I'm a Biological Doctor, PhD and actually I'm Associate Professor of Human Anatomy at University of Bari (Italy). Scientific fields: neuroinflammation, role of microvesicles in human diseases, role of pro-inflammatory mediators in cancer and neurological diseases.
Erythema induratum of Bazin (EIB) is a chronic nodular eruption occurring on the lower legs of yo... more Erythema induratum of Bazin (EIB) is a chronic nodular eruption occurring on the lower legs of young and middleaged women which is considered the most common tuberculid. A 54-year-old woman, in treatment with chemotherapy for breast cancer, presented subcutaneous erythematous plaques and nodules on the lower limbs. She had been diagnosed with EIB 3 years earlier and diagnostic work-up showed at that time signs suggestive of latent tuberculosis. The suspect of a recurrent form of EIB was confirmed by histopathological examination. A peculiar feature of our report consists in the recurrence of EIB, which is regarded as a hyperergic response against M. tuberculosis antigens, in a patient who was receiving chemotherapy with well-known immunosuppressive effects.
Current drug targets. Immune, endocrine and metabolic disorders, 2003
Nitric oxide (NO) is a pleiotropic mediator of numerous biological processes, including smooth mu... more Nitric oxide (NO) is a pleiotropic mediator of numerous biological processes, including smooth muscle relaxation, neurotransmission and defence against pathogens. In addition, NO is involved in the pathogenesis and control of inflammation, tumors, autoimmunity, and infectious and chronic degenerative diseases. NO, a highly reactive radical, is produced from L-arginine and oxygen by the enzyme NO synthase (NOS). Three NOS isoforms have been identified: two distinct NOS isoforms are constitutively expressed in cells, whereas a third isoform, inducible NOS (iNOS), is transcribed in response to specific stimuli. In particular, iNOS is responsible for the discontinuous synthesis of high amounts of NO and was originally characterized in murine macrophages after exposure to cytokines and/or microbial products. A wide range of microorganisms is sensibly inhibited in its development by NO, like fungi, bacteria, protozoa and viruses. Although NO production and its antimicrobial effect appear ...
Current drug targets. Immune, endocrine and metabolic disorders, 2001
Helicobacter (H.) pylori is the causative agent of the peptic ulcer disease and a co-factor in th... more Helicobacter (H.) pylori is the causative agent of the peptic ulcer disease and a co-factor in the development of gastric malignancies. Recently, it has been maintained that chronic H. pylori infections in adults are linked to a higher risk of coronary heart diseases. In this respect, the acute toxic effects of the H. pylori lipopolysaccharide (LPS) on embryonal cardiomyocytes at different developmental stages was evaluated. White Leghorn chick embryos and smooth (S)--form NCTC 11637 strain H. pylori organisms were used. Both whole heath-killed H. pylori suspensions (3.10(6) bacteria/egg) and isolated S-LPS (500 ng/egg) or S-Lipid A (500 ng/egg) were non-lethal to 4-day embryos, becoming moderately lethal (5% to 30%) to 6- and 8-day embryos and highly lethal (> 90%) to 10- to 17-day embryos. The contractile activity of isolated atrial fragments from 10-day embryos was completely inhibited, within 5 min, following treatments with heath-killed H. pylori (3 x 10(6)/ml), or S-LPS (50...
Chemokines are a group of structurally defined small proteins that act as chemoattractants for le... more Chemokines are a group of structurally defined small proteins that act as chemoattractants for leukocytes and are involved in many different biological activities, including leukocyte activation for antimicrobial mechanisms. We studied the effect of the chemokines monocyte chemotactic protein (MCP)-1 and macrophage inflammatory protein (MIP)-1 alpha on nitric oxide release and parasitocidal ability of peripheral blood-derived human macrophages in vitro infected with Leishmania infantum, zymodeme MON1. In infected human macrophages, treatment with MCP-1 or MIP-1 alpha significantly enhanced nitric oxide production and leishmanicidal ability, compared with untreated cells, to the same levels induced by interferon-gamma. Both nitric oxide release and parasitocidal ability of macrophages were significantly reduced by addition of L- N(G)monomethylarginine ( L-NMMA), which is a competitive inhibitor of the L-arginine nitric oxide pathway. These data suggest that MCP-1 and MIP-1 alpha medi...
HHH syndrome is an autosomal recessive urea cycle disorder caused by alterations in the SLC25A15 ... more HHH syndrome is an autosomal recessive urea cycle disorder caused by alterations in the SLC25A15 gene encoding the mitochondrial ornithine carrier 1, which catalyzes the transport of cytosolic ornithine into the mitochondria in exchange for intramitochondrial citrulline. In this study the functional effects of several SLC25A15 missense mutations p.G27R, p.M37R, p.N74A, p.F188L, p.F188Y, p.S200K, p.R275Q and p.R275K have been tested by transport assays in reconstituted liposomes and complementation of Saccharomyces cerevisiae ORT1 null mutant in arginine-less synthetic complete medium. The HHH syndrome-causing mutations p.G27R, p.M37R, p.F188L and p.R275Q had impaired transport and did not complement ORT1∆ cells (except p.M37R slightly after 5days in solid medium). The experimentally produced mutations p.N74A, p.S200K and p.R275K exhibited normal or considerable transport activity and complemented ORT1∆ cells after 3days (p.N74A, p.S200K) or 5days (p.R275K) incubation. Furthermore, the experimentally produced p.F188Y mutation displayed a substantial transport activity but did not complement the ORT1∆ cells in both liquid and solid media. In view of the disagreement in the results obtained between the two methods, it is recommended that the method of complementing the S. cerevisiae ORT1 knockout strain is used complimentary with the measurement of the catalytic activity, in order to distinguish HHH syndrome-causing mutations from isomorphisms.
Endocrine, Metabolic & Immune Disorders - Drug Targets, 2009
Random mutations of the first nucleotide of a coding triplet alter the hydropathic character of 2... more Random mutations of the first nucleotide of a coding triplet alter the hydropathic character of 27 % of the hydrophobic amino acids and of 23 % of the hydrophilic amino acids, while random mutations of the second nucleotide alter the hydropathic character of 82 % of the hydrophobic amino acids and of 47 % of the hydrophilic amino acids. In cases of a change of the hydropathic character, a second random mutation in the previously unmutated first or second nucleotide causes reversion to the original character of an additional 11 % of the originally hydrophobic-coding triplets and an additional 14 % of the originally hydrophilic-coding triplets (on average). Thus, a selection oriented towards the preservation of the hydropathic character of amino acids may be expected to eventually result in a higher conservation of the second nucleotide (as compared to the first). In the case of uncorrected mutations of one of the two first nucleotides, it may be expected that appropriate second mutations in the other unaffected nucleotide will be positively selected. This would result in a positive correlation between the conservation/mutation indexes of the two first nucleotides, as these would be prevailingly either both conserved or both mutated. We examined six groups of coding mRNA sequences: chemokine CXC 1 and 4 and formyl peptide receptors; a group comprising different receptors of the rhodopsin-like superfamily, together with some viral sequences which share significant homologies with these receptors; a group of viral sequences with homologies with the rhodopsin-like receptors; a group of solute carriers. In all the experimental groups the second nucleotide of the triplet was the most conserved and a significant positive correlation existed between conservation/mutation indexes of the two first nucleotides. Similar conservation/mutation patterns could be of more general occurrence in the genome, as a consequence of selection processes.
Various proteins that are required for the building of new complete human immunodeficiency type 1... more Various proteins that are required for the building of new complete human immunodeficiency type 1 virions (HIV-1) are coded by unspliced or partly spliced virus-derived mRNAs. HIV-1 has developed special strategies for moving these mRNAs to the cytoplasm to be translated. In the nucleus of the infected cell the virus-derived protein Regulator of expression of viral proteins (Rev) can bind both the viral intron-containing mRNAs and the cellular co-factor HIV-1 Rev binding protein (HRB) and this complex may be shuttled through the nuclear pores. HRB genes have been relatively well conserved during evolution, from Drosophila to humans. However, as a consequence of reading-frame shifts due to nt insertions/deletions, the protein products generated may differ considerably from the prototypal HRB protein, which comprises one Arf-GAP zinc finger domain, several Phenylalanine-Glycine (FG) motifs and four Asparagine-Proline-Phenylalanine (NPF) motifs. This variability is best exemplified by four HRB proteins of the dog, which are discussed here in more detail. The hypothesis is advanced that atypical HRB proteins may not be able to bind Rev and possibly have other, still undetermined, functions. Since the cellular co-factor HRB is essential for viral replication and spread but is not required for cell viability and main bodily functions, it might be an attractive candidate for anti-HIV-1 drug targeting.
Different toxic agents, derived from bacteria, viruses or cells of the immune system, as well as ... more Different toxic agents, derived from bacteria, viruses or cells of the immune system, as well as mechanical forces generated during cell locomotion are able to open pores in the cell plasma membrane. Most of these biological agents operate through specific receptors. We studied the formation and resealing of the "non-specific" plasma membrane pores generated by the mild non-ionic detergent Triton X-100. In HL-60-derived granulocytic cells plasma membrane pore opening after a 1-h treatment with Triton X-100 is documented by entry into the cell of the membrane impermeant dye ethidium bromide. As a consequence of the opening of pores the intracellular K(+) concentration falls dramatically, the cytosolic pH diminishes and the cell membrane is depolarized. Furthermore the cells acquire a polarized morphology, demonstrating the involvement of the actin cytoskeleton. At the Triton concentration used the membrane lesions are progressively repaired and by 8h the impermeability to ethidium bromide is restored and the intracellular K(+) concentration is virtually normal. Following treatments with Triton+Pertussis toxin, Triton+Cytochalasin, or Triton+Pertussis toxin+Cytochalasin the progress of membrane repair is dramatically slowed and is no longer completed by 8h. It is concluded that the membrane damage activates pertussis-sensitive G-proteins which likely act as sensors of the damage, while both G-proteins and the actin cytoskeleton are involved in the membrane repair mechanism.
Erythema induratum of Bazin (EIB) is a chronic nodular eruption occurring on the lower legs of yo... more Erythema induratum of Bazin (EIB) is a chronic nodular eruption occurring on the lower legs of young and middleaged women which is considered the most common tuberculid. A 54-year-old woman, in treatment with chemotherapy for breast cancer, presented subcutaneous erythematous plaques and nodules on the lower limbs. She had been diagnosed with EIB 3 years earlier and diagnostic work-up showed at that time signs suggestive of latent tuberculosis. The suspect of a recurrent form of EIB was confirmed by histopathological examination. A peculiar feature of our report consists in the recurrence of EIB, which is regarded as a hyperergic response against M. tuberculosis antigens, in a patient who was receiving chemotherapy with well-known immunosuppressive effects.
Current drug targets. Immune, endocrine and metabolic disorders, 2003
Nitric oxide (NO) is a pleiotropic mediator of numerous biological processes, including smooth mu... more Nitric oxide (NO) is a pleiotropic mediator of numerous biological processes, including smooth muscle relaxation, neurotransmission and defence against pathogens. In addition, NO is involved in the pathogenesis and control of inflammation, tumors, autoimmunity, and infectious and chronic degenerative diseases. NO, a highly reactive radical, is produced from L-arginine and oxygen by the enzyme NO synthase (NOS). Three NOS isoforms have been identified: two distinct NOS isoforms are constitutively expressed in cells, whereas a third isoform, inducible NOS (iNOS), is transcribed in response to specific stimuli. In particular, iNOS is responsible for the discontinuous synthesis of high amounts of NO and was originally characterized in murine macrophages after exposure to cytokines and/or microbial products. A wide range of microorganisms is sensibly inhibited in its development by NO, like fungi, bacteria, protozoa and viruses. Although NO production and its antimicrobial effect appear ...
Current drug targets. Immune, endocrine and metabolic disorders, 2001
Helicobacter (H.) pylori is the causative agent of the peptic ulcer disease and a co-factor in th... more Helicobacter (H.) pylori is the causative agent of the peptic ulcer disease and a co-factor in the development of gastric malignancies. Recently, it has been maintained that chronic H. pylori infections in adults are linked to a higher risk of coronary heart diseases. In this respect, the acute toxic effects of the H. pylori lipopolysaccharide (LPS) on embryonal cardiomyocytes at different developmental stages was evaluated. White Leghorn chick embryos and smooth (S)--form NCTC 11637 strain H. pylori organisms were used. Both whole heath-killed H. pylori suspensions (3.10(6) bacteria/egg) and isolated S-LPS (500 ng/egg) or S-Lipid A (500 ng/egg) were non-lethal to 4-day embryos, becoming moderately lethal (5% to 30%) to 6- and 8-day embryos and highly lethal (> 90%) to 10- to 17-day embryos. The contractile activity of isolated atrial fragments from 10-day embryos was completely inhibited, within 5 min, following treatments with heath-killed H. pylori (3 x 10(6)/ml), or S-LPS (50...
Chemokines are a group of structurally defined small proteins that act as chemoattractants for le... more Chemokines are a group of structurally defined small proteins that act as chemoattractants for leukocytes and are involved in many different biological activities, including leukocyte activation for antimicrobial mechanisms. We studied the effect of the chemokines monocyte chemotactic protein (MCP)-1 and macrophage inflammatory protein (MIP)-1 alpha on nitric oxide release and parasitocidal ability of peripheral blood-derived human macrophages in vitro infected with Leishmania infantum, zymodeme MON1. In infected human macrophages, treatment with MCP-1 or MIP-1 alpha significantly enhanced nitric oxide production and leishmanicidal ability, compared with untreated cells, to the same levels induced by interferon-gamma. Both nitric oxide release and parasitocidal ability of macrophages were significantly reduced by addition of L- N(G)monomethylarginine ( L-NMMA), which is a competitive inhibitor of the L-arginine nitric oxide pathway. These data suggest that MCP-1 and MIP-1 alpha medi...
HHH syndrome is an autosomal recessive urea cycle disorder caused by alterations in the SLC25A15 ... more HHH syndrome is an autosomal recessive urea cycle disorder caused by alterations in the SLC25A15 gene encoding the mitochondrial ornithine carrier 1, which catalyzes the transport of cytosolic ornithine into the mitochondria in exchange for intramitochondrial citrulline. In this study the functional effects of several SLC25A15 missense mutations p.G27R, p.M37R, p.N74A, p.F188L, p.F188Y, p.S200K, p.R275Q and p.R275K have been tested by transport assays in reconstituted liposomes and complementation of Saccharomyces cerevisiae ORT1 null mutant in arginine-less synthetic complete medium. The HHH syndrome-causing mutations p.G27R, p.M37R, p.F188L and p.R275Q had impaired transport and did not complement ORT1∆ cells (except p.M37R slightly after 5days in solid medium). The experimentally produced mutations p.N74A, p.S200K and p.R275K exhibited normal or considerable transport activity and complemented ORT1∆ cells after 3days (p.N74A, p.S200K) or 5days (p.R275K) incubation. Furthermore, the experimentally produced p.F188Y mutation displayed a substantial transport activity but did not complement the ORT1∆ cells in both liquid and solid media. In view of the disagreement in the results obtained between the two methods, it is recommended that the method of complementing the S. cerevisiae ORT1 knockout strain is used complimentary with the measurement of the catalytic activity, in order to distinguish HHH syndrome-causing mutations from isomorphisms.
Endocrine, Metabolic & Immune Disorders - Drug Targets, 2009
Random mutations of the first nucleotide of a coding triplet alter the hydropathic character of 2... more Random mutations of the first nucleotide of a coding triplet alter the hydropathic character of 27 % of the hydrophobic amino acids and of 23 % of the hydrophilic amino acids, while random mutations of the second nucleotide alter the hydropathic character of 82 % of the hydrophobic amino acids and of 47 % of the hydrophilic amino acids. In cases of a change of the hydropathic character, a second random mutation in the previously unmutated first or second nucleotide causes reversion to the original character of an additional 11 % of the originally hydrophobic-coding triplets and an additional 14 % of the originally hydrophilic-coding triplets (on average). Thus, a selection oriented towards the preservation of the hydropathic character of amino acids may be expected to eventually result in a higher conservation of the second nucleotide (as compared to the first). In the case of uncorrected mutations of one of the two first nucleotides, it may be expected that appropriate second mutations in the other unaffected nucleotide will be positively selected. This would result in a positive correlation between the conservation/mutation indexes of the two first nucleotides, as these would be prevailingly either both conserved or both mutated. We examined six groups of coding mRNA sequences: chemokine CXC 1 and 4 and formyl peptide receptors; a group comprising different receptors of the rhodopsin-like superfamily, together with some viral sequences which share significant homologies with these receptors; a group of viral sequences with homologies with the rhodopsin-like receptors; a group of solute carriers. In all the experimental groups the second nucleotide of the triplet was the most conserved and a significant positive correlation existed between conservation/mutation indexes of the two first nucleotides. Similar conservation/mutation patterns could be of more general occurrence in the genome, as a consequence of selection processes.
Various proteins that are required for the building of new complete human immunodeficiency type 1... more Various proteins that are required for the building of new complete human immunodeficiency type 1 virions (HIV-1) are coded by unspliced or partly spliced virus-derived mRNAs. HIV-1 has developed special strategies for moving these mRNAs to the cytoplasm to be translated. In the nucleus of the infected cell the virus-derived protein Regulator of expression of viral proteins (Rev) can bind both the viral intron-containing mRNAs and the cellular co-factor HIV-1 Rev binding protein (HRB) and this complex may be shuttled through the nuclear pores. HRB genes have been relatively well conserved during evolution, from Drosophila to humans. However, as a consequence of reading-frame shifts due to nt insertions/deletions, the protein products generated may differ considerably from the prototypal HRB protein, which comprises one Arf-GAP zinc finger domain, several Phenylalanine-Glycine (FG) motifs and four Asparagine-Proline-Phenylalanine (NPF) motifs. This variability is best exemplified by four HRB proteins of the dog, which are discussed here in more detail. The hypothesis is advanced that atypical HRB proteins may not be able to bind Rev and possibly have other, still undetermined, functions. Since the cellular co-factor HRB is essential for viral replication and spread but is not required for cell viability and main bodily functions, it might be an attractive candidate for anti-HIV-1 drug targeting.
Different toxic agents, derived from bacteria, viruses or cells of the immune system, as well as ... more Different toxic agents, derived from bacteria, viruses or cells of the immune system, as well as mechanical forces generated during cell locomotion are able to open pores in the cell plasma membrane. Most of these biological agents operate through specific receptors. We studied the formation and resealing of the "non-specific" plasma membrane pores generated by the mild non-ionic detergent Triton X-100. In HL-60-derived granulocytic cells plasma membrane pore opening after a 1-h treatment with Triton X-100 is documented by entry into the cell of the membrane impermeant dye ethidium bromide. As a consequence of the opening of pores the intracellular K(+) concentration falls dramatically, the cytosolic pH diminishes and the cell membrane is depolarized. Furthermore the cells acquire a polarized morphology, demonstrating the involvement of the actin cytoskeleton. At the Triton concentration used the membrane lesions are progressively repaired and by 8h the impermeability to ethidium bromide is restored and the intracellular K(+) concentration is virtually normal. Following treatments with Triton+Pertussis toxin, Triton+Cytochalasin, or Triton+Pertussis toxin+Cytochalasin the progress of membrane repair is dramatically slowed and is no longer completed by 8h. It is concluded that the membrane damage activates pertussis-sensitive G-proteins which likely act as sensors of the damage, while both G-proteins and the actin cytoskeleton are involved in the membrane repair mechanism.
Uploads
Papers by Maria A Panaro