The university as a safe environment during the SARS-COV-2 pandemic: the experience of Bari Politecnico.

the SARS-CoV-2 pandemic started in December 2019 and still remains a major global health issue. Every country in the world has adopted drastic measures to contain the virus, although their stringency varies among countries, ranging from increased surveillance and focused interventions to strict lockdown (1). Italy was the second country where the disease had a major impact early in the pandemic, such that a strict nationwide lockdown was declared from March 9 to May 3, 2020. Nonetheless, between January and May 2020, there were 210,000 COVID-19 cases in Italy and 29,000 deaths were recorded (2). Due to the lockdown, universities (and in general all educational services) shifted to online classes, with students attending lessons and taking their exams from home. On-site activities were reduced to those considered indispensable. Research activities also had to be modified, such as by the adoption of a smart-working model (3). Between May and August 2020, the number of SARS-CoV-2 infections in Italy decreased. In response, the lockdown was loosened and some activities were restarted, albeit with specific safety protocols (social distancing, use of masks, temperature checks at the workplace entry, environmental disinfection, mixed models of smart and in-office work). These actions were accompanied by periodic serological and PCR screening tests (4).

Using the cytokinesis-block micronucleus cytome assay to evaluate chromosomal DNA damage in chronic renal patients undergoing bicarbonate haemodialysis and haemodiafiltration.

INTRODUCTION: Chronic Renal Failure (CRF) patients are considered to show genomic instability and are associated with a high risk of both cardiovascular diseases and cancer. We explored DNA damage due to two dialysis treatments in 20 patients undergoing bicarbonate haemodialysis (BD), 20 undergoing haemodiafiltration (HDF) and 40 healthy subjects. METHODS: The cytokinesis-block micronucleus (MN) assay was performed on peripheral blood lymphocytes to evaluate genetic damage. RESULTS: A higher frequency of MN in the dialysis groups compared with controls was found. The results do not show a relationship between genetic instability and the type, frequency and duration of haemodialysis. The average BD and HDF treatment time was respectively 3.8 ± 6.3 and 3.7 ± 3.9 yrs. CAT and scintigraphy was independently correlated with high levels of MN. CONCLUSIONS: Overall, the frequency of MN in CRF patients undergoing dialysis therapy was observed to be higher. Further studies need to be performed on a larger number of patients and for a longer period.

Current status of viroid taxonomy.

Viroids are the smallest autonomous infectious nucleic acids known so far. With a small circular RNA genome of about 250-400 nt, which apparently does not code for any protein, viroids replicate and move systemically in host plants. Since the discovery of the first viroid almost forty-five years ago, many different viroids have been isolated, characterized and, frequently, identified as the causal agents of plant diseases. The first viroid classification scheme was proposed in the early 1990s and adopted by the International Committee on Taxonomy of Viruses (ICTV) a few years later. Here, the current viroid taxonomy scheme and the criteria for viroid species demarcation are discussed, highlighting the main taxonomic questions currently under consideration by the ICTV Viroid Study Group. The impact of correct taxonomic annotation of viroid sequence variants is also addressed, taking into consideration the increasing application of next-generation sequencing and bioinformatics for known and previously unrecognized viroids.

Viroid-like RNAs from cherry trees affected by leaf scorch disease: further data supporting their association with mycoviral double-stranded RNAs.

Cherry trees from Spain affected by cherry leaf scorch (CLS), a fungal disease proposed to be caused by Apiognomonia erythrostoma, show symptoms (translucent-chlorotic leaf spots evolving into rusty areas) very similar to those of cherry chlorotic rusty spot disease (CCRS) and Amasya cherry disease, reported in Italy and Turkey, respectively. The three maladies are closely associated with 10-12 double-stranded viral RNAs, and CCRS is additionally associated with two cherry small circular RNAs (cscRNA1 and cscRNA2). Here, we report that a small viroid-like RNA similar to the CCRS-associated cscRNA1 is also present in CLS-affected trees, thus extending the link between the two diseases. Both CLS and CCRS cscRNA1 elements have common features, including sequence identity (88 %), a predicted quasi rod-like conformation with short bifurcations at both termini, and the presence of hammerhead ribozymes in the strands of both polarities. However, cscRNA2, apparently derived from cscRNA1 by deletion of a short hairpin, was not detected in CLS-affected material. Although the biological nature of cscRNAs is unknown, the identification of at least cscRNA1 in different cherry cultivars and in two distinct geographic areas (Spain and Italy), always in close association with the same mycoviral dsRNAs, supports that these viroid-like RNAs could be satellite RNAs.

Viroid-like RNAs from cherry trees affected by leaf scorch disease: further data supporting their association with mycoviral double-stranded RNAs.

Cherry trees from Spain affected by cherry leaf scorch (CLS), a fungal disease proposed to be caused by Apiognomonia erythrostoma, show symptoms (translucent-chlorotic leaf spots evolving into rusty areas) very similar to those of cherry chlorotic rusty spot disease (CCRS) and Amasya cherry disease, reported in Italy and Turkey, respectively. The three maladies are closely associated with 10-12 double-stranded viral RNAs, and CCRS is additionally associated with two cherry small circular RNAs (cscRNA1 and cscRNA2). Here, we report that a small viroid-like RNA similar to the CCRS-associated cscRNA1 is also present in CLS-affected trees, thus extending the link between the two diseases. Both CLS and CCRS cscRNA1 elements have common features, including sequence identity (88%), a predicted quasi rod-like conformation with short bifurcations at both termini, and the presence of hammerhead ribozymes in the strands of both polarities. However, cscRNA2, apparently derived from cscRNA1 by deletion of a short hairpin, was not detected in CLS-affected material. Although the biological nature of cscRNAs is unknown, the identification of at least cscRNA1 in different cherry cultivars and in two distinct geographic areas (Spain and Italy), always in close association with the same mycoviral dsRNAs, supports that these viroid-like RNAs could be satellite RNAs.

Identification of HEV in symptom-free migrants and environmental samples in Italy.

Hepatitis E virus (HEV) is considered an emerging pathogen in industrialized countries. The occurrence of HEV genotypes in samples of faeces from asymptomatic migrants arriving on the coasts of South Italy and environmental samples was investigated. Analyses of sequences were used to compare human and environmental genotypes. A total of 40 stool specimens, 12 samples of untreated urban sewage, 12 samples of treated urban sewage and 12 samples of surface water were analysed. Viruses were concentrated from water samples by the tangential flow ultrafiltration technique. The presence of HEV RNA was detected by nested RT-PCR. Viral isolates were sequenced and phylogenetically characterized. Two (5%) of the 40 faecal samples tested were found to be positive for HEV RNA (G1 and G3 genotypes). The virus was detected in 25% (3/12) of the untreated sewage samples and 25% (3/12) of the surface water samples: all isolates belonged to G3 genotype. None of the treated sewage samples were found to be HEV RNA positive. The virus was detected in the faeces of two asymptomatic subjects, suggesting a potential role for symptom-free HEV carriers as a human reservoir. G3 HEV strains were detected in the untreated sewage, as observed in similar studies conducted in other European countries but differing from another study conducted in Italy recently. Moreover, our results show the first case of HEV isolated from fresh surface waters.

First episode psychosis during the Covid-19 pandemic in Milan, Italy: Diagnostic outcomes at 1-year follow-up.

An influence of the Covid-19 pandemic on First Episode Psychosis (FEP) has been hypothesized. We previously reported an increase of FEP during the early stages of the pandemic in Milan, Italy. Here we report a 1-year follow-up of the same cohort and comparison with a FEP cohort from 2019. The higher proportion of non-chronic psychoses observed during the pandemic (58.62% in 2020 vs 43,75% in 2019) should be confirmed in larger cohorts over a longer follow-up period.

Evaluation of radon exposure risk and lung cancer incidence/mortality in South-eastern Italy.

INTRODUCTION: Radon and its decay products may cause substantial health damage after long-term exposure. The aim of the study was to perform a spatial analysis of radon concentration in the Salento peninsula, province of Lecce (South-eastern Italy) in order to better characterize possible risk for human health, with specific focus on lung cancer. METHODS: Based on previous radon monitoring campaigns carried out in 2006 on behalf of the Local Health Authority (ASL Lecce) involving 419 schools and through the application of kriging estimation method, a radon risk map was obtained for the province of Lecce, in order to determine if areas with higher radon concentrations were overlapping with those characterized by the highest pulmonary cancer incidence and mortality rates. RESULTS: According to our data, areas at higher radon concentrations seem to overlap with those characterized by the highest pulmonary cancer mortality and incidence rates, thus indicating that human exposure to radon could possibly enhance other individual or environmental pro-carcinogenic risk factors (i.e. cigarette smoking, air pollution and other exposures). CONCLUSIONS: The radon risk should be further assessed in the evaluation of the causes resulting in higher mortality and incidence rates for pulmonary cancer in Salento area vs Italian average national data. For these reasons, ASL Lecce in cooperation with ARPA Puglia and CNR-IFC has included the monitoring of individual indoor radon concentrations in the protocol of PROTOS case-control Study, aimed at investigating the role of different personal and environmental risk factors for lung cancer in Salento.

Relationship between the gingival sulcus depth and interleukin-1 isoform concentrations within the adjacent gingival tissue.

BACKGROUND AND OBJECTIVE: While there is substantial information concerning the concentrations of interleukin-1 isoforms within gingival crevicular fluid, there is little information concerning their concentrations within either normal or diseased gingival tissues. Therefore, the aim of this study was to evaluate the relationship between the concentrations of gingival interleukin-1 isoforms and the adjacent sulcular depth. MATERIAL AND METHODS: Interdental gingival papillae were excised and grouped based on adjacent pocket depth and the presence of bleeding on probing. Gingiva adjacent to a sulcus of < or = 3 mm without bleeding on probing were classified as 'normal'; gingiva adjacent to a 3-mm sulcus with bleeding on probing were classified as 'diseased-slight'; gingiva adjacent to a 4-6-mm sulcus featuring bleeding on probing were classified as 'diseased-moderate'; and gingiva adjacent to a sulcus of > 6 mm featuring bleeding on probing were classified as 'diseased-severe'. Tissues were solublized and the concentrations of interleukin-1beta, interleukin-1alpha, interleukin-1 receptor antagonist and interleukin-6 were assessed by enzyme-linked immunosorbent assay. Data were compared by factorial analysis of variance, the post-hoc Tukey test and the Pearson's correlation test. RESULTS: Gingival concentrations of interleukin-6, interleukin-1 receptor antagonist, interleukin-1alpha- and interleukin-1beta were significantly greater at diseased-severe sites than at normal, diseased-slight, or diseased-moderate sites (p < 0.05); the gingival concentrations of interleukin-1 receptor antagonist and interleukin-1alpha were significantly greater at diseased-severe than at diseased-moderate sites (p < 0.05). Interleukin-1 receptor antagonist concentrations were significantly correlated with both interleukin-1alpha and interleukin-1beta concentrations. The ratios of concentrations of the interleukin-1 isoforms were different at the various stages of inflammation. CONCLUSION: Our data indicated a progressive increase in gingival concentrations of interleukin-1 isoforms with increased adjacent sulcular depth. However, within 'diseased' tissues, the proportional concentrations of interleukin-1alpha and -beta to interleukin-1 receptor antagonist were lowest within diseased-severe tissues.

Skin safety and health prevention: an overview of chemicals in cosmetic products.

INTRODUCTION: Cosmetic products contain a wide range of chemicals to which we are exposed every day. The aim of the study was to determine the presence of potential dangerous substances which can cause adverse health effects by examining product labels. MATERIALS AND METHODS: A total of 283 products were collected from various shops in Lecce (Italy) and divided into 3 categories: rinse-off, leave-on and make-up. The label of every product was examined and a list including fragrances, preservatives and other chemicals of concern was created. RESULTS: Fragrances were present in 52.3% of the examined products, mostly limonene (76.9%) and linalool (64.6%) but also citronellol (34.1%), geraniol (31.5%), coumarin (30%) and hexyl cinnamal (29.2%). Preservatives showed a rate of 60% and the most frequently identified were phenoxyethanol (48.7%), sodium benzoate (35.6%), potassium sorbate (22%), methylparaben (15.2%) and MI/MCI (9.9%). The other chemicals of concern were detected in 58% of products; included PEGs (62.3%), acrylate copolymer (34%), petrolatum (17.2%), polysorbates (14,8%), BHT (14.7%), ethylhextyl methoxycinnamate (13.6%), benzophenone-1 (3.7%), benzophenone-3 (4.9%), BHA (1.6%), cocamide DEA and toluene (1.2%). CONCLUSIONS: The use of many of these substances is allowed within certain limits, due to their toxicity at higher concentrations. Other important aspects should be considered as, for instance, the possibility of long-term effects. On the other hand, other substances may induce several acute adverse side-effects, i.e. contact dermatitis and allergic reactions. For these reasons, an enhancement of the criteria used for cosmetics formulation is required since many chemicals used singularly or combined are potentially unsafe.

First Report of Cucumber mosaic virus Infecting Solanum jasminoides in Italy.

Solanum jasminoides Paxton (potato vine or jasmine nightshade) is a vegetatively propagated ornamental species within the Solanaceae family. Recently, symptomless plants of this species were reported as natural hosts of the quarantine pest, Potato spindle tuber viroid (PSTVd) in Italy (1). In January 2008, approximately 1,000 potted, 2-year-old plants of S. jasminoides growing in an ornamental nursery in Sicily showed virus-like mosaic and malformation of leaves. Symptoms were observed on approximately 60% of the plants. Leaf tissue, collected from 30 symptomatic and 10 symptomless plants, was analyzed by double-antibody sandwich-ELISA with polyclonal antisera specific to Cucumber mosaic virus (CMV), Tomato spotted wilt virus, and Impatiens necrotic spot virus (Loewe Biochemica, Sauerlach, Germany). The same samples were also analyzed by tissue-printing hybridization with a PSTVd-specific digoxigenin-labelled riboprobe. All the symptomatic samples tested positive only with antisera against CMV, but negative in all other tests. The symptomless samples were negative in all the performed tests. To confirm the association of CMV with the diseased plants, total RNA was extracted from the same samples (RNeasy Plant Mini Kit; Qiagen, Hilden, Germany) and analyzed by reverse transcription (RT)-PCR using CMV-specific primers MP+5'-CATGGCTTTCCAAGGTACCAG-3' and MP-5'-CTAAAGACCGTTAACCACCTGC-3' that amplify a 844-bp fragment from the MP gene (2). The expected fragment was amplified only from samples of symptomatic tissue. CMV was also detected in mother plants grown in the same nursery and showing same mosaic symptoms. Definitive identification of the pathogen was obtained by cloning and sequencing the RT-PCR product. The obtained sequence (GenBank Accession No. EU828783) had 99 and 98% similarity with the subgroup I-A isolates CMV-LUN (GenBank Accession No. EU432183) and CMV-Fny (GenBank Accession No. DI0538), respectively. To our knowledge, this is the first report of CMV infecting S. jasminoides and it adds a new host to the more than 1,000 species (85 plant families) infected by this virus. The high incidence of the disease in the nursery could be due to propagation of cuttings from an infected source. References: (1) F. Di Serio. J. Plant Pathol. 89:297, 2007. (2) H. X. Lin et al. J. Virol. 78:6666, 2004.

Techno-functional properties of tomato puree fortified with anthocyanin pigments.

This study investigates the effects of tomato puree fortification with several anthocyanin-rich food colorants on bioactive compound content (phenolics, isoprenoids), antioxidant capacity, in vitro biological activities and consumer acceptance. Tomato puree (tp) was added with different anthocyanin extracts from black carrot (Anthocarrot), grape fruit skins (Enocolor), elderberry fruits (Elderberry) or mahaleb cherry fruits (Mahaleb), thus obtaining a 'functional tomato puree' (ftp). The consumer acceptance (colour, flavor, taste, visual appearance) was at high level, except for Mahaleb-added ftp. Compared to the control (tp), the addition of colouring extracts increased significantly the total phenolic content, before pasteurization, in addition to the expected anthocyanin content. However, after pasteurization, mostly Anthocarrot-ftp preserved an increased phenolic (+53%) content, as well as a higher antioxidant capacity (50%), more than the other added-extracts. Consistently, against tp, Anthocarrot-ftp exhibited an increased anti-inflammatory capacity as showed by the reduced expression of vascular cell adhesion molecule (VCAM)-1 in human cultured endothelial cells, under inflammatory conditions.

Interleukin-18 concentrations and the pathogenesis of periodontal disease.

BACKGROUND: Interleukin-18 (IL-18) is reported as an important regulatory cytokine in non-oral inflammation. Our objective was to compare the concentrations of IL-18 within diseased and healthy human gingiva with concentrations of other T(H)1 and T(H)2 cytokines to determine possible effects of IL-18 on gingival inflammation. METHODS: Gingival biopsies were obtained prior to routine tooth extraction. Gingiva was grouped by the depth of the adjacent gingival sulcus: < or =3 healthy (featuring no bleeding on probing) and > or =3 mm diseased (featuring bleeding on probing). Diseased gingiva was subdivided into 3, 4 to 6 and >6 mm groups. Gingival interleukin (IL)-2, IL-4, IL-6, IL-10, IL-12, IL-18, and interferon (IFN)-gamma concentrations were assessed by enzyme linked immunosorbent assay (ELISA). Data were compared by factorial analysis of variance and the Pearson's correlation test. RESULTS: Concentrations of IL-2, IL-4, IL-6, IL-10, IL-18, and IFN-gamma adjacent to 4 to 6 mm diseased sites were greater than adjacent to < or =3 mm healthy sites (P <0.001). IL-12 concentrations were lower within diseased than within healthy gingiva (P <0.001). IL-6 and IL-18 concentrations were greater adjacent to >6 mm sites compared to healthy sites (P <0.001); the concentrations of the other cytokines (except IL-12) were similar to healthy sites. IL-6 and IL-18 concentrations were positively correlated, and IFN-gamma and IL-12 negatively correlated, with the adjacent gingival sulcular depth. CONCLUSIONS: Periodontal inflammation may not successfully resolve because of accumulation of IL-6 and IL-18, and decreased concentrations of IL-12, within diseased gingiva. Because of the highly significant correlation between IL-18 concentration and gingival sulcular depth, IL-18 may be a useful target for either preventive or palliative therapy for periodontitis.

Viroids, the simplest RNA replicons: How they manipulate their hosts for being propagated and how their hosts react for containing the infection.

The discovery of viroids about 45 years ago heralded a revolution in Biology: small RNAs comprising around 350 nt were found to be able to replicate autonomously-and to incite diseases in certain plants-without encoding proteins, fundamental properties discriminating these infectious agents from viruses. The initial focus on the pathological effects usually accompanying infection by viroids soon shifted to their molecular features-they are circular molecules that fold upon themselves adopting compact secondary conformations-and then to how they manipulate their hosts to be propagated. Replication of viroids-in the nucleus or chloroplasts through a rolling-circle mechanism involving polymerization, cleavage and circularization of RNA strands-dealt three surprises: (i) certain RNA polymerases are redirected to accept RNA instead of their DNA templates, (ii) cleavage in chloroplastic viroids is not mediated by host enzymes but by hammerhead ribozymes, and (iii) circularization in nuclear viroids is catalyzed by a DNA ligase redirected to act upon RNA substrates. These enzymes (and ribozymes) are most probably assisted by host proteins, including transcription factors and RNA chaperones. Movement of viroids, first intracellularly and then to adjacent cells and distal plant parts, has turned out to be a tightly regulated process in which specific RNA structural motifs play a crucial role. More recently, the advent of RNA silencing has brought new views on how viroids may cause disease and on how their hosts react to contain the infection; additionally, viroid infection may be restricted by other mechanisms. Representing the lowest step on the biological size scale, viroids have also attracted considerable interest to get a tentative picture of the essential characteristics of the primitive replicons that populated the postulated RNA world.

Symptomatic relief of migraine: multicenter comparison of Cafergot P-B, Cafergot, and placebo.

A multicenter, randomized, double-blind trial was conducted to compare the efficacy of Cafergot P-B with that of its components, Cafergot, pentobarbital, and Bellafoline, and with placebo for the treatment of migraine. Patients with vascular headaches of the migraine type who regularly experienced nervous tension and some form of gastrointestinal distress with their headaches were randomized to one of five treatment groups. They were given treatment packets containing their assigned drug for use during two separate migraine attacks. Patients made pretreatment evaluations of the following symptoms: head pain, nervous tension, nausea, vomiting, anorexia, abdominal cramps, and photophobia. They made posttreatment evaluations of these symptoms 0.5, 1.0, 1.5, 2.0, and 3.0 hours after ingesting their assigned drug. Improvement scores were calculated from the differences between the pretreatment and the posttreatment ratings. Patients also made a final global assessment of their drug's efficacy. All patients who took at least one dose of the study medication and completed a baseline evaluation and at least one postdose evaluation of severity of pain were included in the analysis (n = 254). The comparisons of particular interest were those between Cafergot P-B and Cafergot and between Cafergot P-B and placebo. Cafergot P-B was significantly more effective than Cafergot in relieving head pain at hours 2 and 3, nervous tension, nausea, vomiting, anorexia, and photophobia. Cafergot P-B was significantly more effective than placebo in relieving head pain, nervous tension, nausea (second headache only), vomiting, and photphobia. The incidence of reported adverse effects was no greater with Cafergot P-B than with Cafergot; however, patients given Cafergot P-B reported less vomiting than did patients given Cafergot. The results of this study show that addition of pentobarbital and Bellafoline to Cafergot provides greater relief of pain, vomiting, nervous tension, photophobia, and other symptoms associated with migraine, while reducing the severity of the nausea that may accompany a migraine headache or Cafergot therapy.

Total testing process: appropriateness in laboratory medicine.

BACKGROUND: The need to reduce costs in Laboratory Medicine is often related to the possibility of reducing test requests without taking into account patients' outcomes. Therefore, the term "appropriateness" in Laboratory Medicine as referred to the specific steps (pre-analytical, analytical, post-analytical) and related to the clinical process could allow the improvement of clinical effectiveness and economic efficiency. METHODS: Our experience has shown an improvement in analytical appropriateness (reorganization and re-engineering by Laboratory automation) and pre-analytical appropriateness (critical revision of the panel for cardiac markers) by evaluating the workload and errors rate in the pre-analytical phase. RESULTS: We obtained an economic saving (119,580 euro/year) in cardiac markers request (analytical appropriateness: 60%, pre-analytical appropriateness: 40%) and also an improvement in clinical appropriateness (diagnosis and therapy). CONCLUSIONS: Our data confirm the need to improve communications between physicians and Laboratory Medicine as regards the pre-analytical step and to implement educational programs for defining criteria and procedures. Appropriateness in analytical and post-analytical steps contribute to achieve economic saving (Core lab, POCT) and improvement of the turn-around time (TAT).

Application of a diagnostic algorithm in autoantibody testing: assessment of clinical effectiveness and economic efficiency.

BACKGROUND: Guidelines aim to assist physicians about appropriate health care for specific clinical circumstances. Therefore, they must be continuously updated, integrated and tailored to local situations. METHODS: We applied recently developed guidelines for autoantibody testing by assessing their economic (efficiency) and clinical (effectiveness) impact. Since June 2002, a test order algorithm has been adopted for autoantibody testing requests (3258). In particular, the guidelines were modified taking into account the needs of different departments and the results were compared to those (2762) of the previous period (January-May 2002) that had not been integrated with any diagnostic algorithm. RESULTS: A significant reduction in the number of anti-double stranded DNA (anti-dsDNA) (21.4%) and anti-Extractable Nuclear Antigens (anti-ENA) (19%) was found (p<0.0001), while the number of anti-nuclear antibody (ANA) test was unchanged (p=n.s.); further reduction in clinically inappropriate test request rates (23%) was observed. CONCLUSIONS: The application of guidelines allowed the improvement of diagnostic tests' efficiency and clinical effectiveness (patient's outcomes), thus confirming the need to apply eventual modifications to the diagnostic process taking into consideration different clinical needs.

Leptin within healthy and diseased human gingiva.

BACKGROUND: Plasma leptin concentrations are reported to be elevated in patients with inflammatory diseases. There is no consensus concerning the biological mechanism for this phenomenon. To date, tissue leptin concentrations have not been assessed within normal or inflamed gingiva. The purpose of this study was to assess concentrations of human leptin within healthy and diseased gingiva to define its possible role in periodontal disease progression. METHODS: Healthy (non-hemorrhagic gingiva adjacent to a < or =3 mm gingival sulcus) and inflamed gingiva (hemorrhagic gingiva adjacent to a > or =3 mm periodontal pocket) were studied. Leptin, vascular endothelial growth factor (VEGF; to assess potential vascular expansion), and interleukin-6 (IL-6; to assess periodontal disease activity and severity) concentrations were assessed within solubilized gingival biopsies by enzyme-linked immunosorbent assay. Data were grouped by sulcular depth and compared by factorial analysis of variance, regression analysis, and Scheffé comparisons. RESULTS: Leptin concentrations were highest within gingiva adjacent to a < or =3 mm sulcus and progressively declined within gingiva adjacent to a > or =3 mm sulcus. VEGF concentrations were highest within gingiva adjacent to 4 to 6 mm pockets and nearly equivalent in healthy (< or =3 mm sulcus) and severely diseased gingiva (>6 mm sulcus). IL-6 was positively correlated and leptin negatively correlated with adjacent probing depth; IL-6 concentration was significantly higher and leptin significantly lower in gingiva adjacent to >6 mm pockets compared to sites adjacent to <6 mm pockets (P<0.001). CONCLUSIONS: Human leptin is present within healthy and marginally inflamed gingiva and decreases in concentration as the adjacent probing depth increases. When leptin concentrations decreased (> or =3 mm sulcus), VEGF concentrations increased, suggesting that leptin could be released from gingiva coincident to vascular expansion. Thus, gingiva, in addition to adipose tissue, could be a source of circulating leptin in patients with periodontal disease. This possibility requires further investigation.

Interleukin-11 and IL-17 and the pathogenesis of periodontal disease.

BACKGROUND: Interleukin (IL)-11 and IL-17 are cytokines that modulate the inflammatory process and have not been assessed within normal or inflamed gingival tissues. Our purpose was to compare concentrations of human IL-11 and IL-17 within healthy and diseased human gingiva to determine their possible role in the initiation or progression of periodontal diseases. METHODS: Biopsies from healthy (non-hemorrhagic gingiva adjacent to a < or = 3 mm gingival sulcus) and diseased gingiva (hemorrhagic gingiva adjacent to a > or = 3 mm periodontal pocket) were studied. IL-11, IL-17, RANTES, and IL-6 concentrations were assessed within solubilized gingival biopsies by enzyme-linked immunosorbent assay. Data were compared by factorial analysis of variance and a post-hoc Tukey honestly significant difference (HSD) test. Regression analysis and partial correlation analysis (adjusted for sample weight) were also used to determine correlations between the variables. RESULTS: Interleukin-11 concentrations were highest within gingiva adjacent to 3 mm diseased pockets (P < 0.001), and IL-17 concentrations were highest at 4 to 5 mm sites compared to other sites (P < 0.001). Gingival concentrations of both cytokines were significantly lower in gingiva adjacent to a > or = 6 mm pocket. RANTES concentrations were significantly greater in gingiva adjacent to > or = 6 mm pockets than in tissues derived from other sites (P < 0.001). IL-11, IL-6, and RANTES concentrations were significantly correlated with sulcular depth. CONCLUSIONS: Gingival concentrations of IL-11 and IL-17 are different in diseased gingiva adjacent to 3, 4 to 5, and > or = 6 mm pockets, suggesting that their concentrations change as a consequence of the progression of gingivitis to periodontitis and that both cytokines could have a significant role in this progression. These data may be useful for the design of procedures for prevention of periodontal disease.

Vascular endothelial growth factors and progression of periodontal diseases.

BACKGROUND: Tissues become hemorrhagic and edematous coincident to periodontal diseases; however, there is little information concerning the biologic mechanisms which may produce these changes. Vascular endothelial growth factor (VEGF) is a macromolecule which enhances blood vessel growth and permeability. However, there is no information concerning gingival VEGF concentrations within normal or diseased gingiva. The purpose of this study was to assess changes in gingival concentrations of VEGF during initiation and progression of periodontal diseases and compare them to changes in the number of blood vessel profiles and concentration of recognized markers of periodontal disease severity (interleukin-6[IL-6]). METHODS: Normal (non-hemorrhagic gingiva adjacent to a < or =3 mm gingival sulcus) and inflamed gingiva (hemorrhagic gingiva adjacent to a < or =3 mm, 4 to 6 mm, or >6 mm periodontal pocket) were studied. VEGF and IL-6 concentrations were assessed by ELISA and the number of blood vessels determined by histomorphometric techniques. Data were placed into one of the following groups: < or =3 mm, normal; < or =3 mm, diseased; 4 to 6 mm, diseased; and >6 mm, diseased. These groups were compared by factorial ANOVA and Scheffe comparisons. In addition, groups were compared by simple and multiple regression and regression ANOVA to determine possible correlations between them. RESULTS: VEGF and IL-6 concentrations were significantly lower within normal than within diseased gingiva. The number of blood vessel profiles and mean IL-6 concentrations were highest in diseased tissues adjacent to >6 mm sulci and were significantly correlated with sulcular depth (P <0.001). In contrast, VEGF concentrations were highest within diseased gingiva adjacent to 4 to 6 mm periodontal pockets (P <0.001) and were not correlated with sulcular depth. CONCLUSIONS: VEGF may be a factor in initiation and progression of gingivitis to periodontitis, possibly by promoting expansion of the vascular network coincident to progression of the inflammation.