Emergency laparoscopic ileo-colic resection and primary intracorporeal anastomosis for Crohn's acute ileitis with free perforation and faecal peritonitis: first ever reported laparoscopic treatment.

INTRODUCTION: Laparoscopy for abdominal surgical emergencies is gaining increasing acceptance given the spreading of advanced laparoscopic skills among modern surgeons, as it may allow at the same time an accurate diagnosis and appropriate treatment of acute abdomen. The use of the laparoscopic approach also in case of diffuse peritonitis is now becoming accepted provided hemodynamic stability, despite the common belief in the past decades that such severe condition represented an indication for conversion to open surgery or an immediate contraindication to continue laparoscopy. Crohn's Disease (CD) is a rare cause of acute abdomen and peritonitis, only a few cases of CD acute perforations are reported in the published literature; these cases have always been approached and treated by open laparotomy. CASE DESCRIPTION: We report on a case of a faecal peritonitis due to an acute perforation caused by a terminal ileitis in an undiagnosed CD. The patient underwent diagnostic laparoscopy followed by a laparoscopic ileo-colic resection and primary intracorporeal anastomosis, with a successful postoperative outcome. CONCLUSIONS: Complicated CD has to be considered within the possible causes of small bowel non-traumatic perforation. Emergency laparoscopy with resection and primary intra-corporeal anastomosis can be feasible and may be a safe and effective minimally invasive alternative to open surgery even in case of faecal peritonitis, in selected stable patients and in presence of appropriate laparoscopic colorectal surgical skills and experience. To the best of our knowledge the present experience is the first ever reported case managed with a totally laparoscopic extended ileocecal resection with intracorporeal anastomosis in case of acutely perforated CD and diffuse peritonitis.

Analysis of mid-infrared lasing in active random media.

Lasing behaviour of 2-dimensional active random structures, designed to work in the Mid-IR region, has been investigated at different input powers by varying the amount of scattering intensity. A Monte Carlo based simulation tool has been developed including a model to manage the optical amplification. The analysis of photon travel distance has been considered to show the random lasing behaviour with particular attention on lasing threshold at different scattering intensity. The simulated results are in agreement with experiments.

Modal analysis in 2D media with variable disorder.

Modal properties of 2D disordered optical structures have been numerically analyzed, in the Mid-IR region, varying the amount of scattering and the disorder level. The modal properties study has been carried out through the use of Finite Element Method, highlighting the localized regime transition and investigating the quality factor. The results have been interpreted in a statistical fashion, investigating light diffusion in these structures with the help of Monte Carlo Method. An alternative measure of randomness weight has been proposed to support the numerical results.

Thermally resilient Tm-doped large mode area photonic crystal fiber with symmetry-free cladding.

The design of a Tm-doped photonic crystal fiber with ∼ 80 µm core diameter and robust single-mode guiding is proposed. State-of-art modal discrimination is obtained through the suppression of the inner cladding C(6ν) symmetry, which fosters the delocalization of the LP(11)-like mode. The effects of thermally-induced refractive index change are investigated by means of a computationally-efficient thermal model, and the possibility to obtain wide-band single-mode propagation and effective area exceeding 2500 µm(2) under a heat load of over 300 W/m is demonstrated.

Evidence for complex binding profiles and species differences at the translocator protein (TSPO) (18 kDa).

The translocator protein (TSPO) (18 kDa) is an emerging drug target for the treatment of numerous pathologies including cancer and neurodegenerative disease. However, our limited knowledge of TSPO binding site(s) has hindered the development of TSPO ligands with potential therapeutic effects. We have synthesized a series of pyrrolobenzoxazepines (1-10) to better characterize the interaction of ligands with the TSPO across species, and to determine their functional profiles. All ligands 1-10 displaced the binding of [3H]PK 11195 to the TSPO at nanomolar concentrations, with discrepancies in binding affinity between rat and human TSPO. Interestingly, non-linear regression analysis revealed that some ligands bound to the protein with a Hill slope not equal to 1.0, suggesting possible additional TSPO binding sites with allosteric effects. However, this trend was not conserved between rat and human. When tested for their effects on pregnenolone production in rat C6 glioma cells, nitric oxide release in murine microglia, and cell proliferation in human MCF-7 breast cancer cells, the pyrrolobenzoxazepines (40 µM) displayed functional effects which did not correlate to the binding trend observed in competition assays. We propose that consideration of species differences and binding site cooperativity, plus optimization of currently accepted functional assays, will aid in the development of drugs targeting TSPO that can be used as therapeutics for human disease.

Cut-off analysis of 19-cell Yb-doped double-cladding rod-type photonic crystal fibers.

Yb-doped double-cladding large mode area rod-type photonic crystal fibers are a key component for power scaling in fiber laser systems. Recently, designs with 19-cell core defect, that is with 19 missing air-holes in the center of the photonic crystal cladding, have been proposed, with reported core diameter up to 100 µm. In this paper an analysis of the cut-off wavelength of the first high-order mode in such low-NA fibers is reported, accounting for different approaches for the definition of the cladding effective index. Results have shown that taking into account the finite fiber cross-section and considering the first cladding mode of the actual fiber is mandatory to obtain a correct estimate of the cut-off wavelength.

A therapeutic dose of FK506 does not affect collagen turnover pathways in healthy human gingival fibroblasts.

We previously demonstrated that a high dose of tacrolimus (1 mumol/L) induced expression of matrix metalloproteinase (MMP) proteins in human cultured gingival fibroblasts, suggesting a molecular mechanism maintaining gingival collagen homeostasis in tacrolimus-treated patients. Herein we have analyzed whether the effect on collagen turnover might be influenced by a therapeutic tacrolimus dose. Human gingival fibroblasts were incubated for 72 hours with 10 nmol/L, 100 nmol/L, and 1 mumol/L tacrolimus, or left untreated (CT). Collagen type I and III (COL-I, COL-III), lysyl hydroxylase 2b (LH2b), MMP-1 and -2, tissue inhibitor of MMP-1 and transforming growth factor-beta1 (TGF-beta1) mRNA levels were assayed by reverse-transcriptase polymerase chain reaction, collagen protein levels by dot blot, and MMP activity by sodium dodecyl sulfate zymography. Tacrolimus did not affect COL-I, COL-III, or MMP gene expression, while LH2b and TGF-beta1 tended to be down-regulated after 1 mumol/L FK506. Conversely, protein levels of MMP-1 (P = NS) and MMP-2 (P < .05 vs CT, 10 nmol/L, 100 nmol/L) were up-regulated after 1 mumol/L tacrolimus. Our findings confirmed that a high dose of tacrolimus does not induce interstitial collagen overexpression by gingival fibroblasts and induces up-regulation of MMPs protein levels. Interestingly, at doses corresponding to whole blood trough levels, tacrolimus did not exert any evident effect on collagen turnover pathways, suggesting that tacrolimus is likely to not affect collagen homeostasis in the gingival connective tissue compartment of FK506-immunosuppressed subjects. This effect did not seem to be dose-dependent.

Confinement loss spectral behavior in hollow-core Bragg fibers.

The influence of each cross-section geometric parameter on hollow-core Bragg fiber guiding properties has been numerically investigated. Fabricated fibers have been modeled, giving insight into the spectral behavior of the confinement loss. It has been verified that, by changing the amount of silica and air in the fiber cladding, it is possible to change the reflection conditions undergone by the field within the core, thus shifting the confinement loss spectrum.

Toll-like receptor agonists regulate beta-defensin 2 release in hair follicle.

BACKGROUND: Skin is constantly in contact with different pathogens, which are present in the environment. The hair follicle is particularly susceptible to this microbial invasion as it offers an easy way of access for microorganisms; for this reason it is equipped with defence mechanisms to avoid frequent infections. OBJECTIVES: To analyse the expression pattern of four different members of the toll-like receptor (TLR) family in murine hair follicles and to evaluate the effects of their activation by their specific microbiota-derived agonists, in terms of production of the antimicrobial peptide beta-defensin 2 (DEFB2). METHODS: TLR and DEFB2 protein expression was investigated by immunohistochemistry on murine skin samples. RESULTS: Murine hair follicle expresses TLR2, TLR4 and TLR5; agonists of TLR2, TLR4 and TLR5 but not of TLR9 induced DEFB2 production in this compartment. The strongest DEFB2 expression was observed following TLR4 activation by lipopolysaccharide. CONCLUSIONS: Our data show that the hair follicle is equipped with TLR2, TLR4 and TLR5, and that these receptors are able to respond to microbial stimuli inducing the production of DEFB2 by epithelial cells. This immune response might be important in preserving the skin from microorganism infections.

Major hepatectomy in patients with synchronous colorectal liver metastases: whether or not a contraindication to simultaneous colorectal and liver resection?

OBJECTIVE: Synchronous hepatic lesions account for 15-25% of newly diagnosed colorectal cancer and its optimal timing to surgery is not completely defined, but simultaneous colorectal and liver resection is recently gaining acceptance, at least in patients with a right colonic primary and liver metastases that need a minor hepatectomy to be fully resected. METHOD: From September 2002 to December 2004, 16 patients underwent simultaneous resection as treatment of synchronous colorectal liver resection; in 10 patients (62.5%) a major hepatectomy was performed. RESULTS: The mean duration of intervention was 322.5 +/- 59.5 min, operative mortality and morbidity rates was 0% and 25% respectively; the hospitalization was 14.4 (range 8-60) days on average. Mean follow-up was 14 months and actuarial survival was 76.5% at 1 year and 63.5% at 2 years. CONCLUSION: We concluded that simultaneous colonic and liver resection should be undertaken in selected patients with synchronous colorectal liver resection regardless of the extent of hepatectomy; major liver resection, in fact, seems capable of providing better oncological results, allowing resection of liver micrometastases that, in almost one-third of the patients, are located in the same liver lobe of macroscopic lesions, without increased morbidity rates.

Improved synthesis of the peripheral benzodiazepine receptor ligand [11C]DPA-713 using [11C]methyl triflate.

Recently, the pyrazolopyrimidine, [11C] N,N-Diethyl-2-[2-(4-methoxyphenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-yl]acetamide (DPA-713) has been reported as a new promising marker for the study of peripheral benzodiazepine receptors with positron emission tomography. In the present study, DPA-713 has been labelled from the corresponding nor-analogue using [11C]methyl triflate (CH3OTf). Conditions for HPLC were also modified to include physiological saline (aq. 0.9% NaCl)/ethanol:60/40 as mobile phase making it suitable for injection. The total time of radiosynthesis, including HPLC purification, was 18-20 min. This reported synthesis of [11C]DPA-713, using [11C]CH3OTf, resulted in an improved radiochemical yield (30-38%) compared to [11C]methyl iodide (CH3I) (9) with a simpler purification method. This ultimately enhances the potential of [11C]DPA-713 for further pharmacological and clinical evaluation. These improvements make this radioligand more suitable for automated synthesis which is of benefit where multi-dose preparations and repeated syntheses of radioligand are required.

Single-mode regime of square-lattice photonic crystal fibers.

The modal cutoff of square-lattice photonic crystal fibers with a finite number of air-hole rings has been accurately investigated to our knowledge for the first time. By analyzing the leaky behavior of the second-order mode, we have obtained a phase diagram that describes the regions of single-mode and multimode operation as well as the endlessly single-mode regime. Furthermore, starting from these results, we have obtained the cutoff normalized frequency according to two different formulations of the V parameter previously adopted for fibers with a triangular lattice. A final comparison of the cutoff properties of fibers characterized by a square lattice and a triangular lattice has been carried out.

Caveolin-1 is expressed on multipotent cells of hair follicles and might be involved in their resistance to chemotherapy.

BACKGROUND: Caveolin-1 is the principal protein that composes caveolae, which are vesicular invaginations present on the plasma membrane of different cell types. Caveolae are involved in a variety of cellular functions including regulation of proliferation rate and resistance to chemotherapeutic drugs. Chemotherapy frequently induces alopecia which is reversible most probably due to the low proliferative rate of hair follicle stem cells and due to the expression of proteins which confer resistance. OBJECTIVES: Using a specific animal model and immunohistochemistry, we analysed the expression of both caveolin-1 and the cell proliferation marker beta-catenin, at different stages of the hair follicle cycle, both before and after doxorubicin (DXR) -induced alopecia. METHODS: Seven-week-old C57BL/6 mice were depilated in order to synchronize hair follicle cycle in the anagen phase. Chemotherapy with DXR 15 mg kg(-1) was used to induce alopecia. Control and treated mice were then sacrificed at precise time points and caveolin-1 expression in hairs at different stages of the cycle were analysed by immunohistochemistry. By double immunofluorescence, colocalization of caveolin-1 and cytokeratin-15 was confirmed in the bulge region. The state of proliferation of cells composing hair follicle was assessed by beta-catenin immunohistochemistry. RESULTS: Caveolin-1 was expressed by the cells of the bulge area, the multipotent compartment of the hair follicle, during all phases of growth (anagen), regression (catagen) and resting (telogen). During the anagen phases, nuclear beta-catenin labelling was not observed in bulge cells, but rather in the deeper portion of the follicle. Damaged hair follicles from DXR-treated mice presented bulge cells which still expressed caveolin-1, suggesting that this protein might play a role in their drug resistance. As expected, no beta-catenin nuclear staining was detectable in DXR-treated hair follicles, indicating the complete lack of proliferative processes. The differential localization of caveolin-1 and beta-catenin suggests that the mutually exclusive expression of these proteins is useful for correct hair regrowth, whether during the physiological cycle or after chemotherapy-induced alopecia. CONCLUSIONS: Expression of caveolin-1 within the multipotent cell compartment of the hair follicle can explain the resistance of bulge cells to many chemotherapeutics, suggested by the reversibility of chemotherapy-induced alopecia.

Dispersion properties of square-lattice photonic crystal fibers.

In this paper the guiding properties of photonic crystal fibers with a square lattice of air-holes in a silica matrix have been studied for the first time. The dispersion curves of fibers with different hole-to-hole spacing and air-hole diameter have been accurately calculated. Negative values of the dispersion parameter and the dispersion slope have been obtained with a hole-to-hole spacing of 1 microm. A comparison between fibers with square and triangular lattice has been also performed, taking into account the dispersion properties and the effective area in the wavelength range between 1200 nm and 1600 nm.

Leakage properties of photonic crystal fibers.

An analysis of the con.nement losses in photonic crystal fibers due to the finite numbers of air holes is performed by means of the finite element method. The high flexibility of the numerical method allows us to consider fibers with regular lattices, like the triangular and the honeycomb ones, and circular holes, but also fibers with more complicated cross sections like the cobweb fiber. Numerical results show that by increasing the number of air hole rings the attenuation constant decreases. This dependence is very strong for triangular and cobweb fibers, whereas it is very weak for the honeycomb one.

2-Arylpyrazolo[1,5-a]pyrimidin-3-yl acetamides. New potent and selective peripheral benzodiazepine receptor ligands.

A new class of N,N-diethyl-(2-arylpyrazolo[1,5-a]pyrimidin-3-yl)acetamides (3f-y), as azaisosters of Alpidem, was prepared following a novel synthetic method and their affinities for both the peripheral (PBR) and the central (CBR) benzodiazepine receptors were evaluated. Binding assays were carried out using both [3H]PK 11195 and [3H]Ro 5-4864 as radioligands for PBR, whereas [3H]Ro 15-1788 was used for CBR, in rat kidney and rat cortex, respectively. The tested compounds exhibited a broad range of binding affinities from as low as 0.76 nM to inactivity and most of them proved to be high selective ligands for PBR. The preliminary SAR studies suggested some of the structural features required for high affinity and selectivity; particularly the substituents on the pyrimidine moiety seemed to play an important role in PBR versus CBR selectivity. A subset of the highest affinity compounds was also tested for their ability to stimulate steroid biosynthesis in C6 glioma rat cells and some of these were found to increase pregnenolone formation with potency similar to Ro 5-4864 and PK 11195.

Three-dimensional finite-element beam propagation method: assessments and developments

In recent years the finite-element method (FEM) has been widely applied to three-dimensional beam propagation analysis, and several FEM propagators have been presented. Up to now, as far as we know, an exhaustive, deep, and comparative analysis of these formulations and of the related algorithms has never been presented. We critically analyze and numerically compare, to our knowledge for the first time, different vectorial, semivectorial, and scalar formulations in order to check their performances, point out weaknesses, and suggest future developments. The results obtained highlight once more the inadequacy of scalar approaches in dealing with actual photonics devices and suggest vector formulations worthy of further development and future research.

Gene therapy of experimental brain tumors using neural progenitor cells.

Glioblastomas, the most frequent and malignant of primary brain tumors, have a very poor prognosis. Gene therapy of glioblastomas is limited by the short survival of viral vectors and by their difficulty in reaching glioblastoma cells infiltrating the brain parenchyma. Neural stem/progenitor cells can be engineered to produce therapeutic molecules and have the potential to overcome these limitations because they may travel along the white matter, like neoplastic cells, and engraft stably into the brain. Retrovirus-mediated transfer of the gene for interleukin-4 is an effective treatment for rat brain glioblastomas. Here, we transferred the gene for interleukin-4 into C57BL6J mouse primary neural progenitor cells and injected those cells into established syngeneic brain glioblastomas. This led to the survival of most tumor-bearing mice. We obtained similar results by implanting immortalized neural progenitor cells derived from Sprague-Dawley rats into C6 glioblastomas. We also documented by magnetic resonance imaging the progressive disappearance of large tumors, and detected 5-bromodeoxyuridine-labeled progenitor cells several weeks after the injection. These findings support a new approach for gene therapy of brain tumors, based on the grafting of neural stem cells producing therapeutic molecules.

Benzodiazepine receptor ligands. III. Synthesis and biological evaluation of 2- and/or 3-substituted pyrazolo[5,1-c][1,2,4]benzotriazine 5-oxides.

A new series of 2- and/or 3-substituted pyrazolo [5,1-c][benzotriazine 5-oxides and their 8-chloro derivatives were synthesized, and their benzodiazepine receptor (BZR) affinities were evaluated in vitro in comparison to lead compound 3-ethoxycarbonyl-8-chloropyrazolo[5,1-c][1,2,4]benzotriazine 5-oxide (29) [1,2]. None of the new compounds showed significant affinity for BZR. On the basis of a pharmacophore/receptor model suggested for lead compound 29, some hypotheses to explain the inactivity of new derivatives are discussed.