1,721,104 research outputs found
Antisense Oligonucleotides as Therapeutic Agents
No full textAntisense oligonucleotides can block the expression of specific target genes involved in the development of human diseases. Therapeutic applications of antisense techniques are currently under investigation in many different fields. The use of antisense molecules to modify gene expression is variable in its efficacy and reliability, raising objections about their use as therapeutic agents. However, preliminary results of several clinical studies demonstrated the safety and to some extent the efficacy of antisense oligodeoxynucleotides (ODNs) in patients with malignant diseases. Clinical response was observed in some patients suffering from ovarian cancer who were treated with antisense targeted against the gene encoding for the protein kinase C-alpha. Some hematological diseases treated with antisense oligos targeted against the bcr/abl and the bcl2 mRNAs have shown promising clinica response. Antisense therapy has been useful in the treatment of cardiovascular disorders such as restenosis after angioplasty, vascular bypass graft occlusion, and transplant coronary vasculopathy. Antisense oligonucleotides also have shown promise as antiviral agents. Several investigators are performing trials with oligonucleotides targeted against the human immunodeficiency virus-1 (HIV-1) and hepatitis viruses. Phosphorothioate ODNs now have reached phase I and II in clinical trials for the treatment of cancer and viral infections, so far demonstrating a n acceptable safety and pharmacokinetic profile for continuing their development. The new drug Vitravene, based on a phosphorothioate oligonucleotide designed to inhibit the human cytomegalovirus (CMV), promises that some substantial successes can be reached with the antisense technique
Clinical trials of a new class of therapeutic agents: antisense oligonucleotides
No full textAntisense oligodeoxynucleotides (ODNs) are short stretches of DNA complementary to a target mRNA. The ODNs selectively hybridise to their complementary RNA by Watson-Crick base pairing rules. In theory, the use of antisense ODNs provides a method to specifically inhibit the intracellular expression of any disorder whose genetic aetiology is well known. For this reason, researchers thought that if antisense drugs proved to be so specific there would be no side effects. However, toxicity-related problems arose in initial animal studies of antisense drugs in the early 1990s and since then companies have been using these compounds cautiously. In order to be useful therapeutically, an ODN must (a) exhibit reasonable stability in the physiological environment, (b) be taken up and retained in adequate quantities by the target cells, (c) specifically bind target mRNA with high affinity, (d) have an acceptable therapeutic ratio, free of unwanted toxic and non-specific side effects and (e) be easily synthesised in sufficient quantities to allow clinical use. Most of these criteria have already been met by ODNs recently used in this way. This review describes certain therapeutic applications of antisense techniques currently under investigation in oncology, haematopathology and inflammatory disease
Antisense oligonucleotides as drugs for HIV treatment
No full textNowadays, several million people suffer from AIDS and more than 100 million people are forecasted to be infected with HIV. Among new drugs used to stop HIV virus infection, antisense oligodeoxynucleotides (ODNs) are under investigation and several biotechnology companies are currently developing antisense drugs. Antisense ODNs are short stretches of DNA complementary to a target mRNA. The ODNs selectively hybridise to their complementary RNA by Watson-Crick base pairing rules. In theory, the use of antisense ODNs provides a method to specifically inhibit the intracellular expression of any disorder. This review describes some of the clinical patents in the field of HIV treatments by antisense ODNs. These prior attempts at targeting HIV have largely focused on the nature of the chemical modification used in the ODN moiety. Although each of the described inventions have reported some degree of success in inhibiting some function of the virus, a general therapeutic scheme to target HIV has not yet been found
La percezione delle espressioni facciali di neonati e lattanti: Le madri sono “giudici” esperti?
No full textLa percezione delle espressioni facciali di neonati e lattanti: Le madri sono “giudici” esperti?
No full textThis study was aimed to analyze the meaning that mothers with recent vs. past experience of infants attribute to neonates’ and infants’ facial expressions. Six infants’ facial expressions were videotaped at 3 days, 1 and 3 months, in five different eliciting situations. One hundred and thirty-two mothers (66 mothers with children under 3 vs. 66 mothers with children over 12) were asked to judge the videotaped facial expressions in relation to the activation and pleasure/displeasure dimensions, the recognition of the eliciting situations, and the attribution of a verbal label to each expression. Results indicate that neonates’ and young infants’ facial expressions were more easily interpreted as signals of activation and pleasure/displeasure, rather than as signals of specific emotional states and/or specific eliciting situations. The frequency of correct recognitions of the eliciting situations by the mothers with recent experience of infants was significantly higher than that by the other mothers, but only for the expressions videotaped at 3 months
Pathophysiology of stem cells in restenosis
Full text linkRecent evidence has shown that vascular
function depends not only on cells within the vessels, but
is also significantly modulated by circulating cells
derived from the bone marrow. A number of studies
indicate that an early reendothelialization by circulating
endothelial precursors after vascular injury prevents
excessive cell proliferation and restenosis. Conversely,
other studies concluded that the homing of other cell
fractions, consisting mainly of smooth muscle
precursors, cause pathological remodelling. Different
cell types have been identified and characterized so far
as circulating precursors able to participate in vascular
repair by homing and differentiating towards endothelial
cells or smooth muscle cells. Among these, endothelial
precursor cells, smooth muscle progenitor cells,
mesenchymal stem cells and others have been described.
The origins, the hierarchy, the role and the markers of
these different cell populations are still controversial.
Nevertheless, different strategies have been developed so
far in animal models to induce the mobilization and the
recruitment of stem cells to the injury site, based on
physical training, hormone injection and application of
stem cell-capturing coated stents.
It should also be mentioned that the limited data
currently available derived from clinical trials provide
contrasting results about the effective role of vascular
cell precursors in restenosis prevention, thus indicating
that conclusions derived from studies in animal models
cannot always be directly applied to humans and that
caution should be used in the manipulation of circulating
progenitor cells for therapeutic strategies
Analisi del DNA antico dai reperti ossei umani del 79 d.C. rinvenuti nel sito archeologico di Murecine
No full textBacteriophage T4 late gene expression: Overlapping promoters direct divergent transcription of the base plate gene cluster
No full textEight 5′ ends of RNA molecules which encompass the bacteriophage T4 base plate late genes 51 to 26 region have been mapped by S1 nuclease protection and reverse transcription within a 246-bp DNA segment. Two of eight 5′ ends are initiated at two absolutely conserved late promoter sites, P51 and P26a, that direct RNA synthesis on opposite strands. These two promoters share four of eight promoter sequence base pairs. A third 5′ end arises from another promoter, P26b, which shows one base pair mismatch with respect to the absolutely conserved - 10 sequence. All the other 5′ ends arise from RNA processing and/or degradation. Since no other late transcription promoter sites were found within the base plate cluster sequence, we propose that the two overlapping late promoters, P51 and P26a, direct the expression of the T4 base plate gene cluster, included between map coordinates 114,000 and 121,038: P51 directs the transcription of genes 51, 27, 28, 29, 48, and 54 on the r DNA strand and P26a the transcription of genes 26 and 25 on the / DNA strand. This peculiar promoter configuration might account for the low level of transcription of these late genes. © 1989
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