Giuseppe Bonaventura

Association between interleukin-10 polymorphisms and Alzheimer's disease: a systematic review and meta-analysis.

UNLABELLED It has been hypothesized that polymorphisms of interleukin (IL)-10 genes affect the risk of developing late onset Alzheimers disease (AD). However, results of different studies are often inconsistent. Our aim was to investigate by meta-analysis the association of the common polymorphisms comprehensively defining the genetic variability of the IL-10 gene with AD risk. Fifteen studies investigating the association between IL-10 polymorphisms (-1082, -819, -592) and AD were found and analyzed. The model-free approach was applied to meta-analyze these case-control genetic association studies. Available data suggested an association between -1082 polymorphism and AD risk with a marginal statistical significance (GG versus AG/AA pooled odds ratio [OR]: 0.82, 95% confidence interval CI: 0.65-1.02) and evidence of a moderate degree of between-study heterogeneity (χ2 = 27.13, d.f. = 13, p = 0.01, I2 = 52%). For the -819 and -592 polymorphisms, we did not find an association with AD, but significant between-study heterogeneity made genotype data pooling unacceptable. Analysis by IL-10 haplotype showed that the -1082G/-819C/-592C haplotype is associated with a lower risk of AD, although with a marginal statistical significance, probably due to the low number of studies included (GCC versus other genotypes: OR: 0.61, 95% CI: 0.32-1.15; I2: 85%). Current findings suggest a possible association between -1082 A > G polymorphism and the risk of developing AD; this effect is more evident in the oldest patients. The high degree of between-study heterogeneity, due to several underpowered studies and to other methodological problems of individual studies underlies the need for further methodologically adequate studies.

Heat-shock protein 60 kDa and atherogenic dyslipidemia in patients with untreated mild periodontitis: a pilot study

AbstractIdentification of predictors of cardiovascular risk can help in the prevention of pathologic episodes and the management of patients at all stages of illness. Here, we investigated the relationships between serum levels of Hsp60 and dyslipidemia in patients with periodontitis by performing a cross-sectional study of 22 patients with mild periodontitis without any prior treatment for it (i.e., drug naïve) and 22 healthy controls, matched for age and body mass index (BMI). All subjects were evaluated for periodontal status, gingival inflammation, and oral hygiene. Levels of circulating Hsp60, C-reactive protein (CRP), and plasma lipids were measured, and small, dense low-density lipoproteins (LDL) were indirectly assessed by determining the triglycerides/high-density lipoproteins (HDL) cholesterol ratio. We also assessed by immunohistochemistry Hsp60 levels in oral mucosa of patients and controls. No difference was found in CRP levels or plasma lipids between the two groups, but subjects with periodontitis showed, in comparison to controls, higher levels of small, dense LDL (p  = 0.0355) and circulating Hsp60 concentrations (p < 0.0001). However, levels of mucosal Hsp60 did not change significantly between groups. Correlation analysis revealed that circulating Hsp60 inversely correlated with HDL-cholesterol (r  = −0.589, p  = 0.0039), and positively with triglycerides (r  = +0.877, p < 0.0001), and small, dense LDL (r  = +0.925, p < 0.0001). Serum Hsp60 significantly correlated with the degree of periodontal disease (r  = +0.403, p  = 0.0434). In brief, untreated patients with mild periodontitis had increased small, dense LDL and serum Hsp60 concentrations, in comparison to age- and BMI-matched controls and both parameters showed a strong positive correlation. Our data indicate that atherogenic dyslipidemia and elevated circulating Hsp60 tend to be linked and associated to periodontal pathology. Thus, the road is open to investigate the potential value of elevated levels of circulating Hsp60 as predictor of risk for cardiovascular disease when associated to dyslipidemia in periodontitis patients.

Hsp60 and human aging: Les liaisons dangereuses.

Stressors can cause abnormal intracellular accumulation of Hsp60 and its localization in extramitochondrial sites, secretion, and circulation, with immune system activation. Dysfunction of chaperones associated with their quantitative and qualitative decline with aging (chaperonopathies of aging) characterizes senescence and is a potential causal factor in the physiological deterioration that occurs with it. The role of Hsp60 in aging is not easy to elucidate, because aging is accompanied by pathologies (e.g., cardiovascular and neurodegenerative disorders, osteoporosis, diabetes, cancer, etc.) in which Hsp60 has been implicated but, although those disorders are more frequent in the elderly, they are not unique to them. Therefore, it is difficult to determine what is due to aging and what to an associated disease that can occur regardless of age. Does Hsp60 contribute to the pathogenesis? How and when does Hsp60 interact with the immune system and, thus, contributes to the initiation-progression of the generalized chronic inflammation characteristic of aging? These and related issues are discussed here in the light of reports showing the participation of Hsp60 in aging-associated disorders.

Immunohistochemical expression and distribution of orexin, orphanin and leptin in the major salivary glands of some mammals

The aim of the study was to determine by immunochemistry the expression of leptin, orexin A and orphanin FQ in the major salivary glands (parotid, submandibular and sublingual) of rat, sheep and cow. These peptides, originally synthesized in central nervous system, adipose tissue and peripheral tissues including gastrointestinal tract, play an orexigenic (orphanin and orexin) or anorexigenic (leptin) roles in the intricate neuronal network appointed to the control of nutritional homeostasis. Peptide-specific immunoreactivity was present in the studied salivary glands with various intensities in different species, in the ductal epithelium, sometimes in the acinar epithelium, and in nervous trunks spread in connective tissue stroma. The obtained data show that salivary glands present an unexpected source of orexigenic and anorexigenic peptides which with their autocrine, paracrine, and endocrine mechanisms of action may participate in the control of salivary gland function.

Does orthodontic treatment induces dental pulp cellular death? Caspase-3 and-9, HSP60 and Tunel expression

Objective. To evaluate the hypothesis of human dental pulp cell death during Orthodontic Treatement (O.T.) and the degree of apoptosis through the expression level of the proteins Caspase-3,-9, TUNEL and HSP60. Materials and methods . Human dental Pulp were coming from both male and female patients (N=20; age 10-14years). The technique used was the Straight Wire, which involves Nickel-Titanium or Steel archwires. The increase of pressure applied on teeth was gradual. Some patients were subjected to a premolar extraction after 3 months treatment, and others after 6 months. Samples were Bouin-fixed, paraffin-embedded and afterwards processed for immunohistochemistry using anti-caspase-3,-9 antibody, anti-HSP60 and TUNEL. Results. Increasing of Caspase-3,-9 expression occurred in 3 and 6 months O.T. samples, while in control pulps positivity was detected mainly at odontoblasts level. HSP60 was not expressed in control samples and very weak in 3 months O.T. samples, it was expressed instead in 6 months O.T. samples, the expression of TUNEL is evident in all samples but increased at 3 and 6 months specimen. Conclusion . Our hypothesis is supported by the increasing expression of Caspase-3,-9, HSP60 and TUNEL after 3 and 6 months of orthodontic traction revealing a time-dependent relationship.

Immunohistochemical expression of Cytokeratins in periapical lesions

Objective. This study seeks to clarify the histological origin of apical lesions, through the expression of certain cytokeratins.Study design. In 3 years 30 patients were selected. After clinical and radiological exams were chosen patients who had severe apical lesions and tooth decay with exposure of the pulp chamber left untreated for very long periods (more the 12 months). Serial slides were prepared both for immunohistochemistry and Hematoxylin- Eosin. Material and methods. Twenty specimens coming from the 30 patients were used for our purpose. All periapical lesions were surgically extracted and fixed in Bouin mixture, and embedded in paraffin. Samples were processed immunohistochemically employing the instructions of the Envision Dako cytomation kit. Monoclonal antibobies against Cytokeratins (CKs) 1, 5 , 8, 10 and 14 were used. Slides were observed with Leica Laborlux-S microscope and the image were acquired with NIKON DSL2 System. Each sample has been analyzed with a “double-blind” system by two different operators. Moreover, the digital images acquired have been compared to an image analysis tools by Adobe photoshop CS5 Extended. Results. CKs 1, 5 and 8 are expressed in all samples at external epithelial layer with no statistically significant differences. CK 10 is weakly expressed in some epithelial cells lining the periapical lesion. CK 14 was negative in most samples, and little positive in some specimens. Conclusion. Our results suggest that most of the apical lesions we studied have an epithelial origin. The absence of CK14 positivity may be explained by the fact that during the extirpation of the lesion the basal epithelium remained attached to the surrounding bone.