Reconstruction of the columella with interposition of nasogenian flaps: A case report.

INTRODUCTION: Reconstructing large defects of the columella and upper lip is an interesting challenge in facial reconstruction due to the high visibility of this aesthetic subunit and the difficulties posed by the unique characteristics of the skin in these areas, which differs from that of the surrounding regions. Among the various techniques proposed, the use of local flaps remains the most commonly used and effective method in this type of reconstruction. PRESENTATION OF THE CASE: A 47-year-old man in good clinical condition presented with a nodular lesion on the columella and upper lip. The lesion was excised (revealing it to be a squamous cell carcinoma) and reconstructed using two opposing nasogenian flaps, resulting in an optimal aesthetic and functional restoration. DISCUSSION: The use of local flaps remains the most effective technique for columella defect reconstruction. However, many described techniques require multiple surgical stages or result in visible scarring. Additionally, they do not guarantee effective reconstruction in cases involving the upper lip. On the other hand, the use of free flaps, while more expensive and requiring expert teams, may not ensure optimal color and skin texture matching. CONCLUSIONS: The use of opposing nasogenian flaps allows for a rapid and effective reconstruction of defects involving the columella and upper lip, leading to a swift return to normal life for the patient.

Unusual molecular pattern in Ajugoideae subfamily: the case of Ajuga genevensis L. from Dolomites.

We analysed the ethanolic extract from Ajuga genevensis L. (Lamiaceae) growing in Dolomites, part of Italian Alps. Three new compounds for this species were identified: rosmarinic acid (1), oleanolic acid (2) and maslinic acid (3), representative of two different classes of chemical compounds (phenylpropanoids and pentacyclic triterpenes). A. genevensis resulted to be a valuable source of these compounds endowed with interesting biological activities (i.e. antioxidant, neuroprotective, anti-inflammatory, antiproliferative). The recognition of compounds (1), (2) and (3) may also confirm the ethnomedicinal uses of this plant. From a chemotaxonomical point of view, it is worth noting that iridoids were not evidenced in this accession. Iridoids are considered chemotaxonomic marker in Lamiales, and, in contrast with a previous study on this species, the presence of aucubin was not confirmed. In addition, the presence of large amounts of rosmarinic acid (1) was unexpected for a species that does not belong to subfamily Nepetoideae.

Growth hormone treatment of adolescents with growth hormone deficiency (GHD) during the transition period: results of a survey among adult and paediatric endocrinologists from Italy. Endorsed by SIEDP/ISPED, AME, SIE, SIMA.

Treatment of adolescents with growth hormone deficiency (GHD) during the transition period is a controversial issue. This paper is a contribution from the Italian community of paediatric and adult endocrinologists surveyed in a Delphi panel. The Delphi method is a structured communication technique, originally developed as a systematic, interactive forecasting method that relies on a panel of experts. The experts answer questionnaires in two or more rounds. There was substantial agreement on the definition of the problems associated with the diagnosis and treatment of adolescents with GHD in the transition period, as well as on the identification of the controversial issues which need further studies. There is general consensus on the need of re-testing all isolated idiopathic GHD after at least 30-day withdrawn from treatment, while in patients with multiple pituitary deficiency and low IGF-I levels there is generally no need to re-test. In patients with permanent or confirmed GHD, a starting low rhGH dose (0.01-0.03 mg per day) to be adjusted according to IGF-I concentrations is also widely accepted. For those continuing treatment, the optimal therapeutic schedule to obtain full somatic maturation, normalization of body composition and bone density, cardiovascular function and Quality of Life, need to be evaluated.

Hypericum perforatum L. subsp. perforatum induces inhibition of free radicals and enhanced phototoxicity in human melanoma cells under ultraviolet light.

OBJECTIVES: Our interest continues in discovering phytocomplexes from medicinal plants with phototoxic activity against human melanoma cells; thus the aim of the present study was to assess antioxidant, anti-inflammatory and phototoxic activity of Hypericum perforatum L. subsp. perforatum, and relate these properties to the plant's chemical composition. MATERIALS AND METHODS: Components of H. perforatum subsp. perforatum were extracted by hydroalcoholic solution and chemical profiles of preparations (HyTE-3) performed by HPTLC. Linoleic acid peroxidation and DPPH tests were used to assess antioxidant activity, while MTT assay allowed evaluation of anti-proliferative activity with respect to A375 human melanoma cells after irradiation with UVA dose, 1.8 J/cm(2) . Inhibition of nitric oxide production of macrophages was also investigated. RESULTS: HyTE-3 indicated better antioxidant activity with ß-carotene bleaching test in comparison to DPPH assay (IC50 = 0.89 µg/ml); significant phototoxicity in A375 cells at 78 µg/ml concentration resulted in cell destruction of 50%. HyTE-3 caused significant dose-related inhibition of nitric oxide production in murine monocytic macrophage cell line RAW 264.7 with IC50 value of 342 µg/ml. CONCLUSIONS: The H. perforatum subsp. perforatum-derived product was able to suppress proliferation of human malignant melanoma A375 cells; extract together with UVA irradiation enhanced phototoxicity. This biological activity of antioxidant effects was combined with inhibition of nitric oxide production.

Interleukin-9 and mast cells.

Mast cells are granulated hematopoietic cells derived from stem cells that reside in nearly all tissues and are involved in protection of a host from bacterial infection with a protective and pathogenic activity. Mast cells are important for both innate and adaptive immunity in tissues which are in close contact with the environment. These cells express proinflammatory cytokines such as IL-1, IL-6, IL-8 and tumor necrosis factor which are necessary for innate immunity. Mast cells also produce interleukin-9 and enhance mast cell expression of several cytokines including IL-1beta, IL-5, IL-6, IL-9 and IL-13. In addition, IL-9 can induce mast cell production of TGF-beta which can have proinflammatory downstream effects. IL-9 can function as either a positive or a negative regulator of immune responses and can have a detrimental role in allergy and autoimmunity. Furthermore, IL-9 contributes to disease by promoting mast cell expansion and production of IL-13 which in turn contributes to airway hyperresponsiveness. Here, in this editorial we review the interrelationship between IL-9 and mast cells.

Nutrition and cancer prevention.

Cancer cells invade surrounding tissues and metastasize to distant sites. Diet high in fat is a strong link to, and perhaps causes, a high incidence of tumours. Trans-fatty acid might impair the function and it could be involved in the development of cancer. Cholesterol is also strongly suspected to be involved in the development of tumours, therefore it is important for everyone to eat well, especially for people with cancer to prevent the body tissues from breaking down and helping to rebuild the normal tissue that may have been affected by the treatments. Factors secreted by adipocytes and macrophages such as TNF-alpha and other inflammatory proteins are involved in inflammation in cancer. In addition, MCSF which up-regulates adipocyte tissue is also important for the stimulation of fat cell proliferation and is expressed by human adipocytes. Many cytokines, such as IL-1, IL-6, IL-8, IL-32, IL-33 and MCP-1, are biomarkers for cancer and chronic diseases along with transcription factors NFκB and AP-1; these last two factors are important bioactive substances on the molecular mechanism of the control of genes which in turn affect cellular metabolism. In this paper we revisit the interrelationship between cancer and metabolism.

Epidemiology of SHOX deficiency.

Deletion of short stature homeobox-containing (SHOX) gene, in the pseudoautosomal region (PAR1) of X and Y chromosomes, is an important cause of short stature. Homozygous loss of SHOX results in the more severe Langer mesomelic dysplasia, while SHOX haploinsufficiency cause a wide spectrum of short stature phenotypes, including patients with Turner syndrome, Leri Weill dyschondrosteosis (LWD), and idiopathic short stature (ISS). In Turner syndrome, haploinsufficiency of SHOX gene, as well as short stature, are present in 100%; nevertheless, SHOX deficiency accounts for only two-thirds of Turner patients' short stature. In LWD the prevalence of SHOX gene anomalies varies from 56% to 100%. This wide range might be due to different factors such as selection criteria of patients, sample size, and method used for screening SHOX mutations. The real challenge is to establish the prevalence of SHOX deficiency in ISS children given that published studies have reported this association with a very broad frequency range varying from 1.5% to 15%. An important variable in these studies is represented by the method used for screening SHOX mutations and sometimes by differences in patient selection. Short stature is present by definition in 3 out of 100 subjects; if we consider a frequency of SHOX defects of 3% among ISS, we should expect a population prevalence of 1 in 1000. This prevalence would be higher than that of GH deficiency (1:3,500) and of Turner syndrome (1:2,500 females), suggesting that SHOX deficiency could be one of the most frequent monogenetic causes of short stature.

Pharmacological and phytochemical study on a Sisymbrium officinale Scop. extract.

ETHNOPHARMACOLOGICAL RELEVANCE: The aerial parts of Sisymbrium officinale Scop. are commonly used to treat airway ailments, moreover in antiquity the herbal drug was reputed to possess anticancer properties. The results obtained in present work support the traditional use and the properties ascribed to Sisymbrium officinale. AIM OF THE STUDY: In order to give a scientific basis to the traditional uses of Sisymbrium officinale, this study was aimed to evaluate in vitro the myorelaxant activity, the antimicrobial properties and the antimutagenic effect of an aqueous dry extract of the aerial parts of the plant. A phytochemical characterization of the extract was also performed. MATERIALS AND METHODS: The myorelaxant activity was studied against the contractions induced by carbachol, histamine and leukotriene C(4), in isolated guinea-pig trachea. The antimicrobial activity was tested against six bacteria and one yeast. The Ames test, performed by the preincubation method, was used to study the antimutagenic activity of the extract by its capability to inhibit the mutagenic effect of 2-nitrofluorene, sodium azide, methyl methanesulfonate and 2-aminoanthracene, in Salmonella typhimurium TA98, Salmonella typhimurium TA100 and Escherichia coli WP2uvrA strains. The chemical composition of the extract was analyzed by TLC and HPLC. RESULTS: Sisymbrium officinale showed to reduce the chemically-induced contractions of isolated guinea-pig trachea with major potency against leukotriene C(4) and histamine. The extract did not show any antibacterial activity. The Ames test showed a strong antimutagenic activity against 2-aminoanthracene, in Escherichia coli WP2uvrA and in Salmonella typhimurium TA98 strains. The phytochemical study highlighted the presence of putranjivine, the glucosinolate marker of Sisymbrium officinale, and of proline. CONCLUSIONS: The myorelaxant activity of Sisymbrium officinale offers a scientific basis to its use in traditional medicine. The strong antimutagenic effect suggests further studies to evaluate its possible chemopreventive activity.

Effect of Curcuma zedoaria crude extract against tumor progression and immunomodulation

The aim of the present work was to study the effect of the crude extract of Curcuma zedoaria on peripheral blood cells and tumor progression in C57Bl/6J mice injected with B16F10 murine melanoma cells. The intraperitoneal therapy showed a significant increase in total white and red blood cell counts, a decrease in peritoneal cell number and tumor volume reduction, whereas the oral administration revealed a noteworthy augmentation only in total leukocyte count. These results contribute to evaluate the importance of alternative treatments that employ phytotherapic compounds against tumor progression and its possible immunomodulation.

Chlamydia pneumoniae induces T cell apoptosis through glutathione redox imbalance and secretion of TNF-alpha.

Chlamydia pneumoniae persistent infection has been implicated in the pathogenesis of several chronic inflammatory diseases including atherosclerosis, and we hypothesized that modulation of the apoptosis of macrophages and/or T cells by C. pneumoniae infection may contribute to the development of such diseases. We therefore evaluated apoptosis, cytokine response, and redox status in human primary T cells and macrophages infected with C. pneumoniae. In addition, co-cultures of T cells and macrophages infected with C. pneumoniae were also carried out. Apoptosis, and levels of glutathione (GSH), glutathione disulfide (GSSG), and tumour necrosis factor (TNF)-alpha were measured by flow cytometry, high performance liquid chromatography and enzyme-linked immunosorbent assay. C. pneumoniae induced apoptosis in T cells as well as in co-cultures of T cells and infected macrophages by marked decrease in GSH/GSSG ratio and increased production of TNF-alpha, respectively. The results demonstrate that interaction of C. pneumoniae with T cells and/or macrophages characterized by interference with redox status, and secretion of tumour necrosis factor-alpha culminates in the induction of T cell apoptosis and survival of infected macrophages. In conclusion, the inappropriate T cell response against C. pneumoniae and survival of infected macrophages could explain the persistence of this intracellular obligate pathogen in the host-organism; it may contribute to the development of chronic inflammatory diseases, although further studies are needed to clarify such a complex mechanism.

Bovine lactoferrin inhibits the efficiency of invasion of respiratory A549 cells of different iron-regulated morphological forms of Pseudomonas aeruginosa and Burkholderia cenocepacia.

Pseudomonas aeruginosa and Burkholderia cenocepacia are two important opportunistic respiratory pathogens of cystic fibrosis (CF) patients. Infections caused by these microorganisms are particularly difficult to eradicate because they are usually highly resistant to several currently available broad-spectrum antibiotics. Lactoferrin (Lf), a glycoprotein found in physiological fluids of mammals and present at high concentrations in infected and inflamed tissues, plays an important role in the natural defence mechanism against pathogens and in immune regulation. In the present study, we evaluate the ability of bovine lactoferrin (bLf) to influence P. aeruginosa PAO1 and B. cenocepacia PV1 adhesiveness and invasiveness, using the A549 human bronchial cell line. Three different iron-induced morphological forms of bacteria (free-living, aggregates and biofilm) were assayed. The addition of bLf to cells just before infection had little influence on adhesion efficiency for all three of the morphological forms of B. cenocepacia PV1, while a slight increase in adhesion efficiency by P. aeruginosa PAO1 was noticed. Conversely, invasion of all three morphological forms of both P. aeruginosa and B. cenocepacia was strongly inhibited by the presence of bLf, independently of its degree of iron-binding activity. This is the first report demonstrating an anti-invasive property of bLf for strains of P. aeruginosa and B. cenocepacia.

Primary effusion lymphoma cells undergoing human herpesvirus type 8 productive infection produce C-type retroviral particles.

Primary effusion lymphomas (PELs) are invariably infected by the human herpesvirus 8 (HHV8)that is present in most PEL cells as latent virus but replicates in a subset of permissive cells to produce infectious progeny. Here we show that productively infected PEL cells release C-type retrovirus-like particles encoding an Mn++-dependent RT activity, which is typical of endogenous retroviruses. Strikingly, C-type particles are produced only in cells showing advanced HHV8 morphogenesis. Phorbol esters, which induce productive HHV8 replication and morphogenesis in PEL cells, increase RLP production. Phosphonoacetic acid, a blocker of HHV8 late gene expression, inhibits the production of C-type particles, whereas neutralizing anti-alphaIFN antibodies, which are known to increase HHV8 assembly, increases C-type particle production. These data suggest that factors expressed in advanced stages of HHV8 reactivation support endogenous C-type particle morphogenesis in PEL cells.

Molecular characterization of virulence determinants of Stenotrophomonas maltophilia strains isolated from patients affected by cystic fibrosis.

Stenotrophomonas maltophilia is an emerging nosocomial bacterial pathogen which is currently isolated with increasing frequency from the airways of cystic fibrosis (CF) patients. In this study 13 S. maltophilia strains (11 isolated from the airways of independent CF patients, and two non-CF respiratory reference strains) have been characterized for the expression of several virulence-associated factors. In particular, the ability to form biofilm on abiotic surfaces has been determined and correlated with different features, such as motility, adherence and the ability to invade A549 respiratory epithelial cells. Moreover, the presence of a flagellum-associated gene as well as that of the StmPr1 gene, which encodes an extracellular protease, have been determined by Southern blot hybridization. Our data indicate that the different degree of biofilm formation exhibited by the 11 CF isolates does not correlate with motility, ability to adhere to and invade A549 cells, or with the presence of flagella. On the other hand, among the CF isolates the StmPr1 gene was found only in two strains, both able to establish chronic lung infections in CF patients. Moreover, only four of the strains analyzed show a temperature-independent antibiotic-resistance profile, suggesting either a different origin of these strains or an intervening adaptation to host tissues.

Apyrase, the product of the virulence plasmid-encoded phoN2 (apy) gene of Shigella flexneri, is necessary for proper unipolar IcsA localization and for efficient intercellular spread.

The role in virulence of the Shigella flexneri ospB-phoN2 operon has been evaluated. Here we confirm that OspB is an effector and show that apyrase, the product of phoN2, may be a virulence factor, since it is required for efficient intercellular spreading. Apyrase may be important in a deoxynucleoside triphosphate-hydrolyzing activity-independent manner, suggesting that it may act as an interaction partner in the process of IcsA localization.

Bronchodilator activity of Phymatodes scolopendria (Burm.) Ching and its bioactive constituent.

Phymatodes scolopendria (Burm.) Ching (Polypodiaceae) is widely used in the Eastern coast of Madagascar to treat respiratory disorders. Bioassay-guided fractionation using guinea pig trachea pre-contracted with histamine to monitor the activity led to the isolation of 1,2-benzopyrone (coumarin) as the main active constituent. Effectively, it induced a concentration-dependent relaxation of the histamine with a median effective concentration (EC(50)) of 35.03 microg/ml, or carbachol (EC(50) = 33.41 microg/ml) pre-contracted guinea pig trachea, and also provoked 100% relaxation at 72.10 microg/ml. It was less active either on KCl pre-contracted trachea (EC(50) = 130.78 microg/ml) or endothelium denuded trachea (153.4 +/- 22 microg/ml). It inhibited, in a non-competitive manner, the histamine and the external calcium spasm effect on the isolated trachea but it did not significantly modify the broncho-constrictive activity of KCl. When combined with theophylline, coumarin produced a significant additive relaxing effect on pre-contracted trachea. Furthermore, its bronchodilator effect was not blocked by propranolol. In vivo, pre-treated guinea pig with coumarin showed significant resistance to histamine inhalation, with an adequate dose protecting 50% of the tested animals (AD(50)) of 75 mg/kg. These results indicate that the bronchodilator effect of coumarin is partly due to the endothelium-dependent tracheal relaxation, and may be mediated through a non-specific tracheal relaxation.

Cytotoxic activity of the root extract from Myoschilos oblongum.

The crude methanolic root extract of Myoschilos oblongum exhibited a significant cytotoxic activity against PZ-HPV-7 human prostate cells. Furthermore, two esters of docosanol were isolated from the CH(2)Cl(2) extract.

Growth and puberty in thalassemia major.

Present transfusional regimen protocols increase the life expectancy of patients with beta-thalassemia major, but cause a progressive iron overload that can be prevented or limited only by appropriate iron chelation. Siderosis is responsible for the clinical complications of the disease. Short stature and hypogonadism are extremely frequent in patients with thalassemia. Many factors are responsible for short stature in patients with thalassemia, the most important of which are dysfunction of the GH-IGF-I axis and desferoxamine (DFX)-induced bone dysplasia. Hypogonadism is the most frequent endocrine complication, mostly due to gonadotrophins deficiency secondary to iron overload. Sex steroid treatment for induction of puberty and/or maintenance of sexual characteristics is necessary. Both short stature and hypogonadism are present in a significant percentage of bone marrow transplanted patients with thalassemia. Factors responsible for short stature are previous iron overload, liver impairment, DFX treatment, and toxicity of chemotherapeutic agents. In some patients absence of pubertal development is due to gonadotropin insufficiency, probably secondary to previous iron overload; other patients exhibit hypergonadotrophic hypogonadism due to the toxic effect of chemotherapeutic agents on the gonads. Both groups need hormonal replacement therapy. These data support the need for vigilant follow-up of patients with thalassemia before and after transplantation, in order to treat endocrine dysfunctions at the appropriate age.

[Focal segmental glomerulosclerosis with IgA deposits in a patient with ulcerative colitis]. / Glomerulosclerosi focale segmentale con depositi di IgA in un paziente con rettocolite ulcerosa.

BACKGROUND: Glomerular diseases are described in patients with active ulcerative colitis (UC). Likely drug-induced interstitial nephritis, and nephrotic syndrome due to minimal change disease, have been reported in a few patients with UC on treatment with mesalazine and sulfasalazine (5-ASA). We describe a 33 year-old patient with a 5-years history of UC who recently developed nephrotic syndrome associated with microscopic haematuria. Blood pressure and renal function were normal. The patient was on azathioprine (AZA), mesalazine and sulfasalazine during the last year for his colitis, with good control of bowel disease. Renal biopsy revealed a focal segmental glomerulosclerosis (FSGS) associated with mesangial IgA deposits; no signs of interstitial nephritis were found. 5-ASA was discontinued, AZA was reduced and a rapid remission of the nephrotic syndrome was observed after 6 weeks of steroid therapy (1 mg/kg/day per os) associated with ramipril 5 mg/day, with a follow-up of 9 months. CONCLUSIONS: To our knowledge this is the first report of UC and GSFS associated with IgA deposits. The occurrence of nephrotic syndrome during UC is suggestive of an association between UC and FSGS, but a possible role of mesalazine and /or sulfasalazine in its pathogenesis cannot be excluded. Mesangial IgA deposits could be an "occasional" further occurrence, considering the chronic inflammation of colonic mucosa and the altered immune response of patients with UC.

Expression of beta-tubulin isotypes in human ovarian carcinoma xenografts and in a sub-panel of human cancer cell lines from the NCI-Anticancer Drug Screen: correlation with sensitivity to microtubule active agents.

Paclitaxel resistance has been associated with overexpression of P-glycoprotein and alterations involving tubulin. To investigate the clinical relevance of these in vitro resistance mechanisms, we established 12 human ovarian carcinoma xenografts, using samples from patients before the start of therapy or after paclitaxel treatment. These xenografts showed a wide range of sensitivity to paclitaxel, and in 4 of them, very low levels of multidrug resistance-1 expression were detected. Using quantitative PCR and human specific primers, the expression of five beta-tubulin isotypes was determined. HM40 was the predominant, accounting for 84.7-98.7% of all tubulin; expression of the other four isotypes (Hbeta9, Hbeta4, H5beta, and Hbeta2) was also detected but at lower levels. No correlation could be demonstrated between isotype expression and paclitaxel sensitivity in these 12 xenografts. A similar pattern of beta-tubulin isotype expression was observed in a subset of cell lines from the National Cancer Institute-Anticancer Drug Screen. In these cell lines, however, a significant correlation between increased expression of Hbeta4 isotype and resistance to paclitaxel was found. Taken together, these results suggest that altered expression of specific beta-tubulin isotypes may not play a significant role in paclitaxel sensitivity in vivo and argue against a possible significance in a clinical setting.