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Biomedical subjects

A Villa

Publications and source records attributed to A Villa.

At least 19 recordsLinked to original sources
PubMed2006

Generation of human cortical neurons from a new immortal fetal neural stem cell line.

Isolation and expansion of neural stem cells (NSCs) of human origin are crucial for successful development of cell therapy approaches in neurodegenerative diseases. Different epigenetic and genetic immortalization strategies have been established for long-term maintenance and expansion of these cells in vitro. Here we report the generation of a new, clonal NSC (hc-NSC) line, derived from human fetal cortical tissue, based on v-myc immortalization. Using immunocytochemistry, we show that these cells retain the characteristics of NSCs after more than 50 passages. Under proliferation conditions, when supplemented with epidermal and basic fibroblast growth factors, the hc-NSCs expressed neural stem/progenitor cell markers like nestin, vimentin and Sox2. When growth factors were withdrawn, proliferation and expression of v-myc and telomerase were dramatically reduced, and the hc-NSCs differentiated into glia and neurons (mostly glutamatergic and GABAergic, as well as tyrosine hydroxylase-positive, presumably dopaminergic neurons). RT-PCR analysis showed that the hc-NSCs retained expression of Pax6, Emx2 and Neurogenin2, which are genes associated with regionalization and cell commitment in cortical precursors during brain development. Our data indicate that this hc-NSC line could be useful for exploring the potential of human NSCs to replace dead or damaged cortical cells in animal models of acute and chronic neurodegenerative diseases. Taking advantage of its clonality and homogeneity, this cell line will also be a valuable experimental tool to study the regulatory role of intrinsic and extrinsic factors in human NSC biology.

Cell Differentiation↗
PubMed2006

Intracranial haemorrhage in patients on antithrombotics: clinical presentation and determinants of outcome in a prospective multicentric study in Italian emergency departments.

BACKGROUND: Intracranial haemorrhage (ICH) is the type of stroke associated with the highest death rate, and about 30% of ICH occurs in patients on antithrombotic treatment. This study relates clinical presentations and outcome of ICH patients on oral anticoagulant (OA) or antiplatelet (AP) therapy admitted to 33 Italian emergency departments (ED). METHODS: Consecutive patients were enrolled after cranial computed tomography (CT). Primary outcome was the Modified Rankin Scale (MRS) score at 3 months of follow-up. Common descriptive statistics were computed after stratification for traumatic or spontaneous ICH and identification of the anatomical location of bleeding. Multivariate logistic regression was used to assess predictors of death. RESULTS: We recruited 434 patients on AP therapy and 232 on OA. There were 432 spontaneous and 234 traumatic ICH patients. The proportions of AP and OA patients undergoing neurosurgery were 21.8 and 19.4%, respectively, while < 30% underwent procoagulant medical treatment. At the 3-month follow-up, the case fatality rate was 42.0%, while disability or death (MRS 3-6) was 68.1%. The odds ratio for death in OA versus AP patients was 2.63 (95% CI 1.73-4.00) in the whole population and 2.80 (95% CI 1.77-4.41) in intraparenchymal event patients. Glasgow Coma Scale, age, spontaneous event and anticoagulant use were found to be predictors of death both in traumatic and spontaneous events. CONCLUSION: This study confirms the high prevalence of death or disability in OA and AP patients with ICH. As far as the determinants of mortality and disability are concerned, the results of this study might be useful in the clinical management and allocation of resources in the ED setting. The observed low use of procoagulant therapy highlights the need for ED educational programmes to heighten the awareness of available and effective haemostatic treatments.

Administration, Oral↗
PubMed2006

IVM--the first choice for IVF in Italy.

In March 2004, a new law was introduced in Italy to regulate assisted reproduction; at present it is impossible to use more than a maximum of three oocytes per IVF cycle, nor can embryos or prezygotes (2PN cells) be selected or cryopreserved. The prohibitions introduced by the new law have, on the one hand, reduced the expectations of success of current techniques and, on the other hand, stimulated clinicians and embryologists to work on new therapeutic strategies so as to offer the highest chances of success with the lowest risks. In-vitro maturation (IVM) of oocytes fits very well with these new requirements: ovarian stimulation is avoided and the handling of spare oocytes is facilitated. The IVM protocol is an intriguing alternative to conventional IVF techniques, since it removes the side-effects of drug stimulation, especially ovarian hyperstimulation syndrome, and it also reduces the costs of the entire procedure, both in terms of 'time consumption' and 'patient/society costs for drugs'. In the authors' IVF centre the IVM technique has been used for more than a year, with significant success in terms of maturation and fertilization rates, percentage of embryo transfers, number of pregnancies and, finally, healthy babies born.

Adult↗
PubMed2005

Effects of estrogens on cognition and brain morphology: involvement of the cerebellum.

OBJECTIVES: Sex steroid hormones are implicated in the cognitive processes of the adult brain. Among studies reporting a positive effect of estrogen replacement therapy (ERT) on cognition, the most consistent evidence is that it enhances verbal memory and visuospatial functions. In the present study we investigated the effect of ERT on cognition and on brain morphology in healthy postmenopausal women, taking into account the distinction in current and past ERT users. METHODS: Participants were postmenopausal nondemented women recruited from the community: ERT users were 40 (23 current users, 17 past users), while never users were 43. Forty of recruited subjects gave consent to undergo 3D high resolution MRI (16 current users, 7 past users and 17 never users). Participants underwent MMSE and a battery of neuropsychological tests measuring memory, language, intelligence, attention and visuo-spatial abilities. RESULTS: The past users group outperformed the never users in four tests: Token test, WCST categories, attentional matrices and Rey's delayed list; the current users group outperformed the never users in the Rey's list test. ERT users had greater grey matter volumes mainly in the cerebellum, but an increase was observed also in the parietal and occipital cortex. CONCLUSIONS: ERT use appears to improve linguistic, attentive and planning abilities. Interestingly, the beneficial effects on cognition were detected mainly in the past users subgroup. Here we propose that the trophic effect of estrogens on cerebellum might account for the observed improvement in cognition.

Case-Control Studies↗
PubMed2005

[Treatment of stage IIIB cervical carcinoma. A comparison between radiotherapy, concurrent chemo-radiotherapy and neoadjuvant chemotherapy].

AIM: The aim of this study is to evaluate the effectiveness of radiation, concomitant chemoradiation and primary chemotherapy in the treatment of FIGO stage IIIB cervical carcinoma. METHODS: Between January 1981 and December 2001 94 women with stage IIIB FIGO cervical carcinoma were observed. Exclusive radiotherapy was administered in 30 cases (32%), radiotherapy and radiosensitizing chemotherapy in 20 cases (21%) and primary chemotherapy in 44 cases (47%); among the latter patients 2 (4%) developed neoplastic progression, 28 (64%) underwent surgery and 14 (32%) underwent radiotherapy. RESULTS: After a median follow-up of 69 months, 5-year overall survival of the 3 groups is respectively 23%, 36% and 26% (p=0.7). Total dose to point A greater than 60 Gy and the use of brachyradiotherapy are suggestive for a better outcome among women treated with radiation therapy (5-year overall survival 31% versus 18%, p=0.8 and 33% versus 23%, p=0.4, respectively). Radiologically assessed nodal status is the only statistically significant risk factor (p=0.001). Although not statistically significant, vaginal involvement is a relevant factor influencing survival (p=0.1). Women treated with concomitant chemoradiation showed a better 5-year disease-free survival (45%) when compared to the other treatment groups (radiation alone 27%, primary chemotherapy 30%, p=0.4). CONCLUSIONS: Primary chemotherapy, although useful to allow subsequent surgery, does not yield a survival advantage with respect to the irradiated patients. Among these, concomitant radiosensitizing chemotherapy is likely to improve the disease-free survival.

Adult↗
PubMed2004

Frontotemporal dementia: impact of P301L tau mutation on a healthy carrier.

Frontotemporal dementia (FTD) is the second commonest form of dementia after Alzheimer's disease, but its clinical and biological features are less well known. To uncover its earliest signs, we studied the main clinical, neuroimaging, and biochemical findings in an asymptomatic carrier from a three generation FTD family, bearing the P301L pathogenic mutation in the tau gene. Except for selective impairment on the Verbal Fluency Test for letters, all cognitive tests were normal. The brain computed tomography scan was normal, but the brain single photon emission computed tomography and statistical parametric mapping (SPECT-SPM) scan revealed bilateral frontal lobe hypoperfusion. Levels of total tau, 181P-tau, and Abeta1-42 in the cerebrospinal fluid were increased compared with control values. We conclude that detection of these distinctive abnormalities should improve early diagnostic accuracy for FTD and help distinguish it from Alzheimer's disease.

Adolescent↗
PubMed2004

Tetracycline in combination with sodium dioctylsulfosuccinate show increased antimicrobial activity in resistant microorganisms.

We present evidence that sodium dioctylsulfosuccinate, at non inhibitory concentrations (1000 mg/L), is able to increase the antimicrobial activity of tetracycline in non susceptible bacterial and fungal strains. In culture inhibition tests, pretreatment with sodium dioctylsulfosuccinate caused a 52-fold decrease in the geometric mean MIC to tetracycline in 10 Candida albicans strains (p<0.01), a 165-fold decrease in the geometric mean MIC to tetracycline in 10 E. coli strains (p<0.001) and a significant decrease in the mean MIC of 3 strains of Candida krusei and Candida glabrata. In microbicidal tests, tetracycline in association with sodium dioctylsulfosuccinate killed 10(4) cfu tetracycline-resistant Candida albicans in 15 min and 10(4) CFU resistant E. coli in 3 min (p<0.001). Furthermore, in the N-acetyl-D-glucosamine test to calculate the number of hyphal cells, a combination of tetracycline (50 mg/L) (non inhibitory concentrations) plus sodium dioctylsulfosuccinate (25 mg/L) caused a 50-fold increase in the inhibition of hyphal cells in C. albicans (p<0.001); C. albicans cells treated with tetracycline plus sodium dioctylsolfosuccinate annulled the cell surface hydrophobicity (p<0.001). This increase in antimicrobial activity may be attributed to impairment and alteration of the membrane barrier within the microorganisms and a depletion of the thiol groups (p<0.001) critical to their efficiency.

Anti-Bacterial Agents↗
PubMed2004

Increased microbicidal activity of green tea (Camellia sinensis) in combination with butylated hydroxyanisole.

We have demonstrated that green tea (Camellia sinensis) shows increased antimicrobial activity against bacteria and fungi when used in combination with butylated hydroxyanisole (BHA). Glycolic extract taken from green tea showed only limited activity against Streptococcus mutans and no activity against Candida albicans and certain strains of Escherichia coli. BHA, at non inhibitory concentrations, increased the microbicidal activity of green tea against 10(10) S. mutans (p<0.01), non-susceptible E. coli (p<0.01) and C. albicans (p<0.01). Green tea in combination with BHA reduced the hydrophobicity of S. mutans (p<0.01) and greatly inhibited (p<0.001) the formation of hyphae in C. albicans. The increased antimicrobial activity of green tea is related to an impairment of the barrier function in microorganisms and a depletion of thiol groups. The increased activity of green tea as an oral antimicrobial product is discussed.

Anti-Bacterial Agents↗
PubMed2004

A NMR-compatible and reduced gravity simulation based (NRG) bioreactor for on-line monitoring cell culture metabolism.

We developed a NMR-compatible microgravity-based bioreactor (NRG[R]) that offers the advantage of an analytical non-invasive approach associated to the effects of an optimized suspension culture. The simulated microgravity conditions reached in the bioreactor are analogous to those of commercial apparatus like the Rotating Wall Vessel (RWV) system. The faster proliferation of endothelial cells cultured in the NRG bioreactor (doubling time : 28 +/- 1.7 vs. 43 +/- 5.6 h of the control grown in RWV) are attributed to different oxygenation conditions and medium wash out.

Bioreactors↗
PubMed2003

Association between a polymorphism affecting an AP1 binding site in the promoter of the TCIRG1 gene and bone mass in women.

The TCIRG1 gene encodes a component of the osteoclast vacuolar proton pump and previous work has shown that inactivating mutations of the TCIRG1 cause autosomal recessive osteopetrosis. In order to determine whether allelic variation in TCIRG1 contributes to the regulation of bone mineral density (BMD) in normal individuals, we studied the relationship between polymorphisms of TCIRG1 and BMD in a population-based cohort of 739 perimenopausal women. Five common polymorphisms were identified: two in the promoter, a conservative change within exon 4, one within intron 4 and one within intron 11. One of the promoter polymorphisms (G-1102A) lay within a consensus recognition site for the AP1 transcription factor. There was a significant association between the G-1102A genotype and BMD at the lumbar spine ( P = 0.01) and femoral neck ( P = 0.03). The association remained significant after correcting for age, weight, height, menopausal status/HRT use and smoking ( P = 0.008 for spine BMD and P = 0.03 for hip BMD), and homozygotes for the -1100 "G" allele had BMD values significantly higher than individuals who carried the -1100 "A" allele at both spine ( P = 0.007) and hip ( P = 0.047). Subgroup analysis showed that the association between G-1102A and BMD was restricted to premenopausal women who comprised 50.6% of the study group. None of the other polymorphisms or haplotypes were significantly associated with BMD in the study group as a whole or in any subgroup. Functional studies will need to be performed to determine the mechanisms that underlie this association, but we conclude that, in this relatively large population, allelic variation at the G-1102A site of TCIRG1 accounts for part of the heritable component of BMD in Scottish women, possibly by affecting peak bone mass.

Alleles↗
PubMed2003

Successful treatment of extramammary Paget's disease of the scrotum with imiquimod 5% cream.

Extramammary Paget's disease (EMPD) of the skin is an uncommon malignancy involving the epidermis, which sometimes extends into the dermis. Current treatments for EMPD are surgical excision, Mohs' micrographic surgery or laser ablation. We report a case of a 68-year-old male who presented with recurrent EMPD. The patient refused to have surgery and, as an alternative, he applied imiquimod 5% cream, an immune response modifier, daily for a total of 6 weeks. During the initial weeks of therapy, he experienced moderate erythema. Imiquimod treatment resulted in clinical and histological eradication of EMPD, with no recurrence observed during 6 months of follow-up.

Administration, Topical↗
PubMed2003

Successful treatment of butcher's warts with imiquimod 5% cream.

A unique correlation has been shown to exist between frequent occupational handling of raw meat and development of warts on the hands, leading to the designation of 'butcher's warts'. Numerous treatments are available for warts including cryotherapy, laser therapy and surgical excision. We present a case of a 31-year-old-butcher with a 4-year history of warts on his fingers. Imiquimod 5% cream was applied once daily to the warts for 3 months. Clinical improvement was noted after 1 month, with regression of the warts experienced after 3 months. During 12 months of follow-up, no recurrent lesions were observed.

Adjuvants, Immunologic↗
PubMed2003

Identification and metabolic role of the mitochondrial aspartate-glutamate transporter in Saccharomyces cerevisiae.

The malate-aspartate NADH shuttle in mammalian cells requires the activity of the mitochondrial aspartate-glutamate carrier (AGC). Recently, we identified in man two AGC isoforms, aralar1 and citrin, which are regulated by calcium on the external face of the inner mitochondrial membrane. We have now identified Agc1p as the yeast counterpart of the human AGC. The corresponding gene was overexpressed in bacteria and yeast mitochondria, and the protein was reconstituted in liposomes where it was identified as an aspartate-glutamate transporter from its transport properties. Furthermore, yeast cells lacking Agc1p were unable to grow on acetate and oleic acid, and had reduced levels of valine, ornithine and citrulline; in contrast they grew on ethanol. Expression of the human AGC isoforms can replace the function of Agc1p. However, unlike its human orthologues, yeast Agc1p catalyses both aspartate-glutamate exchange and substrate uniport activities. We conclude that Agc1p performs two metabolic roles in Saccharomyces cerevisiae. On the one hand, it functions as a uniporter to supply the mitochondria with glutamate for nitrogen metabolism and ornithine synthesis. On the other, the Agc1p, as an aspartate-glutamate exchanger, plays a role within the malate-aspartate NADH shuttle which is critical for the growth of yeast on acetate and fatty acids as carbon sources. These results provide strong evidence of the existence of a malate-aspartate NADH shuttle in yeast.

Acetates↗
PubMed2003

Ifosfamide in the treatment of malignant epithelial ovarian tumors.

Ifosfamide is one of the best-known alkylating agents. In advanced epithelial ovarian cancer, it has been tested in association with cisplatin, achieving results equal, if not better than cyclophosphamide, with acceptable toxicity. In second-line therapy, it shows remarkable activity, even in patients refractory to cisplatin already treated with cyclophosphamide, with more severe, but always manageable toxicity. In gynecological sarcomas, ifosfamide is, together with doxorubicin, the reference drug for chemotherapy.

Antineoplastic Agents, Alkylating↗
PubMed2002

Enhanced contact activity of fluconazole in association with antioxidants against fluconazole-resistant organisms.

Fluconazole alone does not demonstrate any contact activity against resistant organisms. Phenolic antioxidants, such as butylated hydroxyanisole, appear to promote fluconazole activity resulting in the killing of 10(4) cfu/mL of 11 resistant Candida albicans strains within 3-15 min and of 10(4) cfu/mL of 10 resistant Escherichia coli strains within 6-15 min. Fluconazole activity was increased by the addition of ethyl alcohol (20%). Antioxidants appear to promote fluconazole activity by increasing cell membrane permeability. This combination has potential advantages in the administration of topical fluconazole.

Antioxidants↗