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1.
J Intellect Disabil Res ; 63(8): 1023-1040, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30985057

RESUMO

BACKGROUND: Students with intellectual disabilities (IDs) have various learning difficulties and are at risk for school failure. Large inter-individual differences are described for reading, but it is unclear how these vary as a function of grade. The aim of this study was to examine various reading fluency, accuracy and comprehension parameters in second-to-eighth-grade Italian children with either borderline intellectual functioning (BIF) or mild ID (MID). METHODS: We examined 106 children with BIF (67 M and 39 F) and 168 children with MID (107 M and 61 F). The children were in the second to eighth grade and were comparable for chronological age (7 to 14 years). They were administered a battery of tests that assessed fluency and accuracy of word, pseudo-word and text reading, as well as text comprehension. Standardised scores allowed us to compare the performance of the two groups with normative values. RESULTS: Children with ID obtained generally low scores compared with normative values. Those with MID had greater difficulty than those with BIF. Furthermore, difficulty was greater for speed than for accuracy measures and for words than for pseudo-words. Difficulty (particularly in the case of reading speed) tended to be pronounced at later grades. Marked individual differences were present independently of MID-BIF subgrouping, as well as stimulus category and reading parameter. CONCLUSIONS: As a group, children with ID showed difficulty in reading acquisition; the effect was greater for children with more severe ID, but large individual differences were observed in children with both BIF and MID. Relatively spared pseudo-word reading skills indicate efficient use of the grapheme-to-phoneme conversion routine. This processing mode may prove more ineffective at higher levels of schooling when even in regular orthographies such as Italian typically developing children rely on lexical activation.


Assuntos
Sucesso Acadêmico , Deficiência Intelectual/fisiopatologia , Leitura , Adolescente , Criança , Feminino , Humanos , Masculino , Índice de Gravidade de Doença
2.
J Mater Chem B ; 5(17): 3217-3229, 2017 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-32263720

RESUMO

Supramolecular gel hybrids obtained by self-assembly of Fmoc-l-phenylalanine (Fmoc-F) in the presence of functionalized halloysite nanotubes (f-HNT) were obtained in biocompatible solvents and employed as carriers for the delivery of camptothecin (CPT) molecules. The synthesis of the new f-HNT material as well as its characterization are described. The properties of the hybrid hydrogels and organogels were analyzed by several techniques. The presence of small amounts of f-HNT allows good dispersion of the tubes and the subsequent formation of homogeneous gels. The experimental results show that f-HNT functions only as an additive in the hybrid gels and does not demonstrate gelator behavior. The in vitro kinetic release from both f-HNT/CPT and Fmoc-F/f-HNT/CPT was studied in media that imitates physiological conditions, and the factors controlling the release process were determined and discussed. Furthermore, the antiproliferative in vitro activities of the gels were evaluated towards human cervical cancer HeLa cells. A comparison of data collected in both systems shows the synergistic action of f-HNT and the gel matrix in controlling the release of CPT in the media and maintaining the drug in its active form. Finally, a comparison with pristine HNT is also reported. This study suggests a suitable strategy to obtain two-component gel hybrids based on nanocarriers with controlled drug carrier capacity for biomedical applications.

3.
Carbohydr Polym ; 152: 548-557, 2016 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-27516303

RESUMO

The purpose of this paper is to show how a functional bionanocomposite film with both antioxidant and antimicrobial activities was successfully prepared by the filling of a pectin matrix with modified Halloysite nanotubes (HNT) containing the essential peppermint oil (PO). Firstly, HNT surfaces were functionalized with cucurbit[6]uril (CB[6]) molecules with the aim to enhance the affinity of the nanofiller towards PO, which was estimated by means of HPLC experiments. The HNT/CB[6] hybrid was characterized by several methods (thermogravimetry, FT-IR spectroscopy and scanning electron microscopy) highlighting the influence of the supramolecular interactions on the composition, thermal behavior and morphology of the filler. Then, a pectin+HNT/CB[6] biofilm was prepared by the use of the casting method under specific experimental conditions in order to favor the entrapment of the volatile PO into the nanocomposite structure. Water contact angle measurements, thermogravimetry and tensile tests evidenced the effects of the modified filler on the thermo-mechanical and wettability properties of pectin, which were correlated to the microscopic structure of the biocomposite film. In addition, PO release in food simulant solvent was investigated at different temperatures (4 and 25°C), whereas the antioxidant activity of the nanocomposite film was estimated using the DPPH method. Finally, we studied the in vitro antibacterial activity of the biofilm against Escherichia coli (Gram-negative) and Staphylococcus aureus (Gram-positive), which were isolated by beef and cow milk, respectively. These experiments were carried out at specific temperatures (4, 37 and 65°C) that can be useful for a multi-step food conservation. This paper puts forwards an easy strategy to prepare a functional sustainable edible film with thermo-sensitive antioxidant/antimicrobial activity.


Assuntos
Silicatos de Alumínio/química , Hidrocarbonetos Aromáticos com Pontes/química , Imidazóis/química , Membranas Artificiais , Nanocompostos/química , Nanotubos/química , Pectinas/química , Óleos de Plantas/química , Silicatos de Alumínio/farmacologia , Antibacterianos/química , Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Hidrocarbonetos Aromáticos com Pontes/farmacologia , Argila , Escherichia coli/fisiologia , Imidazóis/farmacologia , Mentha piperita , Pectinas/farmacologia , Óleos de Plantas/farmacologia , Staphylococcus aureus/fisiologia
4.
Thyroid ; 11(3): 233-44, 2001 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-11327614

RESUMO

Several mechanisms are probably involved in determining the evolution of autoimmune thyroid disease (AITD) towards either hypothyroidism and the clinical syndrome known as Hashimoto's thyroiditis (HT) or toward hyperthyroidism and the symptoms of Graves' disease (GD). To gain further insight into such mechanisms we performed an exhaustive comparative analysis of the expression of key molecules regulating cell death (Fas, Fas ligand [FasL], Bcl-2) and apoptosis in both thyrocytes and thyroid infiltrating lymphocytes (TILs) from patients with either GD or HT. GD thyrocytes expressed less Fas/FasL than HT thyrocytes, whereas GD TILs had higher levels of Fas/FasL than HT TILs. GD thyrocytes expressed increased levels of the antiapoptotic molecule Bcl-2 compared to the low levels detected in HT thyrocytes. The opposite pattern was observed in GD (low Bcl-2) and HT (high Bcl-2) TILs. The patterns of apoptosis observed were consistent with the regulation of Fas, FasL, and Bcl-2 described above. Our findings suggest that in GD thyroid the regulation of Fas/FasL/Bcl2 favors apoptosis of infiltrating lymphocytes, possibly limiting their autoreactive potential and impairing their ability to mediate tissue damage. Moreover, the reduced levels of Fas/FasL and increased levels of Bcl-2 should favor thyrocyte survival and favor the thyrocyte hypertrophy associated with immunoglobulins stimulating the thyrotropin (TSH) receptor. In contrast, the regulation of Fas/FasL/Bcl2 expression in HT promotes thyrocyte apoptosis, tissue damage, and a gradual reduction in thyrocyte numbers leading to hypothyroidism. These findings help define key molecular mechanisms contributing to the clinical outcome of thyroid autoimmunity.


Assuntos
Apoptose , Doenças Autoimunes/patologia , Linfócitos/patologia , Doenças da Glândula Tireoide/imunologia , Glândula Tireoide/patologia , Receptor fas/genética , Adulto , Idoso , Doenças Autoimunes/metabolismo , Proteína Ligante Fas , Feminino , Regulação da Expressão Gênica , Doença de Graves/patologia , Humanos , Linfócitos/química , Masculino , Glicoproteínas de Membrana/análise , Glicoproteínas de Membrana/genética , Pessoa de Meia-Idade , Fenótipo , Proteínas Proto-Oncogênicas c-bcl-2/análise , Proteínas Proto-Oncogênicas c-bcl-2/genética , RNA Mensageiro/análise , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Doenças da Glândula Tireoide/metabolismo , Doenças da Glândula Tireoide/patologia , Glândula Tireoide/química , Tireoidite Autoimune/patologia , Receptor fas/análise , Receptor fas/fisiologia
5.
J Neuroimmunol ; 75(1-2): 9-18, 1997 May.
Artigo em Inglês | MEDLINE | ID: mdl-9143232

RESUMO

The neuropeptide substance P (SP) is a mediator of neuro-inflammation and can play a role by induction of histamine release (HR) and TNF-alpha. However, its effect on the heterogeneous response of mast cells (MC) has not been completely studied. We have established that the SR can induce 25% of HR in highly purified rat uterine MC at diestrous but not at proestrous phases of the reproductive cycle and 88% of HR in peritoneal mast cells (PMC). We also found 2.2 fold increase in TNF-alpha mRNA at diestrous, in SP stimulated uterine MC versus control and 2.7 fold increase in PMC; RT and competitive PCR were used to amplify the TNF-alpha mRNA. We have thereafter investigated the mechanism whereby the binding of SP to sialic acid on the MC membrane, could trigger secretion of histamine and induction of TNF-alpha mRNA. The neuraminidase pretreatment (0.1 U/ml) inhibited SP-stimulated HR from either uterine MC and PMC (98% and 50%, respectively) and totally inhibited SP-stimulated TNF-alpha mRNA levels. The neuraminidase effect was not toxic, since it was not observed in IgE mediated HR and TNF-alpha mRNA levels. In conclusion, the inhibitory effect of the neuraminidase on the SP-mediated increase of histamine and TNF-alpha mRNA, suggests that the SP-sialic acid interaction could have a role in the MC heterogeneous response.


Assuntos
Antagonistas dos Receptores Histamínicos/farmacologia , Liberação de Histamina/efeitos dos fármacos , Mastócitos/metabolismo , Neuraminidase/farmacologia , Substância P/farmacologia , Fator de Necrose Tumoral alfa/genética , Animais , Feminino , Mastócitos/efeitos dos fármacos , Peritônio/citologia , RNA Mensageiro/antagonistas & inibidores , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Receptores de Superfície Celular/fisiologia , Útero/citologia
6.
Mol Hum Reprod ; 2(10): 781-91, 1996 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-9239697

RESUMO

The existence of a biochemical network of embryo-maternal communication implies that various secreted molecules constitute a signal-response mechanism, important for the process of embryo implantation in mammals. Here we report the purification of a protein with an apparent molecular weight of 136 kDa, responsible for a 2000-fold increase in embryo-derived histamine-releasing factor (EHRF) activity. This protein, purified from medium from the in-vitro culture of 2-8-cell human embryos, by means of affinity chromatography, was capable of binding immunoglobulin (Ig)E as demonstrated by immunoblotting and enzyme-linked immunosorbent assays. We found EHRF was capable of inducing release of histamine and cytokines in vitro from rat uterine tissue, collected on day 4 of pregnancy (preimplantation stage of embryo development). When EHRF was used as a secretagogue, granulocyte macrophage-colony stimulating factor (GM-CSF) release increased from 3 to 55 pg/g (P < 0.01) and tumour necrosis factor-alpha (TNF-alpha) release increased from 0 to 2.1 ng/g (P < 0.01), as detected by enzyme-linked immunosorbent assay. A simple method was used to purify uterine mast cells using an IgE-Sepharose affinity chromatography column and the purity (90%) was checked with Dynabeads coupled to specific rat IgE antibody. When purified mast cells were stimulated with EHRF in the same way as the uterine explants, a similar pattern of GM-CSF and TNF-alpha release was obtained. We also describe the reverse transcription-polymerase chain reaction (RT-PCR) of GM-CSF and TNF-alpha mRNA from purified uterine mast cells. On day 4 of pregnancy only the mRNA of TNF-alpha was found and this increased after stimulation with the EHRF. In conclusion, the data presented suggest that uterine mast cells isolated during the preimplantation stage release cytokines in vitro following interaction with an embryo factor.


Assuntos
Fatores Biológicos/isolamento & purificação , Embrião de Mamíferos/metabolismo , Fator Estimulador de Colônias de Granulócitos e Macrófagos/metabolismo , Liberação de Histamina/efeitos dos fármacos , Mastócitos/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Útero/efeitos dos fármacos , Animais , Fatores Biológicos/metabolismo , Fatores Biológicos/farmacologia , Meios de Cultivo Condicionados/química , Implantação do Embrião , Ensaio de Imunoadsorção Enzimática , Feminino , Fertilização in vitro , Fator Estimulador de Colônias de Granulócitos e Macrófagos/genética , Humanos , Imunoglobulina E/imunologia , Peso Molecular , Gravidez , RNA Mensageiro/genética , RNA Mensageiro/isolamento & purificação , Ratos , Ratos Wistar , Estimulação Química , Fator de Necrose Tumoral alfa/genética , Útero/química , Útero/citologia
7.
J Neuroimmunol ; 60(1-2): 107-15, 1995 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-7543905

RESUMO

There is increasing evidence that neuropeptides, steroid hormones and inflammatory cytokines influence the immune response during the reproductive cycle. In the present study, we focus on the effects of neuropeptide Substance P (SP) during the pre-implantation stage of embryo development (day 4 of pregnancy), at pro-estrus and di-estrus (two phases with different hormonal states). We found heterogeneous responses to SP and anti-IgE by the rat uterine mast cells (MCs), as detected by ELISA. In fact, MCs purified from uteri on day 4 of pregnancy released histamine, granulocyte macrophage-colony stimulating factor (GM-CSF) and tumor necrosis factor-alpha (TNF-alpha) in response to anti-IgE, but not to SP. When pre-incubated with SP, the release to anti-IgE was significantly enhanced compared to anti-IgE alone. Exposure of SP to antibodies to SP, prior to pre-incubation with MCs, negated the SP effect on IgE-mediated release. At the pro-estrus phase SP showed similar behavior as on day 4 of pregnancy, whereas at the di-estrus phase SP alone was capable of inducing release of histamine and cytokines from purified uterine MCs. Moreover, non-quantitative RT-PCR analysis of the TNF-alpha mRNA level suggested an SP stimulation at the di-estrus phase, but neither on day 4 of pregnancy nor at the pro-estrus phase. Taken together, these data strongly suggest that SP can modulate IgE-mediated uterine MC release of histamine and inflammatory cytokines in different ways, depending on the phase of the reproductive cycle.


Assuntos
Citocinas/metabolismo , Mastócitos/metabolismo , Reprodução/fisiologia , Substância P/farmacologia , Útero/metabolismo , Animais , Sequência de Bases , Diestro , Desenvolvimento Embrionário , Feminino , Liberação de Histamina , Masculino , Dados de Sequência Molecular , Sondas de Oligonucleotídeos , Gravidez , Proestro , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Fator de Necrose Tumoral alfa/genética , Útero/citologia
8.
J Biol Chem ; 269(22): 15740-8, 1994 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-8195227

RESUMO

We have explored the role of the distal switch II region of the yeast RAS2 protein in determining the response to the nucleotide exchange factor CDC25. We first constructed yeast tester strains in which the deletion of the chromosomal CDC25, RAS1, and RAS2 genes, in combination with the chromosomal suppressor CRI4, resulted in detectable phenotypes in vivo and in vitro. Phenotypes included impaired growth at 37 degrees C, defective glucose-induced cyclic AMP signaling, and low adenylyl cyclase activity of membrane preparations. Tester strains were subsequently used for the reintroduction of various combinations of wild-type and mutated RAS2 and CDC25 genes by genetic techniques, as well as for in vitro reconstitution assays with the corresponding proteins. CDC25 restored both growth and glucose-induced cyclic AMP signaling in the presence, but not in the absence of wild-type RAS2. A gene encoding a RAS2 protein with a mutationally altered switch II region was expressed but was ineffective in reintegrating exchange factor-dependent responses in vivo. Wild-type, but not mutagenically altered, RAS2 proteins were stimulated by exchange factors in vitro. We conclude that the conserved distal switch II region is required for CDC25-dependent activation of RAS.


Assuntos
Proteínas de Ciclo Celular , Proteínas Fúngicas/metabolismo , Genes Fúngicos , Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Proteínas ras , ras-GRF1 , Adenilil Ciclases/metabolismo , Cromossomos Fúngicos , AMP Cíclico/metabolismo , Proteínas Fúngicas/genética , Proteínas de Ligação ao GTP/metabolismo , Genes Supressores , Genótipo , Glucose/farmacologia , Cinética , Mutagênese , Plasmídeos , Mapeamento por Restrição , Saccharomyces cerevisiae/efeitos dos fármacos , Especificidade da Espécie , Supressão Genética
9.
Eur J Immunol ; 24(4): 999-1002, 1994 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-8149968

RESUMO

The autoimmune process leading to the destruction of pancreatic beta-cells is mediated by T lymphocytes. Peripheral T cells from subjects with preclinical and clinical type I diabetes respond weakly in vitro to lectin stimulation. We, therefore, investigated in a group of newly diagnosed diabetic patients the presence of a defect in the signal transduction pathway of the T cell receptor (TcR)/CD3 complex. Following stimulation with anti-CD3-coupled beads, the proliferative response in diabetic T cells was significantly decreased in comparison with that from normal T cells. Interestingly, addition of either recombinant interleukin (IL)-2 or phorbol 12-myristate 13-acetate to the cell culture was able to completely restore impaired anti-CD3-induced proliferation in diabetic T cells, suggesting the presence of a defect through the TcR/CD3 pathway, located upstream of protein kinase C (PKC) activation and resulting in low IL-2 production and proliferation. Intracellular Ca2+ measurements by Fluo-3 labeling and flow cytometry analysis on diabetic and control T cells after anti-CD3 stimulation gave comparable results, indicating that this defect does not involve events leading to intracellular Ca2+ mobilization. In contrast, anti-CD3 stimulation of diabetic T cells resulted in a marked impairment of PKC translocation and CD69 antigen expression, as assessed by peptide substrate phosphorylation and by flow cytometry analysis, respectively. Taken together, our data clearly show the presence in individuals at the onset of the disease of an in vitro defect in the signal transduction pathway of the TcR/CD3 complex, resulting in ineffective PKC activation which is not able to induce normal IL-2 production and proliferation of diabetic T cells.


Assuntos
Diabetes Mellitus Tipo 1/imunologia , Complexo Receptor-CD3 de Antígeno de Linfócitos T/fisiologia , Linfócitos T/imunologia , Antígenos CD/análise , Antígenos de Diferenciação de Linfócitos T/análise , Cálcio/metabolismo , Humanos , Lectinas Tipo C , Ativação Linfocitária , Proteína Quinase C/fisiologia
10.
Yeast ; 9(1): 21-32, 1993 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-8442384

RESUMO

The SCH9 yeast gene, that was previously identified as a suppressor of cdc25 and ras1- ras2-ts temperature-sensitive mutants, encodes a putative protein kinase that positively regulates the progression of yeast cells through the G1 phase of the cell cycle. We have determined the structure of the SCH9 transcription unit, using primer extension and S1 mapping techniques. The corresponding mRNA included an unusually long 5' region of more than 600 nucleotides preceding the major open reading frame (ORF). While the latter corresponded to a protein of 824 amino acids, an upstream open reading frame (uORF) within the 5' leader could potentially encode a 54 amino acid peptide. To investigate the role of the AUGs within the uORF, we engineered chimaeric plasmid vectors in which SCH9 sequences including the promoter, the mRNA leader and the first 514 nucleotides of the major ORF were fused in-frame with beta-galactosidase-coding sequences. Upon introduction into yeast cells, the fusion protein was efficiently expressed. However, mutational disruption of the uORF using oligonucleotide-directed mutagenesis did not affect the level of expression of the fusion protein. This indicates that regulatory mechanisms in Saccharomyces cerevisiae prevent upstream AUGs within the SCH9 mRNA leader sequence from influencing translation from downstream initiation codons.


Assuntos
Fases de Leitura Aberta , Proteínas Quinases/genética , RNA Fúngico/genética , RNA Mensageiro/genética , Saccharomyces cerevisiae/genética , Alelos , Sequência de Aminoácidos , Sequência de Bases , Fase G1 , Regulação Fúngica da Expressão Gênica , Genes Supressores , Dados de Sequência Molecular , Mutação , Proteínas Quinases/química , Saccharomyces cerevisiae/citologia , Saccharomyces cerevisiae/enzimologia , Transcrição Gênica
11.
EMBO J ; 11(8): 2855-62, 1992 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-1639059

RESUMO

We have previously shown that a conserved glycine at position 82 of the yeast RAS2 protein is involved in the conversion of RAS proteins from the GDP- to the GTP-bound form. We have now investigated the role of glycine 82 and neighbouring amino acids of the distal switch II region in the physiological mechanism of activation of RAS. We have introduced single and double amino acid substitutions at positions 80-83 of the RAS2 gene, and we have investigated the interaction of the corresponding proteins with a yeast GDP dissociation stimulator (SDC25 C-domain). Using purified RAS proteins, we have found that the SDC25-stimulated conversion of RAS from the GDP-bound inactive state to the GTP-bound active state was severely impaired by amino acid substitutions at positions 80-81. However, the rate and the extent of conversion from the GDP- to the GTP-bound form in the absence of dissociation factor was unaffected. The insensitivity of the mutated proteins to the dissociation factor in vitro was paralleled by an inhibitory effect on growth in vivo. The mutations did not significantly affect the interaction of RAS with adenylyl cyclase. These findings point to residues 80-82 as important determinants of the response of RAS to GDP dissociation factors. This suggests a molecular model for the enhancement of nucleotide release from RAS by such factors.


Assuntos
Proteínas Fúngicas/metabolismo , Genes Fúngicos , Guanosina Difosfato/metabolismo , Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae/metabolismo , Proteínas ras , Adenilil Ciclases/metabolismo , Sequência de Aminoácidos , Sequência de Bases , Sítios de Ligação , Membrana Celular/metabolismo , Proteínas Fúngicas/genética , Proteínas Fúngicas/isolamento & purificação , Proteínas de Ligação ao GTP/metabolismo , Genótipo , Glicina , Guanilil Imidodifosfato/farmacologia , Cinética , Magnésio/farmacologia , Dados de Sequência Molecular , Mutagênese Sítio-Dirigida , Plasmídeos , Saccharomyces cerevisiae/genética , Proteínas rap de Ligação ao GTP
12.
People Planet ; 1(4): 20, 22, 24-7, 1992.
Artigo em Inglês | MEDLINE | ID: mdl-12344704

RESUMO

PIP: The population, environmental, and economic problems of Haiti must be solved through a national change in attitude, an emphasis on the individual value of children, a social concern for urgent action on sustainable development, and shared responsibility in the international community. The impact of colonialism was to lay waste to subsistence practices which were ecologically balanced. This first nation of self-liberated slaves has problems deeply rooted in the past, which have been worsened by the ruling elite's exploitation. There is extreme poverty, boat people, deforestation, environmental degradation, civil liberty abuses, and a struggle for democracy. Population growth as well as, indirectly, death, hunger, and disease, have contributed to the immigration of Haitians to the US, Canada, France, and neighboring islands. Fertility has been high for the past 20 years. The family planning challenges are discussed in light of the 10% acceptance rate and met demand. The host country's ability to cope with the burden of supplying employment, social services, and legal protection accounts for the reluctance to accept greater numbers of Haitians. Rural-to-urban migration has created nightmares within Haiti. Cite Soleil has a population density of 25,000 people/sq. kilometer, and more than 33% of rural areas is unfit for habitation. The urban slums offer a substandard quality of life due to infiltration of sea water into the soil which prohibits vegetative growth, due to sanitation deficits, and due to inadequate clean water supplies. The example of a small sugar merchant with an income of $40/month reflects the ability to survive but with no provision for empowerment or betterment for the future for the grandchildren in her care. Captain Jacques-Yves Cousteau attests to the difficulties and, maybe, impossibilities of turning around the process of environmental devastation and overpopulation. The ecological problems are primarily due to salinization and deforestation; the pressure for fuelwood has increased since the trade embargo, which prevents importation of butane and propane. Tree planting of 20 million/year yields 2-3 million actually surviving. Destructive fishing, quarrying, and agricultural techniques continue to waste resources.^ieng


Assuntos
Colonialismo , Conservação dos Recursos Naturais , Economia , Emigração e Imigração , Poluição Ambiental , Estudos de Avaliação como Assunto , Planejamento em Saúde , Cooperação Internacional , Dinâmica Populacional , Crescimento Demográfico , Áreas de Pobreza , Pobreza , Abastecimento de Água , América , Região do Caribe , Demografia , Países em Desenvolvimento , Meio Ambiente , Serviços de Planejamento Familiar , Fertilidade , Administração Financeira , Geografia , Haiti , América Latina , América do Norte , Sistemas Políticos , População , Fatores Socioeconômicos , População Urbana , Urbanização
13.
FEBS Lett ; 281(1-2): 235-9, 1991 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-1901802

RESUMO

Ras proteins bind either GDP or GTP with high affinity. However, only the GTP-bound form of the yeast Ras2 protein is able to stimulate adenylyl cyclase. To identify amino acid residues that play a role in the conversion from the GDP-bound to the GTP-bound state of Ras proteins, we have searched for single amino acid substitutions that selectively affected the binding of one of the two nucleotides. We have found that the replacement of glycine-82 of the Ras2 protein by serine resulted in an increased rate of dissociation of Gpp(NH)p, a nonhydrolysable analog of GTP, while the GDP dissociation rate was not significantly modified. Glycine-82 resides in a region that is highly conserved between the yeast and human proteins. However, this residue is structurally distant from residues that participate in the binding of the nucleotide, as determined from the crystal structure of the human H-ras gene product. Therefore, the ability of the nucleotide binding site to discriminate between GDP and GTP is dependent not only on residues that are spatially close to the nucleotide, but also on distant amino acids. This is in agreement with the role of glycine-82 as a pivot point during the transition from the GDP- to the GTP-bound form of the Ras proteins.


Assuntos
Proteínas Fúngicas/metabolismo , Glicina , Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae/metabolismo , Proteínas ras , Sequência de Aminoácidos , Sítios de Ligação , Escherichia coli/genética , Proteínas Fúngicas/genética , Proteínas Fúngicas/isolamento & purificação , Proteínas de Ligação ao GTP/metabolismo , Guanosina Difosfato/metabolismo , Guanosina Trifosfato/metabolismo , Guanilil Imidodifosfato/metabolismo , Modelos Estruturais , Mutagênese Sítio-Dirigida , Plasmídeos , Conformação Proteica , Proteínas Recombinantes/isolamento & purificação , Proteínas Recombinantes/metabolismo , Mapeamento por Restrição , Saccharomyces cerevisiae/genética
14.
J Hepatol ; 12(1): 64-9, 1991 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-2007777

RESUMO

Hepatitis B virus deoxyribonucleic acid (HBV-DNA) was studied by Southern blot analysis in liver biopsy specimens from 75 HBsAg-positive patients with chronic liver disease living in southern Italy. Twenty-seven of the patients were hepatitis delta virus (HDV) superinfected. Intrahepatic HBV-DNA was detected in 54 (72%) patients, 32 (59%) of them with replicative forms. The presence of replicative forms was directly related to liver HBcAg and inversely related to liver HDAg, as shown by multivariate analysis. However, 14 patients with intrahepatic HBV-DNA non-replicative pattern and about half of HDV-infected patients were liver HBcAg and/or serum HBV-DNA positive, mostly in low amounts. Histological inflammatory activity was strongly related to liver HBcAg expression regardless of HDV superinfection, as confirmed by multivariate analysis. Our results confirm previous studies about the concordance between intrahepatic HBV-DNA replicative pattern and liver HBcAg expression and about inhibition by HDV of high-level HBV replication. However, they suggest that low-level HBV replication may have an important role in causing liver damage also among HDV-infected patients, in a population where the spreading of HBV and HDV is a naturally occurring event.


Assuntos
Vírus da Hepatite B/fisiologia , Hepatite D/microbiologia , Hepatopatias/microbiologia , Replicação Viral/fisiologia , Adolescente , Adulto , Idoso , Southern Blotting , Criança , Pré-Escolar , Doença Crônica , Replicação do DNA/fisiologia , DNA Viral/análise , Antígenos de Superfície da Hepatite B/análise , Vírus da Hepatite B/genética , Vírus da Hepatite B/isolamento & purificação , Hepatite D/complicações , Hepatite D/fisiopatologia , Vírus Delta da Hepatite/fisiologia , Humanos , Fígado/química , Fígado/microbiologia , Fígado/patologia , Hepatopatias/complicações , Hepatopatias/fisiopatologia , Masculino , Pessoa de Meia-Idade
16.
J Hepatol ; 9(1): 23-8, 1989 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-2768795

RESUMO

A series of 120 patients with chronic delta hepatitis virus (HDV) were investigated using a newly developed assay for the detection of serum delta RNA and this marker was correlated with other markers of HDV infection. The assay was shown to be both specific and sensitive and provides a direct non-invasive measurement of HDV infectivity. Serum HDV RNA was detected in 51.2% of all patients and in about 64% of those who were liver HDV antigen positive. Its presence was particularly associated with the early stages of the disease where it was found in 83% of cases with chronic active hepatitis (CAH) and progressively less common in CAH associated with cirrhosis and in inactive cirrhosis. The presence of both HBeAg (and HBV DNA) and high levels of HDV RNA in the sera of 5 of the patients analysed, clearly demonstrates simultaneous replication of both HBV and HDV. The serum HDV RNA 'slot blot' assay described in this study should prove invaluable in elucidating further the natural history of delta hepatitis and in monitoring antiviral therapy.


Assuntos
Hepatite D/genética , Vírus Delta da Hepatite/genética , RNA Viral/análise , Adulto , Idoso , Anticorpos Antivirais/análise , Antígenos Virais/análise , Biomarcadores/sangue , Criança , Doença Crônica , Feminino , Hepatite D/imunologia , Humanos , Masculino , Hibridização de Ácido Nucleico , RNA Viral/genética
17.
J Hepatol ; 8(3): 358-66, 1989 May.
Artigo em Inglês | MEDLINE | ID: mdl-2499617

RESUMO

The behaviour of the immune system during liver damage caused by chronic hepatitis delta virus (HDV) infection was evaluated by assessing, in 16 patients with HBsAg+ chronic liver disease and HDV superinfection (15 HBeAg-, 1 HBeAg+), phytohaemagglutinin (PHA)-induced interleukin-2 synthesis and interleukin-2 receptor expression, PHA and staphylococcal enterotoxin B (SEB)-induced gamma-interferon synthesis and, in some cases, the presence of hepatitis B virus DNA (HBV-DNA) within peripheral blood mononuclear cells (PBMC). The results were compared to those obtained in 13 patients without HBV replication (i.e., serum HBV-DNA and liver HBcAg-negative), in 15 with HBV replication (i.e., serum HBV-DNA and/or liver HBcAg-positive) with chronic liver disease without HDV superinfection, and in 15 HBsAg-negative healthy control subjects. The lymphokine pattern in HDV infection was comparable to that of healthy subjects and of HBV non-replicating patients without HDV superinfection. Interleukin-2 receptor expression and gamma-interferon synthesis were however significantly decreased in HDV-negative patients with active HBV replication. HBV-DNA was detected in PBMC from 8 of 23 patients, without any correlation with the lymphokine pattern. Our results suggest that in HDV-related chronic liver disease, immune system alterations are unlikely. HDV superinfection does not affect the occurrence of HBV-DNA sequences within the leukocytes. HBV-DNA in PBMC does not interfere with the interleukin-2 system nor with the gamma-interferon response in HBV- and HDV-related chronic liver disease.


Assuntos
Hepatite D/imunologia , Interferon gama/biossíntese , Interleucina-2/biossíntese , Leucócitos Mononucleares/imunologia , Receptores de Interleucina-2/imunologia , Adulto , Doença Crônica , DNA Viral/análise , Feminino , Antígenos do Núcleo do Vírus da Hepatite B/análise , Antígenos de Superfície da Hepatite B/análise , Antígenos E da Hepatite B/análise , Vírus Delta da Hepatite/imunologia , Vírus Delta da Hepatite/fisiologia , Humanos , Interferon gama/análise , Interleucina-2/análise , Masculino , Receptores de Interleucina-2/análise , Replicação Viral
19.
Minerva Stomatol ; 29(5): 345-58, 1980.
Artigo em Italiano | MEDLINE | ID: mdl-6109235

RESUMO

A double-blind study was made of the activity and tolerance of 400 mg Floctaphenine versus 400 mg Acetylsalicylic Acid (ASA) on ordinary random administration. 48 patients received Floctaphenine and 50 ASA. Menstruating women were included, but not children aged less than 12 yr. Periodontitis, pulpitis, abscesses, extractions and dysodontiasis were the most frequently represented sources of pain. Subjects completing the study were divided into groups: those already treated with other analgesics in the previous 24 hr, those with uninterrupted pain, those with attacks of pain, those for whom one administration was sufficient, menstruating women. Account was also taken of the effect of treatment before or after meals, and the influence of a simultaneously administered antibiotic (the same one in each case). Statistical assessment showed that both drugs were analgesic, but that Floctaphenine was significantly (P < 0.01) better than ASA. The same was true with regard to latency time, duration of the effect, clinical assessment, need for support from other analgesics. The antibiotic appeared to have no appreciable influence of the activity of the two drugs, nor did the time of administration (before or after meals). Much the same picture was apparent in each group. Menstrual status was devoid of influence, though it cannot be stated with equal certainty that whether secondary effects were more frequent. Floctaphenine was very well tolerated. There were 4 somewhat doubtful cases of somnolence (8.33%). It was not certain, in fact, whether this was not an outcome of the relief from pain. ASA was accompanied by stomach pain in 9 cases (18%). This was much more common when it was taken on an empty stomach.


Assuntos
Odontalgia/tratamento farmacológico , ortoaminobenzoatos/uso terapêutico , Adolescente , Adulto , Aspirina/uso terapêutico , Ensaios Clínicos como Assunto , Método Duplo-Cego , Quimioterapia Combinada , Tolerância a Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
20.
Minerva Stomatol ; 29(4): 265-80, 1980.
Artigo em Italiano | MEDLINE | ID: mdl-6109234

RESUMO

The analgesic activity and tolerance of a new non-narcotic synthetic analgesic derive from quinoline has been experimented in a double blind study. Phloctaphenin (200 mg) was compared with 200 mg of Acetylsalicylic acid (ASA). Administration of the drug was randomized: 41 patients received Phloctaphenin and 37 ASA. In addition to normal patients, the study also included menstruating women and, after paediatric check-up, children (i.e. under-12's). The conditions treated included periodontitis, pulpitis, abscesses, caries (with extraction), dysodontiasis and traumas. Patients were subdivided into groups (already treated with analgesics in the previous 24 h, not treated in the previous 24 h, affected by continuous pain, affected by fits of pain, subjects in whom a single drug administration was sufficient, patients in their menstrual period). Account was also taken of the outcome of treatment in relation to meals and of the influence of the association of an antibiotic (always the same). The study showed that both drugs possess analgesic activity but that of Phloctaphenin is statistically superior (almost always highly significant, i.e. P < 0.01) compared to ASA. The same applies to latency and the duration of the effect, the clinical judgment ad the need to administered other drugs. Association with the antibiotic has no influence whatever as might have been presumed considering the period of administration and the times of assessing the pain killing action of the two drugs. Administration before or after meals was irrelevant for both drugs. Statistical study of individual groups confirmed these results. From the viewpoint of side-effects, Phloctaphenin is better tolerated: with this new analgesic, in effect, only 2 debatable cases (4.87%) of side-effects (somnolence) were observed while 6 of the patients treated with ASA (16.20%) presented side-effects: 3 cases of gastric pyrosis (8.10%) before meals and 3 cases (8.10%) of hyperhydrosis after meals.


Assuntos
Odontalgia/tratamento farmacológico , ortoaminobenzoatos/uso terapêutico , Adolescente , Adulto , Aspirina/administração & dosagem , Criança , Pré-Escolar , Ensaios Clínicos como Assunto , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Comprimidos , ortoaminobenzoatos/administração & dosagem , ortoaminobenzoatos/efeitos adversos
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