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Biomedical subjects

M Cimmino

Publications and source records attributed to M Cimmino.

17 recordsLinked to original sources

Inhibition of p38 mitogen activated protein kinase controls airway inflammation in cystic fibrosis.

BACKGROUND: Cystic fibrosis (CF) airways are characterised by chronic inflammation, increased interleukin (IL)-8 secretion, and neutrophil activation which are considered the principal factors of morbidity and mortality in CF patients. Optimising management of this chronic inflammatory response is therefore a key issue of basic and clinical CF research. Several reports have addressed ways to manage CF airways inflammation, and an attractive therapeutic strategy may be the inhibition of the p38-mitogen activated protein kinase (p38-MAP-k) pathway. METHODS: A new ex vivo model was used to study the mucosal inflammatory response to environmental airways stimuli. Nasal biopsy tissues from CF patients and controls were cultured ex vivo for 20 minutes, 4 hours, and 24 hours in the presence of lipopolysaccharide (LPS) from Pseudomonas aeruginosa (PA) with and without the p38-MAP-k inhibitor SB203580. Quantitative mRNA assessment, immunohistochemistry, and Western blots were used to detect the expression and modulation of inflammatory markers. RESULTS: PA-LPS challenge induced a time dependent mucosal inflammation indicated by rapid epithelial activation, IL-8 release, COX-2 upregulation, and neutrophil migration to the upper mucosal layers. Some of these LPS induced changes (IL-8 release and neutrophil migration) were specific to CF tissues. SB203580 significantly controlled all LPS induced mucosal changes in CF tissues. CONCLUSION: These findings provide a rationale and proof of principle for the potential use of p38-MAP-k inhibitors to control inflammation in patients with CF.

Adolescent↗

Tonsillolith. Case report and review of the literature.

Large oropharyngeal concretions--giant tonsillolith--are not very common. Over the last few years only some 50 cases have been reported in the literature. Many tonsilloliths, especially small concretions, are asymptomatic; large concretions, on the contrary, may produce several symptoms. The case is described of a 56-year-old female complaining of dysphagia, odynophagia, sore throat, right otalgia and swelling in right tonsillar fossa. Routine panoramic radiography revealed a radio-opaque area in right tonsil region. Computed tomography of oropharynx was performed and axial slices revealed a calcified cylindrical lesion in posterior pharyngeal region, between palatoglossus and palatopharyngeus muscles. The tonsillolith was easily excised under local anaesthesia. The post-operative course was good with no recurrence. Microscopic examination of the specimen revealed necrotic debris, "ghost" cells, calcifications and inflammatory cells, confirming the diagnosis of tonsillolith. Authors stress that large tonsillar concretions are uncommon, and may be difficult to diagnose since the tonsillolith can also be mistaken for other anatomic and pathologic structures in the oropharyngeal area.

Adolescent↗

Clinical characteristics and genotype analysis of patients with cystic fibrosis and nasal polyposis.

The prevalence of nasal polyps in a group of paediatric patients with cystic fibrosis was prospectively studied in comparison with a control group with cystic fibrosis but without polyps. Clinical variables, including pulmonary function tests, skin testing and mucociliary transport, were carried out in both groups, as well as genotype analysis. Endoscopic intranasal evaluation identified polyps in 29 of 89 patients (33%). Statistical analysis revealed that patients with nasal polyposis had better pulmonary function, a higher rate of Pseudomonas aeruginosa colonization, more hospitalizations, and more prevalence of allergy to Aspergillus fumigatus than did the comparison group. We found no statistically different genotype distribution between the polyposis and the control group. However, it can be emphasized that the prevalence of the compound heterozygous genotype is higher in the nasal polyposis group than in controls. Our observations suggest that other genetic and environmental factors could play an important role in the development of nasal polyposis.

Child↗

European interlaboratory comparison of Lyme borreliosis serology.

Serological testing for Lyme borreliosis was compared in 5 European reference laboratories with a total of 79 sera in order to determine variations in laboratory performance. A considerable range of methods were used and several laboratories employed 2 or 3 genomospecies of Borrelia burgdorferi sensu lato. No laboratory relied routinely on a single test and each weighted the significance of the findings of the various tests differently. A difference in strategy between laboratories in high and low prevalence areas was apparent in that laboratories in low prevalence areas emphasised specificity more than sensitivity and therefore produced fewer false positives, but also missed some cases. Overall agreement between the laboratories was poor and it was concluded that there is a need for a quality assurance scheme within Europe.

Antibodies, Bacterial↗

European Lyme borreliosis clinical spectrum.

At a series of meetings, involving 27 clinicians from 11 countries, case definitions for the diagnosis of Lyme borreliosis in Europe were agreed and are presented here, with appropriate serological criteria, as a diagnostic guide. In a separate study questionnaires directed to clinicians were used to collect information on clinical aspects and risk factors of Lyme borreliosis. Data on the number of Lyme borreliosis patients seen by physicians indicated a low prevalence of the disease in western Europe and a relatively high prevalence in eastern Europe. The most commonly encountered symptom was erythema migrans, followed by neurological manifestations. Cardiac problems were rare. Tick bite was strongly associated with Lyme borreliosis, but the only other significantly associated risk factor was the pastime of gardening.

Diagnostic Errors↗

Lyme borreliosis awareness.

A Lyme borreliosis information leaflet has been produced to promote awareness amongst the general public. It was designed to provide a framework for similar material throughout Europe and complements a questionnaire produced to measure awareness of Lyme borreliosis. This questionnaire can be used to determine the impact of educational campaigns using material such as the leaflet. Feasibility studies showed that the questionnaire successfully highlighted predictable differences between sample groups and also that the leaflet performed well in increasing knowledge in low-awareness groups.

Blood Donors↗

Short-term cold-exposure does not improve insulin sensitivity in rats.

Effects of noradrenergic activation induced by short-term cold-exposure (7 days at 4 degrees C) on whole-body glucose utilization and tissue glucose uptake were investigated in rats. Measurements were realized on anesthetized normothermic animals at four different levels of insulinemia, within physiological range, allowing calculation of insulin sensitivity and responsiveness. Whole-body glucose utilization increased as a logarithmic function of insulinemias, and was always higher in cold-exposed than in control rats. However, neither insulin sensitivity nor responsiveness, literally, appeared different between the two groups. In the diaphragm, the only studied working muscle, glucose uptake was largely higher than in restin muscles. At basal insulin concentration, glucose uptake was higher in cold-exposed than in control rats and increased in the two groups with insulinemia. Among resting muscles, glucose uptake was increased by previous cold exposure in gastrocnemius, soleus, and tibialis. However, insulin sensitivity and responsiveness were found augmented only in the two former. In interscapular brown adipose tissue, glucose uptake was largely higher in cold-exposed than in control rats, but no difference could be evidenced in insulin sensitivity or responsiveness. In white adipose tissues, glucose uptake increased with insulinemia. Insulin responsiveness and sensitivity were higher only in the retroperitoneal depot.

Adipose Tissue↗

[Tissue microdialysis: practical and theoretical aspects].

Microdialysis is now widely used for the study of peripheral tissues. This technique allows the monitoring of metabolites and small molecules from the extracellular compartment as well as local delivery of metabolically active agents to this compartment. The purpose of this review was to present a practical approach (different types of probes, molecular cut-off, perfusion rate, dialysis buffer) and discuss the theoretical aspects of in vivo microdialysis (probe efficiency, recovery, perfusion rate, quantification of tissular metabolism). Our goal was to provide researchers with the practical tools needed for rapid mastery of in vivo tissular microdialysis.

Animals↗

In situ lipolysis measured by in vivo microdialysis during acute cold exposure.

The lipolytic responsiveness of interscapular white adipose tissue was measured, in male Sprague-Dawley rats (355 +/- 12 g, n = 7), by microdialysis before, during, and after an acute cold exposure (1 h at 4 degrees C). Microdialysis probes were perfused with standard Krebs-Ringer buffer to determine basal and stimulated rates of lipolysis. The concentration of glycerol in the dialysate was measured and considered as the lipolytic index. During the experiment, energy expenditure was measured by indirect calorimetry. Cold exposure at 4 degrees C doubled energy expenditure. At the same time, it resulted in a 2.7-fold increase in glycerol release. The present study shows that microdialysis is a perfectly adapted tool to investigate in vivo regulation of adipose tissue on awake, unrestrained rats.

Adipose Tissue↗

European Union Concerted Action on Risk Assessment in Lyme Borreliosis: clinical case definitions for Lyme borreliosis.

The EU Concerted Action on Risk Assessment in Lyme Borreliosis (EUCALB) has consulted other clinicians and scientists in Europe to produce case definitions of the principal manifestations of European Lyme borreliosis. These case definitions will not only be helpful in supporting its own research interests, but are also intended to assist other clinicians in appropriate management and to support further studies aimed at determining the full clinical spectrum of the disease. The case definitions were achieved after a series of meetings organised by EUCALB with other expert clinicians and scientists from twelve European countries. The definitions and the diagnostic criteria presented thus represent the consensus reached at these meetings. The proposed case definitions consider skin, nervous system, cardiac and musculoskeletal presentations and the role of laboratory investigation in supporting diagnosis.

Acrodermatitis↗

Demonstration of in vivo metabolic effects of 3,5-di-iodothyronine.

The objective of the present study was to test in vivo the metabolic effects of 3,5-di-iodothyronine (3,5-T2) in unanesthetized and unrestrained male Sprague-Dawley rats. Amino acid and lipid metabolisms were investigated by breath tests using as tracers the 13C-carboxyl-labeled molecules of leucine, alpha-ketoisocaproic acid (KIC) and octanoic acid, in four different groups of rats: hypothyroid animals (receiving propylthiouracil (PTU) and iopanoic acid), hypothyroid animals treated with either a daily i.p. injection of 3,5-T2 (25 micrograms/100 g body weight), or tri-iodothyronine (T3) (1 microgram/100 g body weight), and control euthyroid animals receiving equivalent volumes of the vehicle solutions. Energy expenditure was measured by continuous monitoring of O2 consumption and CO2 production in these different groups. Daily energy expenditure was decreased by 30% in PTU-treated rats. The chronic treatments with 3,5-T2 and T3 restored daily energy expenditure to the control level. 13CO2 recovered in breath following the i.v. injection of octanoic acid-[1-13C] was decreased in hypothyroid animals compared with control animals (P < 0.05) and restored to control values by T3 and 3,5-T2 treatments. The 13CO2 recovered in breath after i.v. injection of leucine-[1-13C] was increased in PTU-treated compared with control animals (P < 0.05). Chronic treatment with either 3,5-T2 or T3 restored 13CO2 to control values. Excretion of 13CO2 recovered in breath following the i.v. injection of KIC-[1-13C] was increased in PTU-treated compared with control animals. Chronic treatments with either 3,5-T2 or T3 did not restore KIC decarboxylation. These results suggest that 3,5-T2 exerts metabolic effects on energy expenditure, on both lipid beta-oxidation and leucine metabolism in hypothyroid rats. We conclude that 3,5-T2 is a metabolically active iodothyronine.

Amino Acids↗

In situ regulation of lipolysis by insulin and norepinephrine: a microdialysis study during euglycemic-hyperinsulinemic clamp.

Lipolytic responsiveness of subcutaneous and epididymal adipose tissue to norepinephrine (NE) was measured by microdialysis before and during a euglycemic-hyperinsulinemic clamp in male Sprague-Dawley rats (280 +/- 7g, n = 8). Microdialysis probes were perfused with standard Krebs-Ringer buffer without (basal condition [BC]) or with NE 10(-6) mol/L to determine basal and stimulated rates of lipolysis. The dialysate concentration of glycerol was measured (lipolytic index). NE infusion resulted in 3.0- and 4.2-fold increases in glycerol release in abdominal subcutaneous and epididymal adipose tissues, respectively. A euglycemic-hyperinsulinemic clamp at 6 mU/kg.min increased by ninefold the insulinemia (120 +/- 9 U/L). Hyperinsulinemia suppressed basal glycerol release by 57% and 42% in subcutaneous and epididymal adipose depots, respectively (BC + I). Lipolytic responses to NE infusion during a euglycemic-hyperinsulinemic clamp (NE + I) were reduced by 45% and 33% in subcutaneous and epididymal adipose tissues, respectively, as compared with BC. Under BC, the lipolytic response to NE was greater in epididymal than in subcutaneous adipose tissue. Physiological levels of insulin regulated basal lipolysis and counteracted adrenergic stimulation of lipolysis to a similar extent in both superficial (subcutaneous) and intraabdominal (epididymal) adipose tissue. Our findings show that lipolysis is more responsive to NE in epididymal than in subcutaneous adipose tissue. The antilipolytic effects of insulin are similar in both superficial and deep intraabdominal adipose tissues. Furthermore, physiological plasma insulin levels cannot fully antagonize the lipolytic effects of NE.

Adipose Tissue↗

Relationship between dose, mode of administration and effects of triiodothyronine on two hepatic responsive enzymes.

We have examined serum 3,3',5-triiodo-L-thyronine (T3) levels and the activity of two hepatic responsive enzymes [malic enzyme (ME) and alpha-glycerophosphate dehydrogenase (alpha-GPD)] in the livers of hypothyroid rats, under conditions where different doses of T3 (1 and 2.5 micrograms/100 g b.w.) were administered daily for one week either by intraperitoneal injection or by continuous infusions. In infused animals, serum T3 concentrations were constant for the whole period of treatment while in injected groups, widely oscillating diurnal levels were observed. The injection of 2.5 micrograms/100 g b.w. resulted, at the end of the treatment, in serum T3 levels which were higher than in animals receiving the same dose by infusion. No significant differences were observed when the administered dose was 1 microgram/100 g b.w. The basal levels of alpha-GPD and ME, which were markedly reduced in the livers of hypothyroid rats, were returned to normal both in infused rats (both with the dose of 1 microgram and 2.5 micrograms/100 g b.w. of T3) and in rats injected with a dose of 1 microgram/100 g b.w.). On the other hand, the dose of 2.5 micrograms/100 g b.w. when administered by injection, resulted in alpha-GPD and ME activities which were significantly higher even than those found in normal ones. The results indicate that both the diurnal T3 profile and the activity of the two hepatic T3 responsive enzymes are dependent not only on the dose but also on the administration mode.

Animals↗

[Results of a screening for atopy and aspecific bronchial hyperreactivity in 6-year-old children].

In the course of a clinic-anamnestic study performed from November 1984 to April 1985 by the collaborators of USL 40 Maternal-Infantile Service, among the children (1569) of the first primary school, 622 children has been selected for possible, probable and verified asthma. For making deeper the diagnosis, 358 children had gone to the respiratory allergologic section of division of pneumology and respiratory allergology of Cardarelli Hospital. The control group was formed from 12 children without atopic familiarity and without asthmatic tendency. Among the 358 children, 127 were asymptomatic but with familiar anamnesis positive for atopy; 219 had or had suffered allergic symptomatology. The authors had studied all children by Prick-test with a standard battery of allergens and with by methacholine aspecific bronchial reactivity test. The familiar tendency to atopy was present in 81.1% of studied children, with prevalence of maternal tendency (41,83%) in comparison with this of ascendents and collaterals. Among the asymptomatic subjects with atopic familiarity only 27.56% was skin positive for one or more allergens, while 59.82% of symptomatic subjects was skin positive. The bronchial aspecific reactivity with methacholine was increased in the 62% of asymptomatic and in the 84.69% of symptomatic subjects. The aspecific bronchial reactivity level in mean was higher in the children with bronchial asthma but also the subjects with rhinitis and chronic cough has showed a higher level in comparison with adults affected of similar symptomatology. In 8 children the authors have studied the reproduction of PD20 methacholine which was very high.

Age Factors↗