82/109 (75.2%) at the chewing site. Lesions on the opposite side were recorded among 6/109 (5.5%) and among 7/53 (13.2%) non-chewers. Lesions reported among chewers were correlated with the side of chewing and with longer duration of the habit. The difference in the prevalence of white lesions present between cases and controls was significant (P < 0.000). When white lesions were correlated with the durations of chewing and water-pipe and cigarette smoking, results in terms of chewing were highly significant (P = 0.000) and those in terms of water-pipe smoking and cigarette smoking were not significant. CONCLUSION: Habitual chewing of qat fibres by Yemeni women over decades caused mucosal white lesions recorded on the chewing side irrespective of additional noxae as tobacco and water-pipe smoking.

Occult myocardial injury is prevalent amongst elderly patients in the hospital-at-home setting. A retrospective analysis of 213 patients.

Background: Hospital-at-Home (HAH) is a valid alternative for in-hospital stay for a wide variety of clinical indications. Occult myocardial injury, associated with acute illness, mainly occurs in patients with a background of non-obstructive coronary disease. The aim of this study was to describe the prevalence of this phenomenon in our HAH population. Methods: A retrospective description and analysis of data collected for patients admitted to the Sheba beyond's HAH services during 14 months. Results: During a period of 14 months (7/10/21-6/12/22), blood troponin measurements were available for 213 patients (median age 78 years, 52% males) hospitalized mainly for infectious causes. The median HS (highly sensitive) troponin level was 7.7 ng/L (IQR = 13.2 ng/L) (the normal upper limit is 12 ng/L) with 31% of all patients demonstrating an abnormally increased troponin level (68/213). Of all patients, 64% had a background diagnosis of a cardiovascular disease (138/213), of whom, 49% had abnormal HS troponin levels (68/138). No patient suffered from acute cardiac function deterioration and no patient died during their hospital-at-home stay. Conclusion: The prevalence of occult myocardial injury amongst elderly patients admitted to hospital-at-home stay for diagnoses other than myocardial infarction is relatively high but it is not associated with worse short-term clinical outcomes.