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1.
Psychol Med ; 44(12): 2653-60, 2014 Sep.
Article in English | MEDLINE | ID: mdl-25055178

ABSTRACT

BACKGROUND: Sensitivity to punishment (SP) and sensitivity to reward (SR) are personality characteristics that may have relevance for the pathophysiology of eating disorders (EDs). Moreover, personality characteristics are known to modulate the activity of the hypothalamus-pituitary-adrenal (HPA) axis, which is the main component of the endogenous stress response system. As stress has been implicated in the aetiology and the maintenance of EDs, we aimed to study the HPA axis activity in relation to SP and SR, as conceptualized by Gray's reinforcement sensitivity theory (RST), in patients with anorexia nervosa (AN) or bulimia nervosa (BN). METHOD: Twenty-five women with AN, 23 women with BN and 19 healthy women volunteered for the study. HPA axis activity was assessed by measurement of the salivary cortisol awakening response (CAR). The subjects' SP and SR were measured by the behavioural inhibition system (BIS)/behavioural approach system (BAS) scales. RESULTS: The CAR was significantly enhanced in AN patients, but not in BN patients, compared to healthy women. The CAR correlated significantly with BAS measures, negatively in healthy controls and positively in binge-purging AN patients and BN women. SP, measured by the BIS scale, was higher in patients than in controls. CONCLUSIONS: These findings confirm the occurrence of an enhanced activity of the HPA axis in symptomatic AN, but not in symptomatic BN, and show for the first time that the CAR is associated with SR, as conceptualized by the RST, negatively in healthy subjects but positively in binge-purging ED patients.


Subject(s)
Anorexia Nervosa/metabolism , Bulimia Nervosa/metabolism , Hydrocortisone/metabolism , Personality/physiology , Punishment , Reward , Adult , Female , Humans , Young Adult
2.
Cell Death Dis ; 5: e993, 2014 Jan 16.
Article in English | MEDLINE | ID: mdl-24434516

ABSTRACT

Delayed neuronal cell death largely contributes to the progressive infarct development and associated functional impairments after cerebral ischemia or brain trauma. Previous studies exposed a key role for the interaction of the mitochondrial protein apoptosis-inducing factor (AIF) and cytosolic cyclophilin A (CypA) in pathways of programmed cell death in neurons in vitro and in vivo. These studies suggested that pro-apoptotic activities of AIF, such as its translocation to the nucleus and subsequent DNA degradation, depend on the physical interaction of AIF with CypA. Hence, this protein complex may represent a new pharmacological target for inhibiting the lethal action of AIF on the brain tissue. In this study, we show that the AIF amino-acid residues 370-394 mediate the protein complex formation of AIF with CypA. The synthetic AIF(370-394) peptide inhibited AIF/CypA complex formation in vitro by binding CypA with a K(D) of 12 µM. Further, the peptide exerted pronounced neuroprotective effects in a model of glutamate-induced oxidative stress in cultured HT-22 cells. In this model system of AIF-dependent cell death, the AIF(370-394) peptide preserved mitochondrial integrity, as detected by measurements of the mitochondrial membrane potential and quantification of mitochondrial fragmentation. Further, the AIF(370-394) peptide inhibited perinuclear accumulation of fragmented mitochondria, mitochondrial release of AIF to the nucleus and glutamate-induced cell death to a similar extent as CypA-siRNA. These data indicate that the targeting of the AIF-CypA axis is an effective strategy of neuroprotection.


Subject(s)
Apoptosis Inducing Factor/metabolism , Apoptosis , Cyclophilin A/metabolism , Neurons/cytology , Neurons/metabolism , Oxidative Stress , Amino Acid Motifs , Apoptosis Inducing Factor/chemistry , Apoptosis Inducing Factor/genetics , Cyclophilin A/genetics , Down-Regulation , Humans , Mitochondria/enzymology , Mitochondria/metabolism , Neurons/enzymology , Protein Binding
3.
Curr Med Chem ; 20(31): 3803-17, 2013.
Article in English | MEDLINE | ID: mdl-23895692

ABSTRACT

A variety of peptides active in biological pathways have been identified e.g. receptor antagonists or inhibitors of protein-protein interactions and several peptide or peptide-derived compounds are on the drug market or in clinical trials. Through the rational design or the combinatorial preparation and High-throughput screening of arrays of compounds, peptides play a pivotal role for the rapid identification of ligands, but, despite these favorable properties, they often present poorer bioavailability and lower metabolic stability respect to traditional drugs. The process of conversion of a peptide in a small molecule provides the reduction of the peptide to the minimum active sequence (MAS) testing truncated peptides from the C- and N- termini alternatively. Then the influence of individual amino acid on the biological activity is determined by systematically replacing each residue in the peptide with specific amino acids. After structure-activity relationship (SAR) of each amino acid in the sequence has been assessed, the bioactive conformational flexibility is reduced by introducing constraints at various positions. These features are used for the design of a pharmacophore model in which functional groups crucial for activity are pre-positioned. Here we propose a panoramic review of the common principles for the conversion of peptides into small organic molecules and the most interesting findings in peptide-based leads of the last decades.


Subject(s)
Drug Discovery , Peptides/chemistry , Amino Acid Sequence , Animals , Humans
4.
J Colloid Interface Sci ; 389(1): 220-9, 2013 Jan 01.
Article in English | MEDLINE | ID: mdl-23031494

ABSTRACT

There is a growing interest in identifying biomacromolecules such as proteins and peptides to functionalize metallic surfaces through noncovalent binding. One method for functionalizing materials without fundamentally changing their inherent structure is using biorecognition moieties. Here, we proved a general route to select a biomolecule adhesive motif for surface functionalization by comprehensively screening phage displayed peptides. In particular, we selected a genetically engineered M13 bacteriophage and a linear dodecapeptide derived from its pIII domain for recognizing gold surfaces in a specific and selective manner. In the phage context, we demonstrated the adhesive motif was capable to adsorb on gold in a preferential way with a morphological and viscoelastic signature of the adsorbed layer as evidenced by QCM-D and AFM investigations. Out of the phage context, the linear dodecapeptide is reproducibly found to adhere to the gold surface, and by quantitative SPR measurements, high affinity constants (K(eq)~10(6)M(-1), binding energy ~-8 kcal/mol) were determined. We proved that the interactions occurring at gold interface were mainly hydrophobic as a consequence of high frequency of hydrophobic residues in the peptide sequence. Moreover, by CD, molecular dynamics and steered molecular dynamics, we demonstrated that the molecular flexibility only played a minor role in the peptide adsorption. Such noncovalent but specific modification of inorganic surfaces through high affinity biomolecule adsorption represents a general strategy to modulate the functionality of multipurpose metallic surfaces.


Subject(s)
Bacteriophage M13/chemistry , Gold/chemistry , Peptide Library , Peptides/chemistry , Adsorption , Amino Acid Sequence , Bacteriophage M13/genetics , Bacteriophage M13/ultrastructure , Genetic Engineering , Hydrophobic and Hydrophilic Interactions , Surface Plasmon Resonance , Surface Properties
5.
Psychol Med ; 41(9): 1963-9, 2011 Sep.
Article in English | MEDLINE | ID: mdl-21284914

ABSTRACT

BACKGROUND: The stress response involves the activation of the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system (SNS). As a role for stress in determining of the onset and the natural course of eating disorders (EDs) has been proposed, the study of the psychobiology of the stress response in patients with anorexia nervosa (AN) and bulimia nervosa (BN) should be helpful in understanding the pathophysiology of these disorders. The two neurobiological components of the stress response can be easily explored in humans by the measurement of salivary cortisol and α-amylase response to a stressor. Therefore, we assessed salivary cortisol and α-amylase responses to the Trier Social Stress Test (TSST) in symptomatic patients with AN and BN compared to healthy controls. METHOD: Seven AN women, eight BN women and eight age-matched healthy females underwent the TSST between 1530 and 1700 h. Salivary cortisol and α-amylase levels were measured by an enzyme-linked immunosorbent assay (ELISA). RESULTS: Compared to healthy women, AN patients showed a normal cortisol response to the TSST, although this occurred at significantly increased hormone levels, and an almost complete absence of response of α-amylase. BN women, however, exhibited enhanced pre-stress levels of salivary α-amylase but a normal response of the enzyme and cortisol to the TSST. CONCLUSIONS: These findings demonstrate, for the first time, the occurrence of an asymmetry between the HPA axis and SNS components of the stress response in the acute phase of AN but not in BN. The pathophysiological significance of this asymmetry remains to be determined.


Subject(s)
Anorexia Nervosa/metabolism , Bulimia Nervosa/metabolism , Hydrocortisone/metabolism , Saliva/metabolism , Salivary alpha-Amylases/metabolism , Stress, Psychological/metabolism , Adult , Enzyme-Linked Immunosorbent Assay/methods , Female , Humans , Young Adult
6.
AIDS Care ; 20(4): 419-25, 2008 Apr.
Article in English | MEDLINE | ID: mdl-18449818

ABSTRACT

The prevalence of HIV/AIDS among people in midlife and late adulthood has been increasing in Western countries over the last decade. We analyzed data from a prospective, observational multi-centre study on individuals newly diagnosed with HIV between January 2004 and March 2007 in 10 public counselling and testing sites in Latium, Italy. At diagnosis, routine demographic, epidemiological, clinical and laboratory data are recorded, and patients are asked to complete a questionnaire investigating socio-demographic and psycho-behavioural aspects. To analyze the association of individual characteristics with age, we compared older adults (> or = 50 years) with their younger counterpart (18-49 years). To adjust for potential confounding effect of the epidemiological, clinical and behavioural characteristics, to identify factors associated with older age at HIV diagnosis, multivariate logistic regression analysis was performed. Overall, 1073 individuals were identified, 125 of whom (11.6%) were aged 50 years or above. The questionnaire was completed by 41% (440/1073). Compared with their younger counterparts, a higher proportion of older patients were males, born in Italy, reported heterosexual or unknown HIV risk exposure, were never tested for HIV before and were in a more advanced stage of HIV infection at diagnosis. In addition, older adults had a lower educational level and were more frequently living with their partners or children. With respect to psycho-behavioural characteristics, older patients were more likely to have paid money for sex and have never used recreational drugs. Interestingly, no differences were found regarding condom use, which was poor in both age groups. These findings may have important implications for the management of older adults with HIV, who should be targeted by appropriate public health actions, such as opportunistic screening and easier access to healthcare. Moreover, strategies including information on HIV and prevention of risk behaviours are needed.


Subject(s)
Aging/psychology , HIV Infections/psychology , Adolescent , Adult , Aged , Aged, 80 and over , Female , HIV Infections/diagnosis , HIV Infections/epidemiology , Health Knowledge, Attitudes, Practice , Humans , Italy/epidemiology , Male , Middle Aged , Multivariate Analysis , Prospective Studies , Risk Factors , Risk-Taking , Sexual Behavior/psychology , Surveys and Questionnaires
7.
Infection ; 33(2): 61-5, 2005 Apr.
Article in English | MEDLINE | ID: mdl-15827872

ABSTRACT

BACKGROUND: HIV spread among low-risk populations through heterosexual intercourse is a major public health concern. This study was aimed at describing prevalence and determinants of HIV infection among Italian low-risk subjects seeking their first lifetime HIV test. PATIENTS AND METHODS: Information collected between January 1990 and December 2000 at a major counseling and testing site in Rome, Italy, was analyzed. Multiple logistic regression odds ratios (OR) and 95% confidence intervals (CI) were computed. RESULTS: Among the 14,313 study subjects, 64 (0.4%) were seropositive for HIV infection. HIV seropositivity increased with age (OR = 4.0, 95% CI: 2.1-7.6 for >/= 40 years vs 18-24), and it seemed to be more common among men (OR = 1.6, lower 95% CI:0.9). There was no evidence of temporal variations, whereas motivations for HIV testing were strongly associated with HIV prevalence. Testing for alarming symptoms (OR = 13.8) or for heterosexual intercourse (OR = 11.0) were associated with a more than 10-fold increased HIV risk. CONCLUSION: Our findings are consistent with data from other industrialized countries and they show a strong association between HIV seropositivity and reason for first-time testing. Moreover, they indicate a stable trend of HIV prevalence among low-risk persons in the last decade. Further studies on time trends in low-risk populations would be useful to evaluate current HIV prevention programs.


Subject(s)
HIV Infections/epidemiology , Adolescent , Adult , Female , Humans , Male , Odds Ratio , Prevalence , Risk Factors , Rome/epidemiology
8.
J Biol Regul Homeost Agents ; 15(3): 224-8, 2001.
Article in English | MEDLINE | ID: mdl-11693428

ABSTRACT

Viral infections represent one of the areas in which cancer research has made the greatest advances in the last 20 years. In 1981, only two viruses were known to cause human cancer, i.e., the Epstein-Barr virus (EBV) and the hepatitis B virus (HBV). By 1995, it was estimated that approximately 15% of all cancers occurring world-wide were attributable to viral infections, and the oncogenic role of seven viruses [i.e., EBV, HBV, hepatitis C virus (HCV), human papillomavirus (HPV), human immunodeficiency virus (HIV), human herpesvirus-8 (HHV-8), and human T cell leukemia virus type I (HTLV-I)] has been well-established. In this paper, the epidemiological evidence concerning some of the major aspects of the association between viruses and cancer are summarised.


Subject(s)
Neoplasms/etiology , Virus Diseases/complications , Epstein-Barr Virus Infections/complications , HIV Infections/complications , Hepatitis B/complications , Hepatitis C/complications , Humans , Papillomaviridae , Papillomavirus Infections/complications
9.
Dig Liver Dis ; 33(9): 795-802, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11838616

ABSTRACT

Recommendations are made for controlling the transmission of the hepatitis B and hepatitis C viruses from healthcare workers to patients. These recommendations were based both on the literature and on experts' opinions, obtained during a Consensus Conference. The quality of the published information and of the experts' opinions was classified into 6 levels, based on the source of the information. The recommendations can be summarised as follows: all healthcare workers must undergo hepatitis B virus vaccination and adopt the standard measures for infection control in hospitals; healthcare workers who directly perform invasive procedures must undergo serological testing and the evaluation of markers of viral infection. Those found to be positive for: 1) HBsAg and HBeAg, 2) HBsAg and hepatitis B virus DNA, or 3) anti-hepatitis C virus and hepatitis C virus RNA must abstain from directly performing invasive procedures; no other limitations in their activities are necessary. Infected healthcare workers are urged to inform their patients of their infectious status, although this is left to the discretion of the healthcare worker; whose privacy is guaranteed by law. If exposure to hepatitis B virus occurs, the healthcare worker must undergo prophylaxis with specific immunoglobulins, in addition to vaccination.


Subject(s)
Allied Health Personnel/standards , Hepatitis B/transmission , Hepatitis C/transmission , Infection Control/standards , Infectious Disease Transmission, Professional-to-Patient/prevention & control , Occupational Diseases/prevention & control , Risk Management , Algorithms , Hepatitis B/diagnosis , Hepatitis B/prevention & control , Hepatitis B Surface Antigens , Hepatitis C/diagnosis , Hepatitis C/prevention & control , Humans , Serologic Tests , Vaccination
10.
Ann N Y Acad Sci ; 946: 291-309, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11762993

ABSTRACT

Health care workers (HCWs) face a well-recognized risk of acquiring blood-borne pathogens in their workplace, in particular hepatitis B and C viruses (HBV/HBC) and human immunodeficiency virus (HIV). Additionally, infected HCWs performing invasive exposure-prone procedures, including in the cardiac setting, represent a potential risk for patients. An increasing number of infected persons could need specific cardiac diagnostic procedures and surgical treatment in the future, regardless of their sex or age. The risk of acquiring HIV, HCV, HBV infection after a single at-risk exposure averages 0.5%, and 1-2%, and 4-30%, respectively. The frequency of percutaneous exposure ranges from 1 to 15 per 100 surgical interventions, with cardiothoracic surgery reporting the highest rates of exposures; mucocutaneous contamination by blood-splash occurs in 50% of cardiothoracic operations. In the Italian Surveillance (SIROH), a total of 987 percutaneous and 255 mucocutaneous exposures were reported in the cardiac setting; most occurred in cardiology units (46%), and in cardiovascular surgery (44%). Overall, 257 source patients were anti-HCV+, 54 HBsAg+, and 14 HIV+. No seroconversions were observed. In the literature, 14 outbreaks were reported documenting transmission of HBV from 12 infected HCWs to 107 patients, and 2 cases of HCV to 6 patients, during cardiothoracic surgery, especially related to sternotomy and its suturing. The transmission rate was estimated to be 5% to 13% for HBV, and 0.36% to 2.25% for HCV. Strategies in risk reduction include adequate surveillance, education, effective sharps disposal, personal protective equipment, safety devices, and innovative technology-based intraoperative procedures.


Subject(s)
Blood-Borne Pathogens , HIV Infections/transmission , Health Personnel , Hepatitis B/transmission , Hepatitis C/transmission , Infectious Disease Transmission, Patient-to-Professional , Infectious Disease Transmission, Professional-to-Patient , Occupational Diseases/etiology , Cardiomyopathies/complications , HIV Infections/complications , Hepatitis B/complications , Hepatitis C/complications , Humans , Italy , Occupational Exposure , Risk Factors
11.
Int Immunol ; 12(5): 711-9, 2000 May.
Article in English | MEDLINE | ID: mdl-10784617

ABSTRACT

To understand the mechanisms underlying spontaneous remission of proteolipid protein (PLP) 139-151 peptide-induced experimental allergic encephalomyelitis (EAE), an acute autoimmune disease of SJL mice resembling human multiple sclerosis, we examined both the effector response site in the central nervous system (CNS) and the immunization site at different phases of the disease. In the CNS, the frequency of PLP 139-151 peptide-specific IFN-gamma-producing T cells as well as the amount of infiltrating CD4(+) and CD11b(+) cells decreased with recovery. However, IL-4-producing cells were always rare and cyclooxygenase-2(+) cells were numerous only at disease peak in the CNS, suggesting that T(h)2 cytokines and prostaglandins did not determine remission of EAE. By looking at the s.c. site of PLP 139-151 peptide plus adjuvant injection, we found that, although the inflammatory infiltrate was abundant, CD11b(+) cells started to decrease already during disease acute phase and DEC-205(+) cells were numerous only at early time points. We propose that immunization site inflammation is short-lived in PLP 139-151 peptide-induced EAE, and this leads to a temporary autoreactive T cell stimulation and to a self-limited disease.


Subject(s)
Antigens, CD , Encephalomyelitis, Autoimmune, Experimental/immunology , Lectins, C-Type , Acute Disease , Animals , CD11 Antigens/analysis , CD4 Antigens/analysis , Central Nervous System/immunology , Cyclooxygenase 2 , Disease Models, Animal , Encephalomyelitis, Autoimmune, Experimental/chemically induced , Female , Immunization , Immunoenzyme Techniques , Immunohistochemistry , Interferon-gamma/analysis , Interleukin-4/analysis , Isoenzymes/analysis , Membrane Glycoproteins/analysis , Mice , Minor Histocompatibility Antigens , Myelin Proteolipid Protein , Peptide Fragments , Prostaglandin-Endoperoxide Synthases/analysis , Receptors, Cell Surface/analysis , Skin/immunology , Spinal Cord/immunology , Time Factors
12.
J Immunol ; 162(11): 6681-9, 1999 Jun 01.
Article in English | MEDLINE | ID: mdl-10352286

ABSTRACT

CTL responses against multiple hepatitis C virus (HCV) epitopes were detected in 7 of 29 (24.1%) healthy family members (HFM) persistently exposed to chronically HCV-infected patients (HCV-HFM). These precursor CTL were at very low or undetectable frequencies, as determined by limiting dilution analysis. However, when HCV-specific effector CD8+ T cells, freshly isolated from PBMC of HCV-HFM, were assessed by a sensitive enzyme-linked immunospot assay, their frequencies were severalfold higher than those of precursor CTL. These results indicate that the two assays detect two functionally distinct T cell populations and that the effector cells are not assayed by the 51Cr-release assay. Furthermore, the combination of cell depletion and enzyme-linked immunospot analyses showed that the effector cells were confined into a CD8+ CD45RO+ CD28- population. The persistence of effector CD8+ T cells specific for both the structural and nonstructural viral proteins in uninfected HCV-HFM, suggest that: 1) an immunological memory is established upon a subclinical infection without any evidence of hepatitis, in a large cohort of HCV-exposed individuals; 2) because these cells required neither restimulation nor the addition of particular cytokines in vitro for differentiating in effectors, they should be capable of prompt HCV-specific effector function in vivo, possibly providing antiviral protection; and 3) the maintenance of effector T cell responses may be sustained by persisting low-level stimulation induced by inapparent infections.


Subject(s)
Hepacivirus/immunology , Hepatitis C Antibodies/blood , T-Lymphocytes, Cytotoxic/immunology , Adolescent , Adult , Aged , Antigen Presentation , CD28 Antigens/analysis , Cell Line , Cell Separation , Cytotoxicity Tests, Immunologic , Epitopes, T-Lymphocyte/biosynthesis , Epitopes, T-Lymphocyte/metabolism , Female , HLA-A2 Antigen/immunology , HLA-A2 Antigen/metabolism , Hepatitis C Antigens/biosynthesis , Hepatitis C Antigens/metabolism , Humans , Leukocyte Common Antigens/analysis , Leukocytes, Mononuclear/immunology , Lymphocyte Activation , Lymphocyte Count , Male , Middle Aged , Oligopeptides/immunology , Oligopeptides/metabolism , Stem Cells/immunology , T-Lymphocyte Subsets/immunology , T-Lymphocytes, Cytotoxic/metabolism
13.
J Clin Invest ; 102(5): 968-75, 1998 Sep 01.
Article in English | MEDLINE | ID: mdl-9727065

ABSTRACT

High viral and/or antigen load may be an important cause of the T cell hyporesponsiveness to hepatitis B virus (HBV) antigens that is often observed in patients with chronic HBV infection. Reduction of viral and antigen load by lamivudine treatment represents an ideal model for investigating this hypothesis. HLA class II restricted T cell responses and serum levels of HBV-DNA, HBsAg, and HBeAg were studied before and during lamivudine treatment in 12 patients with hepatitis B e antigen positive chronic active hepatitis B to assess possible correlations between viral and/or antigen load and vigor of the T cell response. Cell proliferation to HBV nucleocapsid antigens and peptides and frequency of circulating HBV nucleocapsid-specific T cells were assessed to characterize CD4-mediated responses. A highly significant enhancement of the CD4-mediated response to HBV nucleocapsid antigens was already detectable in most patients 7-14 d after the start of lamivudine treatment. This effect was dramatic and persistent in 10 patients but undetectable in 2. It occurred concomitant with a rapid and marked reduction of viremia. Interestingly, lamivudine also enhanced the responses to mitogens and recall antigens, showing that its effect was not limited to HBV-specific T cells. In conclusion, an efficient antiviral T cell response can be restored by lamivudine treatment in patients with chronic hepatitis B concurrently with reduction of viremia, indicating the importance of viral load in the pathogenesis of T cell hyporesponsiveness in these patients. Since lamivudine treatment can overcome T cell hyporeactivity, combining lamivudine with treatments directed to stimulate the T cell response may represent an effective strategy to induce eradication of chronic HBV infection.


Subject(s)
CD4-Positive T-Lymphocytes/immunology , Hepatitis B/immunology , Hepatitis, Chronic/drug therapy , Lamivudine/therapeutic use , Adult , Antiviral Agents/therapeutic use , Cell Division/immunology , DNA, Viral/blood , Female , Hepatitis B Surface Antigens/blood , Hepatitis B e Antigens/blood , Humans , Male
14.
Recent Results Cancer Res ; 154: 330-6, 1998.
Article in English | MEDLINE | ID: mdl-10027013

ABSTRACT

Cell-mediated immune responses to hepatitis B (HBV) and hepatitis C virus (HCV) antigens are vigorous and multispecific in acute, self-limited infections. Moreover, the prevalent cytokine pattern of circulating virus-specific T cells from patients who recover spontaneously from acute hepatitis is Th1-like. Longitudinal analysis of the T cell response to HCV antigens from the early stages of HCV infection in patients who recover from hepatitis and those who do not indicates that weaker responses and a prevalent Th2 pattern of cytokine production is associated with viral persistence and chronic evolution of disease. Although similar sequential studies are missing in hepatitis B, the observation that HBV-specific T cell responses are very weak or totally undetectable in the peripheral blood of patients with long-lasting chronic hepatitis B suggests that strength and quality of virus-specific T cell responses at the early stages of infection may influence the final outcome of both hepatitis B and C. While T cell hyporesponsiveness seems to be an important determinant for HBV persistence once chronic hepatitis has developed, this mechanism appears to be less critical in chronic HCV infection, because the vigor and quality of HCV-specific T cell responses seem to improve as a function of the duration of infection. This is shown by the finding that HCV-specific CD4- and CD8-mediated responses are easily detectable in the peripheral blood of patients with long-lasting chronic hepatitis C and that production of Th1 cytokines predominates within their livers. HCV therefore seems to be able to persist even in the face of an active T cell response and to acquire the capacity to survive within a host environment apparently unfavorable to its persistence. The high variability of HCV may explain its efficiency in escaping immune surveillance.


Subject(s)
Hepatitis B/immunology , Hepatitis C/immunology , T-Lymphocytes/immunology , Humans , Immunity, Cellular , T-Lymphocytes, Cytotoxic/immunology
15.
J Am Coll Cardiol ; 30(4): 947-54, 1997 Oct.
Article in English | MEDLINE | ID: mdl-9316523

ABSTRACT

OBJECTIVES: The present study examined whether angina 48 h before myocardial infarction provides protection in adult and elderly patients. BACKGROUND: The mortality rate for coronary artery disease is greater in elderly than in young patients. In experimental studies, ischemic preconditioning affords an endogenous form of protection against ischemia-reperfusion injury in adult but not in senescent hearts. Angina before myocardial infarction, a clinical equivalent of experimental ischemic preconditioning, has a protective effect in adult patients. It is not known whether angina before myocardial infarction is also protective in aged patients. METHODS: We retrospectively verified whether antecedent angina within 48 h of myocardial infarction exerts a beneficial effect on in-hospital outcomes in adult (< 65 years old, n = 293) and elderly (> or = 65 years old, n = 210) patients. RESULTS: In-hospital death was more frequent in adult patients without than in those with previous angina (10% vs. 2.6%, p < 0.01), as were congestive heart failure or shock (10.7% vs. 3.3%, p < 0.02) and the combined end points (in-hospital death and congestive heart failure or shock) (20.7% vs. 5.9%, p < 0.0003). In contrast, the presence or absence of previous angina before acute myocardial infarction in elderly patients seems not to influence the incidence of in-hospital death (14.4% vs. 15.2%, p = 0.97), congestive heart failure or shock (11.0% vs. 11.9%, p = 0.99) and the combined end points (25.4% vs. 27.1%, p = 0.89). Logistic regression analysis models for in-hospital end points show that previous angina is a positive predictor in adult but not in elderly patients. CONCLUSIONS: The presence of angina before acute myocardial infarction seems to confer protection against in-hospital outcomes in adults; this effect seemed to be less obvious in elderly patients. This study suggests that the protection afforded by angina in adult patients may involve the occurrence of ischemic preconditioning, which seems to be lost in senescent patients.


Subject(s)
Aging/physiology , Angina Pectoris/complications , Ischemic Preconditioning, Myocardial , Myocardial Infarction/etiology , Adult , Age Factors , Aged , Female , Heart Failure/etiology , Hospital Mortality , Humans , Incidence , Logistic Models , Male , Middle Aged , Myocardial Infarction/mortality , Myocardial Infarction/prevention & control , Predictive Value of Tests , Retrospective Studies , Shock, Cardiogenic/etiology , Time Factors
16.
Minerva Ginecol ; 49(5): 225-8, 1997 May.
Article in Italian | MEDLINE | ID: mdl-9304085

ABSTRACT

The authors present one personal case of paraurethral acquired cyst (Skene's cyst) during pregnancy, presenting symptoms of micturitional obstruction. Clinical behaviour during pregnancy, labour induction and surgical ablation of the cyst during puerperium are illustrated. Differential diagnosis is analyzed. The advantages of proposed surgical techniques are discussed: agobiopsy, marsupialization, surgical ablation. Eventually the authors determine which is the most suitable therapeutic option during pregnancy.


Subject(s)
Cysts/diagnosis , Pregnancy Complications/diagnosis , Urethral Diseases/diagnosis , Adult , Cysts/pathology , Cysts/surgery , Diagnosis, Differential , Female , Humans , Pregnancy , Pregnancy Complications/pathology , Pregnancy Complications/surgery , Pregnancy Trimester, Third , Urethra/pathology , Urethra/surgery , Urethral Diseases/pathology , Urethral Diseases/surgery
17.
Ann Ital Med Int ; 12(2): 63-6, 1997.
Article in Italian | MEDLINE | ID: mdl-9333315

ABSTRACT

Up to the present, pancreatic complications due to cryptosporidium parvum infection have been described only in a few patients with acquired immunodeficiency syndrome (AIDS). We report our experience with 3 subjects with AIDS who presented with acute or chronic pancreatitis related to cryptosporidiosis. All 3 patients had abdominal pain resistant to analgesics, increased serum amylase and abnormalities at both sonography and computed tomography. Endoscopic retrograde cholangiopancreotography revealed papillary stenosis in all patients; one patient also had stenosis of the Wirsung duct. Cryptosporidium was found in both bile and stool samples in all patients, while viral cultures were negative, even in the 2 patients who had cytomegalovirus retinitis. Endoscopic sphincterotomy temporally relieved abdominal pain in all patients, but did not prevent either acute or recurrent pancreatic inflammation. Several antibiotic therapeutic protocols were ineffective against the parasite.


Subject(s)
AIDS-Related Opportunistic Infections/complications , Cryptosporidiosis/complications , Cryptosporidium parvum , Pancreatitis/etiology , AIDS-Related Opportunistic Infections/diagnosis , AIDS-Related Opportunistic Infections/drug therapy , Adult , Animals , Anti-HIV Agents/therapeutic use , Bile/microbiology , Cholangiopancreatography, Endoscopic Retrograde , Cryptosporidiosis/diagnosis , Cryptosporidiosis/drug therapy , Cryptosporidium parvum/isolation & purification , Feces/microbiology , Humans , Male , Pancreatitis/diagnosis , Pancreatitis/surgery , Recurrence , Sphincterotomy, Endoscopic
18.
J Chemother ; 8(1): 63-6, 1996 Feb.
Article in English | MEDLINE | ID: mdl-8835112

ABSTRACT

The aim of this randomized, comparative, double-blind study was to determine the efficacy of zidovudine (ZVD) either alone or in combination with recombinant granulocyte-colony stimulating factors (rG-CSF) and erythropoietin (Epo) in asymptomatic HIV-infected subjects with a CD4+ cell count < 500/mm3, classified as CDC II stage. We recruited 20 HIV Ab+ asymptomatic patients who were randomized into two groups: A and B. Group A was treated with ZVD at the dosage of 500 mg daily in combination with rG-CSF (10 micrograms/Kg/biweekly) and Epo (50 IU/Kg/biweekly). Group B was treated with ZVD (500 mg/day) alone. The primary end-point was progression to an AIDS-defining event and the secondary end-point included changes in the CD4+ cell count, p24 Ag status, beta-2-microglobulin, and ferritin levels. The patients of Group A showed no significant changes in transaminase, ferritin and beta-2-microglobulin levels while CD4 cells, Hb and neutrophil levels increased significantly compared to Group B (p < 0.001) and baseline values (p < 0.05). Conversely, 5 patients in Group B showed a significant decrease in CD4 cells (p < 0.01), Hb and neutrophil levels (p < 0.01) compared to baseline values, while beta-2-microglobulin increased (p < 0.05) compared to initial values. Our preliminary study may indicate that the combination of zidovudine with these hematopoietic growth factors could reduce the possibility of virus-related hematologic toxicity and could be more efficacious than zidovudine alone in prolonged therapy.


Subject(s)
Antiviral Agents/therapeutic use , Erythropoietin/therapeutic use , Granulocyte Colony-Stimulating Factor/therapeutic use , HIV Infections/drug therapy , HIV Seropositivity/drug therapy , Reverse Transcriptase Inhibitors/therapeutic use , Zidovudine/therapeutic use , Adult , CD4 Lymphocyte Count/drug effects , CD4-Positive T-Lymphocytes/drug effects , Double-Blind Method , Drug Therapy, Combination , Erythropoietin/administration & dosage , Female , Granulocyte Colony-Stimulating Factor/administration & dosage , HIV Infections/immunology , HIV Seropositivity/immunology , Humans , Male , Recombinant Proteins/therapeutic use , Zidovudine/administration & dosage
19.
J Gerontol A Biol Sci Med Sci ; 50A(1): M23-7, 1995 Jan.
Article in English | MEDLINE | ID: mdl-7814785

ABSTRACT

BACKGROUND: We studied the effects of age and hypertension on responses to chronotropic dose (CD25) and standing-induced changes in the ratio of electrical systole (QT) to electromechanical systole (QS2) in order to identify their role on beta adrenoceptor sensitivity and to verify the value of QT/QS2 ratio as a noninvasive parameter of beta-adrenoceptor sensitivity. METHODS: We enrolled 33 normal subjects and 37 hypertensive patients (WHO stage I and II) (age range 21-82 years). RESULTS: CD25 was significantly age-related in normotensive and hypertensive subjects, whereas standing-induced QT/QS2 changes were age-related in normotensive subjects only When we divided subjects into three age groups, beta-adrenoceptor sensitivity was found to be lower in hypertensives than normotensives in the two groups under age 60, but was not affected in those over age 60. This suggests that hypertension influences beta-adrenoceptor sensitivity in younger subjects, but not in elderly patients, whose beta-adrenoceptor sensitivity is already reduced. CONCLUSIONS: CD25 does not predict standing-induced QT/QS2 ratio changes; therefore, during autonomic stimulation, QT/QS2 ratio seems not to be significantly related to beta adrenergic sensitivity.


Subject(s)
Aging/physiology , Electrocardiography , Heart Rate/drug effects , Hypertension/physiopathology , Isoproterenol/pharmacology , Receptors, Adrenergic, beta/physiology , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Posture , Receptors, Adrenergic, beta/drug effects , Stimulation, Chemical
20.
Arch Gerontol Geriatr ; 20(1): 63-8, 1995.
Article in English | MEDLINE | ID: mdl-15374258

ABSTRACT

Congestive heart failure (CHF) represents the most frequent cause of death and disability in the elderly. The prevalence of impairment of cognitive abilities is very high in aging and several clinical studies have demonstrated high association between cardiovascular diseases (in particular CHF) and cognitive deterioration. However, little attention has been paid to the decline of cognitive functioning during congestive heart failure in elderly patients. In this paper an overview of studies investigating this association is offered, suggesting that hemodynamic alterations due to heart failure and cognitive deteriorations are very frequently associated in aging, increasing morbidity and mortality risks. Moreover, preliminary results of a prospective study on hospitalized elderly patients with heart disease are reported (CHF Italian Study). These data show that some psychosocial variables (illiteracy, depression, and particularly cognitive deterioration) determine a significant increase of the risk to develop heart failure. This paper confirms that a multidimensional approach is necessary to better characterize and treat elderly patients, in particular those with CHF. More attention should be paid to encourage mild physical activity, to provide emotional support to patients and also to assess their general cognitive abilities. Studies on large populations of patients with heart disease have to be designed to investigate psychosocial and cognitive status in these patients.

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