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Introduction Hereditary angioedema due to C1-inhibitor deficiency (C1-INH-HAE type I) or dysfunction (C1-INH-HAE type II) is a rare disease characterized by recurrent episodes of edema with an estimated frequency of 1:50,000 in the global population without racial or gender differences. In this study we present the results of a nationwide survey of C1-INH-HAE patients referring to 17 Italian centers, the Italian network for C1-INH-HAE, ITACA. Methods Italian patients diagnosed with C1-INH-HAE from 1973 to 2013 were included in the study. Diagnosis of C1-INH-HAE was based on family and/or personal history of recurrent angioedema without urticaria and on antigenic and/or functional C1-INH deficiency. Results 983 patients (53% female) from 376 unrelated families were included in this survey. Since 1973, 63 (6%) patients diagnosed with C1-INH-HAE died and data from 3 patients were missing when analysis was performed. Accordingly, the minimum prevalence of HAE in Italy in 2013 is 920:59,394,000 inhabitants, equivalent to 1:64,935. Compared to the general population, patients are less represented in the early and late decades of life: men start reducing after the 5 th decade and women after the 6 th . Median age of patients is 45 (IQ 28-57), median age at diagnosis is 26 years (IQ 13-41). C1-INH-HAE type 1 are 87%, with median age at diagnosis of 25 (13-40); type 2 are 13% with median age at diagnosis of 31 (IQ 16-49). Functional C1INH is ≤50% in 99% of patients. Antigen C1INH is ≤50% in 99% of type 1. C4 is ≤50% in 96% of patients. The chance of having C1-INH-HAE with C4 plasma levels >50% is < 0.05. Conclusion This nationwide survey of C1-INH-HAE provides for Italy a prevalence of 1:64,935. C1-INH-HAE patients listed in our database have a shorter life expectancy than the general population. An increased awareness of the disease is needed to reduce this discrepancy. Measurement of C4 antigen can exclude diagnosis of C1-INH-HAE with an accuracy > 95%. This parameter should be therefore considered for initial screening in differential diagnosis of angioedema.

Two randomized trials evaluated the effect of the bradykinin-receptor antagonist icatibant in patients with hereditary angioedema presenting with acute attacks. The primary end point in each trial was the median time to clinically significant relief of symptoms. In one trial, the primary end point was reached significantly faster with icatibant than with tranexamic acid. In the other trial, the primary end point was not reached significantly faster with icatibant than with placebo. Hereditary angioedema is an autosomal dominant disorder caused by a deficiency of C1 esterase inhibitor, which has a regulatory role in the classic complement pathway and in the coagulation, fibrinolytic, and kallikrein–kinin (contact-system) cascades. Reduced activity of C1 esterase inhibitor may result in an elevated plasma level of bradykinin, 1 , 2 the key mediator of symptoms in hereditary angioedema. 3 , 4 Patients with hereditary angioedema present with acute attacks of subcutaneous and submucosal edema that can affect the upper airways, face, extremities, genitals, and gastrointestinal tract. 5 – 7 Pharyngolaryngeal edema, which is potentially life-threatening because of the risk of upper-airway obstruction, can also . . .

Hereditary angioedema (HAE) is a rare autosomic-dominant disorder characterized by a deficiency of C1 esterase inhibitor which causes episodic swellings of subcutaneous tissues, bowel walls and upper airways that are disabling and potentially life-threatening. We evaluated n = 17 patients with confirmed HAE diagnosis during attack and remission state and n = 19 healthy subjects. The samples were tested for a panel of IL (Interleukin)-17-type cytokines (IL-1β, IL-6, IL-10, granulocyte–macrophage colony stimulating factor (GM-CSF), IL-17, IL-21, IL-22, IL-23) and transforming growth factor-beta (TGF-β) subtypes. Data indicate that there are variations of cytokine levels in HAE subjects comparing the condition during the crisis respect to the value in the remission phase, in particular type 17 signature cytokines are increased, whereas IL-23 is unmodified and TGF-β3 is significantly reduced. When comparing healthy and HAE subjects in the remission state, we found a significant difference for IL-17, GM-CSF, IL-21, TGF-β1 and TGF-β2 cytokines. These results confirm and extend our previous findings indicating that in HAE there is operating an inflammatory activation process, which involves also T helper 17 (Th17) cytokines and TGF-β isoforms, associated with localized angioedema attacks and characterized by elevated bradykinin levels.

Background: The purpose of this study was to evaluate the involvement of inflammatory mediators in patients undergoing Lichtenstein tension-free hernioplasty (LH) using polypropylene prosthetic materials or conventional Bassini hernia repair (BH). Methods: Thirty patients male with unilateral inguinal hernia without complications or recurrence were included in this study. Randomly, patients underwent LH or BH. Peripheral venous bloods samples were collected 24 hours prior to surgery and then 6, 24, 48 and 168 hours postoperatively. Results: We present evidences that LH patients showed a higher increased serum level of fibrinogen, C-reactive protein, alpha-1-antitrypsin, and interleukin-6 than BH patients. Postoperative visual analogue scales for pain were reduced on mobilization for patients undergoing LH compared with BH. Neutrophils were significantly increased only in LH compared with baseline. Ceruloplasmin, transferrin, and albumin levels were unmodified after BH or LH. Conclusions: In conclusion our data show that although LH induces less pain and more rapid postoperative recovery, it is associated with an higher inflammatory response compared with BH, likely due to polypropylene mesh.

The background of this article is as follows: Few data are available about the persistence of serum-specific IgG antibodies to L. infantum after acute VL. The objective of this article is to evaluate the persistence of antibodies against L. infantum in patients healed from acute VL, and the kinetic of the same antibodies observed in 2 cases of VL relapse and 2 cases of resistance to therapy. The methods which we used to obtain our objective are the following: 55 apparently immunocompetent, HIV-negative patients were examined for antibodies to L. infantum by IFAT over 14 years period, and we got the following results: Serum-specific IgG antibodies titers decrease slowly, but constantly. In the patients with a diagnosis of VL relapse, the kinetic of antibodies was characterized by an initial reduction, and a subsequent antibody levels rapidly increase, while in the patients with a clinical and parasitological diagnosis of VL not responding to specific therapy, we demonstrated persistent high level of antibodies to L. infantum . Finally, we conclude that specific antibodies to L. infantum might persist for many years, and decrease slowly, but steadily. The persistence of these specific antibodies is not related to poor therapeutic response or prognosis, but an acute increase in their levels might be a sentinel of a VL relapse, while persistence of high antibody levels could suggest a resistance to therapy.

The aim of this study was to evaluate changes in the production of some cytokines (interleukins [ILs]-6, -10, -1, and -1ra), vascular endothelial growth factor, and beta-fibroblast growth factor after polypropylene mesh implantation. Twenty female patients were divided into 2 groups. In 1 group, hernia repair was performed with conventional sutures (CR), whereas in the other group polypropylene mesh (MR) was used. Growth factors and cytokines production was analyzed in wound drain fluids based on the amount produced during 24 hours. IL-1 increased substantially in MR patients on postoperative days 1 and 2. IL1-ra and IL-10 production was always significantly higher in CR patients. IL-6 production did not show any considerable difference between the 2 groups. Vascular endothelial growth factor production was significantly higher in the MR than the CR group at all time points, whereas beta-fibroblast growth factor production was higher in the MR than the CR group only on postoperative day 1. Our data suggest that different surgical procedures induce various levels of inflammation and that implantation of prostheses significantly stimulates the inflammatory response.

Human rickettsial diseases comprise a variety of clinical entities caused by microorganisms belonging to the genera Rickettsia, Orientia, Ehrlichia, and Anaplasma. These microorganisms are characterized by a strictly intracellular location which has, for long, impaired their detailed study. In this paper, the critical steps taken by these microorganisms to play their pathogenic roles are discussed in detail on the basis of recent advances in our understanding of molecular Rickettsia-host interactions, preferential target cells, virulence mechanisms, three-dimensional structures of bacteria effector proteins, upstream signalling pathways and signal transduction systems, and modulation of gene expression. The roles of innate and adaptive immune responses are discussed, and potential new targets for therapies to block host-pathogen interactions and pathogen virulence mechanisms are considered.

Recently discovered chemically modified tetracyclines (CMTs) have shown in vitro and in vivo anti‐proliferative and anti‐tumour activities. Here, we evaluated in vitro the anti‐proliferative and apoptotic activity of six different dedimethylamino chemically modified tetracyclines (CMT‐1, CMT‐3, CMT‐5, CMT‐6, CMT‐7 and CMT‐8) in sensitive and multidrug resistant myeloid leukaemia cells (HL60 and HL60R) in vitro. Three of these compounds (CMT‐5, CMT‐6, CMT‐7) showed low cytotoxic activity both in sensitive and in resistant cells, CMT‐3 was endowed with a high anti‐proliferative activity only in sensitive cells and was moderately effective as apoptosis inducing agent, with an activity similar to that shown by doxycycline. On the contrary, CMT‐1 and CMT‐8 were very effective as programmed cell death inducing agents. The apoptotic pathway activated by these compounds involved the activation of caspases, especially caspase‐9 and, for CMT‐1, also the activation of Fas. Interestingly CMT‐8, but not CMT‐1, was able to induce apoptosis in multidrug resistant HL60R and in Fas‐ligand resistant HUT78B1 cell lines. These properties, together with others previously described (e.g. anti‐metastatic and anti‐osteolytic activities), suggest that CMT‐8 may have important applications in the clinical management of cancer. The comparative analysis of structure‐activity relationship of CMT‐8 and doxycycline suggests that the C‐5 hydroxy moiety may play an important role in conferring activity in multidrug resistant cells. These findings appear to support the hypothesis that CMT‐8 may represent an interesting lead for the development of a new class of potent apoptosis inducer agents active in multidrug resistant and Fas‐ligand resistant malignancies. British Journal of Pharmacology (2001) 133, 306–314; doi:10.1038/sj.bjp.0704068

Background: The purpose of this study was to evaluate the involvement of proinflammatory cytokines (interferon-γ [INF-γ], interleukin [IL]-6) and anti-inflammatory cytokines (IL-4, IL-l0, IL-13) in patients undergoing Lichtenstein tension-free hernioplasty (LH) using polypropylene prosthetic materials or conventional Bassini hernia (BH) repair. Methods: Thirty-five male patients (age range 25 to 60 years) with unilateral inguinal hernia without complications or recurrence were included in this study. Randomly, patients underwent conventional operation and had their inguinal hernia repair performed with polypropylene mesh. Peripheral venous blood samples were collected 24 hours prior to surgery and then 6, 24, 48, and 168 hours postoperatively. Fifteen healthy controls were included. Results: We present evidence that LH patients showed both an increased serum level of Thelper 1 (Th1)-like cytokines (IFN-γ) and an increase in Thelper 2 (Th2)-like cytokines (IL-6 and IL-l0), associated with a slight reduction of peripheral blood mononuclear cells (PBMC) producing IL-6 and a normal level of PBMC producing IFN-γ, IL-l0, IL-13, and IL-4. Whereas BH patients showed in part an amplification of Th2-like cells, characterized by the sustained serum production of IL-6 and IL-l0, associated with an increase in IL-l0 secreted by in vitro stimulated PMBC. Conclusions: Our data show that LH is associated with a higher production of inflammatory cytokines (IFN-γ and IL-6) compared with BH, likely induced by the presence of the polypropylene prostheses.