Glucocerebrosidase (GCase) activity modulation by 2-alkyl trihydroxypiperidines: Inhibition and pharmacological chaperoning.

The enzyme glucocerebrosidase (GCase) has become an important therapeutic target due to its involvement in pathological disorders consequent to enzyme deficiency, such as the lysosomal storage Gaucher disease (GD) and the neurological Parkinson disease (PD). Pharmacological chaperones (PCs) are small compounds able to stabilize enzymes when used at sub-inhibitory concentrations, thus rescuing enzyme activity. We report the stereodivergent synthesis of trihydroxypiperidines alkylated at C-2 with both configurations, by means of the stereoselective addition of Grignard reagents to a carbohydrate-derived nitrone in the presence or absence of Lewis acids. All the target compounds behave as good GCase inhibitors, with IC50 in the micromolar range. Moreover, compound 11a behaves as a PC in fibroblasts derived from Gaucher patients bearing the N370/RecNcil mutation and the homozygous L444P mutation, rescuing the activity of the deficient enzyme by up to 1.9- and 1.8-fold, respectively. Rescues of 1.2-1.4-fold were also observed in wild-type fibroblasts, which is important for targeting sporadic forms of PD.

The persistent problem of late HIV diagnosis in people with AIDS: a population-based study in Italy, 1999-2013.

OBJECTIVES: Despite the wide accessibility to free human immunodeficiency virus (HIV) testing and combined antiretroviral therapy (cART), late HIV diagnosis remains common with severe consequences at individual and population level. This study aimed to describe trends of late HIV testing and to identify their determinants in the late cART era in Italy. STUDY DESIGN: We conducted a population-based, nationwide analysis of the Italian National AIDS Registry data (AIDS - acquired immune deficiency syndrome) for the years 1999-2013. METHODS: Late testers (LTs) were defined as people with AIDS (PWA) whose first HIV-positive test preceded AIDS diagnosis by 3 months or less. Odds ratios (ORs) with the corresponding 95% confidence intervals (CIs) were estimated to examine factors associated with being LTs. Joinpoint analysis was used to estimate annual percent changes (APCs) of LTs' proportion over time. RESULTS: Among 20,753 adult PWA, 50.8% were LTs. Italian PWA showed a lower proportion of LTs than non-Italian PWA (46.5% vs 68.2%). Among Italian PWA, the odds of being LTs was higher in men than in women (OR = 2.62, 95% CI: 2.38-2.90); in the age groups below 35 years and over 49 years at diagnosis (OR = 1.24, 95% CI: 1.12-1.37 and OR = 1.51, 95% CI: 1.38-1.67, respectively) vs PWA aged 35-49 years; and in those infected through sexual contact as compared with injecting drug use (OR = 13.34, 95% CI: 12.06-14.76 for heterosexual contact and OR = 8.13, 95% CI: 7.30-9.06 for male-to-male sexual contact). The proportion of LTs increased over time among Italians, especially in the latest period (APC2006-2013 = 5.3, 95% CI: 3.8-6.9). The LTs' proportion resulted higher, though stable, among PWA aged ≥50 years. Conversely, an increasing trend was observed among PWA aged 18-34 years (APC = 5.3, 95% CI: 4.5-6.1). The LTs' proportion was persistently higher among PWA who acquired HIV infection through sexual contact, even if a marked increase among injecting drug users was observed after 2005 (APC = 11.4, 95% CI: 5.7-17.5). CONCLUSIONS: The increasing trend of LTs' proportion in the late cART era highlights the need of new strategies tailored to groups who may not consider themselves to be at a high risk of infection. Active promotion of early testing and continuous education of infection, especially among young people, need to be implemented.

Making patient centered care a reality: a survey of patient educational programs in Italian Cancer Research and Care Institutes.

BACKGROUND: Educational intervention represents an essential element of care for cancer patients; while several single institutions develop their own patient education (PE) programs on cancer, little information is available on the effective existence of PE programs at the level of research and care institutes. In Italy such institutes--Istituti di Ricovero e Cura a Carattere Scientifico--are appointed by the Ministry of Health, and 11 (Cancer Research & Care Istitute-CRCI) of the 48 are specific for cancer on the basis of specific requirements regarding cancer care, research and education. Therefore, they represent an ideal and homogeneous model through which to investigate PE policies and activities throughout the country. The objective of this study was to assess PE activities in Italian CRCI. METHODS: We carried out a survey on PE strategies and services through a questionnaire. Four key points were investigated: a) PE as a cancer care priority, b) activities that are routinely part of PE, c) real involvement of the patients, and d) involvement of healthcare workers in PE activities. RESULTS: Most CRCI (85%) completed the survey. All reported having ongoing PE activities, and 4 of the 11 considered PE an institutional activity. More than 90% of CRCI organize classes and prepare PE handouts, while other PE activities (e.g., Cancer Information Services, mutual support groups) are less frequently part of institutional PE programs. Patients are frequently involved in the organization and preparation of educational activities on the basis of their own needs. Various PE activities are carried out for caregivers in 8 (73%) out of 11 institutes. Finally, health care workers have an active role in the organization of PE programs, although nurses take part in these activities in only half of CRCI and pharmacists are seldom included. CONCLUSIONS: The information arising from our research constitutes a necessary framework to identify areas of development and to design new strategies and standards to disseminate the culture of PE. This may ultimately help and stimulate the establishment of institutional integrated PE programs, including policies and interventions that can benefit a significant proportion of cancer patients.

Kaposi' s sarcoma in HIV-positive patients: the state of art in the HAART-era.

Kaposi's sarcoma (KS) is a multicentric angioproliferative cancer of endothelial origin typically occurring in the context of immunodeficiency, i.e. coinfection with Human Immonodeficiency Virus (HIV) or transplantation. The incidence of KS has dramatically decreased in both US and Europe in the Highly Active Antiretroviral Therapy (HAART) era. However, KS remains the second most frequent tumor in HIV-infected patients worldwide and it has become the most common cancer in Sub-Saharan Africa. In 1994, Yuan Chang et al discovered a novel γ-herpesvirus in biopsy specimens of human KS. Epidemiologic studies showed that KS-associated herpesvirus (KSHV) or human herpesvirus-8 (HHV-8) was the etiological agent associated with all subtypes of KS. KS has a variable clinical course ranging from very indolent forms to a rapidly progressive disease. HAART represents the first treatment step for slowly progressive disease. Chemotherapy (CT) plus HAART is indicated for visceral and/or rapidly progressive disease. The current understanding of KS as a convergence of immune evasion, oncogenesis, inflammation and angiogenesis has prompted investigators to develop target therapy, based on anti-angiogenic agents as well as metalloproteinase and cytokine signaling pathway inhibitors. These drugs may represent effective strategies for patients with AIDS-associated KS, which progress despite chemotherapy and/or HAART. In this review, we focus on the current state of knowledge on KSHV epidemiology, pathogenesis and therapeutic options.

Rumen microbial community and milk quality in Holstein lactating cows fed olive oil pomace as part in a sustainable feeding strategy.

The use of alternative feed ingredients from the Agro-industry could be an efficient tool to improve the sustainability of dairy cow production. Since the richness in polyphenols, olive oil pomace (OOP), produced during olive oil milling, seems a promising by-product to ameliorate milk's nutritional value. The aim of this study was to test the use of OOP produced by means of a new technology (biphasic with stone deprivation) in dairy cow feeding strategy to evaluate the effect on animal performances, rumen microbiota, biohydrogenation processes and milk quality by a multidisciplinary approach. Forty multiparous Italian-Friesian dairy cows, at middle lactation, were randomly allotted into two homogenous groups and fed respectively a commercial diet (CON) and the experimental diet (OOPD) obtained by adding OOP to CON as partial replacement of maize silage. The two diets were formulated to be isoproteic and isoenergetic. The same diets were tested also in an in vitro trial aimed to evaluate their rumen degradability (% DEG). The dietary supplementation with OOP did not affect DM intake, rumen % DEG and milk production. The milk's nutritional quality was improved by increasing several important functional fatty acids (FAs; i.e., linoleic acid, conjugated linoleic acid, oleic acid, vaccenic acid). This finding was related to a decrease in rumen liquor biohydrogenation rate of unsaturated FAs. The stochiometric relation between volatile FA production in the rumen and methanogenesis suggested that OOP lowers the methane potential production (CON = 0.050 mol/L vs OOPD = 0.024 mol/L, SEM = 0.005, P = 0.0011). Rumen microbiota and fungi community did not be strongly altered by OOP dietary inclusion because few bacteria were affected at the genus level only. Particularly, Acetobacter, Prevotellaceae_UCG-004, Prevotellaceae_UCG-001, Eubacterium coprostanoligenes, Lachnospira, Acetitomaulatum, Lachnospiraceae_NK3A20 group were more abundant with OOPD condition (P < 0.05). Data reported in this study confirm that the use of OOP in dairy cow feeding can be an interesting strategy to improve milk nutritional quality increasing functional FA content without compromising the rumen degradability of the diet or causing strong perturbation of rumen ecosystem and maintaining animal performances.

Exposure to animals and increased risk of marginal zone B-cell lymphomas of the ocular adnexae.

BACKGROUND: Ocular adnexal marginal zone B-cell lymphoma (OAMZL) has been associated with Chlamydophila psittaci, an infection that may be transmitted by carrier animals. However, it is still unclear whether exposure to animals affects the risk of OAMZL in comparison with other lymphoma histotypes. We therefore investigated the role of professional and/or domestic exposures to animals in the occurrence of OAMZL, as compared with other types of lymphoma. METHODS: A hospital-based case-control study was carried out on 43 consecutive OAMZL patients (cases) and 87 consecutive patients with nodal non-Hodgkin's lymphomas (NHLs; controls). Multiple logistic regression (MLR) odds ratios (ORs), and 95% confidence intervals (CIs) were used to estimate the association between exposures to animals and OAMZL risk. RESULTS: A higher proportion of cases reported a lifetime exposure to household animals (79.1% vs 64.4% among controls), with a non-statistical significant MLR-OR of 2.18 (95% CI: 0.85-5.62). The OAMZL cases more frequently reported a history of occupation in breeding and/or slaughtering than controls (34.9% vs 6.9%), with an overall increased risk of 7.69 (95%CI: 2.65-22.34). CONCLUSION: These results indicate that, compared with nodal NHLs, the risk of OAMZL is markedly increased by contact with animals, particularly by occupational exposures.

Antiblastic treatment, for solid tumors, during pregnancy: a crucial decision.

Cancer is the second leading cause of death during the reproductive years complicating between 0.02 percent and 0.1 percent of pregnancies. The incidence is expected to rise with the increase in age of childbearing. The most common types of pregnancy-associated cancers are: cervical cancer, breast cancer, malignant melanoma, Hodgkin's lymphoma, non-Hodgkin's lymphoma and ovarian cancer. The relatively rare occurrence of pregnancy-associated cancer precludes conducting large, prospective studies to examine diagnostic, management and outcome issues. The treatment of pregnancy-associated cancer is complex since it may be associated with adverse fatal effects. In pregnant patients diagnosed with cancer during the first trimester, treatment with multidrug anti-cancer chemotherapy is associated with an increased risk of congenital malformations, spontaneous abortions or fetal death, and therefore, should follow a strong recommendation for pregnancy termination. Second and third trimester exposure is not associated with teratogenic effect but increases the risk of intrauterine growth retardation and low birth weight. There are no sufficient data regarding the teratogenicity of most cytotoxic drugs. Almost all chemotherapeutic agents were found to be teratogenic in animals and for some drugs only experimental data exist. Moreover, no pharmacokinetic studies have been conducted in pregnant women receiving chemotherapy in order to understand whether pregnant women should be treated with different doses of chemotherapy. This article reviews the available data regarding the different aspects of the treatment of cancer during pregnancy.

Hepatocellular carcinoma in HIV positive patients.

Highly active antiretroviral therapy (HAART) has dramatically changed the natural history of HIV-1-infected patients leading to increased survival and a better quality of life. Hepatitis C virus (HCV) and hepatitis B virus (HBV) infections are common among HIV-1-infected subjects and represent the most important risk factors for hepatocellular carcinoma (HCC). Whether HIV plays a direct role in hepatocellular carcinoma (HCC) pathogenesis remains to be established.HCC clinical course depends on stage of cancer disease, performance status and comorbidities. Therapeutic options include liver transplantation, local antiblastic chemotherapy and biological drugs. In the HIV setting few data are available about treatment options. The increased longevity of patients with HIV imposes new strategies for prevention and therapeutic management of patients. The aim of this article is to provide an up-to-date review of HIV-related HCC in the HAART era.

MTHFR polymorphisms in gastric cancer and in first-degree relatives of patients with gastric cancer.

Two common mutations, 677 C-->T and a1298 A-->C, in the methylenetetrahydrofolate reductase gene (MTHFR) reduce the activity of MTHFR and folate metabolism. Familial aggregation in a variable but significant proportion of gastric cancer (GC) cases suggests the importance of genetic predisposition in determining risk. In this study, we evaluate MTHFR polymorphisms in 57 patients with a diagnosis of GC, in 37 with a history of GC in first-degree relatives (GC-relatives), and in 454 blood donors. Helicobacter pylori (HP) infection was also determined. An increased risk was found for 677TT in GC patients with respect to blood donors (odds ratio (OR) = 1.98), and statistical significance was sustained when we compared sex-age-matched GC patients and donors (OR = 2.37). The 677TT genotype association with GC was found in women (OR = 3.10), while a reduction in the 667C allele frequency was present in both the sex. No statistically significant association was detected when 677-1298 genotype was stratified by sex and age. Men of GC-relatives showed a higher 1298C allele frequency than donors (OR = 4.38). Between GC and GC-relatives, HP infection frequency was similar. In conclusion, overall findings support the hypothesis that folate plays a role in GC risk. GC-relatives evidence a similar 677TT frequency to that found in the general population.

Plasma HHV-8 viral load in HHV-8-related lymphoproliferative disorders associated with HIV infection.

This is a mono-institutional analysis of the clinical features, immunological and virological findings, and prognostic factors of patients with HIV infection and HHV-8-lymphoproliferative disorders. Patients with Multicentric Castleman Disease and HHV-8-related lymphoma diagnosed and treated from April 1987 to June 2004 were included in the study. HHV-8 and HIV plasma viral load, CD4+ count, hematologic parameters, and general wellbeing (performance status) were assessed at the onset of the diseases and analyzed in order to identify possible prognostic factors. Nine patients with Multicentric Castleman disease, and 16 with HHV-8-related lymphomas (13 primary effusion lymphomas and 3 solid lymphomas), were diagnosed and treated out of 327 HIV-related non-Hodgkin's lymphomas. Four patients with Multicentric Castleman disease received only antiretroviral drugs; 5 HAART plus oral etoposide. Nine patients with primary effusion lymphoma were treated with a CHOP-like regimen (Cyclophosphamide, Prednisone anthracyclines, Vinca alkaloids, Bleomycin, Etoposide) and HAART; 1 with etoposide and HAART, 1 with HAART alone. The patients with solid lymphoma underwent CHOP-like chemotherapy. Patients with Multicentric Castleman disease showed lower median values of HHV-8 viral load and longer overall survival compared with HHV-8-related lymphomas. Patients with viral load of HHV-8, >40,000 cp/ml had a significant shorter overall survival. In the univariate analysis, HHV-8-related lymphoma, HHV-8 viral load >40,000 cp/ml and performance status >2 were associated with an increased risk of death. Multivariate analysis confirmed the diagnosis of lymphoma as an independent predictor of shorter survival.

Long-term human B cell lines dependent on interleukin-4 and antibody to CD40.

CD40 is a 45- to 50-kilodalton transmembrane glycoprotein expressed on B lymphocytes, epithelial cells, and some carcinoma cell lines. Human resting B lymphocytes entered a state of sustained proliferation when incubated with both the mouse fibroblastic Ltk- cell line that had been transfected with the human Fc receptor (Fc gamma RII/CDw32) and monoclonal antibodies to CD40. In combination with interleukin-4, factor-dependent long-term normal human B cell lines were generated that were consistently negative for Epstein-Barr viral infection. Thus, cross-linking of CD40 is likely to represent an important phenomenon in the clonal expansion of B cells.

Honey extracts inhibit PTP1B, upregulate insulin receptor expression, and enhance glucose uptake in human HepG2 cells.

Honey is a food known for its medical properties. In this work, we have studied the impact of different types of honey on insulin signalling pathway. We found that honey extracts inhibit the enzyme PTP1B, one of the main negative regulators of insulin receptor signalling. HPLC-MS analysis allowed us to confirm the presence of several natural PTP1B inhibitors in the honey extracts analysed. Statistical analysis methods show a correlation between specific 1H-NMR resonance frequencies/HPLC peaks and the inhibitory power of the samples. This finding will allow the prediction of the biological properties of honey samples applying relative simple analytical methods. Finally, we demonstrated that the treatment of HepG2 cells with honey extracts enhances the expression of insulin receptor, and stimulates glucose uptake. For the first time, our results demonstrate that bioactive components of honey could improve glycaemic control by both inhibiting PTP1B and stimulating the expression of insulin receptor in liver cells.

Recent thymic emigrants in lymphoma patients with and without human immunodeficiency virus infection candidates for autologous peripheral stem cell transplantation.

Signal joint T cell receptor excision circles (sjTRECs) have been reported as a clinical marker to measure the potential for recovery of the immune system after immunosuppressive treatments. The aim of this study was to investigate the thymic regenerative potential in 55 human immunodeficiency virus (HIV)-1 infected (HIV(+)) and non-infected (HIV(-)) lymphoma patients, candidates for autologous stem cell transplantation (ASCT). Moreover, the possible associations between sjTRECs and other immunological and clinical parameters were examined. SjTRECs levels in peripheral blood mononuclear cells (PBMCs) were quantified by real-time polymerase chain reaction and T lymphocyte subsets were analysed by flow cytometry. Our data showed that sjTRECs were reduced in lymphoma patients compared to healthy controls, although a weak significant association between low sjTRECs levels and increasing age was maintained [odds ratio (OR) = 4.00; 95% confidence interval (CI) 1.09-17.17]. We found that different chemotherapeutic treatments seem to induce similar effects on the thymic reservoir, independently from their intensity (type and number of cycles of previous chemotherapy). Results from multivariate models including adjustment for patients' sex, type of lymphoma and type of chemotherapy showed that thymic output was independent from HIV infection (OR, 0.95; 95% CI 0.20-4.48). SjTRECs levels correlated with naive T cell subsets in overall lymphoma patients and after stratification by HIV infection (r > 0.37). HIV replication should be maximally suppressed to properly evaluate thymic output by sjTREC markers. Our results suggested that de novo T cell generation is maintained partially in pretreated recurrent lymphoma patients, candidates for ASCT, and could contribute to restore the immune function after transplantation.

Insulin inhibits platelet-derived growth factor-induced cell proliferation.

Cellular behavior can be considered to be the result of a very complex spatial and temporal integration of intracellular and extracellular signals. These signals arise from serum-soluble factors as well as from cell-substrate or cell-cell interactions. The current approach in mitogenesis studies is generally to analyze the effect of a single growth factor on serum-starved cells. In this context, a metabolic hormone such as insulin is found to be a mitogenic agent in many cellular types. In the present study, we have considered the effect of insulin stimulation in platelet-derived growth factor (PDGF)-activated NIH-3T3 and C2C12 cells. Our results show that insulin is able to inhibit strongly both NIH-3T3 and C2C12 cell growth induced by PDGF, one of the most powerful mitotic agents for these cell types. This inhibitory effect of insulin is due primarily to a premature down-regulation of the PDGF receptor. Thus, when NIH-3T3 or C2C12 cells are stimulated with both PDGF and insulin, we observe a decrease in PDGF receptor phosphorylation with respect to cells treated with PDGF alone. In particular, we find that costimulation with insulin leads to a reduced production of H2O2 with respect to cell stimulation with PDGF alone. The relative low concentration of H2O2 in PDGF/insulin-costimulated cell leads to a limited down-regulation of protein tyrosine phosphatases, and, consequently, to a reduced PDGF receptor phosphorylation efficiency. The latter is very likely to be responsible for the insulin-dependent inhibition of PDGF-receptor mitogenic signaling.

Targeted therapies and adverse drug reactions in oncology: the role of clinical pharmacist in pharmacovigilance.

Background The majority of adverse drug reactions (ADRs) reported in the summary of product characteristics (SPCs) are based on pivotal clinical trials, performed under controlled conditions and with selected patients. Objectives (1) to observe ADRs in the real-world setting and to evaluate if the supervision of the pharmacist impacts on the management of ADRs and on the satisfaction of patients; (2) to sensitise health professionals and patients on the need to increase the reporting of ADRs, in compliance with Pharmacovigilance. Setting CRO Aviano, Italian National Cancer Institute. Method From February 2013 to April 2015, we conducted an observational study enrolling 154 patients (≥ 18 years) undergoing treatment with at least one of ten targeted-therapies included in the study. Main outcome ADR reporting in the real-world setting. Patient satisfaction with clinical pharmacist support. Results Reported ADRs in the real setting do not always correspond with data described in the respective SPCs. Unknown ADRs were also identified such as hyperglycaemia with lenalidomide and sorafenib; and hypomagnesaemia with bevacizumab. We also observed a 124.3% increase in spontaneous reports. Conclusion This study shows the high value of active pharmacovigilance programs, and our results might be a starting point for developing a randomised trial which should aim to demonstrate the impact of the pharmacist on improving patient's adherence and in measuring the difference in ADRs reports in the different arms followed or not by the pharmacist.

Dynamics of HIV-1 mRNA expression in patients with long-term nonprogressive HIV-1 infection.

A large number of evidences indicate that progression of HIV disease is driven by an increase in viral burden. It is still unclear, however, to what extent this is contributed by the dysregulation of the molecular mechanisms governing virus gene expression at the transcriptional or posttranscriptional levels. To address this issue, several quantitative virologic parameters (including provirus transcriptional activity and splicing pattern) were analyzed in individuals with nonprogressive HIV infection and compared with those of a matched group of progressor patients. Exact quantification was achieved by a competitive PCR procedure using a multicompetitor template. Nonprogressors were characterized by striking differences in the levels of viremia, provirus copy number, and overall levels of all viral mRNA classes in peripheral blood mononuclear cells. Additionally, the transcriptional activity of the proviral DNA in these patients was mainly engaged in the production of multiprocessed transcripts, with a pattern resembling the early phases of the experimental infection. Taken together, these results show that both viral load and provirus transcription pattern are remarkably different in infected individuals nonprogressing toward overt disease, and further support the notion that disease progression is accompanied by a change in the kinetics of HIV gene expression.

Effects of subcutaneous interleukin-2 therapy on CD4 subsets and in vitro cytokine production in HIV+ subjects.

HIV infection is characterized by the reduction of the CD4+, CD45RA+, CD26+, and CD28+ lymphocyte subsets and of the in vitro production of IL-2, IL-4, and interferon-gamma; on the contrary, chemokine production is usually increased. These abnormalities are only partially restored by antiretroviral chemotherapy. Therapy with interleukin-2 has been proposed to restore the functions of the immune system, but the mechanisms by which IL-2 exerts its activities are unknown. The aim of this study was to define the effects of rIL-2 administration on CD4+, CD45RA+, CD45R0+, and CD26+ lymphocytes and on the in vitro production of IL-2, IL-4, IL-10, IFN-gamma, RANTES, and sCD30 in HIV+ patients. 10 HIV+ patients with CD4 cell counts between 200 and 500 cells/mm3 were treated with six cycles of subcutaneous recombinant IL-2 administration, in combination with zidovudine and didanosine. This therapeutic regimen resulted in a remarkable increase in the number of CD4+ cells and in the prolonged reduction of the levels of viremia. CD45R01 cells were expanded during the first cycle of therapy, while CD45RA+/CD26+ cells predominated after the third cycle. At this time, the in vitro production of IL-2, IL-4, IFN-gamma, and sCD30 were significantly upregulated. These results demonstrate that rIL-2 in HIV+ patients induces the reconstitution of the CD4/CD45RA lymphocytes subtype. This expanded cell population recovered the ability to produce in vitro IL-2, IL-4, and IFN-gamma. These effects may be beneficial to HIV+ patients by improving their immune response to microorganisms or vaccines.

Deposition of metallic silver coatings by Aerosol Assisted MOCVD using two new silver ß-diketonate adduct metalorganic precursors.

This work reports two new silver metalorganic precursors for the chemical vapor deposition of Ag metallic coatings. Both precursors are based on ß-diketonate adducts, namely, Ag(hfac)(L) (H-hfac = 1,1,1,5,5,5-hexafluoro-2,4-pentanedione), where L is 1,10-phenanthroline (phen) or 2,5,8,11-tetraoxadodecane (triglyme). Using these ligands, the designed precursors have better solubility in alcoholic solvents and are less toxic and costly than previously reported ones. The new precursors have been characterized and their crystallographic structure solved. With the new triglyme precursor, [Ag(triglyme)2]+[Ag(hfac)2]-, pure metallic Ag coatings made of Ag nanoparticles about 20 nm in diameter were succesfully deposited on glass and Si substrates using Aerosol Assisted Metalorganic CVD (AA-CVD).

Kaposi's Sarcoma Herpesvirus: twenty years after its discovery.

Twenty years after the discovery of Kaposi's Sarcoma Herpes Virus (KSHV), many aspects of the pathogenesis have been discovered and innovative approaches are presently applied to the diagnosis and treatment of KSHV associated diseases. The virus is coupled to different types of cancers, as well as to syndromes combined with increased inflammatory response or with immunoreconstitution in immunocompromised hosts. The etiopathological diagnosis of KSHV associated cancers relies on the demonstration of the virus in tumor samples, as well as in the peripheral blood of infected subjects. Novel treatment strategies related to the pathogenetic events of KSHV associated diseases have been recently studied, that are based on drugs able to induce oncolysis by promoting a viral lytic phase or on the blockade of v-IL6, a cytokine with tumor promoting activities. In addition, antiangiogenetic strategies have also been applied to treat KSHV associated cancers. Despite these important discoveries, some aspects of KSHV associated diseases are presently not completely clear and, consequently, response to treatment strategies is still suboptimal.

Immunophenotypic and molecular genetic characterization of a case of CD8+ B cell chronic lymphocytic leukemia.

We report the case of a patient with chronic B lymphocytic leukemia, with stable clinical and hematological conditions in the absence of any treatment. The flow cytometry analysis of the patient's cells revealed a CD19+, CD5+, IgM+, IgD+, lambda chain-phenotype, along with an unusual expression of CD8 alpha/alpha homodimer. B cells did not stain with the anti CD8 beta monoclonal antibody T8/2T8 5H7. Molecular biology analyses confirmed the monoclonal rearrangements of immunoglobulin heavy and lambda light chain genes in the presence of a germline configuration of T cell receptor genes. Moreover, an abnormal configuration of the CD8A gene was found in the CD8+B lymphocytic clone. We suggest that the aberrant expression of the CD8 gene could be related to its abnormal configuration.