Maria Lo Presti

Intestinal permeability and genetic determinants in patients, first-degree relatives, and controls in a high-incidence area of Crohn's disease in Southern Italy.

OBJECTIVE:A defect of gastrointestinal barrier function is considered to represent an important step in the pathogenesis of Crohns disease (CD) but the mechanisms leading to an increased intestinal permeability (IP) are poorly understood. Since IP is influenced by pro-inflammatory mediators, it seems likely that a genetically determined abnormal immune response may lead to a loss of barrier function.METHODS:In a geographic area in Southern Italy with high incidence of CD we investigated IP (lactulose/mannitol testing) together with the three main mutations of the NOD2/CARD15 and the D299G polymorphism of the toll-like receptor (TLR)-4 gene in 23 families of CD patients (patients and first-degree relatives).RESULTS:Forty-eight percent of CD patients and 40% of their healthy relatives were found to have an abnormal IP compared to 5% of an appropriate control population (p < 0.0001). IP, however, was not associated with the L1007finsC mutation of the NOD2/CARD15 or the D299G variant of the TLR-4 gene. Allele frequency of the only L1007finsC mutation of CARD15 was significantly increased in patients (8.7%, p < 0.003) and in relatives (8.3%, p < 0.024) compared with controls (2.4%), whereas the D299G variant of the TLR-4 gene was found to be increased only in relatives (8.3%, p < 0.022), but not in patients (4.3%) compared with the control population (1.7%).CONCLUSIONS:There was no association between IP and genetic markers. Our findings showed a very high proportion of healthy first-degree relatives to bare alterations suggested to constitute determinants of CD. Mutations of NOD2/CARD15 or TLR-4, however, do not lead to permeability defects emphasizing the importance of additional environmental and/or genetic factors for pathogenesis.

Severe CMV-related pneumonia complicated by the hemophagocytic lymphohistiocytic (HLH) syndrome in quiescent Crohn's colitis: harmful cure?

In April 2009, a 32-year-old female was diagnosed with Crohn’s colitis; her history was positive for psoriasis and a cesarean section. The patient responded well to prednisone and a subsequent induction therapy with infliximab (5 mg/kg, three infusions); thereafter, she was set on azathioprine maintenance treatment (2.2 mg/kg/day). Eight months later, while in perfect clinical and biochemical remission, she developed high-grade fever (39.5 C) and was admitted on the third day to our unit. On admission, her temperature was 38.8 C, pulse rate 112 bpm, respiratory rate 35 breaths/min, and oxygen saturation of 82% on room air. The spleen was palpable 2 cm under the costal margin. The rest of the physical examination was unremarkable. Blood parameters showed pancytopenia (hemoglobin 8.1 g/dL; leukocytes 1260 el/lL x, platelets 53,000 el/lL), high levels of C-reactive protein, absent NK activity, hypertriglyceridemia (426 mg/ dL), and high values of serum ferritin (1260 lg/L). A chest film revealed bilateral infiltrates (Fig. 1A) and an ultrasound evaluation of the abdomen was negative except for a slightly enlarged spleen. Blood and urine cultures as well as serology for a number of viral and bacterial pathogens was performed and a combined broad spectrum antibiotic and antifungal treatment and methylprednisolone (20 mg/day) was started. On the second day she was transferred to the ICU because of increasing respiratory distress. Blood and urine culture were negative for bacteria and fungi. Serological studies for leishmaniasis, parvovirus B19, and human immunodeficiency virus (HIV) were negative. Polymerase chain reaction on peripheral blood was positive for CMV (2670 gEq/100,000 cells), while it was negative for human herpes virus (HHV)-6, HHV-8, and Epstein– Barr virus (EBV). Adding ganciclovir (5 mg/kg b.i.d. i.v.) to therapy the clinical picture improved within 20 days and the patient was discharged after a final control chest film (Fig. 1B) on oral valganciclovir (450 mg b.i.d.) until repeated negative results for CMV and normalization of peripheral lymphocyte subpopulations. After 1 year the patient is still in clinical remission without any therapy. Systemic infections due to CMV are well known in patients with inflammatory bowel disease (IBD), but usually associated with acute flares of disease and additive antiviral therapy improves outcome of colitis. Screening for latent CMV infection before immunosuppressive therapy is usually not recommended. In our patient with Crohn’s colitis, CMV pneumonia developed while under thiopurine monotherapy and in deep clinical remission similar to FIGURE 1. X-ray of the chest at the moment of diagnosis of CMV pneumonia (A) showing bilateral infiltrates and after resolution (B).

Seasonal variations of Teucrium flavum L. essential oil.

Abstract Essential oils from the aerial parts of Sicilian Teucrium flavum L., isolated by using microwave-assisted hydrodistillation (MHD), were analyzed for the first time at various seasonal stages (vegetative and budding stage) by means of GC/MS and GC-FID; the flowers and fruits were also subjected to examination. More than 80 compounds were identified as oil components. The leaf, flower and fruit oils were characterized by a predominance of sesquiterpenes, such as β-ryophyllene (3–5 g/100 g), germacrene D (4–14 g/100 g), β-bisabolene (32–49 g/100 g); the total amount of sesquiterpene hydrocarbons contained in each oil was 56–70 g/100 g, the oxygenated derivatives were in the range of 9–20 g/100 g. The monoterpene hydrocarbons in all samples (leaves, flowers, fruits) were contained in very low amounts, from 0.2 to 1.6 g/100 g, and were the least representative fraction of the oils. Oxygenated aliphatic compounds, especially esters, were also detected. The results can be useful to support, by means of a safe reliable sample preparation (MHD) and analytical (GC) technique, the research on medicinal plants belonging to Mediterranean flora.

Volatile Constituents of Tagetes bipinata L.

Abstract The essential oil of Tagetes bipinata L. (fam. Asteraceae) has been investigated by means of GC-FID and GC/MS. The use of a novel GC/MS library provided with a retention index filter tool has led to the identification of 36 volatiles. Accurate quantitative analysis has been carried out through the measurement of correction factors and analytical data have been expressed as g/100 g for each volatile determined. Major constituents of the oil were (Z)-β-ocimene (32.57 g/100 g), dihydrotagetone (9.38 g/100 g), (Z)-tagetone (4.62 g/100 g), (Z)- and (E)-ocimenone (3.07 and 2.51 g/100 g, respectively) and limonene (2.53 g/100 g). The total identified fraction accounted for 60.13 g/100 g.