TGF-β and IL-17 serum levels and specific immunotherapy

Two new T cell subsets may be involved in allergic rhinitis (AR) pathogenesis: Th17 and T regulatory cells, mainly producing IL-17 and TGF-β respectively. Successful Sublingual Immunotherapy (SLIT) induces relevant immunological changes, thus the aim of this study was to evaluate serum IL-17 and TGF-β levels in AR patients treated with SLIT for 2 years. Patients' blood samples were collected before initiating SLIT (baseline), three months after the end of the first pre-seasonal SLIT course, and at the end of the second pre-seasonal course. IL-17 was detectable only in the most severe allergic patients. SLIT significantly induced an increase in serum TGF-β levels. There was moreover a significant relationship between TGF-β and symptom severity and drug use at the end of the study. Therefore, this study provides clinically relevant evidence that two pre-seasonal SLIT courses may significantly affect serum TGF-β levels.     

Allergy to pollens from Betulaceae and Corylaceae in a Mediterranean area (Genoa, Italy)--a ten-year retrospective study.

Allergy to pollens from Betulaceae and Corylaceae is becoming a leading problem in Genoa, a northern Mediterranean area in Italy. The results of a 10-year retrospective study on combined observations both on the aerobiological presence of Betulaceae and Corylaceae pollens (Alnus, Corylus, Ostrya) and on the incidence of positive SPT in the allergic population living in the same area are reported. Among 3473 patients suffering from seasonal respiratory allergy with positive SPT to one or more pollens, 558 (16.06%) showed SPT positivity to Betulaceae and/or Corylaceae pollens, both isolated and associated with other allergens. These patients suffered from winter or early spring hay fever, with a high incidence of bronchial asthma. A statistically significant increase (0.02 < p < 0.05) in the number of these sensitizations from 1981 to 1990 has been observed. Some possible explanations for this phenomenon, including an increase in the total amount of local airborne pollens, are suggested. About 24% of the patients with positive SPT to these pollens referred oral allergic syndrome associated with the ingestion of some foods, especially apples and nuts, with or without other additional clinical symptoms.     

Temporal Lobe Epilepsy in Children: Electroclinical Study of 77 Cases

Summary:  Purpose: Temporal lobe epilepsy (TLE) is probably more difficult to recognize in children than in adults. In fact, ictal symptoms in children are less stereotyped and less obvious, and the neuropathological substrate is more heterogeneous than in adults. The aim of this study is to examine the relationships between etiology, age at onset and electroclinical findings in 77 children with TLE, 32 of whom were surgically treated.
Methods: Electroclinical study including video-EEG recording of seizures in 77 children with TLE. The investigation focused on the first five initial ictal symptoms.
Results: Age at onset was less than 3 years in 39 cases, between 3 and 6 years in 17 cases and older than 6 years in 21 cases. Auras also occurred in younger children but were more common after the age of 6 years. A peculiar initial ictal semiology consisted in staring with arrest, lip cyanosis, and very slight oral automatisms. In some cases, EEG recordings documented seizures starting independently on both temporal lobes. Based on electroclinical and neuroradiological features, we recognized three subgroups: symptomatic TLE due to cortical malformations or nonevolutive tumors, TLE with mesial temporal sclerosis, and cryptogenic TLE.
Conclusions: A correct electroclinical and neuroradiological approach allows in several cases early recognition of TLE even when onset is earlier than the age of 6 years. A correct definition of the localization relies primarily on video-EEG recording of the seizures, possibly repeated during follow up in cases lacking obvious neuroradiological correlation.     

Phase variation in H type I and Lewis a epitopes of Helicobacter pylori lipopolysaccharide

Helicobacter pylori NCTC 11637 lipopolysaccharide (LPS) expresses the human blood group antigens Lewis x (Le(x)), Le(y), and H type I. In this report, we demonstrate that the H type I epitope displays high-frequency phase variation. One variant expressed Le(x) and Le(y) and no H type I as determined by serology; this switch was reversible. Insertional mutagenesis in NCTC 11637 of JHP563 (a poly(C) tract containing an open reading frame homologous to glycosyltransferases) yielded a transformant with a serotype similar to the phase variant. Structural analysis of the NCTC 11637 LPS confirmed the loss of the H type I epitope. Sequencing of JHP563 in strains NCTC 11637, an H type I-negative variant, and an H type I-positive switchback variant showed a C14 (gene on), C13 (gene off), and C14 tract, respectively. Inactivation of strain G27, which expresses Le(x), Le(y), H type I, and Le(a), yielded a transformant that expressed Le(x) and Le(y). We conclude that JHP563 encodes a beta3-galactosyltransferase involved in the biosynthesis of H type I and Le(a) and that phase variation in H type I is due to C-tract changes in this gene. A second H type I-negative variant (variant 3a) expressed Le(x) and Le(a) and had lost both H type I and Le(y) expression. Inactivation of HP093-HP094 resulted in a transformant expressing Le(x) and lacking Le(y) and H type I. Structural analysis of a mutant LPS confirmed the serological data. We conclude that the HP093-HP094 alpha2-fucosyltransferase (alpha2-FucT) gene product is involved in the biosynthesis of both Le(y) and Le(x). Finally, we inactivated HP0379 in strain 3a. The transformant had lost both Le(x) and Le(a) expression, which demonstrates that the HP0379 gene product is both an alpha3- and an alpha4-FucT. Our data provide understanding at the molecular level of how H. pylori is able to diversify in the host, a requirement likely essential for successful colonization and transmission.     

Cardio-respiratory adjustments and cost of locomotion in school children during backpack walking (the Italian Backpack Study)

The use of a school backpack is one of the possible causes of back pain in children. Oxygen consumption ( ), pulmonary ventilation, and heart rate (f _c) were measured in 35 pre-pubertal subjects [17 girls and 18 boys, mean (SD) age 11.3 (0.6) years]. They took part in a four-step experiment: (1) standing for 5 min, (2) walking at 3 km·h^–1 for 7 min, (3) walking at 3 km·h^–1 for 7 min carrying a school backpack weighing 8 kg, and (4) walking at 7 km·h^–1 for 5 min with no load. The occurrence of back pain in the last 2–3 years and during the last 15 days was assessed for the subjects by means of a questionnaire. Mean (SD) standing was 215 (45) ml^.min^–1 during walking at 3 km·h^–1, 503 (101) ml^.min^–1 during walking without a load, and increased to 541 (98) ml^.min^–1 during walking with a load (P<0.01). Carrying a backpack increased f _c only minimally. The energy cost of walking at 3 km^.h^–1 without the backpack was 10.0 (2.0) ml O₂ ^.m^–1, and with the backpack was 10.8 (1.9) ml O₂ ^.m^–1 (P<0.01). The net energy cost of locomotion was 0.129 (0.032) ml^.kg body mass^–1.m^–1 for the unloaded condition and slightly lower, at 0.123 (0.025) ml^.kg body mass^–1.m^–1 during loaded walking (P<0.05). Ventilation did not change significantly between unloaded and loaded conditions. When the data were assessed according to the occurrence of back pain, the f _c/ slope was significantly lower in children without back pain, even though the net energy cost of locomotion was similar. Overall, these data suggest that the cardiovascular effortrequired for locomotion while carrying a backpack is minimal. However, fatigability and back pain are more likely to take place in less physical performing subjects. Thus, the occurrence of back pain in schoolchildren during locomotion while carrying a backpack may improve with an improvement in their level of fitness. Electronic Publication     

Suppression of tumorigenicity and anchorage-independent growth of BK virus-transformed mouse cells by human chromosome 11.

Viral transformation models may be useful for detecting and mapping human tumor suppressor genes. BK virus (BKV), a human papovavirus, readily transforms rodent cells but is unable to transform human cells, suggesting that oncosuppressive functions expressed in human cells control BKV oncogenic activity. We have transferred human chromosome 11 to BKV-transformed mouse cells. All of the cell clones were suppressed in the tumorigenic phenotype and anchorage-independent growth, except one clone which was nontumorigenic but maintained the ability to grow in soft agar. Cytogenetic analysis and DNA hybridization with chromosome 11-specific probes showed that all the reverted hybrids had an intact human chromosome 11, except the clone growing in semisolid medium which had lost the short arm. The results suggest that a gene located on 11p controls anchorage independence, whereas a gene on 11q controls the tumorigenicity of BKV-transformed cells. BKV T-antigen was expressed in all the hybrid clones at the same level as in the parental cell line, indicating that the putative human tumor suppressor gene(s) do not inhibit expression of the viral oncogene and must operate by another mechanism in inducing reversion of the oncogenic phenotype. Since BKV-transformed mouse cells are highly susceptible to retrovirus infection, this model can be used for searching and cloning tumor suppressor gene(s) by retrovirus-mediated "insertional mutagenesis".     

Salivary Epithelial Cells as Model to Study Immune Response Against Cutaneous Pathogens

The human skin not only provides passive protection as a physical barrier against external injury, but also mediates active surveillance via epidermal cell surface receptors that recognize and respond to potential invaders. Primary keratinocytes and immortalized cell lines, the commonly used sources to investigate immune responses of cutaneous epithelium are often difficult to obtain and/or potentially exhibit changes in cellular genetic make‐up. Here we investigated the possibility of using salivary epithelial cells (SEC) to evaluate the host response to cutaneous microbes. Elevated secretion of IFN‐γ and IL‐12 was observed in the SEC stimulated with Staphylococcus aureus, a transient pathogen of the skin, as mono species biofilm as compared to SEC stimulated with a commensal microbe, the Staphylococcus epidermidis. Co‐culture of the SEC with both microbes as dual species biofilm elicited maximum cytokine response. Stimulation with S. aureus alone but not with S. epidermidis alone induced maximum toll‐like receptor‐2 (TLR‐2) expression in the SEC. Exposure to dual species biofilm induced a sustained upregulation of TLR‐2 in the SEC for up to an hour. The data support novel application of the SEC as efficient biospecimen that may be used to investigate personalized response to cutaneous microflora.     

Current guidelines for the management of celiac disease: A systematic review with comparative analysis

BACKGROUND Wheat and other gluten-containing grains are widely consumed,providing approximately 50%of the caloric intake in both industrialised and developing countries.The widespread diffusion of gluten-containing diets has rapidly led to a sharp increase in celiac disease prevalence.This condition was thought to be very rare outside Europe and relatively ignored by health professionals and the global media.However,in recent years,the discovery of important diagnostic and pathogenic milestones has led to the emergence of celiac disease(CD)from obscurity to global prominence.These modifications have prompted experts worldwide to identify effective strategies for the diagnosis and follow-up of CD.Different scientific societies,mainly from Europe and America,have proposed guidelines based on CD's most recent evidence.AIM To identify the most recent scientific guidelines on CD,aiming to find and critically analyse the main differences.METHODS We performed a database search on PubMed selecting papers published between January 2010 and January 2021 in the English language.PubMed was lastly accessed on 1 March 2021.RESULTS We distinguished guidelines from 7 different scientific societies whose reputation is worldwide recognized and representative of the clinical practice in different geographical regions.Differences were noted in the possibility of a no-biopsy diagnosis,HLA testing,follow-up protocols,and procedures.CONCLUSION We found a relatively high concordance between the guidelines for CD.Important modifications have occurred in the last years,especially about the possibility of a no-biopsy diagnosis in children.Other modifications are expected in the next future and will probably involve the extension of the non-invasive diagnosis to the adult population and the follow-up modalities.     

Cardiovascular Effects of a Single Slow Release Lanreotide Injection in Patients with Acromegaly and Left Ventricular Hypertrophy

In our study we assessed the effects of a single i.m. injection of slow-release Lanreotide (30 mg) (SR-L), a new long-acting somatostain analog, on circulating GH levels, baseline cardiac function (M-mode, 2D guided, doppler-echocardiographic study) and cardiopulmonary response to exercise (cycloergometric test, performed using a computer drived, electrically braked cycle ergometer), tested at baseline, after 7 and 14 days from the injection in 10 acromegalic patients (5 M, 5 F, mean age 57.7 ± 3.1 yrs, body mass index (BMI) 27 ± 0.8 kg/m², blood pressure 141 ± 6.5/82 ± 3 mmHg). SR-L administration decreased GH levels in acromegalic patients (mean±SEM) from 16.1 ± 6.9 to 10.8 ± 5.1 µg/L (p = 0.045) after 7 days and to 11.9 ± 5 µg/L (p = 0.078) after 14 days from the injection. Moreover, we observed a significant (p<0.05) decrease in systolic blood pressure and heart rate at the 7th (135 ± 6.1 vs 141 ± 6.5 mmHg, and 68 ± 2.1 vs 74 ± 2.1 bpm) and 14th (137 ± 6.2 vs 141 ± 6.5 mmHg, and 72 ± 2 vs 74 ± 2.1 bpm) day of the study with respect to the baseline values. After SR-L administration we also found an increase in ejection fraction (69 ± 2 vs 63 ± 2.3% at 7th day, p = 0.006; 65 ± 2.3 vs 63 ± 2.3% at the 14th day, p = 0.027) and shortening fraction (40.8 ± 1.8 vs 36.6 ± 1.9% at 7th day, p = 0.005; 38.7 ± 1.8 vs 36.6 ± 1.9% at the 14th day, p = 0.045). The positive acute cardiac response to SR-L injection was also demonstrated by the increase in A/E velocity ratios at 7th (1.14 ± 0.1 vs 0.98 ± 0.07, p = 0.016) and 14th (1.04 ± 0.08 vs 0.98 ± 0.07, p = 0.008) day of the study. After SR-L injection, exercise capacity and VO₂ at anaerobic thresold were also increased with respect to the baseline test: 61.1 ± 8.2 vs 38.9 ± 6.8 watts (p = 0.002) and 1012.4 ± 71.5 vs 915.3 ± 77.8 mL/min (p = 0.033) after 7 days, and 61.4 ± 7.2 vs 38.9 ± 6.8 watts (p = 0.002) and 1010.1 ± 62.5 vs 915.3 ± 77.8 mL/min (p = 0.010) after 14 days from the injection. In conclusion, these results suggest that in acromegalic patients: (1) SR-L causes a rapid improvement in baseline cardiac function and in cardiopulmonary performance during exercise in acromegaly; (2) the endocrine (decrease in GH levels) and echocardiographic responses to SR-L are maximal after 7 days from the injection, whereas the effect of SR-L on the exercise performance are longer lasting.