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Biomedical subjects

S Marino

Publications and source records attributed to S Marino.

At least 19 recordsLinked to original sources
PubMed2003

Effects of cholecystokinin tetrapeptide (CCK(4)) and of anxiolytic drugs on GABA outflow from the cerebral cortex of freely moving rats.

The effect of cholecystokinin tetrapeptide (CCK(4)) and of different anxiolytic drugs on GABA outflow from the cerebral cortex was investigated in freely moving rats, by using the epidural cup technique. CCK(4) (3-30 microg/kg, i.p.) increased GABA outflow and induced objective signs of anxiety. These neurochemical and behavioral responses were prevented by the CCK(B) antagonist GV150013 at 0.1 microg/kg (i.p.). At higher doses (up to 30 microg/kg) this compound per se reduced GABA release and caused sedation, suggesting the presence of a CCKergic positive tonic modulation on GABA interneurons. Similarly the GABA(A) receptors modulator, diazepam (2mg/kg, i.p.) and the 5-HT(1A) agonist buspirone (3mg/kg, i.p.) reduced GABA outflow and caused the expected behavioral effects (reduced muscle tone, mild 5-HT syndrome) which were prevented by the respective, selective antagonists, flumazenil (1mg/kg, i.p.) and NAN-190 (3mg/kg, i.p.). These findings support the idea that GV150013, diazepam and buspirone inhibit GABAergic cortical activity, through the respective receptors. This neurochemical effect may represent the end-effect of various anxiolytic compounds affecting the cortical circuitry.

Adamantane↗
PubMed2002

Computing DIT from energy expenditure measures in a respiratory chamber: a direct modeling method.

The possibility of computing Diet Induced Thermogenesis (DIT) is an important feature of metabolic investigations. However, methodological problems have affected the determination of DIT in the indirect calorimetric chamber. DIT has been commonly estimated by regressing energy expenditure on a measure of physical activity. Although used for many years as the only feasible approach to calculate DIT in a respiratory chamber, this traditional method has been criticized because of an apparent underestimation of the DIT, but no alternative method has been suggested so far. The present work proposes to estimate DIT directly by means of a mathematical model. This approach also allows to simultaneously estimate other parameters, namely resting energy expenditure (REE), physical activity (PA) and physical exercise (PE).

Adult↗
PubMed2001

Effects of cholecystokinin tetrapeptide (CCK(4)) and anxiolytic drugs on the electrically evoked [(3)H]5-hydroxytryptamine outflow from rat cortical slices.

The outflow of [(3)H]5-hydroxytryptamine ([(3)H]5-HT) from electrically stimulated rat cortical slices was measured to ascertain the modulatory role of endogenous cholecystokinin (CCK) on the amine outflow and to test the hypothesis that different anxiolytic compounds inhibit 5-HT secretion. The [(3)H]5-HT outflow evoked at 10 Hz was increased up to +30% by CCK(4) 300-1000 nM, the effect being prevented by the CCK(B) receptor antagonist GV 150013, 3 nM. The limited sensitivity to CCK(4) seemed to depend on 5-HT auto-receptor feedback because pre-treatment with 100 nM methiothepin enhanced the [(3)H]5-HT outflow and lowered the CCK(4) threshold concentration from 300 to 30 nM. In addition, pre-treatment with 1 microM bacitracin to inhibit CCK metabolism increased [(3)H]5-HT efflux. This effect was concentration-dependently counteracted by GV150013 suggesting the presence of an endogenous CCK positive modulation. GV150013 30 nM, the 5-HT(1A) partial agonist buspirone 300 nM and the GABA(A) receptor modulator diazepam 10 nM, known to have anxiolytic properties, all significantly reduced the [(3)H] amine outflow from cortical slices by about 20%. This inhibition depended on their interaction with their respective receptors, which seemed to restrain the activity of functionally interconnected glutamatergic interneurones. In fact, APV (50 microM) and NBQX (10 microM) prevented the effect of the anxiolytic compounds. Thus, anxiolytic drugs with different receptor targets can reduce 5-HT outflow by dampening the glutamatergic signal, and in turn, the secretory process of the serotonergic nerve ending.

Adamantane↗
PubMed2001

Yttrium-aluminum-garnet laser therapy of esophageal granular cell tumor.

BACKGROUND: Granular cell tumor (GCT) is a rare lesion. Approximately 4% to 6% of these tumors occur in the gastrointestinal tract, one-third of them affecting the esophagus. Almost all GCTs are benign lesions. Approximately 1% to 3% are malignant. Endoscopic ultrasonography (EUS) is a diagnostic support. The best treatment for esophageal GCT is not yet clear, whether surgical excision, periodic observation, endoscopic excision, or yttrium-aluminum-garnet (YAG) laser therapy. METHODS: From November 1992 to December 2000, four patients with GCTs of the esophagus were observed. All the patients underwent EUS evaluation and endoscopic YAG laser therapy of the esophageal neoplasm. At each session, a biopsy at the tumor site was obtained. The treatment was continued until endoscopic and histologic evidence of the tumor disappeared. RESULTS: After the YAG laser therapy, no evidence of the tumor was found in any of the four patients with esophageal GCT. At this writing, the patients remain disease free after a mean follow-up period of 66 months. No complication has been observed. Only four sessions for each patient were necessary to eliminate the tumor. CONCLUSIONS: Therapy with YAG laser was effective in all four patients with esophageal GCT, and complete necrosis of the submucosal neoplastic cells was achieved. Endoscopic YAG laser therapy appears to be a good compromise between esophageal dissection and long-term observation without tumor excision. Esophageal laser therapy is safe if correctly used, and previous EUS evaluation increases treatment safety.

Adult↗
PubMed2001

Effects of two-carbon bridge region methoxylation of benztropine: discovery of novel chiral ligands for the dopamine transporter.

6-Methoxylated and 8-oxygenated benztropines were prepared and evaluated for their DAT and SERT activity (binding and uptake inhibition). Methoxylation at the two-carbon bridge of benztropine produced a novel class of potent and selective DAT ligands. An interesting enantioselectivity was also observed for this new class of chiral benztropines. The inactivity of the 8-oxygenated analogues seems to point out that, unlike cocaine and its analogues, interactions of benztropine ligands with DAT may be strongly governed by the nitrogen atom.

Benztropine↗
PubMed2001

Antimicrobial activity of Argentine plants used in the treatment of infectious diseases. Isolation of active compounds from Sebastiania brasiliensis.

Different extracts of Sebastiania brasiliensis, Sebastiania klotszchiana, Polygonum punctatum, Lithraea molleoides and Myrcianthes cisplatensis, all plants growing in Entre Ríos Province and traditionally used as antiseptics, were tested against a set of Gram positive and Gram negative bacteria and fungi. All the species, with the exception of M. cisplatensis, presented activity against some of the microorganisms tested. A 50% hydroalcoholic extract of S. brasiliensis was selected for bioguided fractionation. Two antimicrobial compounds identified as methylgallate (MIC 128 microg/ml) and protocatechuic acid (MIC 128 microg/ml) were isolated apart from quercetin, kaempferol, quercitrin and gallic acid.

Anti-Bacterial Agents↗
PubMed2001

Different limit to the body's ability of increasing fat-free mass.

It is a common understanding that fat-free mass (FFM) increases with body weight. However, limited information is available as to the relationship between weight increase and changes in body composition. We performed the present study to determine quantitatively the relationship between body composition, total body weight, age, and sex. Body composition data were obtained by isotopic dilution on 273 subjects ranging in body mass index (BMI) from about 13 to 70 kg/m(2). Adipose free tissue (AFT) was modeled as a nonlinear, increase-limited function of body weight. Model parameters were evaluated as functions of sex, age, and height. The relationship between AFT and body weight was very well approximated by means of the nonlinear model (R(2) =.95), with maximal AFT being determined by both sex and height and with AFT growth rate determined only by sex. AFT clearly shows a nonlinear behavior, tending to increase less and less with progressively increasing body weight. With the proposed model, an asymptotic maximal AFT may be postulated. The organism seems to have an intrinsic limitation to how much skeletal muscle development may take place to accommodate the necessities of an ever-increasing load. These limits are different between the sexes, with women tending to approach more rapidly than men a lower maximal AFT for the same height.

Adipose Tissue↗
PubMed2000

Induction of medulloblastomas in p53-null mutant mice by somatic inactivation of Rb in the external granular layer cells of the cerebellum.

Medulloblastomas are among the most common malignancies in childhood, and they are associated with substantial mortality and morbidity. The molecular pathogenesis as well as the ontogeny of these neoplasms is still poorly understood. We have generated a mouse model for medulloblastoma by Cre-LoxP-mediated inactivation of Rb and p53 tumor suppressor genes in the cerebellar external granular layer (EGL) cells. GFAP-Cre-mediated recombination was found both in astrocytes and in immature precursor cells of the EGL in the developing cerebellum. GFAP-Cre;Rb(LoxP/LoxP);p53(-/- or LoxP/LoxP) mice developed highly aggressive embryonal tumors of the cerebellum with typical features of medulloblastoma. These tumors were identified as early as 7 weeks of age on the outer surface of the molecular layer, corresponding to the location of the EGL cells during development. Our results demonstrate that loss of function of RB is essential for medulloblastoma development in the mouse and strongly support the hypothesis that medulloblastomas arise from multipotent precursor cells located in the EGL.

Animals↗
PubMed2000

Electroosmotic Phenomena in Fractures.

Electroosmotic phenomena in fractures have been investigated in the linear limit for various double-layer thicknesses. The effects of the geometrical parameters were systematically studied for deterministic sinusoidal and random self-affine fractures. The numerical results show a definite influence of the surface amplitude on electroosmotic processes. For self-affine fractures, the roughness or Hurst exponent has a much larger incidence than the correlation parameter between the two surfaces. All the electroosmotic coupling coefficients can be gathered in a single relationship which depends on a characteristic length scale Lambda, applicable to every configuration. Such a length was already found useful for porous media, but the relationship is different. Copyright 2000 Academic Press.

Journal Article↗
PubMed2000

Differentiation and histological analysis of embryonic stem cell-derived neural transplants in mice.

We report here that neural transplantation of in vitro-differentiated embryonic stem (ES) cells provides a versatile strategy for gene transfer into the central nervous system. ES cells were subjected to an optimized in vitro differentiation protocol to obtain embryoid bodies. These aggregates were stereotaxically transplanted into the brain of recipient adult mice, where they followed a strictly controlled differentiation pattern and eventually formed mature neural grafts. A marker gene, introduced into the ROSA26 locus allowed for precise determination of the fate of the descendants of the transplanted embryoid bodies and revealed that not only neurons but also astrocytes, oligodendrocytes and even microglial cells were graft-derived. Evaluation of long-term experiments showed viable grafts with a stable transgene expression and proved that this approach provides a tool for reliable gene expression within a spatially delimited area of neural tissue.

Animals↗
PubMed2000

Efficacies of two new antifungal agents, the triazole ravuconazole and the echinocandin LY-303366, in an experimental model of invasive aspergillosis.

The efficacy of ravuconazole, a new triazole antifungal agent, and the echinocandin LY-303366 were evaluated in an immunosuppressed, temporarily leukopenic rabbit model of invasive aspergillosis. Oral therapy with ravuconazole at a dosage of 30 mg/kg of body weight per day or the echinocandin LY-303366, given intravenously in a dosage of 5 or 10 mg/kg, was begun 24 h after a lethal or sublethal challenge, and results were compared with those for amphotericin B therapy and untreated controls. Prophylaxis was also studied with LY-303366 given at a dosage of 5 or 10 mg/kg/day 48 h before lethal or sublethal challenge. Ravuconazole eliminated mortality, cleared aspergillus antigen from the serum, and eliminated Aspergillus fumigatus organisms from tissues of both lethally and sublethally challenged immunosuppressed animals with invasive aspergillosis. Although LY-303366, at both doses, prolonged survival and reduced aspergillus antigenemia, it did not eliminate aspergillus organisms from organ tissues. The half-lives of ravuconazole and LY-303366 in rabbits were 13 and 12.5 h, respectively, and no accumulation of either drug was seen after 6 days of treatment. Although LY-303366 showed activity in this rabbit model of invasive aspergillosis, ravuconazole was the more active agent, comparable to amphotericin B. Additional studies are needed to determine the potential of ravuconazole for use in the treatment of this infection.

Anidulafungin↗
PubMed1999

The oncogene and Polycomb-group gene bmi-1 regulates cell proliferation and senescence through the ink4a locus.

The bmi-1 gene was first isolated as an oncogene that cooperates with c-myc in the generation of mouse lymphomas. We subsequently identified Bmi-1 as a transcriptional repressor belonging to the mouse Polycomb group. The Polycomb group comprises an important, conserved set of proteins that are required to maintain stable repression of specific target genes, such as homeobox-cluster genes, during development. In mice, the absence of bmi-1 expression results in neurological defects and severe proliferative defects in lymphoid cells, whereas bmi-1 overexpression induces lymphomas. Here we show that bmi-1-deficient primary mouse embryonic fibroblasts are impaired in progression into the S phase of the cell cycle and undergo premature senescence. In these fibroblasts and in bmi-1-deficient lymphocytes, the expression of the tumour suppressors p16 and p19Arf, which are encoded by ink4a, is raised markedly. Conversely, overexpression of bmi-1 allows fibroblast immortalization, downregulates expression of p16 and p19Arf and, in combination with H-ras, leads to neoplastic transformation. Removal of ink4a dramatically reduces the lymphoid and neurological defects seen in bmi-1-deficient mice, indicating that ink4a is a critical in vivo target for Bmi-1. Our results connect transcriptional repression by Polycomb-group proteins with cell-cycle control and senescence.

Animals↗
PubMed1999

Endoscopic palliation of esophageal and cardial cancer: neodymium-yttrium aluminum garnet laser therapy.

The aim of this study was to evaluate the impact of laser palliation on symptoms such as dysphagia and bleeding in patients with esophageal and cardial carcinomas. From November 1992 to October 1997, 174 patients with unresectable esophageal and cardial carcinomas were treated with neodymium-yttrium aluminum garnet laser therapy. The indications for palliative treatment were advanced tumor in 96 patients and high surgical risk in 78. The tumor involved the esophagus and cardia in 107 and 67 patients respectively. The mean length of the tumors was 6 cm. Two laser sessions (range 1-4) were necessary for recanalization. During the follow-up, the average interval between the laser sessions was 2 months. Overall, no early and late complications or hospital mortality occurred. The quality of palliation was excellent or good in 82%, of the patients. The mean survival time was 6 months, and mortality was not related to the procedure. Endoscopic laser therapy in patients with vegetant or hemorrhagic carcinomas may represent the best therapy, with acceptable morbidity and mortality rates and satisfactory functional results.

Adult↗
PubMed1999

[Palliative treatment of esophageal and cardial carcinoma].

Recent series reported increasing incidence of esophageal and cardial cancers with prognosis still severe in spite of surgical progress. The late diagnosis reduces the chance of radical surgery; on the other hand about 80-90% of patients develop local or distant recurrence. Therefore the treatment of esophageal and cardial cancer is often palliative: surgical resection is reserved only to selected cases. Endoscopic palliation was the treatment of choice in a total of 265 patients 174 of which received laser therapy and 91 prosthesis intubation. The results it good in about 80% of cases.

Adenocarcinoma↗
PubMed1999

[Transformation of Waldenström disease into chronic myeloid leukemia].

The authors describe a case of a 83 years old patient affected with Waldenström disease whose shift in chronic myelogenous leukaemia is surprising because the quickness of the fact and, even more, because the following very fast appearance of quickly fatal paravertebral granulocytic sarcoma, as extramedullary blast crisis expression. This feature appears unusual in old subject.

Age Factors↗
PubMed1998

Embryonic lethality and liver degeneration in mice lacking the metal-responsive transcriptional activator MTF-1.

We have shown previously that the heavy metal-responsive transcriptional activator MTF-1 regulates the basal and heavy metal-induced expression of metallothioneins. To investigate the physiological function of MTF-1, we generated null mutant mice by targeted gene disruption. Embryos lacking MTF-1 die in utero at approximately day 14 of gestation. They show impaired development of hepatocytes and, at later stages, liver decay and generalized edema. MTF-1(-/-) embryos fail to transcribe metallothionein I and II genes, and also show diminished transcripts of the gene which encodes the heavy-chain subunit of the gamma-glutamylcysteine synthetase, a key enzyme for glutathione biosynthesis. Metallothionein and glutathione are involved in heavy metal homeostasis and detoxification processes, such as scavenging reactive oxygen intermediates. Accordingly, primary mouse embryo fibroblasts lacking MTF-1 show increased susceptibility to the cytotoxic effects of cadmium or hydrogen peroxide. Thus, MTF-1 may help to control metal homeostasis and probably cellular redox state, especially during liver development. We also note that the MTF-1 null mutant phenotype bears some similarity to those of two other regulators of cellular stress response, namely c-Jun and NF-kappaB (p65/RelA).

Animals↗
PubMed1998

Degeneration of the cerebellar granule cell layer in transgenic mice expressing genes of human foamy virus.

Transgenic mice expressing various combinations of structural and regulatory genes of human foamy virus (HFV) develop a neurodegenerative syndrome. delta gpe transgenic mice (which express the auxiliary bel-1 and bet genes along with truncated forms of gag, pol, and env) develop a severe neurological syndrome consisting mainly of spastic tetraparesis and blindness, and show neuronal loss in the hippocampus and cerebral cortex. In addition, mice in two of eight delta gpe lines developed an ataxic gait. Here we studied the phenotype of these two lines, and show that these mice exhibit progressive degeneration of their cerebellar granule cells beginning at 4-8 weeks of age. Transgenic mRNA and HFV proteins accumulate in cerebellar granule cells immediately before the onset of degeneration. The Purkinje cell layer is largely unaffected by this pathological process. Probably due to the loss of granule cell processes, the cerebellar molecular layer is narrowed in the late stages of the disease. These findings indicate that HFV gene products can be neurotoxic for cerebellar granule cells.

Animals↗