Systemic pro-inflammatory cytokine status following therapeutic hypothermia in a piglet hypoxia-ischemia model

BACKGROUND: Inflammatory cytokines are implicated in the pathogenesis of perinatal hypoxia-ischemia (HI). The influence of hypothermia (HT) on cytokines after HI is unclear. Our aim was to assess in a piglet asphyxia model, under normothermic (NT) and HT conditions: (i) the evolution of serum cytokines over 48 h and (ii) cerebrospinal fluid (CSF) cytokine levels at 48 h; (iii) serum pro/anti-inflammatory cytokine profile over 48 h and (iv) relation between brain injury measured by magnetic resonance spectroscopy (MRS) and brain TUNEL positive cells with serum cytokines, serum pro/anti-inflammatory cytokines and CSF cytokines. METHODS: Newborn piglets were randomized to NT (n = 5) or HT (n = 6) lasting 2-26 h after HI. Serum samples were obtained 4-6 h before, during and at 6-12 h intervals after HI; CSF was obtained at 48 h. Concentrations of interleukin (IL)-1beta, -4, -6, -8, -10 and TNF-alpha were measured and pro/anti-inflammatory status compared between groups. White matter and thalamic voxel lactate/N-acetyl aspartate (Lac/NAA) (a measure of both oxidative metabolism and neuronal loss) were acquired at baseline, after HI and at 24 and 36 h. RESULTS: Lac/NAA was reduced at 36 h with HT compared to NT (p = 0.013 basal ganglia and p = 0.033 white matter). HT showed lower serum TNF-alpha from baseline to 12 h (p < 0.05). Time-matched (acquired within 5 h of each other) serum cytokine and MRS showed correlations between Lac/NAA and serum IL-1beta and IL-10 (all p < 0.01). The pro/anti-inflammatory ratios IL-1beta/IL-10, IL-6/IL-10, IL-4/IL-10 and IL-8/IL-10 were similar in NT and HT groups until 36 h (24 h for IL-6/IL-10); after this, 36 h pro/anti-inflammatory cytokine ratios in the serum were higher in HT compared to NT (p < 0.05), indicating a pro-inflammatory cytokine surge after rewarming in the HT group. In the CSF at 48 h, IL-8 was lower in the HT group (p < 0.05). At 48 h, CSF TNF-alpha correlated with Lac/NAA (p = 0.02) and CSF IL-8 correlated with white matter TUNEL positive cell death (p = 0.04). CONCLUSIONS: Following cerebral HI, there was a systemic pro-inflammatory surge after rewarming in the HT group, which is counterintuitive to the putative neuroprotective effects of HT. While serum cytokines were variable, elevations in CSF inflammatory cytokines at 48 h were associated with MRS Lac/NAA and white matter cell death

Immunohistochemical Analysis of Matrix Metalloproteinases-1,-9 and Tenascin in Odontogenic Lesions

Ameloblastoma (ABL) and keratocystic odontogenic tumor (KOT) are benign odontogenic tumors with local aggressive behaviors. The purpose of our study was to compare MMP-1, MMP-9 and tenascin staining patterns between “aggressive” ameloblastoma / keratocystic odontogenic tumors and “non-aggressive” radicular cysts (RC)/ dentigerous cysts (DC). Ameloblastoma, keratocystic odontogenic tumor, radicular cyst (RC) and dentigerous cyst (DC) specimens were chosen from the archives of Gazi University Faculty of Dentistry, Department of Oral Pathology, and immunohistochemically stained with MMP-1, -9 and tenascin antibodies. The immunohistochemical expressions were noted and statistically analyzed. The ABLs and KOTs showed significantly higher MMP-1 and -9 positivity than the RCs and DCs (p<0.05). The ABL and KOT basement membranes showed more continuous tenascin expression. Tenascin intensity was significantly higher in the ABLs and KOTs compared to the RCs and DCs (p<0.05). The results suggest that higher expression of MMP-1 and -9 may play an essential role in the growth and progression of these tumors. Continuous tenascin positivity may reflect strong connective tissue reaction against the invasive epithelial parts of ABLs and KOTs

Osteo-cementum Producing Odontogenic Myxomas. A Literature Review of a Distinctive Variant

INTRODUCTION: Odontogenic myxoma (OM) is a benign neoplasm of mesenchymal origin with growth characteristics, clinical behaviour and radiographic presentation similar to those of ameloblastoma. It is an intraosseous neoplasm characterized by stellate and spindleshaped cells embedded in loose myxoid or mucoid extracellular matrix. Although sometimes bony islands that represent residual trabeculae are found throughout the lesion, the formation of osteocement-like calcified spherules within the tumour is an extremely rare phenomenon. REVIEW: We report a very rare case of an OM of the left maxilla exhibiting osteo-cementous metaplasia within the substance of the tumour and beyond the facial skeleton, in the nasopharynx. A review of all four similar cases previously reported in the literature is also presented. CONCLUSION: Whether or not this property to produce significant amounts of bone can be associated with a different biological behavior for this specific variant of OM remains to be proved with the study of more similar cases

Why prevent, diagnose and treat congenital toxoplasmosis?

Evidence that prevention, diagnosis and treatment of toxoplasmosis is beneficial developed as follows: anti-parasitic agents abrogate Toxoplasma gondiitachyzoite growth, preventing destruction of infected, cultured, mammalian cells and cure active infections in experimental animals, including primates. They treat active infections in persons who are immune-compromised, limit destruction of retina by replicating parasites and thereby treat ocular toxoplasmosis and treat active infection in the fetus and infant. Outcomes of untreated congenital toxoplasmosis include adverse ocular and neurologic sequelae described in different countries and decades. Better outcomes are associated with treatment of infected infants throughout their first year of life. Shorter intervals between diagnosis and treatment in utero improve outcomes. A French approach for diagnosis and treatment of congenital toxoplasmosis in the fetus and infant can prevent toxoplasmosis and limit adverse sequelae. In addition, new data demonstrate that this French approach results in favorable outcomes with some early gestation infections. A standardized approach to diagnosis and treatment during gestation has not yet been applied generally in the USA. Nonetheless, a small, similar experience confirms that this French approach is feasible, safe, and results in favorable outcomes in the National Collaborative Chicago-based Congenital Toxoplasmosis Study cohort. Prompt diagnosis, prevention and treatment reduce adverse sequelae of congenital toxoplasmosis