Corpus callosum infarction: radiological and histological findings

Journal of Neurology -     

Circulating mitochondrial DNA increases with age and is a familiar trait: Implications for “inflamm‐aging”

Mitochondrial components, including mitochondrial DNA (mtDNA), when released extracellularly, can act as “damage‐associated molecular pattern” (DAMP) agents and cause inflammation. As many elderly people are characterized by a low‐grade, chronic inflammatory status defined “inflamm‐aging,” we evaluated if circulating mtDNA can contribute to this phenomenon. Eight hundred and thirty‐one Caucasian subjects were enrolled in the study, including 429 siblings aged 90–104 (90+ siblings). mtDNA plasma levels increased gradually after the fifth decade of life. In 90+ subjects, mtDNA values of two members of the same sibling relationship were directly correlated, suggesting a role for familiar/genetic background in controlling the levels of circulating mtDNA. The subjects with the highest mtDNA plasma levels had the highest amounts of TNF‐α, IL‐6, RANTES, and IL‐1ra; the subjects with the lowest mtDNA levels had the lowest levels of the same cytokines. In vitro stimulation of monocytes with mtDNA concentrations similar to the highest levels observed in vivo resulted in an increased production of TNF‐α, suggesting that mtDNA can modulate the production of proinflammatory cytokines. Our findings therefore show that circulating mtDNA increases with age, and can significantly contribute to the maintenance of the low‐grade, chronic inflammation observed in elderly people.     

Biological activities of dermatological interest by the water extract of the microalga Botryococcus braunii

The use of microalgae in the skin care market is already established although the scientific rationale for their benefit was not clearly defined. In this work, the biological activities of dermatologic interest of the water extract from the microalga Botryococcus braunii (BBWE) were evaluated by a battery of in vitro assays. At concentrations ranging from 0.1 to 0.001?% (w/v) BBWE promoted adipocytes differentiation by inhibiting hormone-sensitive lipase, thus promoting triglyceride accumulation in the cells. BBWE also induced gene expression of proteins involved in the maintenance of skin cells water balance such as aquaporin-3 (AQP3), filaggrin (FLG) and involucrin (INV). 0.1?% BBWE increased the gene expression of AQP3 of 2.6-folds, that of FLG and INV of 1.5- and 1.9-folds, respectively. Moreover, it induced the biosynthesis of collagen I and collagen III by 80 and 40?%, respectively, compared to the untreated control. BBWE antioxidant activity, evaluated by oxygen radical absorbance capacity (ORAC) assay, was of 43.5?μmol Trolox per gram of extract: a quite high value among those found for other microalgae extracts. BBWE inhibited the inducible nitric oxide synthase (iNOS) gene expression and the consequent nitrite oxide (NO) production under oxidative stress. At a concentration of 0.02?% BBWE reduced by 50?% the expression of iNOS and by about 75?% the NO production. Taken together, the results demonstrated that B. braunii water extract exerted an array of biological activities concurring with the skin health maintenance; therefore, it is a potential bioactive ingredient to be included in cosmetic products.     

Are Diabetes,Hypertension, and Obesity Independent Risk Factors for Endometrial Polyps?

Study ObjectiveTo investigate whether diabetes, hypertension (HTN), and obesity can be considered risk factors for endometrial polyps (EPs) independently of age and menopausal status.DesignRetrospective analysis (Canadian Task Force classification III).SettingDepartment of Obstetrics and Gynecology of the University of Foggia, Italy.PatientsA total of 353 Caucasian women undergoing office hysteroscopy to assess abnormal uterine bleeding, infertility, cervical polyps, and abnormal sonographic patterns.InterventionsDemographic characteristics and data on diabetes, HTN, and menopausal status were collected and anthropometric parameters were analyzed. Vaginoscopic hysteroscopy was performed with a 5-mm continuous-flow operative office hysteroscope. When present, EPs were treated during the same procedure by means of 5-Fr scissors or electrode.Measurements and Main ResultsIn 134 (38%) of 353 cases, EPs were found. Univariable and multivariable analysis were performed to verify the presence of a statistically significant association among age, menopause, HTN, obesity, diabetes (independent variables), and the presence of EPs. Univariable logistic analysis showed a statistically significant association among age, menopause, HTN, obesity, and the presence of EPs. However, when multivariable logistic regression was performed, all the independent variables, except age, lost statistical significance (OR 1.05, 95% CI 1.02–1.07, p <.001).ConclusionAlthough it appears that EP is a disorder of aging, the significance of diabetes, HTN, and obesity, as well as menopause, on the development of EPs should be reconsidered.     

Development and characterization of rhVEGF-loaded poly(HEMA–MOEP) coatings electrosynthesized on titanium to enhance bone mineralization and angiogenesis

Osteointegration of titanium implants could be significantly improved by coatings capable of promoting both mineralization and angiogenesis. In the present study, a copolymeric hydrogel coating, poly-2-hydroxyethyl methacrylate-2-methacryloyloxyethyl phosphate (P(HEMA–MOEP)), devised to enhance calcification in body fluids and to entrap and release growth factors, was electrosynthesized for the first time on titanium substrates and compared to poly-2-hydroxyethyl methacrylate (PHEMA), used as a blank reference. Polymers exhibiting negatively charged groups, such as P(HEMA–MOEP), help to enhance implant calcification. The electrosynthesized coatings were characterized by X-ray photoelectron spectroscopy and atomic force microscopy. MG-63 human osteoblast-like cell behaviour on the coated specimens was investigated by scanning electron microscopy, MTT viability test and osteocalcin mRNA detection. The ability of negatively charged phosphate groups to promote hydroxyapatite-like calcium phosphate deposition on the implants was explored by immersing them in simulated body fluid. Similar biological responses were observed in both coated specimens, while calcium-phosphorus globules were detected only on P(HEMA–MOEP) surfaces pretreated with alkaline solution. Testing of the ability of P(HEMA–MOEP) hydrogels to entrap and release human recombinant vascular endothelial growth factor, to tackle the problem of insufficient oxygen and nutrient delivery, suggested that P(HEMA–MOEP)-coated titanium prostheses could represent a multifunctional material suitable for bone restoration applications.     

Development of TaqMan allelic specific discrimination assay for detection of the most common Sardinian Wilson's disease mutations. Implications for genetic screening

Wilson's disease (WD) is an autosomal recessive disorder caused by a defective function of the copper transporting ATP7B protein. Analysis of ATP7B gene in the Sardinian population revealed the presence of six common mutations that together account for 85% of WD chromosomes. We have developed an automated approach for the detection of these 6 common Sardinian mutations based on TaqMan technology. Ten DNA samples of WD patients carrying different combinations of the six most common Sardinian mutations and normal controls previously analysed were used in triplicate to set up the allelic discrimination assays. The system was validated in 96 samples obtained from WD patients carrying different combinations of the most common mutations under investigation. The results showed that allelic discrimination is a valid method that could be used for efficient diagnosis of single cases but also for a mass screening.     

Long-term results regarding the use of recombinant interferon alpha-2b in the treatment of II type mixed essential cryoglobulinemia

Thirty-three patients with II type mixed essential cryoglobulinemia (MEC) were randomized into two groups: one to receive combined therapy including prednisone plus interferon, the other to receive prednisone therapy. Interferon was administered as induction treatment (3 Mu/day) and then as maintenance therapy (3 Mu three times a week). 83% of the combined therapy patients responded as opposed to 27% of the prednisone treated patients. Among the patients that responded to combined therapy, nine of them had a complete response, four a partial response, and two a minor response. None of the patients treated with prednisone therapy responded completely but only two had a partial and two a minor response. Four patients (three of combined therapy and one of prednisone therapy) showed proteinuria before the treatment which improved at the end of the induction therapy. Ten patients showed anti-HCV positivity which remained unchanged after the treatment. Three patients showed liver involvement secondary to cryoglobulinemia and an improvement of histological pattern after the induction with combined therapy. One patient showed an improvement of peripheral neuropathy after induction with the combined therapy. These data suggest the effectiveness of interferon given as induction and as maintenance treatment in the therapy of II type mixed essential cryoglobulinemia.     

DNA damage induced by 4,4'-methylenedianiline in primary cultures of hepatocytes and thyreocytes from rats and humans

4,4'-Methylenedianiline (MDA), an aromatic amine used in various industrial processes and previously found to induce tumor development in liver and thyroid of mice and rats, was evaluated for its DNA-damaging activity in primary cultures of hepatocytes and thyreocytes from rat and human donors. After exposure for 4 and 20 h to MDA concentrations ranging from 10 to 180 microM, a statistically significant increase in the frequency of DNA lesions was revealed by the Comet assay in primary hepatocytes and thyreocytes from donors of both species, the response being dose dependent up to 56-100 microM MDA. DNA fragmentation was more marked after 4 than after 20 h exposure in all four cell types. DNA was damaged to a lesser extent in human hepatocytes and thyreocytes than in corresponding rat cells and in both species in hepatocytes than in thyreocytes. In both rat and human hepatocytes a 20-h exposure to the same MDA concentrations elicited a modest amount of DNA repair synthesis, as evaluated by autoradiography. Evidence of a partial reduction of DNA damage, and therefore of only partial DNA repair, was observed in rat hepatocytes and in rat and human thyreocytes incubated for 16 h in MDA-free medium after a 4-h MDA treatment. A 4-h exposure to 56, 100, and 180 microM MDA did not induce DNA lesions in primary cultures of cells from three rat organs, kidney, urinary bladder mucosa, and brain, which are resistant to MDA carcinogenic activity. Under the same experimental conditions any evidence of DNA damage was absent in primary kidney and urinary bladder cells from human donors. Taken as a whole the results of this work indicate that MDA is specifically activated to DNA-damaging reactive species by hepatocytes and thyreocytes in both rats and humans and thus suggest that liver and thyroid might be the targets of the carcinogenic activity of MDA also in humans.     

DNA damage in tissues of rat treated with potassium canrenoate

Potassium canrenoate (PC), a competitive aldosterone antagonist previously found to increase tumor incidence in rats and to produce genotoxic effects in in vitro systems, was examined in rats to acquire information on its genotoxic activity in vivo. Intragastric administration of 1/2 LD50 produced, as revealed by the Comet assay, a modest but statistically significant increase in the frequency of DNA lesions in liver but not in thyroid and bone marrow of male rats, and in thyroid and bone marrow but not in liver of female rats. In contrast with the frankly positive responses observed in primary cultures of rat hepatocytes (Martelli et al., Mutagenesis 14 (1999) 463-472) any evidence of DNA repair and micronuclei formation was absent in liver of rats treated with 1/2 LD50, and initiation of enzyme-altered liver preneoplastic lesions did not occur in the liver of rats given 100 mg/kg PC once a week for 6 successive weeks. A high and dose-dependent frequency of DNA lesions was found to occur in testes and ovaries of rats given single doses ranging from 1/8 to 1/2 LD50.