Continous alert for rickettsiosis in Sicily: molecular characterization of Rickettsia sp. obtained from ticks and human beings (1986-2001)

Several strains of Rickettsia sp. were isolated from patients in western Sicily with MSF (Mediterranean Spotted Fever) as well as ticks. Strains isolated were examined by PCR and identified as belonging to R. conorii sp. Importantly a strain of Israeli Spotted Fever Rickettsiae, obtained from a tick, was also identified. Our data prove that strains other than the classical R. conorii also circulate in Sicily.     

Applications of carbon nanotubes in drug delivery

The development of new and efficient drug delivery systems is of fundamental importance to improve the pharmacological profiles of many classes of therapeutic molecules. Many different types of drug delivery systems are currently available. Within the family of nanomaterials, carbon nanotubes (CNT) have emerged as a new alternative and efficient tool for transporting and translocating therapeutic molecules. CNT can be functionalised with bioactive peptides, proteins, nucleic acids and drugs, and used to deliver their cargos to cells and organs. Because functionalised CNT display low toxicity and are not immunogenic, such systems hold great potential in the field of nanobiotechnology and nanomedicine.     

Activity of olive oil phenols on lymphomonocyte cytosolic calcium

Phenols, present in the Mediterranean diet, have antioxidant properties and are free radical scavengers; however, the molecular mechanisms of their beneficial effects are not yet fully understood. The level of cytosolic calcium ([Ca2+]i) is an important signal also in nonexcitable cells, including immune cells, and regulates fundamental processes. In this paper, we determine [Ca2+]i in human lymphomonocytes incubated with two olive oil phenols: 3,4-(dihydroxyphenyl)ethanol and p-(hydroxyphenyl)ethanol. Both tested phenols increase [Ca2+]i in a dose-dependent way. This effect is antagonized by nifedipine and is noticeable both in the presence and in the absence of calcium in the extracellular medium.     

Uncommon Alu-mediated NF1 microdeletion with a breakpoint inside the NF1 gene

Neurofibromatosis type 1 (NF1) microdeletion syndrome is caused by haploinsufficiency of the NF1 gene and of gene(s) located in adjacent flanking regions. Most of the NF1 deletions originate by nonallelic homologous recombination between repeated sequences (REP-P and -M) mapped to 17q11.2, while a few uncommon deletions show unusual breakpoints. We characterized an uncommon 1.5-Mb deletion of an NF1 patient displaying a mild phenotype. We applied high-resolution FISH analysis allowing us to obtain the sequence of the first junction fragment of an uncommon deletion showing the telomeric breakpoint inside the IVS23a of the NF1 gene. Sequence analysis of the centromeric and telomeric boundaries revealed that the breakpoints were present in the AluJb and AluSx regions, respectively, showing 85% homology. The centromeric breakpoint is localized inside a chi-like element; a few copies of this sequence are also located very close to both breakpoints. The in silico analysis of the breakpoint intervals, aimed at identifying consensus sequences of several motifs usually involved in deletions and translocations, suggests that Alu sequences, probably associated with the chi-like element, might be the only recombinogenic motif directly mediating this large deletion.     

Acute noise stress analgesia in relation to 5-HT2 and mu-opioid receptor changes in the frontal cortex of young mice

A number of studies have reported that exposure to stress provoked behavioural changes, including analgesia, in rodents. Differences have been observed in these responses to different types of stress and a link between hormones and neurotransmitters proposed. We studied the effect of acute noise stress on nociception and the possible changes in the serotonergic and opioidergic systems in young mice of both sexes. Naloxone pre-treatment was also investigated. Noise stress was produced by a sound source, nociception was measured by the hot-plate test and binding characteristics were evaluated by a radioligand binding technique using membrane preparation from the total frontal cortex. Acute noise stress provoked an antinociceptive effect, associated with an increase in plasma corticosterone levels, a decrease in the number of 5-HT2 receptors in stressed male and female mice and a decrease in the number of mu receptors in both sexes. The behavioural and biochemical effects were antagonized by 1 mg/kg of naloxone. Acute noise stress behaves like other types of stress on nociception. The opioidergic system seems to be involved in this behaviour but also the serotonergic system may play a role. Sex differences were detected in the number of 5-HT2 and mu receptors between male and female mice not subjected to stress, while the percentage decrease in 5-HT2 and mu receptors did not differ significantly between the two sexes.     

Drazepinone, a trisubstituted tetrahydronaphthofuroazepinone with herbicidal activity produced by Drechslera siccans

When grown in a minimal-defined medium, a strain of Drechslera siccans, a pathogenic fungus isolated from seeds of Lolium perenne, produced phytotoxic metabolites. This strain is one of the best toxin producers among several grass pathogenic fungal strains collected and tested to find phytotoxins to be used as natural herbicides of monocot weeds. From the culture filtrates of D. siccans, we isolated a new phytotoxic trisubstituted naphthofuroazepinone, named drazepinone, and characterised it as a 3,5,12a-trimethyl-2,5,5a,12a-tetrahydro-1H-naphtho[2',3':4,5]furo[2,3-b]azepin-2-one. Assayed at 2 microg microl(-1) solution the novel metabolite proved to have broad-spectrum herbicidal properties, without antibacterial and antifungal activities, and low zootoxic activity. Its original chemical structure and the interesting biological properties make drazepinone a potential natural herbicide.     

Vaccine-induced CD8+ central memory T cells in protection from simian AIDS

Critical to the development of an effective HIV vaccine is the identification of adaptive immune responses that prevent infection or disease. In this study we demonstrate in a relevant nonhuman primate model of AIDS that the magnitude of vaccine-induced virus-specific CD8(+) central memory T cells (T(CM)), but not that of CD8(+) effector memory T cells, inversely correlates with the level of SIVmac251 replication, suggesting their pivotal role in the control of viral replication. We propose that effective preventive or therapeutic T cell vaccines for HIV-1 should induce long-term protective central memory T cells.     

Hepatitis C virus drives the unconstrained monoclonal expansion of VH1-69-expressing memory B cells in type II cryoglobulinemia: a model of infection-driven lymphomagenesis

Chronic hepatitis C virus infection causes B cell lymphoproliferative disorders that include type II mixed cryoglobulinemia and lymphoma. This virus drives the monoclonal expansion and, occasionally, the malignant transformation of B cells producing a polyreactive natural Ab commonly encoded by the V(H)1-69 variable gene. Owing to their property of producing natural Ab, these cells are reminiscent of murine B-1 and marginal zone B cells. We used anti-Id Abs to track the stages of differentiation and clonal expansion of V(H)1-69(+) cells in patients with type II mixed cryoglobulinemia. By immunophenotyping and cell size analysis, we could define three discrete stages of differentiation of V(H)1-69(+) B cells: naive (small, IgM(high)IgD(high)CD38(+)CD27(-)CD21(high)CD95(-)CD5(-)), "early memory" (medium-sized, IgM(high)IgD(low)CD38(-)CD27(+)CD21(low)CD95(+)CD5(+)), and "late memory" (large-sized, IgM(low)IgD(low-neg)CD38(-)CD27(low)CD21(low-neg)CD5(-)CD95(-)). The B cells expanded in cryoglobulinemia patients have a "memory" phenotype; this fact, together with the evidence for intraclonal variation, suggests that antigenic stimulation by hepatitis C virus causes the unconstrained expansion of activated V(H)1-69(+) B cells. In some cases, these cells replace the entire pool of circulating B cells, although the absolute B cell number remains within normal limits. Absolute monoclonal V(H)1-69(+) B lymphocytosis was seen in three patients with cryoglobulinemia and splenic lymphoma; in two of these patients, expanded cells carried trisomy 3q. The data presented here indicate that the hepatitis C virus-driven clonal expansion of memory B cells producing a V(H)1-69(+) natural Ab escapes control mechanisms and subverts B cell homeostasis. Genetic alterations may provide a further growth advantage leading to an overt lymphoproliferative disorder.