Ilenia Pepe

New Insight into Immunity and Immunopathology of Rickettsial Diseases

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.

Milder forms of atherogenic dyslipidemia in ovulatory versus anovulatory polycystic ovary syndrome phenotype

BACKGROUND Dyslipidemia is common in women with polycystic ovary syndrome (PCOS) but its prevalence in different PCOS phenotypes is still largely unknown. METHODS We measured plasma lipids and lipoproteins in 35 anovulatory PCOS (age: 25 +/- 6 years, BMI: 28 +/- 6 kg/m(2)), 15 ovulatory PCOS (age: 30 +/- 6 years, BMI: 25 +/- 3 kg/m(2)) and 27 healthy women (controls) age- and BMI-matched with ovulatory PCOS. PCOS was diagnosed by the presence of clinical or biologic hyperandrogenism associated with chronic anovulation and/or polycystic ovaries at ultrasound. In women with normal menses chronic anovulation was indicated by low serum progesterone levels (<9.54 nmol/l) during midluteal phase (days 21-24) in two consecutive menstrual cycles. RESULTS Total cholesterol, triglycerides and low-density lipoprotein (LDL)-cholesterol levels increased and high-density lipoprotein (HDL)-cholesterol decreased from controls to ovulatory and then to anovulatory PCOS (all P < 0.05). Levels of lipoprotein(a) (Lp(a)) and small, dense LDL increased (P < 0.0001 for both) and LDL size reduced (P < 0.005) between groups. Insulin resistance (by HOMA) showed a positive correlation with triglycerides and small, dense LDL and an inverse correlation with HDL-cholesterol and LDL size (P < 0.05 for all) in both PCOS phenotypes. No significant correlations were found with testosterone levels. At multivariate analysis, insulin resistance was independently associated with HDL-cholesterol and small, dense LDL in both PCOS phenotypes and with triglyceride concentrations in ovulatory PCOS only. CONCLUSIONS Women with ovulatory PCOS showed milder forms of atherogenic dyslipidemia than anovulatory PCOS and this seemed to be related to the extent of insulin resistance. Future prospective studies are needed to assess the relative contribution of such alterations on cardiovascular risk.

Atherogenic forms of dyslipidaemia in women with polycystic ovary syndrome

Objective:  Dyslipidaemia is very common in patients with polycystic ovary syndrome (PCOS) but, beyond plasma lipids, atherogenic lipoprotein (Lp) and apolipoprotein (apo) alterations are still ill defined.

Fecal Assays Detect Hypersensitivity to Cow's Milk Protein and Gluten in Adults With Irritable Bowel Syndrome

BACKGROUND & AIMS Some patients with irritable bowel syndrome (IBS)-like symptoms suffer from food hypersensitivity (FH); their symptoms improve when they are placed on elimination diets. No assays identify patients with FH with satisfactory levels of sensitivity. We determined the frequency of FH among patients with symptoms of IBS and the ability of fecal assays for tryptase, eosinophil cationic protein (ECP), or calprotectin to diagnose FH. METHODS The study included 160 patients with IBS, 40 patients with other gastrointestinal diseases, and 50 healthy individuals (controls). At the start of the study, patients completed a symptom severity questionnaire, fecal samples were assayed, and levels of specific immunoglobulin E were measured. Patients were observed for 4 weeks, placed on an elimination diet (without cows milk and derivatives, wheat, egg, tomato, and chocolate) for 4 weeks, and kept a diet diary. Those who reported improvements after the elimination diet period were then diagnosed with FH, based on the results of a double-blind, placebo-controlled, oral food challenge (with cows milk proteins and then with wheat proteins). RESULTS Forty of the patients with IBS (25%) were found to have FH. Levels of fecal ECP and tryptase were significantly higher among patients with IBS and FH than those without FH. The ECP assay was the most accurate assay for diagnosis of FH, showing 65% sensitivity and 91% specificity. CONCLUSIONS Twenty-five percent of patients with IBS have FH. These patients had increased levels of fecal ECP and tryptase, indicating that they might cause inflammation in patients with IBS. Fecal assays for ECP could be used to identify FH in patients with IBS.

Leukotriene receptor antagonists in monotherapy or in combination with antihistamines in the treatment of chronic urticaria: a systematic review

In vitro and in vivo clinical and experimental data have suggested that leukotrienes play a key role in inflammatory reactions of the skin. Antileukotriene drugs, ie, leukotriene receptor antagonists and synthesis inhibitors, are a class of anti-inflammatory drugs that have shown clinical efficacy in the management of asthma and in rhinitis with asthma. We searched MEDLINE database and carried out a manual search on journals specializing in allergy and dermatology for the use of antileukotriene drugs in urticaria. Montelukast might be effective in chronic urticaria associated with aspirin (ASA) or food additive hypersensitivity or with autoreactivity to intradermal serum injection (ASST) when taken with an antihistamine but not in mild or moderate chronic idiopathic urticaria [urticaria without any possible secondary causes (ie, food additive or ASA and other NSAID hypersensitivity, or ASST)]. Evidence for the effectiveness of zafirlukast and the 5-lipoxygenase inhibitor, zileuton, in chronic urticaria is mainly anecdotal. In addition, there is anecdotal evidence of effectiveness of antileukotrienes in primary cold urticaria, delayed pressure urticaria and dermographism. No evidence exists for other physical urticarias, including cholinergic, solar and aquagenic urticarias, vibratory angioedema, and exercise-induced anaphylaxis.

Antiendomysium antibodies assay in the culture medium of intestinal mucosa: an accurate method for celiac disease diagnosis.

Background Celiac disease (CD) diagnosis is becoming more difficult as patients with no intestinal histology lesions may also be suffering from CD. Aim To evaluate the diagnostic accuracy of antiendomysium (EmA) assay in the culture medium of intestinal biopsies for CD diagnosis. Patients and methods The clinical charts of 418 patients with CD and 705 non-CD controls who had all undergone EmA assay in the culture medium were reviewed. Results EmA assay in the culture medium had a higher sensitivity (98 vs. 80%) and specificity (99 vs. 95%) than serum EmA/antibodies to tissue transglutaminase (anti-tTG) assay. All patients with CD who were tested as false-negatives for serum EmA and/or anti-tTG (32 adults and 39 children) carried the human leukocyte antigen alleles associated to CD. Furthermore, during the follow-up, four patients with negative-serum EmA/anti-tTG, normal villi architecture, and positive-EmAs in the culture medium, developed villous atrophy and underwent gluten-free diet with consequent resolution of the symptoms and complete intestinal histology recovery. Conclusion EmA assay in the culture medium should be included in the diagnostic criteria for CD diagnosis in ‘seronegative’ patients.

Aging and Oral Health: Effects in Hard and Soft Tissues

Changing demographics, including an increase in life expectancy and the growing numbers of elderly has recently focused attention on the need for geriatric dental care. Ageing affects oral tissues in addition to other parts of the human body, and oral health (including oral mucosa, lips, teeth and associated structures, and their functional activity) is an integral component of general health; indeed, oral disease can cause pain, difficulty in speaking, mastication, swallowing, maintaining a balanced diet, not to mention aesthetical considerations and facial alterations leading to anxiety and depression. The World Health Organization recommends the adoption of certain strategies for improving the oral health of the elderly, including the management and maintenance of oral conditions which are necessary for re-establishing effective masticatory function. Oral health is often neglected in the elderly, and oral diseases associated with aging are complex, adversely affecting the quality of life. Although oral health problems are not usually associated with death, oral cancers result in nearly 8,000 deaths each year, and more than half of these occur at an age of 65 years plus. This report, which is dedicated to geriatric physicians, geriatric dentistry and specialists in oral medicine reviews age-related oral changes in elderly patients and efforts to summarize the effects of aging in hard and soft oral tissues.

High prevalence of polycystic ovary syndrome in women with mild hirsutism and no other significant clinical symptoms

OBJECTIVE To verify the conclusions of the Endocrine Society Guidelines that patients with mild hirsutism and no other important clinical signs (menstrual irregularities, infertility, central obesity, acanthosis nigricans, rapid progression of the hirsutism, clitoromegaly) should not be further studied. DESIGN Retrospective study in patients referred because of mild hirsutism and no other clinical signs. SETTING Department of Clinical Medicine of the University of Palermo. PATIENT(S) One hundred fifty-two patients with mild hirsutism. INTERVENTION(S) Measurement of serum testosterone, dehydroepiandrosterone sulfate, 17-OH-Progesterone, assessment of ovulation by measurement of progesterone in 21 to 24 days and ovarian ultrasound. RESULT(S) In 72 (47%) patients a diagnosis of polycyctic ovarian syndrome (PCOS) was performed. Polycyctic ovarian syndrome patients included 56 patients with the mild ovulatory form (OV-PCOS) but also 16 patients with the anovulatory form (classic PCOS). Three (2%) patients had nonclassic adrenal hyperplasia. CONCLUSION(S) Because of the high prevalence of PCOS and the possibility of finding nonclassic 21-hydroxylase deficiency, patients with mild hirsutism need a diagnostic evaluation that should include 17-hydroxyprogesterone measurement plus assessment of ovulation and ovarian ultrasound.

Clinical importance of eosinophil count in nasal fluid in patients with allergic and non-allergic rhinitis.

Eosinophil count in nasal fluid (ECNF) was used to differentiate nasal pathologies. Receiver Operating Characteristic (ROC) curve analysis and the area under the curve (AUC) were performed to evaluate the ECNFs accuracy in distinguishing allergic rhinitis (AR) from non-allergic rhinitis (NAR). We also evaluated the accuracy of ECNF in recognizing patients with mild and severe symptoms of rhinitis and patients with ineffective and effective clinical responses to antihistamines. 1,170 consecutive adult patients with a clinical history of rhinitis were studied. ECNFs median in AR was 6.0 and 2.0 in NAR and the best cut-off value was > 3.0, AUC = 0.75. ECNFs median in AR with mild nasal symptoms was 3.0 and 7.0 with severe symptoms, and the best cut-off value was 4.0, AUC = 0.90. ECNFs median in NAR with mild nasal symptoms was 2.0 and 8.5 with severe symptoms, and the best cut-off value was > 4.0, AUC = 0.86. ECNFs median in AR with effective clinical response to antihistamines was 4.0 and 8.0 with ineffective response, the best cut-off value was ≤ 5.0, AUC = 0.94. ECNFs median in NAR with an effective clinical response to antihistamines was 1.0 and 2.0 with ineffective response, and the best cut-off value was ≤ 3.0, AUC = 0.64. Our results suggest an interesting practical use of ECNF data as evaluator of the clinical severity both AR and NAR. As predictor of the clinical response to antihistamines, ECNF is accurate only in patients with AR. The ECNFs performance was moderately accurate in distinguish patients with AR and NAR.

PREVALENCE OF ANTIBODIES ANTI-BARTONELLA HENSELAE IN WESTERN SICILY: CHILDREN, BLOOD DONORS, AND CATS

To evaluate seroprevalence of B. henselae infection both in Sicilian children and healthy blood donors. Furthermore, circulation of Bartonella in the natural reservoir was also studied. Two hundred forty-three children, living in Sicily (Palermo), affected by various diseases, without clinical features suggesting B. henselae infection, together with 122 healthy blood donors were serologically investigated for IgG and IgM antibodies by indirect fluorescent antibody test (IFAT). One hundred twenty stray and 62 pet cats were also analyzed only for IgG. Among children 25.1% had IgG antibodies to B. henselae; 18.5% showed a titer 1:64, 2.4% 1:128, 2.4% 1:256, 0.8% 1:512, 0.4% 1:1024, and 0.4% 1:5120. Among healthy blood donors 11.4% had IgG class antibodies to B. henselae; 9.8% showed a titer 1:64 and 1.6% 1:128. All the human serum samples did not show positive results for B. henselae IgM class antibodies. Stray cats (68.3%) and pet cats (35.4%) also had IgG class antibodies to B. henselae. We demonstrated high frequency of serologic evidence of past B. henselae infection, in young Italian children, affected by various diseases, apparently free of any clinical features suggesting B. henselae infection. This observation is supported by high circulation of Bartonella in cats.