Barbara Zechini

Bio: Barbara Zechini is an academic researcher from Sapienza University of Rome. The author has contributed to research in topics: Hepatitis C virus & Viral load. The author has an hindex of 8, co-authored 10 publications receiving 544 citations.

Hepatotoxicity development during antiretroviral therapy containing protease inhibitors in patients with HIV: the role of hepatitis B and C virus infection.

Abstract: To evaluate the occurrence of hepatotoxicity in patients during antiretroviral therapy (ART) that contains protease inhibitors and the role of hepatitis viruses in its development, we performed a retrospective study including 1325 HIV-infected patients treated with ART for at least 6 months. Presence or absence of hepatitis viruses, alanine aminotransferase (ALT), total bilirubin, CD4 cell count, and plasma HIV RNA levels were evaluated. Hepatotoxicity developed in a few study subjects without coinfection, whereas it was significantly higher in coinfected patients. Univariate logistic regression analysis showed that viral hepatitis coinfections are independent risk factors for hepatotoxicity. After 6 months of treatment, ritonavir was associated with higher rates of severe hepatotoxicity in the coinfected group; in fact, ritonavir seems to be the most strongly hepatotoxic agent among coinfected patients. After 12 months of therapy, hepatotoxicity occurred more frequently in patients with hepatitis C virus who did not respond to antiretroviral therapy (ART), whereas patients who did respond to ART showed decreased ALT levels. Hepatotoxicity is not exclusively an effect of drug toxicity, and the presence of hepatitis coinfection is an independent risk factor. Moreover, chronic hepatotoxicity mainly occurs in patients who did not respond to therapy. Conversely, patients who did respond to ART seemed to show improvement of chronic liver infection.

Inhibitors of multidrug resistant efflux systems in bacteria.

Abstract: Resistance of bacteria to many classes of antibiotics is an increasing problem worldwide. Multidrug resistance efflux pumps are recognized as an important component of resistance in both Gram-positive and Gram-negative bacteria. Some bacterial efflux pumps may be selective for one substrate, such as tetracycline, or transport antibiotics of different classes, conferring a multiple drug resistance (MDR) phenotype. Efflux pump inhibitors (EPIs) are promising therapeutic agents, as they should restore the activity of standard antibiotics. The efflux pump inhibitor-antibiotic combination is expected to increase the intracellular concentration of antibiotics that are expelled by efflux pumps, decrease the intrinsic bacterial resistance to antibiotics, reverse the acquired resistance associated with efflux pumps overexpression, and reduce the frequency of the emergence of resistant mutant strains. In recent years, different classes of EPIs have been described and tested, including analogues of antibiotic substrates and new molecules. This review focuses on the families of MDR efflux pumps, and on the current progress for the clinical use of EPIs. The present article is a good review of the recent patents related to efflux pump inhibitors.

Hymenolepis diminuta infection in a child living in the urban area of Rome, Italy.

Abstract: We report a case of Hymenolepis diminuta infection in an Italian child affected by tuberous sclerosis. Praziquantel is the drug of choice for the treatment of H. diminuta infection. However, considering the patient's neurological disease, we decided to use not praziquantel but niclosamide, which proved equally effective.

Correlation of serum aminotransferases with HCV RNA levels and histological findings in patients with chronic hepatitis C: the role of serum aspartate transaminase in the evaluation of disease progression.

Abstract: ObjectivesTo investigate whether HCV RNA levels can be considered to be predictors of hepatocellular injury in patients with chronic hepatitis C, and whether aminotransferase levels are markers of liver damage.MethodsWe performed a retrospective study on 112 patients with chronic hepatitis C. For ea

The Challenge of Efflux-Mediated Antibiotic Resistance in Gram-Negative Bacteria

Abstract: The global emergence of multidrug-resistant Gram-negative bacteria is a growing threat to antibiotic therapy. The chromosomally encoded drug efflux mechanisms that are ubiquitous in these bacteria greatly contribute to antibiotic resistance and present a major challenge for antibiotic development. Multidrug pumps, particularly those represented by the clinically relevant AcrAB-TolC and Mex pumps of the resistance-nodulation-division (RND) superfamily, not only mediate intrinsic and acquired multidrug resistance (MDR) but also are involved in other functions, including the bacterial stress response and pathogenicity. Additionally, efflux pumps interact synergistically with other resistance mechanisms (e.g., with the outer membrane permeability barrier) to increase resistance levels. Since the discovery of RND pumps in the early 1990s, remarkable scientific and technological advances have allowed for an in-depth understanding of the structural and biochemical basis, substrate profiles, molecular regulation, and inhibition of MDR pumps. However, the development of clinically useful efflux pump inhibitors and/or new antibiotics that can bypass pump effects continues to be a challenge. Plasmid-borne efflux pump genes (including those for RND pumps) have increasingly been identified. This article highlights the recent progress obtained for organisms of clinical significance, together with methodological considerations for the characterization of MDR pumps.

Drug-induced liver injury.

Abstract: Many drugs and environmental chemicals are capable of evoking some degree of liver injury. The liver represents a primary target for adverse drug reactions due to its central role in biotransformation and excretion of foreign compounds, its portal location within the circulation exposing it to a wide variety of substances, and its anatomic and physiologic structure. Drug-induced liver injury (DILI) remains the single most common adverse indication leading to drug candidate failure or withdrawal from the market. However, the absolute incidence of DILI is low, and this presents a challenge to mechanistic studies. DILI remains unpredictable making prevention very difficult. In this chapter, we focus on the current understanding of DILI. We begin with an overview regarding the significance and epidemiology of DILI and then examine the clinical presentation and susceptibility factors related to DILI. This is followed by a review of the current literature regarding the proposed pathogenesis of DILI, which involves the participation of a drug, or most often a reactive metabolite of the drug, that either directly affects cellular function or elicits an immune response. It is our hope that this chapter will shed light on the major problems associated with DILI in regards to the pharmaceutical industry, drug regulatory agencies, physicians and pharmacists, and patients.

Care of patients with chronic hepatitis B and HIV co-infection: recommendations from an HIV-HBV International Panel.

Abstract: Liver disease caused by chronic hepatitis B virus (HBV) infection is currently an important cause of morbidity and mortality among HIV-infected patients in the western world where classical opportunistic complications of severe immunodeficiency have declined dramatically as a result of the widespread use of potent antiretroviral therapies. Over the past few years several consensus reports have addressed the issue of viral hepatitis and HIV co-infection. However as a result of the larger impact of hepatitis C virus (HCV) they have focused mainly on HIV and HCV co-infection whereas only a few reports have devoted particular attention to hepatitis B. There are several reasons to highlight HBV in HIV positive individuals. (excerpt)

Bacterial Multidrug Efflux Pumps: Much More Than Antibiotic Resistance Determinants.

Abstract: Bacterial multidrug efflux pumps are antibiotic resistance determinants present in all microorganisms. With few exceptions, they are chromosomally encoded and present a conserved organization both at the genetic and at the protein levels. In addition, most, if not all, strains of a given bacterial species present the same chromosomally-encoded efflux pumps. Altogether this indicates that multidrug efflux pumps are ancient elements encoded in bacterial genomes long before the recent use of antibiotics for human and animal therapy. In this regard, it is worth mentioning that efflux pumps can extrude a wide range of substrates that include, besides antibiotics, heavy metals, organic pollutants, plant-produced compounds, quorum sensing signals or bacterial metabolites, among others. In the current review, we present information on the different functions that multidrug efflux pumps may have for the bacterial behaviour in different habitats as well as on their regulation by specific signals. Since, in addition to their function in non-clinical ecosystems, multidrug efflux pumps contribute to intrinsic, acquired, and phenotypic resistance of bacterial pathogens, the review also presents information on the search for inhibitors of multidrug efflux pumps, which are currently under development, in the aim of increasing the susceptibility of bacterial pathogens to antibiotics.

Care of patients coinfected with HIV and hepatitis C virus: 2007 updated recommendations from the HCV-HIV International Panel.

Abstract: Chronic hepatitis C (HCV) infection is currently oneof the most clinically relevant comorbidities in theHIV population; overall, it affects one third of HIV-positive individuals [1]. Progression to end-stage liverdisease occurs faster in coinfected patients [2–4] anddecompensated cirrhosis is one of the main causes ofhospitalization and death in this population [5–8].However, the risk of hepatotoxicity using antiretroviraldrugs is increased in subjects with underlying HCVinfection [9,10]. Therefore, the optimal managementof chronic HCV in HIV-positive patients is currentlyapriority.Several guidelines for caring for HCV infection in HIV-positive individuals have been released [11–15]. Becausenew and relevant information has recently appeared, it isconvenient to update them. Eleven areas have beenidentified in which new recommendations are particu-larly needed:management of patients with persistently normalaminotransferasesliver fibrosis assessment: when and howpredictors of response to anti-HCV therapy in coinfectedpatientsoptimal dosages of pegylated interferon (pegIFN) andribavirin (RBV)optimal duration of anti-HCV therapytreatment of non-responders and/or relapserscare of patients with end-stage liver diseasetreatment of acute HCV infection in HIV-infectedindividualsmanagement of patients with multiple hepatitis virusesinteractions between HCV medications and antiretroviraldrugshepatotoxicity of antiretroviral drugs.