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L Orlando

Publications and source records attributed to L Orlando.

At least 19 recordsLinked to original sources

Ancient DNA analysis reveals divergence of the cave bear, Ursus spelaeus, and brown bear, Ursus arctos, lineages.

The cave bear, Ursus spelaeus, represents one of the most frequently found paleontological remains from the Pleistocene in Europe. The species has always been confined to Europe and was contemporary with the brown bear, Ursus arctos. Relationships between the cave bear and the two lineages of brown bears defined in Europe, as well as the origins of the two species, remain controversial, mainly due to the wide morphological diversity of the fossil remains, which makes interpretation difficult [1, 2]. Sequence analysis of ancient DNA is a useful tool for resolving such problems because it provides an independent source of data [3]. We previously amplified a short DNA fragment of the mitochondrial DNA control region (mt control region) of a 40,000-year-old Ursus spelaeus sample [4]. In this paper, we describe the DNA analysis of two mtDNA regions, the control region and the cytochrome b gene. Control region sequences were obtained from ten samples of cave bears ranging from 130,000 to 20,000 years BP, and one particularly well-conserved sample gave a complete cyt b sequence. Our data demonstrate that cave bears split largely before the lineages of brown bears around 1.2 million years ago. Given its abundance, its wide distribution in space and time, and its large morphological diversity, the cave bear is a promising model for direct observation of the evolution of sequences throughout time, extinction periods, and the differentiation of populations shaped by climatic fluctuations during the Pleistocene.

Animals↗

New LTP molecule.

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Focal Adhesion Kinase 2↗

Vinorelbine, cisplatin and continuous infusion of 5-fluorouracil (ViFuP) in metastatic breast cancer patients: a phase II study.

PURPOSE: Chemotherapy regimens for patients with advanced breast cancer or large primary tumours (including locally advanced disease) usually contain anthracyclines, taxanes or both. We investigated a multi-agent regimen for patients for whom anthracyclines and/or taxanes may not be suitable. We assessed efficacy in terms of response rate and time to progression of a combination with continuous infusion 5-fluorouracil (5-FU), vinorelbine and cisplatin (ViFuP regimen), as a first or subsequent line treatment for metastatic breast cancer patients. PATIENTS AND METHODS: One hundred consecutive patients with advanced breast cancer were treated with 5-FU 200 mg/m2 administered continuously through a permanent central venous line; vinorelbine was given on days 1 and 3 at a dose of 20 mg and cisplatin was administered at 60 mg/m2 on day one. Therapy was given every three weeks. The median age was 50 years (range 23-72). Fifty-two patients had received prior chemotherapy for metastatic breast cancer, and sixty-one percent had previously received anthracyclines, thirty-five percent taxanes and twenty-nine percent 5-FU as a bolus injection. All patients were assessable for toxicity, four patients were not assessable for response. RESULTS: There were four complete responses (4%). Forty-nine patients had a partial response (overall response rate, 55%; 95% confidence interval (CI): 45%-65%). After a median follow-up of 10.2 months, median duration of response is 5.2 months (range 1.5-20.7+ months), time to progression (TTP) is 6.8 months (range 0.3-24.7 months). Acute toxicity, including myelosuppression, was mild: only 18% of patients had grade 4 granulocytopenia and one patient experienced grade 4 diarrhea. Only 15% of patients had any non-hematological grade 3 toxicity including nausea (4%), stomatitis (4%), diarrhea (2%), fatigue (1%), fever (1%), photosensitivity (1%), hand-foot syndrome (1%). Grade 2 alopecia was observed only in six patients (6%). Eleven patients developed a right diaphragmatic supra elevation, while deep vein thrombosis, central venous catheter associated, occurred in eight patients. CONCLUSIONS: We identified a combination chemotherapy with noteworthy efficacy and well tolerated subjectively as either a first- or second-line treatment for metastatic breast cancer patients. The regimen warrants further development focusing on the comparison with either continuous administration of oral fluoropyrimidine derivatives.

Adult↗

Nobel objections.

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Dopamine↗

Treatment of infrabony pocket with a collagen membrane supported by cancellous bovine bone.

BACKGROUND: Treatment of infrabony pockets with guided tissue regeneration (GTR) methods using absorbable membranes supported by bone substitutes has gained wide acceptance. Our objective is to observe the clinical variations obtained with the use of these materials in a prospective clinical study. METHODS: Nine patients were treated with GTR at nine infrabony pockets using a double layered collagen membrane and deproteinized cancellous bovine bone associated with root conditioning by application of tetracycline-HCl. The nine patients included in this study had adult periodontitis, were non-smokers and responded well to initial therapy. The sites evaluated had probing pocket depths of at least 5 mm and an angular defect of at least 2 mm. The clinical parameters considered were probing pocket depth (PPD), clinical attachment level (CAL) and gingival recession (REC). Some indexes were also evaluated: the modified Quigley and Hein's Plaque index (PI), O'Leary's bleeding index (FMBS) and the Löe and Sillness gingival index (GI). These parameters were measured one week before surgery and at the control visit after an average of 22.9 months. After the removal of the sutures on the eighth day the patients received professional oral hygene every four months at their private dentists' offices. The baseline and the final measurements were compared with the Student OtO-test to verify the statistical significance of this case series. RESULTS: The mean values of PI, FMBS and GI remained unvaried (p>0.05). Results showed an average decrease in PPD of 4.0+/-2.7 mm (p=0.0002), an average increase of CAL of 4.1+/-2.1 mm (p=0.0001) and an average decrease in recession of 0.2+/-1.2 mm (p=0.594). The value of statistical significance was set at p=0.05. CONCLUSIONS: We can conclude that the materials used in this study behaved well clinically and that the surgical technique described has given results that, within the limits of the number of cases reported, has modified the PPD and CAL in a significant manner.

Adult↗

Novel role for the NMDA receptor redox modulatory site in the pathophysiology of seizures.

Redox-active compounds modulate NMDA receptors (NMDARs) such that reduction of NMDAR redox sites increases, and oxidation decreases, NMDAR-mediated activity. Because NMDARs contribute to the pathophysiology of seizures, redox-active compounds also may modulate seizure activity. We report that the oxidant 5, 5'-dithio-bis(2-nitrobenzoic acid) (DTNB) and the redox cofactor pyrroloquinoline quinone (PQQ) suppressed low Mg(2+)-induced hippocampal epileptiform activity in vitro. Additionally, in slices exposed to 4-7 microM bicuculline, DTNB and PQQ reversed the potentiation of evoked epileptiform responses by the reductants dithiothreitol and Tris(2-carboxyethyl)phosphine (TCEP). NMDA-evoked whole-cell currents in CA1 neurons in slices were increased by TCEP and subsequently decreased by DTNB or PQQ at the same concentrations that modulated epileptiform activity. However, DTNB and PQQ had little effect on baseline NMDA-evoked currents in control medium, and PQQ did not alter NMDAR-dependent long-term potentiation. In contrast, in slices returned to control medium after low Mg(2+)-induced ictal activity, DTNB significantly inhibited NMDAR-mediated currents, indicating endogenous reduction of NMDAR redox sites under this epileptogenic condition. These data suggested that PQQ and DTNB suppressed spontaneous ictal activity by reversing pathological NMDAR redox potentiation without inhibiting physiological NMDAR function. In vivo, PQQ decreased the duration of chemoconvulsant-induced seizures in rat pups with no effect on baseline behavior. Our results reveal endogenous potentiation of NMDAR function via mass reduction of redox sites as a novel mechanism that may enhance epileptogenesis and facilitate the transition to status epilepticus. The results further suggest that redox-active compounds may have therapeutic use by reversing NMDAR-mediated pathophysiology without blocking physiological NMDAR function.

Animals↗